tDCS Publications

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This bibliographic resource includes a selection of peer-reviewed publications indexed on PubMed. The inclusion of these reports in this bibliography does not in any way imply an endorsement of the protocol or results reported in these studies by Soterix Medical. It remains the responsibility of the device user to remain informed of all current, relevant tDCS practices. tDCS is an investigational medical technique and has not been cleared by the FDA and therefore can only be used for research under appropriate Institutional Review Board guidelines.
Authors Title Year Journal
Varga ET, Terney D, Atkins MD, Nikanorova M, Jeppesen DS, Uldall P, Hjalgrim H, Beniczky S Transcranial direct current stimulation in refractory continuous spikes and waves during slow sleep: A controlled study. 2011 Epilepsy research
Cathodal transcranial direct current stimulation (tDCS) decreases cortical excitability. The purpose of the study was to investigate whether cathodal tDCS could interrupt the continuous epileptiform activity. Five patients with focal, refractory continuous spikes and waves during slow sleep were recruited. Cathodal tDCS and sham stimulation were applied to the epileptic focus, before sleep (1mA; 20min). Cathodal tDCS did not reduce the spike-index in any of the patients.
Hesse MD, Sparing R, Fink GR Ameliorating spatial neglect with non-invasive brain stimulation: From pathophysiological concepts to novel treatment strategies. 2011 Neuropsychological rehabilitation
Neglect is a multifaceted, complex syndrome, in which patients fail to detect or respond to stimuli or parts thereof located contralesionally. Non-invasive brain stimulation by means of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) may not only be useful as diagnostic research tools to explore the pathophysiology of neglect, but also for ameliorating its symptoms. Current approaches for modulating neglect non-invasively are mainly based on the neurophysiological concept of interhemispheric inhibition, which suggests a pathological overactivation of the contralesional hemisphere due to reduced inhibitory influences from the lesioned one. Within this framework, non-invasive brain stimulation mainly aims to inhibit the contralesional hemisphere to allow for rebalancing the system. However, facilitatory protocols for enhancing the ipsilesional neural circuitry might also prove useful. In this review, we discuss the contribution of non-invasive brain stimulation to current pathological concepts of neglect, the promising results of the proof-of-principle studies currently available as well as the specific aspects to be systematically investigated before broader clinical trials may eventually suggest a routine clinical application.
Marangolo P, Marinelli CV, Bonifazi S, Fiori V, Ceravolo MG, Provinciali L, Tomaiuolo F Electrical stimulation over the left inferior frontal gyrus (IFG) determines long-term effects in the recovery of speech apraxia in three chronic aphasics. 2011 Behavioural brain research
A number of studies have shown that modulating cortical activity by means of transcranial direct current stimulation (tDCS) affects the performance of both healthy and brain-damaged subjects. In this study, we investigated the potential of tDCS for the recovery of apraxia of speech in 3 patients with stroke-induced aphasia. Over 2 weeks, three aphasic subjects participated in a randomized double-blinded experiment involving intensive language training for their articulatory difficulties in two tDCS conditions. Each subject participated in five consecutive daily sessions of anodic tDCS (20min, 1mA) and sham stimulation over the left inferior frontal gyrus (referred to as Broca's area) while they performed a repetition task. By the end of each week, a significant improvement was found in both conditions. However, all three subjects showed greater response accuracy in the anodic than in the sham condition. Moreover, results for transfer of treatment effects, although different across subjects, indicate a generalization of the recovery at the language test. Subjects 2 and 3 showed a significant improvement in oral production tasks, such as word repetition and reading, while Subjects 1 and 2 had an unexpected significant recovery in written naming and word writing under dictation tasks. At three follow-ups (1 week, 1 and 2 months after the end of treatment), response accuracy was still significantly better in the anodic than in sham condition, suggesting a long-term effect on the recovery of their articulatory gestures.
Schlaug G, Marchina S, Wan CY The Use of Non-invasive Brain Stimulation Techniques to Facilitate Recovery from Post-stroke Aphasia. 2011 Neuropsychol Rev
Aphasia is a common symptom after left hemispheric stroke. Neuroimaging techniques over the last 10-15 years have described two general trends: Patients with small left hemisphere strokes tend to recruit perilesional areas, while patients with large left hemisphere lesions recruit mainly homotopic regions in the right hemisphere. Non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have been employed to facilitate recovery by stimulating lesional and contralesional regions. The majority of these brain stimulation studies have attempted to block homotopic regions in the right posterior inferior frontal gyrus (IFG) to affect a presumed disinhibited right IFG (triangular portion). Other studies have used anodal or excitatory tDCS to stimulate the contralesional (right) fronto-temporal region or parts of the intact left IFG and perilesional regions to improve speech-motor output. It remains unclear whether the interhemispheric disinhibition model, which is the basis for motor cortex stimulation studies, also applies to the language system. Future studies could address a number of issues, including: the effect of lesion location on current density distribution, timing of the intervention with regard to stroke onset, whether brain stimulation should be combined with behavioral therapy, and whether multiple brain sites should be stimulated. A better understanding of the predictors of recovery from natural outcome studies would also help to inform study design, and the selection of clinically meaningful outcome measures in future studies.
McKinley RA, Bridges N, Walters CM, Nelson J Modulating the brain at work using noninvasive transcranial stimulation. 2011 NeuroImage
This paper proposes a shift in the way researchers currently view and use transcranial brain stimulation technologies. From a neuroscience perspective, the standard application of both transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) has been mainly to explore the function of various brain regions. These tools allow for noninvasive and painless modulation of cortical tissue. In the course of studying the function of an area, many studies often report enhanced performance of a task during or following the stimulation. However, little follow-up research is typically done to further explore these effects. Approaching this growing pool of cognitive neuroscience literature with a neuroergonomics mindset (i.e., studying the brain at work), the possibilities of using these stimulation techniques for more than simply investigating the function of cortical areas become evident. In this paper, we discuss how cognitive neuroscience brain stimulation studies may complement neuroergonomics research on human performance optimization. And, through this discussion, we hope to shift the mindset of viewing transcranial stimulation techniques as solely investigatory basic science tools or possible clinical therapeutic devices to viewing transcranial stimulation techniques as interventional tools to be incorporated in applied science research and systems for the augmentation and enhancement of human operator performance.
Boggio PS, Ferrucci R, Mameli F, Martins D, Martins O, Vergari M, Tadini L, Scarpini E, Fregni F, Priori A Prolonged visual memory enhancement after direct current stimulation in Alzheimer's disease. 2011 Brain stimulation
BACKGROUND: Immediately after patients with Alzheimer's disease (AD) receive a single anodal transcranial direct current stimulation (tDCS) session their memory performance improves. Whether multiple tDCS sessions improve memory performance in the longer term remains unclear. OBJECTIVE: In this study we aimed to assess memory changes after five consecutive sessions of anodal tDCS applied over the temporal cortex in patients with AD. METHODS: A total of 15 patients were enrolled in two centers. Cognitive functions were evaluated before and after therapeutic tDCS. tDCS was delivered bilaterally through two scalp anodal electrodes placed over the temporal regions and a reference electrode over the right deltoid muscle. The stimulating current was set at 2 mA intensity and was delivered for 30 minutes per day for 5 consecutive days. RESULTS: After patients received tDCS, their performance in a visual recognition memory test significantly improved. We found a main effect of tDCS on memory performance, i.e., anodal stimulation improved it by 8.99% from baseline, whereas sham stimulation decreased it by 2.62%. tDCS failed to influence differentially general cognitive performance measures or a visual attention measure. CONCLUSIONS: Our findings show that after patients with AD receive anodal tDCS over the temporal cerebral cortex in five consecutive daily sessions their visual recognition memory improves and the improvement persists for at least 4 weeks after therapy. These encouraging results provide additional support for continuing to investigate anodal tDCS as an adjuvant treatment for patients with AD.
Javadi AH, Walsh V Transcranial direct current stimulation (tDCS) of the left dorsolateral prefrontal cortex modulates declarative memory. 2011 Brain stimulation
BACKGROUND: Previous studies have claimed that weak transcranial direct current stimulation (tDCS) induces persisting activity changes in the human motor cortex and working memory, but to date no studies have evaluated the effects of tDCS on declarative memory. OBJECTIVE: Our aim was to determine whether anodal and cathodal transcranial direct current stimulation would differentially modify performance in a word memorization task during encoding or recognition when administered over the left dorsolateral prefrontal cortex (DLPFC). METHODS: In two experiments, 32 participants underwent a series of word memorization tasks. This task was performed during sham, anodal, and cathodal stimulation applied over the left DLPFC. Moreover, participants in the first experiment performed the same task with anodal tDCS of the primary motor cortex (M1). RESULTS: During encoding, anodal stimulation of the left DLPFC improved memory, whereas cathodal stimulation of the same area impaired memory performance in later recognition. Anodal stimulation of M1 had no effect on later recognition. During recognition cathodal stimulation of the left DLPFC impaired recognition compared with sham stimulation of the same area and anodal stimulation had a trend toward improving the recognition. CONCLUSIONS: The results indicated that active stimulation of the left DLPFC leads to an enhancement or impairment of verbal memorization depending on the polarity of the stimulation. Furthermore, this effect was specific to the site of stimulation.
Venkatakrishnan A, Sandrini M Combining Transcranial Direct Current Stimulation and neuroimaging: Novel insights in understanding neuroplasticity. 2011 Journal of neurophysiology
In recent years, non-invasive brain stimulation techniques like transcranial direct current stimulation (tDCS) have gained immense popularity owing to their effects on modulating cortical activity and consequently motor and cognitive performance. However, the neurophysiology underlying such neuroplastic changes is less understood. This mini-review will critically evaluate the contemporary approach of combined tDCS and neuroimaging as a means to provide novel insights in understanding the neurophysiological and neuroplastic processes modulated by this brain stimulation technique. We will end by briefly suggesting further lines of inquiry.
Pena-Gomez C, Vidal-Pineiro D, Clemente IC, Pascual-Leone A, Bartres-Faz D Down-regulation of negative emotional processing by transcranial direct current stimulation: effects of personality characteristics. 2011 PLoS ONE
Evidence from neuroimaging and electrophysiological studies indicates that the left dorsolateral prefrontal cortex (DLPFC) is a core region in emotional processing, particularly during down-regulation of negative emotional conditions. However, emotional regulation is a process subject to major inter-individual differences, some of which may be explained by personality traits. In the present study we used transcranial direct current stimulation (tDCS) over the left DLPFC to investigate whether transiently increasing the activity of this region resulted in changes in the ratings of positive, neutral and negative emotional pictures. Results revealed that anodal, but not cathodal, tDCS reduced the perceived degree of emotional valence for negative stimuli, possibly due to an enhancement of cognitive control of emotional expression. We also aimed to determine whether personality traits (extraversion and neuroticism) might condition the impact of tDCS. We found that individuals with higher scores on the introversion personality dimension were more permeable than extraverts to the modulatory effects of the stimulation. The present study underlines the role of the left DLPFC in emotional regulation, and stresses the importance of considering individual personality characteristics as a relevant variable, although replication is needed given the limited sample size of our study.
Hesse S, Waldner A, Mehrholz J, Tomelleri C, Pohl M, Werner C Combined Transcranial Direct Current Stimulation and Robot-Assisted Arm Training in Subacute Stroke Patients: An Exploratory, Randomized Multicenter Trial. 2011 Neurorehabilitation and neural repair
BACKGROUND: No rehabilitation intervention has effectively improved functional use of the arm and hand in patients with severe upper limb paresis after stroke. Pilot studies suggest the potential for transcranial direct current stimulation and bilateral robotic training to enhance gains. OBJECTIVE: In a double-blind, randomized trial the combination of these interventions was tested. METHODS: This study randomized 96 patients with an ischemic supratentorial lesion of 3 to 8 weeks' duration with severe impairment of motor control with a Fugl-Meyer score (FMS) for the upper limb <18 into 3 groups. For 6 weeks, group A received anodal stimulation of the lesioned hemisphere, group B received cathodal stimulation of the nonlesioned side for 20 minutes at 2.0 mA, and group C received sham stimulation. The electrodes were placed over the hand area and above the contralateral orbit. Contemporaneously, the subjects practiced 400 repetitions each of 2 different bilateral movements on a robotic assistive device. RESULTS: The groups were matched at onset. The FMS improved in all patients at 6 weeks (P < .001). No between-group differences were found; initial versus finish FMS scores were 7.8 ± 3.8 versus 19.1 ± 14.4 in group A, 7.9 ± 3.4 versus 18.8 ± 10.5 in group B, and 8.2 ± 4.4 versus 19.2 ± 15.0 in group C. No significant changes between groups were present at 3 months. CONCLUSIONS: Neither anodal nor cathodal transcranial direct current stimulation enhanced the effect of bilateral arm training in this exploratory trial of patients with cortical involvement and severe weakness. Unilateral hand training and upregulation of the nonlesioned hemisphere might also be tried in this POPULATION:
Holland R, Leff AP, Josephs O, Galea JM, Desikan M, Price CJ, Rothwell JC, Crinion J Speech facilitation by left inferior frontal cortex stimulation. 2011 Curr. Biol.
Electrophysiological studies in humans and animals suggest that noninvasive neurostimulation methods such as transcranial direct current stimulation (tDCS) can elicit long-lasting [1], polarity-dependent [2] changes in neocortical excitability. Application of tDCS can have significant and selective behavioral consequences that are associated with the cortical location of the stimulation electrodes and the task engaged during stimulation [3-8]. However, the mechanism by which tDCS affects human behavior is unclear. Recently, functional magnetic resonance imaging (fMRI) has been used to determine the spatial topography of tDCS effects [9-13], but no behavioral data were collected during stimulation. The present study is unique in this regard, in that both neural and behavioral responses were recorded using a novel combination of left frontal anodal tDCS during an overt picture-naming fMRI study. We found that tDCS had significant behavioral and regionally specific neural facilitation effects. Furthermore, faster naming responses correlated with decreased blood oxygen level-dependent (BOLD) signal in Broca's area. Our data support the importance of Broca's area within the normal naming network and as such indicate that Broca's area may be a suitable candidate site for tDCS in neurorehabilitation of anomic patients, whose brain damage spares this region.
Brunoni AR, Fregni F, Pagano RL Translational research in transcranial direct current stimulation (tDCS): a systematic review of studies in animals. 2011 Rev Neurosci
Abstract Recent therapeutic human studies testing transcranial direct current stimulation (tDCS) has shown promising results, although many questions remain unanswered. Translational research with experimental animals is an appropriate framework for investigating its mechanisms of action that are still undetermined. Nevertheless, animal and human studies are often discordant. Our aim was to review tDCS animal studies, examining and comparing their main findings with human studies. We performed a systematic review in Medline and other databases, screening for animal studies in vivo that delivered tDCS. Studies in vitro and using other neuromodulatory techniques were excluded. We extracted data according to Animal Research: Reporting In Vivo Experiments (ARRIVE) guidelines for reporting in vivo animal research. Thus, we collected data on sample characteristics (size, gender, weight and specimen) and methodology (experimental procedures, experimental animals, housing and husbandry, as well as analysis). We also collected data on methods for delivering tDCS (location, size, current and current density of electrodes and electrode montage), experimental effects (polarity-, intensity- and after-effects) and safety. Only 12 of 48 potentially eligible studies met our inclusion criteria and were reviewed. Quality assessment reporting was only moderate and studies were heterogeneous regarding tDCS montage methodology, position of active and reference electrodes, and current density used. Nonetheless, almost all studies demonstrated that tDCS had positive immediate and long-lasting effects. Vis-à-vis human trials, animal studies applied higher current densities (34.2 vs. 0.4 A/m(2), respectively), preferred extra-cephalic positions for reference electrodes (60% vs. 10%, respectively) and used electrodes with different sizes more often. Potential implications for translational tDCS research are discussed.
Paulus W Transcranial electrical stimulation (tES - tDCS; tRNS, tACS) methods. 2011 Neuropsychological rehabilitation
Weak transcranial direct current stimulation (tDCS) with a homogenous DC field at intensities of around 1 mA induces long-lasting changes in the brain. tDCS can be used to manipulate brain excitability via membrane polarisation: cathodal stimulation hyperpolarises, while anodal stimulation depolarises the resting membrane potential, whereby the induced after-effects depend on polarity, duration and intensity of the stimulation. A variety of other parameters influence tDCS effects; co-application of neuropharmacologically active drugs may most impressively prolong or even reverse stimulation effects. Transcranial alternating stimulation (tACS) and random noise stimulation (tRNS) are used to interfere with ongoing neuronal oscillations and also finally produce neuroplastic effects if applied with appropriate parameters.
Homan P, Kindler J, Federspiel A, Flury R, Hubl D, Hauf M, Dierks T Muting the voice: a case of arterial spin labeling-monitored transcranial direct current stimulation treatment of auditory verbal hallucinations. 2011 Am J Psychiatry
Teo F, Hoy KE, Daskalakis ZJ, Fitzgerald PB Investigating the Role of Current Strength in tDCS Modulation of Working Memory Performance in Healthy Controls. 2011 Front Psychiatry
Transcranial direct current stimulation (tDCS) is a brain stimulation technique that has the potential to improve working memory (WM) deficits in many clinical disorders. The aim of this study was to investigate the role of current strength on the ability of anodal tDCS to improve WM, and secondly to investigate the time course of effects. Twelve healthy participants underwent three stimulation sessions consisting of 20 min of either 1 mA anodal tDCS, 2 mA anodal tDCS, or sham tDCS to the left dorsolateral prefrontal cortex (DLPFC) localized via F3, all whilst completing a WM task. Intra-stimulation and post-stimulation WM performances were measured using the n-back and Sternberg tasks respectively. Results revealed no significant improvements in participants' accuracy, but a significant interaction was found with respect to current strength and time for accurate reaction time. The finding provides partial support for the hypothesis, in that it appears current strength may affect aspects of WM performance. However, more research is needed, and a higher difficulty level of WM tasks is one of the suggestions discussed for future research.
Frank E, Schecklmann M, Landgrebe M, Burger J, Kreuzer P, Poeppl TB, Kleinjung T, Hajak G, Langguth B Treatment of chronic tinnitus with repeated sessions of prefrontal transcranial direct current stimulation: outcomes from an open-label pilot study. 2011 Journal of neurology
Tinnitus is the perception of sound in the absence of an environmental sound source. Abnormal activity in central auditory pathways is considered as the neuronal correlate of tinnitus. However, there is increasing evidence from neuroimaging studies for an additional involvement of the frontal cortex in the pathophysiology of tinnitus, especially concerning its attentional and emotional aspects. Recently, in a subgroup of tinnitus patients, temporary reduction of tinnitus intensity and tinnitus-related distress has been reported after bifrontal tDCS with the anode over the right and the cathode over the left dorsolateral prefrontal cortex (DLPFC). The aim of this study was to investigate whether repeated application of bifrontal tDCS results in longer-lasting reduction of tinnitus and may represent a potential treatment approach. Thirty-two patients with chronic and treatment-resistant tinnitus received six sessions of bifrontal tDCS (1.5 mA, 30 min, two sessions per week) with the anode over the right and the cathode over the left DLPFC. Treatment outcome was assessed with several standardized tinnitus questionnaires, numeric rating scales, and a depression scale. In the entire group, beneficial effects of bifrontal tDCS on tinnitus were found for numeric rating scores of loudness, unpleasantness, and discomfort, but not in tinnitus or depression scales. Exploratory analysis revealed an effect of gender on treatment effects with female patients demonstrating a better response in several scores. Our open-label pilot study suggests some beneficial effect of bifrontal tDCS (anode right and cathode left) in the treatment of severe tinnitus, warranting further controlled studies.
Bolognini N, Vallar G, Casati C, Abdul Latif L, El-Nazer R, Williams J, Banco E, Macea DD, Tesio L, Chessa C, Fregni F Neurophysiological and Behavioral Effects of tDCS Combined With Constraint-Induced Movement Therapy in Poststroke Patients. 2011 Neurorehabilitation and neural repair
BACKGROUND: Recovery of motor function after stroke may depend on a balance of activity in the neural network involving the affected and the unaffected motor cortices. OBJECTIVE: To assess whether transcranial direct current stimulation (tDCS) can increase the training-induced recovery of motor functions. METHODS: In an exploratory study, 14 patients with chronic stroke and mean Fugl-Meyer Upper Extremity Motor Assessment of 29 (range = 8-50) entered a double-blind sham-controlled study, aimed to investigate neurophysiological and behavioral effects of bihemispheric tDCS (cathodal stimulation of the unaffected motor cortex and anodal stimulation of the affected motor cortex), combined with constraint-induced movement therapy (CIMT). RESULTS: Patients in both groups demonstrated gains on primary outcome measures, that is, Jebsen Taylor Hand Function Test, Handgrip Strength, Motor Activity Log Scale, and Fugl-Meyer Motor Score. Gains were larger in the active tDCS group. Neurophysiological measurements showed a reduction in transcallosal inhibition from the intact to the affected hemisphere and increased corticospinal excitability in the affected hemisphere only in the active tDCS/CIMT group. Such neurophysiological changes correlated with the magnitude of the behavioral gains. Both groups showed a reduction in corticospinal excitability of the unaffected hemisphere. CONCLUSIONS: CIMT alone appears effective in modulating local excitability but not in removing the imbalance in transcallosal inhibition. Bihemispheric tDCS may achieve this goal and foster greater functional recovery.
Vanneste S, De Ridder D Bifrontal transcranial direct current stimulation modulates tinnitus intensity and tinnitus-distress-related brain activity. 2011 Eur. J. Neurosci.
Bifrontal transcranial direct current stimulation (tDCS), with the anodal electrode overlying the right and the cathodal electrode overlying the left dorsolateral prefrontal cortex, has been shown to suppress tinnitus significantly in 30% of patients. The source localized resting-state electrical activity is recorded before and after bifrontal tDCS in patients who respond to tDCS to unravel the mechanism by which tDCS suppresses tinnitus. The present electroencephalography study (N = 12) provides support for the ability of bifrontal tDCS to suppress tinnitus intensity and tinnitus-related distress by modulation of the pregenual anterior cingulate cortex, parahippocampal area and right primary auditory cortex in resting-state spontaneous brain activity. These findings provide direct support for tDCS having an impact not only directly on the underlying dorsolateral prefrontal cortex but also indirectly on functionally connected brain areas relevant for tinnitus distress and tinnitus intensity, respectively.
Mordillo-Mateos L, Turpin-Fenoll L, Millan-Pascual J, Nunez-Perez N, Panyavin I, Gomez-Arguelles JM, Botia-Paniagua E, Foffani G, Lang N, Oliviero A Effects of simultaneous bilateral tDCS of the human motor cortex. 2011 Brain stimulation
BACKGROUND: Transcranial direct current stimulation (tDCS) is a noninvasive technique that has been investigated as a therapeutic tool for different neurologic disorders. Neuronal excitability can be modified by application of DC in a polarity-specific manner: anodal tDCS increases excitability, while cathodal tDCS decreases excitability. Previous research has shown that simultaneous bilateral tDCS of the human motor cortex facilitates motor performance in the anodal stimulated hemisphere much more than when the same hemisphere is stimulated using unilateral anodal motor cortex tDCS. OBJECTIVE: The main purpose of this study was to determine whether simultaneous bilateral tDCS is able to increase cortical excitability in one hemisphere whereas decreasing cortical excitability in the contralateral hemisphere. To test our hypothesis, cortical excitability before and after bilateral motor cortex tDCS was evaluated. Moreover, the effects of bilateral tDCS were compared with those of unilateral motor cortex tDCS. METHODS: We evaluated cortical excitability in healthy volunteers before and after unilateral or bilateral tDCS using transcranial magnetic stimulation. RESULTS: We demonstrated that simultaneous application of anodal tDCS over the motor cortex and cathodal tDCS over the contralateral motor cortex induces an increase in cortical excitability on the anodal-stimulated side and a decrease in the cathodal stimulated side. We also used the electrode montage (motor cortex-contralateral orbit) method to compare the bilateral tDCS montage with unilateral tDCS montage. The simultaneous bilateral tDCS induced similar effects to the unilateral montage on the cathode-stimulated side. On the anodal tDCS side, the simultaneous bilateral tDCS seems to be a slightly less robust electrode arrangement compared with the placement of electrodes in the motor cortex-contralateral orbit montage. We also found that intersubject variability of the excitability changes that were induced by the anodal motor cortex tDCS using the bilateral montage was lower than that with the unilateral montage. CONCLUSIONS: This is the first study in which cortical excitability before and after bilateral motor cortex tDCS was extensively evaluated, and the effects of bilateral tDCS were compared with unilateral motor cortex tDCS. Simultaneous bilateral tDCS seems to be a useful tool to obtain increases in cortical excitability of one hemisphere whereas causing decreases of cortical excitability in the contralateral hemisphere (e.g.,to treat stroke).
Nakamura-Palacios EM, de Almeida Benevides MC, da Penha Zago-Gomes M, de Oliveira RW, de Vasconcellos VF, de Castro LN, da Silva MC, Ramos PA, Fregni F Auditory event-related potentials (P3) and cognitive changes induced by frontal direct current stimulation in alcoholics according to Lesch alcoholism typology. 2011 The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)
Frontal lobe dysfunction is a hallmark of alcohol dependence. Recent studies have shown that a simple but powerful technique of cortical modulation - transcranial direct current stimulation (tDCS) - can induce significant cognitive changes. We therefore aimed to assess the clinical and electrophysiological (as indexed by P3) effects of tDCS of left dorsolateral prefrontal cortex (DLPFC) in different types of alcoholic patients according to Lesch's typology. We enrolled 49 alcoholic subjects, aged between 18 and 75 yr, during the subacute abstinence period to participate in this study. Subjects underwent event-related potential (ERP) registration of alcohol-related and neutral sounds before, during and after active tDCS (1 mA, 35 cm2, during 10 min) or sham procedure in a counterbalanced and randomized order. Frontal assessment battery (FAB) and five items of the Obsessive Compulsive Drinking Scale were applied at the beginning and at the end of each experimental session. ERP analysis showed an increase in the mean amplitude of P3 associated with alcohol-related sounds after tDCS. This effect was not seen for neutral sounds. This change was more pronounced in Lesch IV alcoholics. Secondary exploratory analysis showed a significant improvement of FAB performance after active tDCS compared to sham tDCS in Lesch IV alcoholics only. We showed clinical and electrophysiological evidence of tDCS-induced frontal activity enhancement that was specific for Lesch IV alcoholics. Given that frontal dysfunction may contribute to the loss of control over drinking behaviour, local increase in frontal activity induced by tDCS might have a beneficial clinical impact in the future.
Hammer A, Mohammadi B, Schmicker M, Saliger S, Munte TF Errorless and errorful learning modulated by transcranial direct current stimulation. 2011 BMC Neurosci
Rubio-Morell B, Rotenberg A, Hernandez-Exposito S, Pascual-Leone A [The use of noninvasive brain stimulation in childhood psychiatric disorders: new diagnostic and therapeutic opportunities and challenges]. 2011 Rev Neurol
Novel diagnostic and therapeutic approaches based on noninvasive brain stimulation offer some promise in the field of childhood psychiatric disorders. There are two primary methods of noninvasive brain stimulation currently available: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Both noninvasive neuromodulation techniques appear to rely on modulating brain plasticity and thus open new hopes in the treatment of brain circuit and plasticity disorders. Since many childhood psychiatric disorders involve disturbances in the timing or mechanisms of plasticity within frontostriatal circuits, and the developing brain shows a greater capacity of brain plasticity, noninvasive brain stimulation might induce greater benefits in this population than in adults. Although the utilization of TMS and tDCS remains limited in children, there is enough evidence for their rational, safe use in this population. In this paper, we review the principles of noninvasive brain stimulation and the diagnostic and therapeutic applications in child-hood psychiatric disorders in order to inform its development into safe and reliable diagnostic and effective therapeutic approaches in pediatric psychiatry.
Datta A, Baker JM, Bikson M, Fridriksson J Individualized model predicts brain current flow during transcranial direct-current stimulation treatment in responsive stroke patient. 2011 Brain Stimul
Although numerous published reports have demonstrated the beneficial effects of transcranial direct-current stimulation (tDCS) on task performance, fundamental questions remain regarding the optimal electrode configuration on the scalp. Moreover, it is expected that lesioned brain tissue will influence current flow and should therefore be considered (and perhaps leveraged) in the design of individualized tDCS therapies for stroke. The current report demonstrates how different electrode configurations influence the flow of electrical current through brain tissue in a patient who responded positively to a tDCS treatment targeting aphasia. The patient, a 60-year-old man, sustained a left hemisphere ischemic stroke (lesion size = 87.42 mL) 64 months before his participation. In this study, we present results from the first high-resolution (1 mm(3)) model of tDCS in a brain with considerable stroke-related damage; the model was individualized for the patient who received anodal tDCS to his left frontal cortex with the reference cathode electrode placed on his right shoulder. We modeled the resulting brain current flow and also considered three additional reference electrode positions: right mastoid, right orbitofrontal cortex, and a "mirror" configuration with the anode over the undamaged right cortex. Our results demonstrate the profound effect of lesioned tissue on resulting current flow and the ability to modulate current pattern through the brain, including perilesional regions, through electrode montage design. The complexity of brain current flow modulation by detailed normal and pathologic anatomy suggest: (1) That computational models are critical for the rational interpretation and design of individualized tDCS stroke-therapy; and (2) These models must accurately reproduce head anatomy as shown here.
Dockery CA, Liebetanz D, Birbaumer N, Malinowska M, Wesierska MJ Cumulative benefits of frontal transcranial direct current stimulation on visuospatial working memory training and skill learning in rats. 2011 Neurobiology of learning and memory
Transcranial direct current stimulation (tDCS) of the prefrontal cortex, which non-invasively alters cortical activity, has been established to affect executive functions in humans. We hypothesized that changes in excitability by tDCS, found to improve cognitive functions dependent on moderate prefrontal cortex activity, would operate similarly in animals as in humans. To verify this we performed experiments using a rat behavioral model of visuospatial working memory and skill learning paired with tDCS of the frontal cortex. The effect of anodal/cathodal tDCS was examined in three sessions using the allothetic place avoidance alternation task (APAAT) and later re-examined without stimulation. Stimulation had no measurable short term effect on on-going place avoidance learning. However, in the follow-up session on day 21 the rats previously treated with cathodal tDCS showed significantly more efficient place avoidance and skill retention in comparison to the controls. This demonstrates a long-term benefit of diminished excitability by frontal tDCS when paired with training on working memory and skill learning in a novel task. The presented behavioral model provides a tool to evaluate the underlying mechanisms of how tDCS modulates neural network function to support successful behavior.
Vercammen A, Rushby JA, Loo C, Short B, Weickert CS, Weickert TW Transcranial direct current stimulation influences probabilistic association learning in schizophrenia. 2011 Schizophr. Res.
Schizophrenia is associated with heterogeneity in symptoms, cognition and treatment response. Probabilistic association learning, involving a gradual learning of cue-outcome associations, activates a frontal-striatal network in healthy adults. Studies of probabilistic association learning in schizophrenia have shown frontal-striatal dysfunction although considerable heterogeneity in performance has also been reported. Anodal transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex has been shown to improve probabilistic association learning in healthy adults. The aim of the current study was to determine the extent to which anodal tDCS to the left dorsolateral prefrontal cortex would reverse probabilistic association learning deficits in schizophrenia. Prior to tDCS, 20 people with schizophrenia performed an initial baseline assessment without stimulation. Anodal tDCS was administered continuously for 20min at an intensity of 2.0mA to the left dorsolateral prefrontal cortex in a single-blind, counterbalanced, sham-controlled, cross-over design while participants performed 150 trials of a probabilistic association learning test. Although anodal tDCS failed to improve probabilistic association learning based on the whole sample performance, greater variance in the active relative to the sham conditions suggested a subset of people may respond to treatment. Further correlation, regression and cluster analyses revealed differential effects of baseline performance on active tDCS and sham treatment and that there was a subset of people with schizophrenia who displayed improvement with tDCS suggesting that anodal tDCS to the dorsolateral prefrontal cortex may facilitate access to existing prefrontal cortex neural reserves in people with schizophrenia who show adequate capacity to learn at baseline.
Bolognini N, Maravita A Uncovering Multisensory Processing through Non-Invasive Brain Stimulation. 2011 Front Psychol
Most of current knowledge about the mechanisms of multisensory integration of environmental stimuli by the human brain derives from neuroimaging experiments. However, neuroimaging studies do not always provide conclusive evidence about the causal role of a given area for multisensory interactions, since these techniques can mainly derive correlations between brain activations and behavior. Conversely, techniques of non-invasive brain stimulation (NIBS) represent a unique and powerful approach to inform models of causal relations between specific brain regions and individual cognitive and perceptual functions. Although NIBS has been widely used in cognitive neuroscience, its use in the study of multisensory processing in the human brain appears a quite novel field of research. In this paper, we review and discuss recent studies that have used two techniques of NIBS, namely transcranial magnetic stimulation and transcranial direct current stimulation, for investigating the causal involvement of unisensory and heteromodal cortical areas in multisensory processing, the effects of multisensory cues on cortical excitability in unisensory areas, and the putative functional connections among different cortical areas subserving multisensory interactions. The emerging view is that NIBS is an essential tool available to neuroscientists seeking for causal relationships between a given area or network and multisensory processes. With its already large and fast increasing usage, future work using NIBS in isolation, as well as in conjunction with different neuroimaging techniques, could substantially improve our understanding of multisensory processing in the human brain.
Bullard LM, Browning ES, Clark VP, Coffman BA, Garcia CM, Jung RE, van der Merwe AJ, Paulson KM, Vakhtin AA, Wootton CL, Weisend MP Transcranial direct current stimulation's effect on novice versus experienced learning. 2011 Exp Brain Res
Transcranial direct current stimulation (TDCS) is a non-invasive form of brain stimulation applied via a weak electrical current passed between electrodes on the scalp. In recent studies, TDCS has been shown to improve learning when applied to the prefrontal cortex (e.g., Kincses et al. in Neuropsychologia 42:113-117, 2003; Clark et al. Neuroimage in 2010). The present study examined the effects of TDCS delivered at the beginning of training (novice) or after an hour of training (experienced) on participants' ability to detect cues indicative of covert threats. Participants completed two 1-h training sessions. During the first 30 min of each training session, either 0.1 mA or 2.0 mA of anodal TDCS was delivered to the participant. The anode was positioned near F8, and the cathode was placed on the upper left arm. Testing trials immediately followed training. Accuracy in classification of images containing and not-containing threat stimuli during the testing sessions indicated: (1) that mastery of threat detection significantly increased with training, (2) that anodal TDCS at 2 mA significantly enhanced learning, and (3) TDCS was significantly more effective in enhancing test performance when applied in novice learners than in experienced learners. The enhanced performance following training with TDCS persisted into the second session when TDCS was delivered early in training.
Binkofski F, Loebig M, Jauch-Chara K, Bergmann S, Melchert UH, Scholand-Engler HG, Schweiger U, Pellerin L, Oltmanns KM Brain Energy Consumption Induced by Electrical Stimulation Promotes Systemic Glucose Uptake. 2011 Biological psychiatry
BACKGROUND: Controlled transcranial stimulation of the brain is part of clinical treatment strategies in neuropsychiatric diseases such as depression, stroke, or Parkinson's disease. Manipulating brain activity by transcranial stimulation, however, inevitably influences other control centers of various neuronal and neurohormonal feedback loops and therefore may concomitantly affect systemic metabolic regulation. Because hypothalamic adenosine triphosphate-sensitive potassium channels, which function as local energy sensors, are centrally involved in the regulation of glucose homeostasis, we tested whether transcranial direct current stimulation (tDCS) causes an excitation-induced transient neuronal energy depletion and thus influences systemic glucose homeostasis and related neuroendocrine mediators. METHODS: In a crossover design testing 15 healthy male volunteers, we increased neuronal excitation by anodal tDCS versus sham and examined cerebral energy consumption with (31)phosphorus magnetic resonance spectroscopy. Systemic glucose uptake was determined by euglycemic-hyperinsulinemic glucose clamp, and neurohormonal measurements comprised the parameters of the stress systems. RESULTS: We found that anodic tDCS-induced neuronal excitation causes an energetic depletion, as quantified by (31)phosphorus magnetic resonance spectroscopy. Moreover, tDCS-induced cerebral energy consumption promotes systemic glucose tolerance in a standardized euglycemic-hyperinsulinemic glucose clamp procedure and reduces neurohormonal stress axes activity. CONCLUSIONS: Our data demonstrate that transcranial brain stimulation not only evokes alterations in local neuronal processes but also clearly influences downstream metabolic systems regulated by the brain. The beneficial effects of tDCS on metabolic features may thus qualify brain stimulation as a promising nonpharmacologic therapy option for drug-induced or comorbid metabolic disturbances in various neuropsychiatric diseases.
Zheng X, Alsop DC, Schlaug G Effects of transcranial direct current stimulation (tDCS) on human regional cerebral blood flow. 2011 Neuroimage
Transcranial direct current stimulation (tDCS) can up- and down-regulate cortical excitability depending on current direction, however our abilities to measure brain-tissue effects of the stimulation and its after-effects have been limited so far. We used regional cerebral blood flow (rCBF), a surrogate measure of brain activity, to examine regional brain-tissue and brain-network effects during and after tDCS. We varied the polarity (anodal and cathodal) as well as the current strength (0.8 to 2.0mA) of the stimulation. Fourteen healthy subjects were randomized into receiving either anodal or cathodal stimulation (two subjects received both, one week apart) while undergoing Arterial Spin Labeling (ASL) in the MRI scanner with an alternating off-on sampling paradigm. The stimulating, MRI-compatible electrode was placed over the right motor region and the reference electrode over the contralateral supra-orbital region. SPM5 was used to process and extract the rCBF data using a 10mm spherical volume of interest (VOI) placed in the motor cortex directly underneath the stimulating scalp electrode. Anodal stimulation induced a large increase (17.1%) in rCBF during stimulation, which returned to baseline after the current was turned off, but exhibited an increase in rCBF again in the post-stimulation period. Cathodal stimulation induced a smaller increase (5.6%) during stimulation, a significant decrease compared to baseline (-6.5%) after cessation, and a continued decrease in the post-stimulation period. These changes in rCBF were all significant when compared to the pre-stimulation baseline or to a control region. Furthermore, for anodal stimulation, there was a significant correlation between current strength and the increase in rCBF in the on-period relative to the pre-stimulation baseline. The differential rCBF after-effects of anodal (increase in resting state rCBF) and cathodal (decrease in resting state rCBF) tDCS support findings of behavioral and cognitive after-effects after cathodal and anodal tDCS. We also show that tDCS not only modulates activity in the brain region directly underlying the stimulating electrode but also in a network of brain regions that are functionally related to the stimulated area. Our results indicate that ASL may be an excellent tool to investigate the effects of tDCS and its stimulation parameters on brain activity.
Buttkus F, Baur V, Jabusch HC, de la Cruz Gomez-Pellin M, Paulus W, Nitsche MA, Altenmuller E Single-session tDCS-supported retraining does not improve fine motor control in musician's dystonia. 2011 Restor. Neurol. Neurosci.
Focal dystonia in musicians (MD) is a task-specific movement disorder with a loss of voluntary motor control during instrumental playing. Defective inhibition on different levels of the central nervous system is involved in the pathophysiology. Sensorimotor retraining is a therapeutic approach to MD and aims to establish non-dystonic movements. Transcranial direct current stimulation (tDCS) modulates cortical excitability and alters motor performance. In this study, tDCS of the motor cortex was expected to assist retraining at the instrument.
Monte-Silva K, Ruge D, Teo JT, Paulus W, Rothwell JC, Nitsche MA D2 receptor block abolishes theta burst stimulation-induced neuroplasticity in the human motor cortex. 2011 Neuropsychopharmacology
Dopamine (DA) is a neurotransmitter with an important influence on learning and memory, which is thought to be due to its modulatory effect on plasticity at central synapses, which in turn depends on activation of D1 and D2 receptors. Methods of brain stimulation (transcranial direct current stimulation, tDCS; paired associative stimulation, PAS) lead to after-effects on cortical excitability that are thought to resemble long-term potentization (LTP)/long-term depression (LTD) in reduced preparations. In a previous study we found that block of D2 receptors abolished plasticity induced by tDCS but had no effect on the facilitatory plasticity induced by PAS. We postulated that the different effect of D2 receptor block on tDCS- and PAS-induced plasticity may be due to the different focality and associativity of the stimulation techniques. However, alternative explanations for this difference could not be ruled out. tDCS also differs from PAS in other aspects, as tDCS induces plasticity by subthreshold neuronal activation, modulating spontaneous activity, whereas PAS induces plasticity via phasic suprathreshold stimulation. The present study in 12 volunteers examined effects of D2 receptor blockade (sulpiride (SULP) 400 mg), on the LTP/LTD-like effects of theta burst transcranial magnetic stimulation (TBS), which has less restricted effects on cortical synapses than that of PAS, and does not induce associative plasticity, similar to tDCS, but on the other hand induces cortical excitability shifts by suprathreshold (rhythmic) activation of cortical neurons similarly to PAS. Administration of SULP blocked both the excitatory and inhibitory effects of intermittent (iTBS) and continuous TBS (cTBS), respectively. As the reduced response to TBS following SULP resembles its effect on tDCS, the results support an effect of DA on plasticity, which might be related to the focality and associativity of the plasticity induced.
Thirugnanasambandam N, Sparing R, Dafotakis M, Meister IG, Paulus W, Nitsche MA, Fink GR Isometric contraction interferes with transcranial direct current stimulation (tDCS) induced plasticity - evidence of state-dependent neuromodulation in human motor cortex. 2011 Restor. Neurol. Neurosci.
Background and Purpose: Neuroplastic alterations of cortical excitability and activity represent the likely neurophysiological foundation of learning and memory formation. Beyond their induction, alterations of these processes by subsequent modification of cortical activity, termed metaplasticity, came into the focus of interest recently. Animal slice experiments demonstrated that neuroplastic excitability enhancements, or diminutions, can be abolished by consecutive subthreshold stimulation. These processes, termed de-potentiation, and de-depression, have so far not been explored in humans. Methods: We combined neuroplasticity induction by transcranial direct current stimulation (tDCS) applied to the hand area of primary motor cortex (M1), which can be used to induce long-lasting excitability enhancements or reductions, dependent on the polarity of stimulation, with short-lasting voluntary muscle contraction (VMC), which itself does not induce plastic cortical excitability changes. Corticospinal and intra-cortical M1 excitability were monitored by different transcranial magnetic stimulation (TMS) protocols. Results: VMC reduced or tended to reverse the anodal tDCS-driven motor cortical excitability enhancement and the cathodal tDCS-induced excitability diminution. Our findings thus demonstrate de-potentiation- and de-depression-like phenomena at the system level in the human motor cortex. Conclusion: This neurophysiological study may contribute to a better understanding of the balance between induction and reversal of plasticity associated with motor learning and rehabilitation processes.
Demirtas-Tatlidede A, Vahabzadeh-Hagh AM, Bernabeu M, Tormos JM, Pascual-Leone A Noninvasive Brain Stimulation in Traumatic Brain Injury. 2011 The Journal of head trauma rehabilitation
OBJECTIVE:: To review novel techniques of noninvasive brain stimulation (NBS), which may have value in assessment and treatment of traumatic brain injury (TBI). METHODS:: Review of the following techniques: transcranial magnetic stimulation, transcranial direct current stimulation, low-level laser therapy, and transcranial Doppler sonography. Furthermore, we provide a brief overview of TMS studies to date. MAIN FINDINGS:: We describe the rationale for the use of these techniques in TBI, discuss their possible mechanisms of action, and raise a number of considerations relevant to translation of these methods to clinical use. Depending on the stimulation parameters, NBS may enable suppression of the acute glutamatergic hyperexcitability following TBI and/or counter the excessive GABAergic effects in the subacute stage. In the chronic stage, brain stimulation coupled to rehabilitation may enhance behavioral recovery, learning of new skills, and cortical plasticity. Correlative animal models and comprehensive safety trials seem critical to establish the use of these modalities in TBI. CONCLUSIONS:: Different forms of NBS techniques harbor the promise of diagnostic and therapeutic utility, particularly to guide processes of cortical reorganization and enable functional restoration in TBI. Future lines of safety research and well-designed clinical trials in TBI are warranted to determine the capability of NBS to promote recovery and minimize disability.
Floel A, Suttorp W, Kohl O, Kurten J, Lohmann H, Breitenstein C, Knecht S Non-invasive brain stimulation improves object-location learning in the elderly. 2011 Neurobiology of aging
Remembering the location of objects, an integral part of everyday life, is known to decline with advancing age and early in the course of neurodegenerative dementia. Here, we aimed to test if object-location learning and its retention could be modified by noninvasive brain stimulation. In a group of 20 elderly (mean age 62.1 years) right-handed individuals, we applied transcranial direct current stimulation (tDCS; 20 minutes, 1 mA) over the right temporoparietal cortex, while subjects acquired the correct position of buildings on a street map using an associative learning paradigm. Each subject participated in a randomized and balanced order in 1 session of anodal tDCS and 1 session of sham stimulation, in a double-blind design with 2 parallel versions of the task. Outcome measures were learning success at the end of each session, and immediate as well as delayed (1 week) free recall. We found that subjects performed comparably in the learning task in the 2 conditions, but showed improved recall 1 week after learning with anodal tDCS compared with learning with sham stimulation. In conclusion, retention of object-location learning in the elderly may be modulated by noninvasive brain stimulation, a finding of potential relevance not only for normal aging but also for memory deficits in pathological aging.
Clark VP, Coffman BA, Trumbo MC, Gasparovic C Transcranial direct current stimulation (tDCS) produces localized and specific alterations in neurochemistry: a ¹H magnetic resonance spectroscopy study. 2011 Neurosci. Lett.
Transcranial direct current stimulation (tDCS) has been found to produce significant changes in behavior, including a large increase of learning and performance for a difficult visual perceptual task (Clark et al., NeuroImage 2010). The mechanisms by which tDCS produces these behavioral effects are currently uncertain. One hypothesis is that anodal tDCS leads to increased metabolic activity in the brain, which enhances cognitive and memory processes. Here we examined the neuronal mechanisms by which tDCS influences learning by measuring changes in brain metabolite concentrations using proton magnetic resonance spectroscopy (¹H MRS). As perception and learning can also influence neurochemistry, here we applied tDCS during rest. MRS data was obtained before and after 2.0 mA of anodal tDCS was applied for 30 min over electrode site P4, with the cathode placed on the contralateral arm. MRS data were acquired from the right parietal lobe beneath the anodal tDCS electrode, and from the homologous regions of the left hemisphere once before and once after tDCS. Significantly higher combined glutamate and glutamine levels were found in right parietal cortex, beneath the stimulating electrode, with non-significant increases in homologous regions of the opposite hemisphere. In addition, a significant interaction between hemispheres was found for tDCS effects on tNAA. These results suggest that changes in glutamatergic activity and tNAA may be related to the mechanisms by which tDCS influences learning and behavior.
Munneke MA, Stegeman DF, Hengeveld YA, Rongen JJ, Schelhaas HJ, Zwarts MJ Transcranial direct current stimulation does not modulate motor cortex excitability in patients with amyotrophic lateral sclerosis. 2011 Muscle Nerve
Amyotrophic lateral sclerosis (ALS) is a progressive disease caused by the degeneration of upper and lower motor neurons. The etiology of ALS is unclear, but there is evidence that loss of cortical inhibition could be related to motor neuron degeneration. We sought to determine whether cathodal transcranial direct current stimulation (tDCS) can reduce cortical excitability in patients with ALS.
Mulquiney PG, Hoy KE, Daskalakis ZJ, Fitzgerald PB Improving working memory: Exploring the effect of transcranial random noise stimulation and transcranial direct current stimulation on the dorsolateral prefrontal cortex. 2011 Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
OBJECTIVE: The aim of this study was to determine if working memory (WM) performance is significantly improved after the delivery of transcranial random noise stimulation (tRNS) to the left dorsolateral prefrontal cortex (DLPFC), compared to an active comparator or sham. METHODS: Ten participants undertook three experimental sessions in which they received 10min of anodal tDCS (active comparator), tRNS or sham tDCS whilst performing the Sternberg WM task. Intra-stimulation engagement in a WM task was undertaken as this has been previously shown to enhance the effects of tDCS. Experimental sessions were separated by a minimum of 1week. Immediately prior to and after each stimulation session the participants were measured on speed and accuracy of performance on an n-back task. RESULTS: There was significant improvement in speed of performance following anodal tDCS on the 2-back WM task; this was the only significant finding. CONCLUSIONS: The results do not provide support for the hypothesis that tRNS improves WM. However, the study does provide confirmation of previous findings that anodal tDCS enhances some aspects of DLPFC functioning. Methodological limitations that may have contributed to the lack of significant findings following tRNS are discussed. SIGNIFICANCE: Anodal tDCS may have significant implications for WM remediation in psychiatric conditions, particularly schizophrenia.
Dmochowski JP, Datta A, Bikson M, Su Y, Parra LC Optimized multi-electrode stimulation increases focality and intensity at target. 2011 J Neural Eng
Transcranial direct current stimulation (tDCS) provides a non-invasive tool to elicit neuromodulation by delivering current through electrodes placed on the scalp. The present clinical paradigm uses two relatively large electrodes to inject current through the head resulting in electric fields that are broadly distributed over large regions of the brain. In this paper, we present a method that uses multiple small electrodes (i.e. 1.2 cm diameter) and systematically optimize the applied currents to achieve effective and targeted stimulation while ensuring safety of stimulation. We found a fundamental trade-off between achievable intensity (at the target) and focality, and algorithms to optimize both measures are presented. When compared with large pad-electrodes (approximated here by a set of small electrodes covering 25 cm(2)), the proposed approach achieves electric fields which exhibit simultaneously greater focality (80% improvement) and higher target intensity (98% improvement) at cortical targets using the same total current applied. These improvements illustrate the previously unrecognized and non-trivial dependence of the optimal electrode configuration on the desired electric field orientation and the maximum total current (due to safety). Similarly, by exploiting idiosyncratic details of brain anatomy, the optimization approach significantly improves upon prior un-optimized approaches using small electrodes. The analysis also reveals the optimal use of conventional bipolar montages: maximally intense tangential fields are attained with the two electrodes placed at a considerable distance from the target along the direction of the desired field; when radial fields are desired, the maximum-intensity configuration consists of an electrode placed directly over the target with a distant return electrode. To summarize, if a target location and stimulation orientation can be defined by the clinician, then the proposed technique is superior in terms of both focality and intensity as compared to previous solutions and is thus expected to translate into improved patient safety and increased clinical efficacy.
DaSilva AF, Volz MS, Bikson M, Fregni F Electrode positioning and montage in transcranial direct current stimulation. 2011 J Vis Exp
Transcranial direct current stimulation (tDCS) is a technique that has been intensively investigated in the past decade as this method offers a non-invasive and safe alternative to change cortical excitability. The effects of one session of tDCS can last for several minutes, and its effects depend on polarity of stimulation, such as that cathodal stimulation induces a decrease in cortical excitability, and anodal stimulation induces an increase in cortical excitability that may last beyond the duration of stimulation. These effects have been explored in cognitive neuroscience and also clinically in a variety of neuropsychiatric disorders--especially when applied over several consecutive sessions. One area that has been attracting attention of neuroscientists and clinicians is the use of tDCS for modulation of pain-related neural networks. Modulation of two main cortical areas in pain research has been explored: primary motor cortex and dorsolateral prefrontal cortex. Due to the critical role of electrode montage, in this article, we show different alternatives for electrode placement for tDCS clinical trials on pain; discussing advantages and disadvantages of each method of stimulation.
Hasan A, Nitsche MA, Rein B, Schneider-Axmann T, Guse B, Gruber O, Falkai P, Wobrock T Dysfunctional long-term potentiation-like plasticity in schizophrenia revealed by transcranial direct current stimulation. 2011 Behav. Brain Res.
Neural and cortical plasticity represent the ability of the brain to reorganize its function in response to a challenge. Plasticity involves changing synaptic activity and connectivity. Long-term-potentiation is one important mechanism underlying these synaptic changes. Disturbed neuronal plasticity is considered to be part of the pathophysiology of schizophrenia and has been linked to the different clinical features of this severe illness. The aim of the present study was to investigate nonfocal cortical plasticity and cortical excitability in recent-onset and multi-episode schizophrenia compared with healthy subjects. Nonfocal cortical plasticity can be induced in the motor cortex of healthy subjects with anodal transcranial direct current stimulation. Animal and human research indicates that this long-term-potentiation-like plasticity is glutamate-dependent and that these plasticity shifts can last for several hours. Transcranial direct current stimulation-induced plasticity was monitored by transcranial magnetic stimulation-generated motor evoked potentials. Well-characterized transcranial magnetic stimulation protocols were applied to determine the physiological basis of plasticity changes. Multi-episode schizophrenia patients showed significantly reduced long-term-potentiation-like plasticity compared to recent-onset schizophrenia patients and healthy controls. All schizophrenia patients demonstrated reduced cortical inhibition. Our results indicate that the long-term-potentiation-like plasticity deficit in schizophrenia patients is related to the disease course. Disturbances of N-methyl-d-aspartate, gamma-aminobutyric acid and dopamine receptors may account for this plasticity deficit. LTP-like plasticity deficits might be related to disturbed information processing in schizophrenia patients.
Franks I Pain: Transcranial direct current stimulation reduces post-ERCP pain. 2011 Nat Rev Gastroenterol Hepatol
Martin DM, Alonzo A, Mitchell PB, Sachdev P, Galvez V, Loo CK Fronto-extracephalic transcranial direct current stimulation as a treatment for major depression: An open-label pilot study. 2011 Journal of affective disorders
BACKGROUND: Several recent trials have reported transcranial direct current stimulation (tDCS) to be effective in treating depression, though the relative benefits of different electrode montages remain unexplored. Whereas all recent studies have used a bifrontal (BF) electrode montage, studies published in the 1960s and 1970s placed one electrode in an extracephalic position, with some positive reports of efficacy. This study investigated the efficacy and safety of tDCS given with a fronto-extracephalic (F-EX) montage. METHODS: 2mA tDCS was administered for 20min every weekday over four weeks in 11 participants with a Major Depressive Episode who had previously shown inadequate response to, or relapsed following, a course of BF tDCS. For F-EX tDCS the anode was placed on the left dorsolateral prefrontal cortex and the cathode on the right upper arm. Depression severity and neuropsychological function were assessed before and after the treatment course. Antidepressant response was compared across an equivalent treatment period for both montages. RESULTS: F-EX tDCS was shown to be safe and well tolerated. Depression ratings improved after acute treatment on the Montgomery Åsberg Depression Rating Scale (p<0.001). Participants showed greater initial treatment response with F-EX tDCS than with BF tDCS (p<0.001). LIMITATIONS: This was an open label pilot study. The two comparison treatments were applied consecutively. CONCLUSION: F-EX tDCS appears to be safe and to have antidepressant effects, and may lead to more rapid improvement than tDCS given with a BF montage.
You DS, Kim DY, Chun MH, Jung SE, Park SJ Cathodal transcranial direct current stimulation of the right Wernicke's area improves comprehension in subacute stroke patients. 2011 Brain Lang
Previous studies have shown the appearance of right-sided language-related brain activity in right-handed patients after a stroke. Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) have been shown to modulate excitability in the brain. Moreover, rTMS and tDCS have been found to improve naming in non-fluent post-stroke aphasic patients. Here, we investigated the effect of tDCS on the comprehension of aphasic patients with subacute stroke. We hypothesized that tDCS applied to the left superior temporal gyrus (Wernicke's area) or the right Wernicke's area might be associated with recovery of comprehension ability in aphasic patients with subacute stroke. Participants included right-handed subacute stroke patients with global aphasia due to ischemic infarct of the left M1 or M2 middle cerebral artery. Patients were randomly divided into three groups: patients who received anodal tDCS applied to the left superior temporal gyrus, patients who received cathodal tDCS applied to the right superior temporal gyrus, and patients who received sham tDCS. All patients received conventional speech and language therapy during each period of tDCS application. The Korean-Western Aphasia Battery (K-WAB) was used to assess all patients before and after tDCS sessions. After intervention, all patients had significant improvements in aphasia quotients, spontaneous speech, and auditory verbal comprehension. However, auditory verbal comprehension improved significantly more in patients treated with a cathode, as compared to patients in the other groups. These results are consistent with the role of Wernicke's area in language comprehension and the therapeutic effect that cathodal tDCS has on aphasia patients with subacute stroke, suggesting that tDCS may be an adjuvant treatment approach for aphasia rehabilitation therapy in patients in an early stage of stroke.
Floel A, Meinzer M, Kirstein R, Nijhof S, Deppe M, Knecht S, Breitenstein C Short-term anomia training and electrical brain stimulation. 2011 Stroke
Language training success in chronic aphasia remains only moderate. Electric brain stimulation may be a viable way to enhance treatment efficacy.
Schneider HD, Hopp JP The use of the Bilingual Aphasia Test for assessment and transcranial direct current stimulation to modulate language acquisition in minimally verbal children with autism. 2011 Clin Linguist Phon
Minimally verbal children with autism commonly demonstrate language dysfunction, including immature syntax acquisition. We hypothesised that transcranial direct current stimulation (tDCS) should facilitate language acquisition in a cohort (n = 10) of children with immature syntax. We modified the English version of the Bilingual Aphasia Test (BAT) to test only basic canonical subject-verb-object sentences. We tested syntactic accuracy after teaching then testing all vocabulary from the subsequent syntax test to ensure validity of syntactic scoring. We used scaffolding sentences for syntax training. All procedures were performed both before and after tDCS. Results demonstrated a large effect size of the difference between pre-/post-tDCS groups (p < 0.0005, d = 2.78), indicating syntax acquisition. Combining a modified BAT with tDCS constitutes effective modalities for assessment and treatment of immature syntax in children with autism. Future studies should explore the BAT for patients with an inability to use or understand language, in particular bilingual children with autism.
Dell'osso B, Zanoni S, Ferrucci R, Vergari M, Castellano F, D'Urso N, Dobrea C, Benatti B, Arici C, Priori A, Altamura AC Transcranial direct current stimulation for the outpatient treatment of poor-responder depressed patients. 2011 European psychiatry : the journal of the Association of European Psychiatrists
Transcranial direct current stimulation (tDCS) is a selective, painless, brain stimulation technique that allows the electric stimulation of specific cortical regions. TDCS has been recently used as investigational intervention for major depression and treatment resistant depression (TRD) with encouraging results. The present study was aimed to investigate the efficacy and tolerability of tDCS in major depressives with poor response to pharmacological treatment. Twenty-three depressed patients, with a diagnosis of major depressive disorder or bipolar disorder, were treated with augmentative tDCS for 5 days, two sessions per day in a blind-rater trial. The course of depressive symptoms was analyzed using repeated measures ANOVA for HAM-D and MADRS total scores. A qualitative analysis on the basis of the HAM-D response was performed as well. Both analyses were conducted at three time-points: T0 (baseline), T1 (endpoint tDCS) and T2 (end of the first week of follow-up). All patients completed the trial without relevant side-effects. A significant reduction of HAM-D and MADRS total scores was observed during the study (P<0.0001). Treatment response (endpoint HAM-D reduction ≥50%) was obtained by four patients (17.4%) at T1 and by seven patients (30.4%) at T2 and remission (endpoint HAM-D<8) by three patients (13.0%) at T1 and by four subjects (17.4%) at T2. Present findings support the efficacy and good tolerability of tDCS in the acute treatment of patients with TRD with clinical benefit being progressive and extended to the first week of follow-up. Further sham-controlled trials with longer follow-up are needed to confirm present results.
Halko MA, Datta A, Plow EB, Scaturro J, Bikson M, Merabet LB Neuroplastic changes following rehabilitative training correlate with regional electrical field induced with tDCS. 2011 Neuroimage
Transcranial direct current stimulation (tDCS) has recently emerged as a promising approach to enhance neurorehabilitative outcomes. However, little is known about how the local electrical field generated by tDCS relates to underlying neuroplastic changes and behavior. To address this question, we present a case study analysis of an individual with hemianopia due to stroke and who benefited from a combined visual rehabilitation training and tDCS treatment program. Activation associated with a visual motion perception task (obtained by functional magnetic resonance imaging; fMRI) was used to characterize local changes in brain activity at baseline and after training. Individualized, high-resolution electrical field modeling reproducing precise cerebral and lesioned tissue geometry, predicted distortions of current flow in peri-lesional areas and diffuse clusters of peak electric fields. Using changes in fMRI signal as an index of cortical recovery, correlations to the electrical field map were determined. Significant correlations between the electrical field and change in fMRI signal were region specific including cortical areas under the anode electrode and peri-lesional visual areas. These patterns were consistent with effective tDCS facilitated rehabilitation. We describe the methodology used to analyze tDCS mechanisms through combined fMRI and computational modeling with the ultimate goal of developing a rationale for individualized therapy.
Schambra HM, Abe M, Luckenbaugh DA, Reis J, Krakauer JW, Cohen LG Probing for hemispheric specialization for motor skill learning: a transcranial direct current stimulation study. 2011 J. Neurophysiol.
Convergent findings point to a left-sided specialization for the representation of learned actions in right-handed humans, but it is unknown whether analogous hemispheric specialization exists for motor skill learning. In the present study, we explored this question by comparing the effects of anodal transcranial direct current stimulation (tDCS) over either left or right motor cortex (M1) on motor skill learning in either hand, using a tDCS montage to better isolate stimulation to one hemisphere. Results were compared with those previously found with a montage more commonly used in the field. Six groups trained for three sessions on a visually guided sequential pinch force modulation task with their right or left hand and received right M1, left M1, or sham tDCS. A linear mixed-model analysis for motor skill showed a significant main effect for stimulation group (left M1, right M1, sham) but not for hand (right, left) or their interaction. Left M1 tDCS induced significantly greater skill learning than sham when hand data were combined, a result consistent not only with the hypothesized left hemisphere specialization for motor skill learning but also with possible increased left M1 responsiveness to tDCS. The unihemispheric montage effect size was one-half that of the more common montage, and subsequent power analysis indicated that 75 subjects per group would be needed to detect differences seen with only 12 subjects with the customary bihemispheric montage.
Vallar G, Bolognini N Behavioural facilitation following brain stimulation: Implications for neurorehabilitation. 2011 Neuropsychological rehabilitation
Studies showing facilitation of behavioural performance by transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS) in sensory and perceptual domains, spatial attention, working memory, and executive and emotional tasks are reviewed. In these domains the performance of neurologically unimpaired participants may be modulated, with behavioural facilitation or interference, by TMS, and by tDCS. The mapping of the frequency-dependent effects of TMS, and of the polarity-dependent effects of tDCS on behaviour does not systematically and mechanistically result in an increase or decrease of behavioural performance. Factors such as the parameters of the cerebral stimulation (localisation, duration, intensity), and the features of the task (complexity, phase of training) contribute to determine the final net effect on the participants' performance. Non-invasive brain stimulation (NIBS), which modulates learning, and appears to have, under some conditions, long lasting effects, is a promising tool to be used in the rehabilitation of a variety of neurological and cognitive disorders, that typically involve repeated behavioural training sessions.
Scelzo E, Giannicola G, Rosa M, Ciocca M, Ardolino G, Cogiamanian F, Ferrucci R, Fumagalli M, Mameli F, Barbieri S, Priori A Increased short latency afferent inhibition after anodal transcranial direct current stimulation. 2011 Neurosci. Lett.
Transcranial direct current stimulation (tDCS), a technique for central neuromodulation, has been recently proposed as possible treatment in several neurological and psychiatric diseases. Although shifts on focal brain excitability have been proposed to explain the clinical effects of tDCS, how tDCS-induced functional changes influence cortical interneurones is still largely unknown. The assessment of short latency afferent inhibition (SLAI) of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS), provides the opportunity to test non-invasively interneuronal cholinergic circuits in the human motor cortex. The aim of the present study was to assess whether anodal tDCS can modulate interneuronal circuits involved in SLAI. Resting motor threshold (RMT), amplitude of unconditioned MEPs and SLAI were assessed in the dominant hemisphere of 12 healthy subjects (aged 21-37) before and after anodal tDCS (primary motor cortex, 13min, 1mA). SLAI was assessed delivering electrical conditioning stimuli to the median nerve at the wrist prior to test TMS given at the interstimulus interval (ISI) of 2ms. Whereas RMT and the amplitude of unconditioned MEPs did not change after anodal tDCS, SLAI significantly increased. In conclusion, anodal tDCS-induced effects depend also on the modulation of cortical interneuronal circuits. The enhancement of cortical cholinergic activity assessed by SLAI could be an important mechanism explaining anodal tDCS action in several pathological conditions.
Auvichayapat P, Auvichayapat N Basic knowledge of transcranial direct current stimulation. 2011 J Med Assoc Thai
Transcranial direct current stimulation (tDCS) was a neurophysiologic technique using weak electrical currents (1-2 mA) to modulate the activity of neurons in the brain. It was discovered in the 1960s, and then reintroduced by the reasonably well-controlled experiments 12 years ago. They suggested that electrodes placed on the head can produce noticeable neurological changes depended on the current direction.
Orban de Xivry JJ, Marko MK, Pekny SE, Pastor D, Izawa J, Celnik P, Shadmehr R Stimulation of the human motor cortex alters generalization patterns of motor learning. 2011 J. Neurosci.
It has been hypothesized that the generalization patterns that accompany learning carry the signatures of the neural systems that are engaged in that learning. Reach adaptation in force fields has generalization patterns that suggest primary engagement of a neural system that encodes movements in the intrinsic coordinates of joints and muscles, and lesser engagement of a neural system that encodes movements in the extrinsic coordinates of the task. Among the cortical motor areas, the intrinsic coordinate system is most prominently represented in the primary sensorimotor cortices. Here, we used transcranial direct current stimulation (tDCS) to alter mechanisms of synaptic plasticity and found that when it was applied to the motor cortex, it increased generalization in intrinsic coordinates but not extrinsic coordinates. However, when tDCS was applied to the posterior parietal cortex, it had no effects on learning or generalization in the force field task. The results suggest that during force field adaptation, the component of learning that produces generalization in intrinsic coordinates depends on the plasticity in the sensorimotor cortex.
Paquette C, Sidel M, Radinska BA, Soucy JP, Thiel A Bilateral transcranial direct current stimulation modulates activation-induced regional blood flow changes during voluntary movement. 2011 Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that induces changes in cortical excitability: anodal stimulation increases while cathodal stimulation reduces excitability. Imaging studies performed after unilateral stimulation have shown conflicting results regarding the effects of tDCS on surrogate markers of neuronal activity. The aim of this study was to directly measure these effects on activation-induced changes in regional cerebral blood flow (ΔrCBF) using positron emission tomography (PET) during bilateral tDCS. Nine healthy subjects underwent repeated rCBF measurements with (15)O-water and PET during a simple motor task while receiving tDCS or sham stimulation over the primary motor cortex (M1). Motor evoked potentials (MEPs) were also assessed before and after real and sham stimulation. During tDCS with active movement, ΔrCBF in M1 was significantly lower on the cathodal than the anodal side when compared with sham stimulation. This decrease in ΔrCBF was accompanied by a decrease in MEP amplitude on the cathodal side. No effect was observed on resting or activated rCBF relative to sham stimulation. We thus conclude that it is the interaction of cathodal tDCS with activation-induced ΔrCBF rather than the effect on resting or activated rCBF itself which constitutes the physiological imaging correlate of tDCS.Journal of Cerebral Blood Flow & Metabolism advance online publication, 11 May 2011; doi:10.1038/jcbfm.2011.72.
Lindenberg R, Zhu LL, Ruber T, Schlaug G Predicting functional motor potential in chronic stroke patients using diffusion tensor imaging. 2011 Human brain mapping
Electrophysiological and neuroimaging studies suggest that the integrity of ipsilesional and inter-hemispheric motor circuits is important for motor recovery after stroke. However, the extent to which each of these tracts contributes to the variance in outcome remains unclear. We examined whether diffusion tensor imaging (DTI)-derived measures of corticospinal and transcallosal tracts predict motor improvement in an experimental neurorehabilitation trial. 15 chronic stroke patients received bihemispheric transcranial direct current stimulation and simultaneous physical/occupational therapy for five consecutive days. Motor impairment was assessed prior to and after the intervention. At baseline, the patients underwent DTI; probabilistic fiber tracking was used to reconstruct the pyramidal tract (PT), alternate descending motor fibers (aMF), and transcallosal fibers connecting primary motor cortices (M1-M1). Ipsilesional corticospinal tracts (PT, aMF) and M1-M1 showed significantly decreased fractional anisotropy (FA) and increased directional diffusivities when compared to age-matched healthy controls. Partial correlations revealed that greater gains in motor function were related to higher FA values and lower directional diffusivities of transcallosal and ipsilesional corticospinal tracts. M1-M1 diffusivity had the greatest predictive value. An additional slice-by-slice analysis of FA values along the corticospinal tracts demonstrated that the more the ipsilesional FA profiles of patients resembled those of healthy controls, the greater their functional improvement. In conclusion, our study shows that DTI-derived measures can be used to predict functional potential for subsequent motor recovery in chronic stroke patients. Diffusivity parameters of individual tracts and tract combinations may help in assessing a patient's individual recovery potential and in determining optimal neurorehabilitative interventions. Hum Brain Mapp, 2011. © 2011 Wiley-Liss, Inc.
Brunoni AR, Fregni F Clinical trial design in non-invasive brain stimulation psychiatric research. 2011 Int J Methods Psychiatr Res
Major depressive disorder (MDD) trials - investigating either non-pharmacological or pharmacological interventions - have shown mixed results. Many reasons explain this heterogeneity, but one that stands out is the trial design due to specific challenges in the field. We aimed therefore to review the methodology of non-invasive brain stimulation (NIBS) trials and provide a framework to improve clinical trial design. We performed a systematic review for randomized, controlled MDD trials whose intervention was transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in MEDLINE and other databases from April 2002 to April 2008. We created an unstructured checklist based on CONSORT guidelines to extract items such as power analysis, sham method, blinding assessment, allocation concealment, operational criteria used for MDD, definition of refractory depression and primary study hypotheses. Thirty-one studies were included. We found that the main methodological issues can be divided in to three groups: (1) issues related to phase II/small trials, (2) issues related to MDD trials and, (3) specific issues of NIBS studies. Taken together, they can threaten study validity and lead to inconclusive results. Feasible solutions include: estimating the sample size a priori; measuring the degree of refractoriness of the subjects; specifying the primary hypothesis and statistical tests; controlling predictor variables through stratification randomization methods or using strict eligibility criteria; adjusting the study design to the target population; using adaptive designs and exploring NIBS efficacy employing biological markers. In conclusion, our study summarizes the main methodological issues of NIBS trials and proposes a number of alternatives to manage them.
List J, Duning T, Meinzer M, Kurten J, Schirmacher A, Deppe M, Evers S, Young P, Floel A Enhanced Rapid-Onset Cortical Plasticity in CADASIL as a Possible Mechanism of Preserved Cognition. 2011 Cerebral cortex (New York, N.Y. : 1991)
Ischemic small vessel disease (SVD) may lead to cognitive impairment, but cognitive deficits with a given burden of SVD vary significantly. The underlying mechanisms of impaired or preserved cognition are unknown. Here, we investigated the impact of ischemic SVD on rapid-onset cortical plasticity, as induced with a paired-associative stimulation protocol. To exclude concomitant effects of aging, we examined 12 middle-aged patients (48.3 ± 8.3 years) with cerebral autosomal dominant arteriopathy with subcortical infarctions and leucoencephalopathy (CADASIL) who suffered from severe ischemic SVD and a group of 12 age-matched controls (49.9 ± 8.3 years). Cognitive status, motor performance and learning, and motor cortex excitability in response to cathodal transcranial direct current stimulation (ctDCS) were assessed. White matter integrity was analyzed by conventional magnetic resonance imaging and diffusion tensor imaging. We found that cognitive and motor functions were largely preserved in CADASIL patients, while rapid-onset cortical plasticity was significantly higher in the CADASIL group compared with controls (repeated measures analysis of variance [group × time] interaction: P = 0.03). This finding was even more pronounced in patients with higher white matter lesion load. ctDCS revealed no evidence of cortical dysplasticity. We conclude that increased rapid-onset cortical plasticity may contribute to largely preserved cognitive and motor function despite extensive ischemic SVD.
Montenegro RA, Farinatti Pde T, Fontes EB, Soares PP, Cunha FA, Gurgel JL, Porto F, Cyrino ES, Okano AH Transcranial direct current stimulation influences the cardiac autonomic nervous control. 2011 Neurosci. Lett.
To investigate whether the manipulation of brain excitability by transcranial direct current stimulation (tDCS) modulates the heart rate variability (HRV), the effect of tDCS applied at rest on the left temporal lobe in athletes (AG) and non-athletes (NAG) was evaluated. The HRV parameters (natural logarithms of LF, HF, and LF/HF) was assessed in 20 healthy men before, and immediately after tDCS and sham stimulation. After anodal tDCS in AG the parasympathetic activity (HF(log)) increased (P<0.01) and the sympathetic activity (LF(log)) and sympatho-vagal balance (LF/HF(log)) decreased (P<0.01), whereas no significant effects were detected in NAG (P>0.05). No significant changes in HRV indexes were provoked by sham stimulation in both AG and NAG (P>0.05). In conclusion, tDCS applied on the left temporal lobe significantly increased the overall HRV in AG, enhancing the parasympathetic and decreasing the sympathetic modulation of heart rate. Consequently the sympatho-vagal balance decreased at rest in AG but not in NAG. Releasing a weak electric current to stimulate selected brain areas may induce favorable effects on the autonomic control to the heart in highly fit subjects.
Cambiaghi M, Teneud L, Velikova S, Gonzalez-Rosa JJ, Cursi M, Comi G, Leocani L Flash visual evoked potentials in mice can be modulated by transcranial direct current stimulation. 2011 Neuroscience
Transcranial direct current stimulation (tDCS) in humans has been shown to affect the size of visual evoked potentials (VEPs) in a polarity-dependent way. VEPs have been widely employed in mice to study the visual system in physiological and pathological conditions and are extensively used as animal models of neurological and visual disorders. The present study was performed to evaluate whether mice VEPs could be modulated by tDCS in the same manner as in humans. We describe here the effects of 10 min tDCS (anodal, cathodal or no stimulation) on flash-VEPs in C57BL/6 mice under sevoflurane anesthesia. VEP amplitudes of the first major peak (P1) were analyzed before, at 0, 5 and 10 min after tDCS. Compared with no stimulation condition, anodal tDCS increased P1 amplitude slightly more than 25%, while cathodal stimulation had opposite effects, with a decrease of P1 amplitude by about 30%. After-effects tended to reverse toward basal levels within 10 min after tDCS. These results, suggesting polarity-dependent modulation similar to what described in humans of tDCS effects on VEPs, encourage the use of mice models to study tDCS mechanisms of action and explore therapeutic applications on neurological models of disease.
McCambridge AB, Bradnam LV, Stinear CM, Byblow WD Cathodal transcranial direct current stimulation of the primary motor cortex improves selective muscle activation in the ipsilateral arm. 2011 J. Neurophysiol.
Proximal upper limb muscles are represented bilaterally in primary motor cortex. Goal-directed upper limb movement requires precise control of proximal and distal agonist and antagonist muscles. Failure to suppress antagonist muscles can lead to abnormal movement patterns, such as those commonly experienced in the proximal upper limb after stroke. We examined whether noninvasive brain stimulation of primary motor cortex could be used to improve selective control of the ipsilateral proximal upper limb. Thirteen healthy participants performed isometric left elbow flexion by contracting biceps brachii (BB; agonist) and left forearm pronation (BB antagonist) before and after 20 min of cathodal transcranial direct current stimulation (c-tDCS) or sham tDCS of left M1. During the tasks, motor evoked potentials (MEPs) in left BB were acquired using single-pulse transcranial magnetic stimulation of right M1 150-270 ms before muscle contraction. As expected, left BB MEPs were facilitated before flexion and suppressed before pronation. After c-tDCS, left BB MEP amplitudes were reduced compared with sham stimulation, before pronation but not flexion, indicating that c-tDCS enhanced selective muscle activation of the ipsilateral BB in a task-specific manner. The potential for c-tDCS to improve BB antagonist control correlated with BB MEP amplitude for pronation relative to flexion, expressed as a selectivity ratio. This is the first demonstration that selective muscle activation in the proximal upper limb can be improved after c-tDCS of ipsilateral M1 and that the benefits of c-tDCS for selective muscle activation may be most effective in cases where activation strategies are already suboptimal. These findings may have relevance for the use of tDCS in rehabilitation after stroke.
Antal A, Paulus W A case of refractory orofacial pain treated by transcranial direct current stimulation applied over hand motor area in combination with NMDA agonist drug intake. 2011 Brain Stimul
A female patient presented with persistent orofacial pain on the right side for 3 years, attributed to a viral infection. The pain had remained largely pharmacoresistant, reaching a value of 8/10 on the visual analogue scale.
Andrews SC, Hoy KE, Enticott PG, Daskalakis ZJ, Fitzgerald PB Improving working memory: the effect of combining cognitive activity and anodal transcranial direct current stimulation to the left dorsolateral prefrontal cortex. 2011 Brain Stimul
Transcranial direct current stimulation (tDCS), applied to the left dorsolateral prefrontal cortex (DLPFC) has been found to improve working memory (WM) performance in both healthy and clinical participants. However, whether this effect can be enhanced by cognitive activity undertaken during tDCS has not yet been explored.
Freitas C, Mondragon-Llorca H, Pascual-Leone A Noninvasive brain stimulation in Alzheimer's disease: systematic review and perspectives for the future. 2011 Exp. Gerontol.
A number of studies have applied transcranial magnetic stimulation (TMS) to physiologically characterize Alzheimer's disease (AD) and to monitor effects of pharmacological agents, while others have begun to therapeutically use TMS and transcranial direct current stimulation (tDCS) to improve cognitive function in AD. These applications are still very early in development, but offer the opportunity of learning from them for future development.
Garin P, Gilain C, Van Damme JP, de Fays K, Jamart J, Ossemann M, Vandermeeren Y Short- and long-lasting tinnitus relief induced by transcranial direct current stimulation. 2011 Journal of neurology
A significant proportion of the population suffers from tinnitus, a bothersome auditory phantom perception that can severely alter the quality of life. Numerous experimental studies suggests that a maladaptive plasticity of the auditory and limbic cortical areas may underlie tinnitus. Accordingly, repetitive transcranial magnetic stimulation (rTMS) has been repeatedly used with success to reduce tinnitus intensity. The potential of transcranial direct current stimulation (tDCS), another promising method of noninvasive brain stimulation, to relieve tinnitus has not been explored systematically. In a double-blind, placebo-controlled and balanced order design, 20 patients suffering from chronic untreatable tinnitus were submitted to 20 minutes of 1 mA anodal, cathodal and sham tDCS targeting the left temporoparietal area. The primary outcome measure was a change in tinnitus intensity or discomfort assessed with a Visual Analogic Scale (VAS) change-scale immediately after tDCS and 1 hour later. Compared to sham tDCS, anodal tDCS significantly reduced tinnitus intensity immediately after stimulation; whereas cathodal tDCS failed to do so. The variances of the tinnitus intensity and discomfort VAS change-scales increased dramatically after anodal and cathodal tDCS, whereas they remained virtually unchanged after sham tDCS. Moreover, several patients unexpectedly reported longer-lasting effects (at least several days) such as tinnitus improvement, worsening, or changes in tinnitus features, more frequently after real than sham tDCS. Anodal tDCS is a promising therapeutic tool for modulating tinnitus perception. Moreover, both anodal and cathodal tDCS seem able to alter tinnitus perception and could, thus, be used to trigger plastic changes.
Roche N, Lackmy A, Achache V, Bussel B, Katz R Effects of anodal transcranial direct current stimulation over the leg motor area on lumbar spinal network excitability in healthy subjects. 2011 J. Physiol. (Lond.)
In recent years, two techniques have become available for the non-invasive stimulation of human motor cortex: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). The effects of TMS and tDCS when applied over motor cortex should be considered with regard not only to cortical circuits but also to spinal motor circuits. The different modes of action and specificity of TMS and tDCS suggest that their effects on spinal network excitability may be different from that in the cortex. Until now, the effects of tDCS on lumbar spinal network excitability have never been studied. In this series of experiments, on healthy subjects, we studied the effects of anodal tDCS over the lower limb motor cortex on (i) reciprocal Ia inhibition projecting from the tibialis anterior muscle (TA) to the soleus (SOL), (ii) presynaptic inhibition of SOL Ia terminals, (iii) homonymous SOL recurrent inhibition, and (iv) SOL H-reflex recruitment curves. The results show that anodal tDCS decreases reciprocal Ia inhibition, increases recurrent inhibition and induces no modification of presynaptic inhibition of SOL Ia terminals and of SOL-H reflex recruitment curves. Our results indicate therefore that the effects of tDCS are the opposite of those previously described for TMS on spinal network excitability. They also indicate that anodal tDCS induces effects on spinal network excitability similar to those observed during co-contraction suggesting that anodal tDCS activates descending corticospinal projections mainly involved in co-contractions.
Mendonca ME, Santana MB, Baptista AF, Datta A, Bikson M, Fregni F, Araujo CP Transcranial DC stimulation in fibromyalgia: optimized cortical target supported by high-resolution computational models. 2011 J Pain
In this study we aimed to determine current distribution and short-term analgesic effects of transcranial direct current stimulation (tDCS) in fibromyalgia using different electrode montages. For each electrode montage, clinical effects were correlated with predictions of induced cortical current flow using magnetic resonance imaging-derived finite element method head model. Thirty patients were randomized into 5 groups (Cathodal-M1 [primary motor cortex], Cathodal-SO [supra-orbital area], Anodal-M1, Anodal-SO, and Sham) to receive tDCS application (2 mA, 20 minutes) using an extracephalic montage. Pain was measured using a visual numerical scale (VNS), pressure pain threshold (PPT), and a body diagram (BD) evaluating pain area. There was significant pain reduction in cathodal-SO and anodal-SO groups indexed by VNS. For PPT there was a trend for a similar effect in anodal-SO group. Computer simulation indicated that the M1-extracephalic montage produced dominantly temporo-parietal current flow, consistent with lack of clinical effects with this montage. Conversely, the SO-extracephalic montage produced current flow across anterior prefrontal structures, thus supporting the observed analgesic effects. Our clinical and modeling findings suggest that electrode montage, considering both electrodes, is critical for the clinical effects of M1-tDCS as electric current needs to be induced in areas associated with the pain matrix. These results should be taken into consideration for the design of pain tDCS studies. PERSPECTIVE: Results in this article support that electrode montage is a critical factor to consider for the clinical application of tDCS for pain control, as there is an important correlation between the location of induced electrical current and tDCS-induced analgesic effects.
Kang EK, Paik NJ Effect of a tDCS electrode montage on implicit motor sequence learning in healthy subjects. 2011 Exp Transl Stroke Med
Benninger DH, Lomarev M, Lopez G, Pal N, Luckenbaugh DA, Hallett M Transcranial direct current stimulation for the treatment of focal hand dystonia. 2011 Mov. Disord.
The treatment of writer's cramp, a task-specific focal hand dystonia, needs new approaches. A deficiency of inhibition in the motor cortex might cause writer's cramp. Transcranial direct current stimulation modulates cortical excitability and may provide a therapeutic alternative. In this randomized, double-blind, sham-controlled study, we investigated the efficacy of cathodal stimulation of the contralateral motor cortex in 3 sessions in 1 week. Assessment over a 2-week period included clinical scales, subjective ratings, kinematic handwriting analysis, and neurophysiological evaluation. Twelve patients with unilateral dystonic writer's cramp were investigated; 6 received transcranial direct current and 6 sham stimulation. Cathodal transcranial direct current stimulation had no favorable effects on clinical scales and failed to restore normal handwriting kinematics and cortical inhibition. Subjective worsening remained unexplained, leading to premature study termination. Repeated sessions of cathodal transcranial direct current stimulation of the motor cortex yielded no favorable results supporting a therapeutic potential in writer's cramp. © 2011 Movement Disorder Society.
O'Connell NE, Wand BM, Marston L, Spencer S, Desouza LH Non-invasive brain stimulation techniques for chronic pain. A report of a Cochrane systematic review and meta-analysis. 2011 Eur J Phys Rehabil Med
Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES) and transcranial direct current stimulation (tDCS).
Cattaneo Z, Pisoni A, Papagno C Transcranial direct current stimulation over Broca's region improves phonemic and semantic fluency in healthy individuals. 2011 Neuroscience
Previous studies have demonstrated that transcranial direct current stimulation (tDCS) can be proficiently used to modulate attentional and cognitive functions. For instance, in the language domain there is evidence that tDCS can fasten picture naming in both healthy individuals and aphasic patients, or improve grammar learning. In this study, we investigated whether tDCS can be used to increase healthy subjects' performance in phonemic and semantic fluency tasks, that are typically used in clinical assessment of language. Ten healthy individuals performed a semantic and a phonemic fluency task following anodal tDCS applied over Broca's region. Each participant underwent a real and a sham tDCS session. Participants were found to produce more words following real anodal tDCS both in the phonemic and in the semantic fluency. Control experiments ascertained that this finding did not depend upon unspecific effects of tDCS over levels of general arousal or attention or upon participants' expectations. These data confirm the efficacy of tDCS in transiently improving language functions by showing that anodal stimulation of Broca's region can enhance verbal fluency. Implications of these results for the treatment of language functions in aphasia are considered.
Borckardt JJ, Romagnuolo J, Reeves ST, Madan A, Frohman H, Beam W, George MS Feasibility, safety, and effectiveness of transcranial direct current stimulation for decreasing post-ERCP pain: a randomized, sham-controlled, pilot study. 2011 Gastrointest. Endosc.
Emerging evidence shows that transcranial direct current stimulation (tDCS), a minimally invasive brain stimulation technique, has analgesic effects in chronic pain patients and in healthy volunteers with experimental pain. No studies have examined the analgesic effects of tDCS immediately after surgical/endoscopic procedures. Endoscopy investigating abdominal pain, especially ERCP, can cause significant postprocedural pain.
Hamilton RH, Chrysikou EG, Coslett B Mechanisms of aphasia recovery after stroke and the role of noninvasive brain stimulation. 2011 Brain Lang
One of the most frequent symptoms of unilateral stroke is aphasia, the impairment or loss of language functions. Over the past few years, behavioral and neuroimaging studies have shown that rehabilitation interventions can promote neuroplastic changes in aphasic patients that may be associated with the improvement of language functions. Following left hemisphere strokes, the functional reorganization of language in aphasic patients has been proposed to involve both intrahemispheric interactions between damaged left hemisphere and perilesional sites and transcallosal interhemispheric interactions between the lesioned left hemisphere language areas and homotopic regions in the right hemisphere. A growing body of evidence for such reorganization comes from studies using transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), two safe and noninvasive procedures that can be applied clinically to modulate cortical excitability during post-stroke language recovery. We discuss a hierarchical model for the plastic changes in language representation that occur in the setting of dominant hemisphere stroke and aphasia. We further argue that TMS and tDCS are potentially promising tools for enhancing functional recovery of language and for further elucidating mechanisms of plasticity in patients with aphasia.
Hsu TY, Tseng LY, Yu JX, Kuo WJ, Hung DL, Tzeng OJ, Walsh V, Muggleton NG, Juan CH Modulating inhibitory control with direct current stimulation of the superior medial frontal cortex. 2011 Neuroimage
The executive control of voluntary action involves not only choosing from a range of possible actions but also the inhibition of responses as circumstances demand. Recent studies have demonstrated that many clinical populations, such as people with attention-deficit hyperactivity disorder, exhibit difficulties in inhibitory control. One prefrontal area that has been particularly associated with inhibitory control is the pre-supplementary motor area (Pre-SMA). Here we applied non-invasive transcranial direct current stimulation (tDCS) over Pre-SMA to test its role in this behavior. tDCS allows for current to be applied in two directions to selectively excite or suppress the neural activity of Pre-SMA. Our results showed that anodal tDCS improved efficiency of inhibitory control. Conversely, cathodal tDCS showed a tendency towards impaired inhibitory control. To our knowledge, this is the first demonstration of non-invasive intervention tDCS altering subjects' inhibitory control. These results further our understanding of the neural bases of inhibitory control and suggest a possible therapeutic intervention method for clinical populations.
Jacobson L, Javitt DC, Lavidor M Activation of Inhibition: Diminishing Impulsive Behavior by Direct Current Stimulation over the Inferior Frontal Gyrus. 2011 Journal of cognitive neuroscience
A common feature of human existence is the ability to reverse decisions after they are made but before they are implemented. This cognitive control process, termed response inhibition, refers to the ability to inhibit an action once initiated and has been localized to the right inferior frontal gyrus (rIFG) based on functional imaging and brain lesion studies. Transcranial direct current stimulation (tDCS) is a brain stimulation technique that can facilitate as well as impair cortical function. To explore whether response inhibition can be improved through rIFG electrical stimulation, we administered focal tDCS before subjects performed the stop signal task (SST), which measures response inhibition. Notably, activation of the rIFG by unilateral anodal stimulation significantly improved response inhibition, relative to a sham condition, whereas the same tDCS protocol did not affect response time in the go trials of the SST and in a control task. Furthermore, the SST was not affected by tDCS at a control site, the right angular gyrus. Our results are the first demonstration of response inhibition improvement with brain stimulation over rIFG and further confirm the rIFG involvement in this task. Although this study was conducted in healthy subjects, present findings with anodal rIFG stimulation support the use of similar paradigms for the treatment of cognitive control impairments in pathological conditions.
Kumar S, Wagner CW, Frayne C, Zhu L, Selim M, Feng W, Schlaug G Noninvasive brain stimulation may improve stroke-related dysphagia: a pilot study. 2011 Stroke
Treatment options for stroke-related dysphagia are currently limited. In this study, we investigated whether noninvasive brain stimulation in combination with swallowing maneuvers facilitates swallowing recovery in dysphagic stroke patients during early stroke convalescence.
Vanneste S, Focquaert F, Van de Heyning P, De Ridder D Different resting state brain activity and functional connectivity in patients who respond and not respond to bifrontal tDCS for tinnitus suppression. 2011 Exp Brain Res
Tinnitus is an ongoing phantom percept. It has been demonstrated that bifrontal transcranial direct current stimulation (tDCS) can reduce tinnitus. In this study, one group of patients reported a substantial improvement in their tinnitus perception, whereas another group described minor or no beneficial effect at all. The objective was to verify whether the activity and connectivity of the resting brain is different for people who will respond to bifrontal tDCS for tinnitus in comparison with non-responders. Higher gamma band activity was demonstrated in right primary and secondary auditory cortex and right parahippocampus for responders. It has been shown that gamma band activity in the auditory cortex is correlated with tinnitus loudness and that the anterior cingulate is involved in tinnitus distress. People who were going to respond to bifrontal tDCS also demonstrated an increased functional connectivity in the gamma band between the right dorsolateral prefrontal cortex (DLPFC) and the right parahippocampus as well as the right DLPFC and subgenual anterior cingulate cortex (sgACC). An analysis revealed that responders to bifrontal tDCS also experienced a larger suppression effect on TMS placed over the right temporal cortex (i.e. auditory cortex) than non-responders. Responders to bifrontal tDCS seem to differ in resting brain activity compared to non-responders in the right auditory cortex and parahippocampal area. They also have a different functional connectivity between DLPFC and, respectively, the sgACC and parahippocampal area. These connectivities might explain the suppression effect for both tinnitus loudness and tinnitus-related distress.
Lang N, Nitsche MA, Dileone M, Mazzone P, De Andres-Ares J, Diaz-Jara L, Paulus W, Di Lazzaro V, Oliviero A Transcranial direct current stimulation effects on I-wave activity in humans. 2011 J. Neurophysiol.
Transcranial direct current stimulation (tDCS) of the human cerebral cortex modulates cortical excitability noninvasively in a polarity-specific manner: anodal tDCS leads to lasting facilitation and cathodal tDCS to inhibition of motor cortex excitability. To further elucidate the underlying physiological mechanisms, we recorded corticospinal volleys evoked by single-pulse transcranial magnetic stimulation of the primary motor cortex before and after a 5-min period of anodal or cathodal tDCS in eight conscious patients who had electrodes implanted in the cervical epidural space for the control of pain. The effects of anodal tDCS were evaluated in six subjects and the effects of cathodal tDCS in five subjects. Three subjects were studied with both polarities. Anodal tDCS increased the excitability of cortical circuits generating I waves in the corticospinal system, including the earliest wave (I1 wave), whereas cathodal tDCS suppressed later I waves. The motor evoked potential (MEP) amplitude changes immediately following tDCS periods were in agreement with the effects produced on intracortical circuitry. The results deliver additional evidence that tDCS changes the excitability of cortical neurons.
Hortensius R, Schutter DJ, Harmon-Jones E When anger leads to aggression: induction of relative left frontal cortical activity with transcranial direct current stimulation increases the anger-aggression relationship. 2011 Social cognitive and affective neuroscience
The relationship between anger and aggression is imperfect. Based on work on the neuroscience of anger, we predicted that anger associated with greater relative left frontal cortical activation would be more likely to result in aggression. To test this hypothesis, we combined transcranial direct current stimulation (tDCS) over the frontal cortex with interpersonal provocation. Participants received insulting feedback after 15 min of tDCS and were able to aggress by administering noise blasts to the insulting participant. Individuals who received tDCS to increase relative left frontal cortical activity behaved more aggressively when they were angry. No relation between anger and aggression was observed in the increase relative right frontal cortical activity or sham condition. These results concur with the motivational direction model of frontal asymmetry, in which left frontal activity is associated with anger. We propose that anger with approach motivational tendencies is more likely to result in aggression.
Geroin C, Picelli A, Munari D, Waldner A, Tomelleri C, Smania N Combined transcranial direct current stimulation and robot-assisted gait training in patients with chronic stroke: a preliminary comparison. 2011 Clin Rehabil
To evaluate whether robot-assisted gait training combined with transcranial direct current stimulation is more effective than robot-assisted gait training alone or conventional walking rehabilitation for improving walking ability in stroke patients.
Antal A, Kriener N, Lang N, Boros K, Paulus W Cathodal transcranial direct current stimulation of the visual cortex in the prophylactic treatment of migraine. 2011 Cephalalgia
The purpose of this study was to determine whether transcranial direct current stimulation (tDCS) can be an effective prophylactic therapy for migraine and migraine-associated pain.
Holt RL, Mikati MA Care for child development: basic science rationale and effects of interventions. 2011 Pediatr. Neurol.
The past few years have witnessed increasing interest in devising programs to enhance early childhood development. We review current understandings of brain development, recent advances in this field, and their implications for clinical interventions. An expanding body of basic science laboratory data demonstrates that several interventions, including environmental enrichment, level of parental interaction, erythropoietin, antidepressants, transcranial magnetic stimulation, transcranial direct current stimulation, hypothermia, nutritional supplements, and stem cells, can enhance cerebral plasticity. Emerging clinical data, using functional magnetic resonance imaging and clinical evaluations, also support the hypothesis that clinical interventions can increase the developmental potential of children, rather than merely allowing the child to achieve an already predetermined potential. Such interventions include early developmental enrichment programs, which have improved cognitive function; high-energy and high-protein diets, which have increased brain growth in infants with perinatal brain damage; constraint-induced movement therapy, which has improved motor function in patients with stroke, cerebral palsy, and cerebral hemispherectomy; and transcranial magnetic stimulation, which has improved motor function in stroke patients.
Bradnam LV, Stinear CM, Byblow WD Cathodal transcranial direct current stimulation suppresses ipsilateral projections to presumed propriospinal neurons of the proximal upper limb. 2011 J. Neurophysiol.
This study investigated whether cathodal transcranial direct current stimulation (c-tDCS) of left primary motor cortex (M1) modulates excitability of ipsilateral propriospinal premotoneurons (PNs) in healthy humans. Transcranial magnetic stimulation (TMS) of the right motor cortex was used to obtain motor evoked potentials (MEPs) from the left biceps brachii (BB) while participants maintained contraction of the left BB. To examine presumed PN excitability, left BB MEPs were compared with those conditioned by median nerve stimulation (MNS) at the left elbow. Interstimulus intervals between TMS and MNS were set to produce summation at the C3-C4 level of the spinal cord. MNS facilitated BB MEPs elicited at TMS intensities near active motor threshold but inhibited BB MEPs at slightly higher intensities, indicative of putative PN modulation. c-tDCS suppressed the facilitatory and inhibitory effects of MNS. Sham tDCS did not alter either component. There was no effect of c-tDCS and sham tDCS on nonconditioned left BB MEPs or on the ipsilateral silent period of left BB. Right first dorsal interosseous MEPs were suppressed by c-tDCS. These results indicate that M1 c-tDCS can be used to modulate excitability of ipsilateral projections to presumed PNs controlling the proximal arm muscle BB. This technique may hold promise for promoting motor recovery of proximal upper limb function after stroke.
Fujiwara T, Tsuji T, Honaga K, Hase K, Ushiba J, Liu M Transcranial direct current stimulation modulates the spinal plasticity induced with patterned electrical stimulation. 2011 Clin Neurophysiol
Patterned sensory electrical stimulation (PES) has been shown to induce plasticity in spinal reciprocal Ia inhibition of the calf muscles. To study the cortical modulation of spinal plasticity, we examined the effects of giving transcranial direct current stimulation (tDCS) to the motor cortex before PES.
Stagg CJ, Bachtiar V, Johansen-Berg H The role of GABA in human motor learning. 2011 Curr. Biol.
GABA modification plays an important role in motor cortical plasticity. We therefore hypothesized that interindividual variation in the responsiveness of the GABA system to modification influences learning capacity in healthy adults. We assessed GABA responsiveness by transcranial direct current stimulation (tDCS), an intervention known to decrease GABA. The magnitude of M1 GABA decrease induced by anodal tDCS correlated positively with both the degree of motor learning and the degree of fMRI signal change within the left M1 during learning. This study therefore suggests that the responsiveness of the GABAergic system to modification may be relevant to short-term motor learning behavior and learning-related brain activity.
Goldman RL, Borckardt JJ, Frohman HA, O'Neil PM, Madan A, Campbell LK, Budak A, George MS Prefrontal cortex transcranial direct current stimulation (tDCS) temporarily reduces food cravings and increases the self-reported ability to resist food in adults with frequent food craving. 2011 Appetite
This study examined whether a 20-min session of prefrontal transcranial direct current stimulation (tDCS) (anode over the right prefrontal cortex and cathode over the left prefrontal cortex) would reduce food cravings and increase the self-reported ability to resist foods in 19 healthy individuals who reported frequent food cravings. Participants viewed computerized images of food and used computerized visual analogue scales to rate food cravings and inability to resist foods before, during, and after receiving either real or sham tDCS. This study employed a randomized within-subject crossover design; participants received both real and sham tDCS and were blind to the condition. Food cravings ratings were reduced in both conditions, however, the percent change in cravings ratings from pre- to post-stimulation was significantly greater for real stimulation than for sham. The percent change in inability to resist food from pre- to post-stimulation also showed a greater decrease in the real condition than for sham. Post hoc analyses suggest that active prefrontal tDCS acutely and significantly decreased food cravings ratings for sweet foods and carbohydrates more so than sham tDCS. No significant differences were seen in the amount of food ingested between real and sham tDCS. These findings in healthy subjects indicate that tDCS is able to temporarily reduce food cravings and improve the self-reported ability to resist foods.
Stagg CJ, Nitsche MA Physiological basis of transcranial direct current stimulation. 2011 Neuroscientist
Since the rediscovery of transcranial direct current stimulation (tDCS) about 10 years ago, interest in tDCS has grown exponentially. A noninvasive stimulation technique that induces robust excitability changes within the stimulated cortex, tDCS is increasingly being used in proof-of-principle and stage IIa clinical trials in a wide range of neurological and psychiatric disorders. Alongside these clinical studies, detailed work has been performed to elucidate the mechanisms underlying the observed effects. In this review, the authors bring together the results from these pharmacological, neurophysiological, and imaging studies to describe their current knowledge of the physiological effects of tDCS. In addition, the theoretical framework for how tDCS affects motor learning is proposed.
Marshall L, Kirov R, Brade J, Molle M, Born J Transcranial electrical currents to probe EEG brain rhythms and memory consolidation during sleep in humans. 2011 PLoS ONE
Previously the application of a weak electric anodal current oscillating with a frequency of the sleep slow oscillation (∼0.75 Hz) during non-rapid eye movement sleep (NonREM) sleep boosted endogenous slow oscillation activity and enhanced sleep-associated memory consolidation. The slow oscillations occurring during NonREM sleep and theta oscillations present during REM sleep have been considered of critical relevance for memory formation. Here transcranial direct current stimulation (tDCS) oscillating at 5 Hz, i.e., within the theta frequency range (theta-tDCS) is applied during NonREM and REM sleep. Theta-tDCS during NonREM sleep produced a global decrease in slow oscillatory activity conjoint with a local reduction of frontal slow EEG spindle power (8-12 Hz) and a decrement in consolidation of declarative memory, underlining the relevance of these cortical oscillations for sleep-dependent memory consolidation. In contrast, during REM sleep theta-tDCS appears to increase global gamma (25-45 Hz) activity, indicating a clear brain state-dependency of theta-tDCS. More generally, results demonstrate the suitability of oscillating-tDCS as a tool to analyze functions of endogenous EEG rhythms and underlying endogenous electric fields as well as the interactions between EEG rhythms of different frequencies.
Parazzini M, Fiocchi S, Rossi E, Paglialonga A, Ravazzani P Transcranial direct current stimulation: estimation of the electric field and of the current density in an anatomical human head model. 2011 IEEE Trans Biomed Eng
This paper investigates the spatial distribution of the electric field and of the current density in the brain tissues induced by transcranial direct current stimulation of the primary motor cortex. A numerical method was applied on a realistic human head model to calculate these field distributions in different brain structures, such as the cortex, the white matter, the cerebellum, the hippocampus, the medulla oblongata, the pons, the midbrain, and the thalamus. The influence of varying the anode area, the cathode area, and the injected current was also investigated. An electrode area as the one typically used in clinical practice (i.e., both electrodes equal to 35 cm(2)) resulted into complex and diffuse amplitude distributions over all the examined brain structures, with the region of maximum induced field being below or close to the anode. Variations in either the anode or cathode area corresponded to changes in the field amplitude distribution in all the brain tissues, with the former variation producing more diffuse effects. Variations in the injected current resulted, as could be expected, in linearly correlated changes in the field amplitudes.
Stagg CJ, Jayaram G, Pastor D, Kincses ZT, Matthews PM, Johansen-Berg H Polarity and timing-dependent effects of transcranial direct current stimulation in explicit motor learning. 2011 Neuropsychologia
Transcranial direct current stimulation (tDCS) is attracting increasing interest as a therapeutic tool for neurorehabilitation, particularly after stroke, because of its potential to modulate local excitability and therefore promote functional plasticity. Previous studies suggest that timing is important in determining the behavioural effects of brain stimulation. Regulatory metaplastic mechanisms exist to modulate the effects of a stimulation intervention in a manner dependent on prior cortical excitability, thereby preventing destabilization of existing cortical networks. The importance of such timing dependence has not yet been fully explored for tDCS. Here, we describe the results of a series of behavioural experiments in healthy controls to determine the importance of the relative timing of tDCS for motor performance. Application of tDCS during an explicit sequence-learning task led to modulation of behaviour in a polarity specific manner: relative to sham stimulation, anodal tDCS was associated with faster learning and cathodal tDCS with slower learning. Application of tDCS prior to performance of the sequence-learning task led to slower learning after both anodal and cathodal tDCS. By contrast, regardless of the polarity of stimulation, tDCS had no significant effect on performance of a simple reaction time task. These results are consistent with the idea that anodal tDCS interacts with subsequent motor learning in a metaplastic manner and suggest that anodal stimulation modulates cortical excitability in a manner similar to motor learning.
Brunoni AR, Amadera J, Berbel B, Volz MS, Rizzerio BG, Fregni F A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. 2011 Int. J. Neuropsychopharmacol.
Transcranial direct current stimulation (tDCS) is a non-invasive method of brain stimulation that has been intensively investigated in clinical and cognitive neuroscience. Although the general impression is that tDCS is a safe technique with mild and transient adverse effects (AEs), human data on safety and tolerability are largely provided from single-session studies in healthy volunteers. In addition the frequency of AEs and its relationship with clinical variables is unknown. With the aim of assessing tDCS safety in different conditions and study designs, we performed a systematic review and meta-analysis of tDCS clinical trials. We assessed Medline and other databases and reference lists from retrieved articles, searching for articles from 1998 (first trial with contemporary tDCS parameters) to August 2010. Animal studies, review articles and studies assessing other neuromodulatory techniques were excluded. According to our eligibility criteria, 209 studies (from 172 articles) were identified. One hundred and seventeen studies (56%) mentioned AEs in the report. Of these studies, 74 (63%) reported at least one AE and only eight studies quantified AEs systematically. In the subsample reporting AEs, the most common were, for active vs. sham tDCS group, itching (39.3% vs. 32.9%, p>0.05), tingling (22.2% vs. 18.3%, p>0.05), headache (14.8% vs. 16.2%, p>0.05), burning sensation (8.7% vs. 10%, p>0.05) and discomfort (10.4% vs. 13.4%, p>0.05). Meta-analytical techniques could be applied in only eight studies for itching, but no definite results could be obtained due to between-study heterogeneity and low number of studies. Our results suggested that some AEs such as itching and tingling were more frequent in the tDCS active group, although this was not statistically significant. Although results suggest that tDCS is associated with mild AEs only, we identified a selective reporting bias for reporting, assessing and publishing AEs of tDCS that hinders further conclusions. Based on our findings, we propose a revised adverse effects questionnaire to be applied in tDCS studies in order to improve systematic reporting of tDCS-related AEs.
Chi RP, Snyder AW Facilitate insight by non-invasive brain stimulation. 2011 PLoS ONE
Our experiences can blind us. Once we have learned to solve problems by one method, we often have difficulties in generating solutions involving a different kind of insight. Yet there is evidence that people with brain lesions are sometimes more resistant to this so-called mental set effect. This inspired us to investigate whether the mental set effect can be reduced by non-invasive brain stimulation. 60 healthy right-handed participants were asked to take an insight problem solving task while receiving transcranial direct current stimulation (tDCS) to the anterior temporal lobes (ATL). Only 20% of participants solved an insight problem with sham stimulation (control), whereas 3 times as many participants did so (p = 0.011) with cathodal stimulation (decreased excitability) of the left ATL together with anodal stimulation (increased excitability) of the right ATL. We found hemispheric differences in that a stimulation montage involving the opposite polarities did not facilitate performance. Our findings are consistent with the theory that inhibition to the left ATL can lead to a cognitive style that is less influenced by mental templates and that the right ATL may be associated with insight or novel meaning. Further studies including neurophysiological imaging are needed to elucidate the specific mechanisms leading to the enhancement.
Dell'Osso B, Priori A, Altamura AC Efficacy and safety of transcranial direct current stimulation in major depression. 2011 Biol. Psychiatry
Manto MU, Hampe CS, Rogemond V, Honnorat J Respective implications of glutamate decarboxylase antibodies in stiff person syndrome and cerebellar ataxia. 2011 Orphanet J Rare Dis
To investigate whether Stiff-person syndrome (SPS) and cerebellar ataxia (CA) are associated with distinct GAD65-Ab epitope specificities and neuronal effects.
Kwon YH, Jang SH The enhanced cortical activation induced by transcranial direct current stimulation during hand movements. 2011 Neurosci. Lett.
The aim of this study is to evaluate whether tDCS applied on the primary motor cortex (M1) in company with hand movements could enhance cortical activation, using functional MRI (fMRI). Twelve right-handed normal subjects were recruited. Real tDCS and sham tDCS with hand movements were applied during fMRI scanning. Subjects performed grasp-release hand movements at a metronome-guided frequency of 1Hz, while direct current with 1.0mA was delivered to the primary motor cortex. The averaged cortical map and the intensity index were compared between real tDCS with hand movements and sham tDCS with hand movements. Our result showed that cortical activation on the primary sensorimotor cortex was observed under both of two conditions; real tDCS with hand movements and sham tDCS with hand movements. Voxel count and peak intensity were 365.10±227.23 and 5.66±1.97, respectively, in the left primary sensorimotor cortex during real tDCS with right hand movements; in contrast, those were 182.20±117.88 and 4.12±0.88, respectively, during sham tDCS with right hand movements. Significant differences in voxel count and peak intensity were observed between real tDCS and sham tDCS (p<0.05). We found that anodal tDCS application during motor task enhanced cortical activation on the underlying targeted motor cortex, compared with the same motor task without tDCS. Therefore, it seemed that tDCS induced more cortical activity and modulated brain function when concurrently applied with motor task.
McFadden JL, Borckardt JJ, George MS, Beam W Reducing procedural pain and discomfort associated with transcranial direct current stimulation. 2011 Brain Stimul
Transcranial direct current stimulation (tDCS) appears to have modulatory effects on the excitability of cortical brain tissue. Though tDCS as presently applied causes no apparent harm to brain structure or function, a number of uncomfortable sensations can occur beneath the electrodes during stimulation, including tingling, pain, itching, and burning sensations. Therefore, we investigated the effect of topically applied Eutectic mixture of local anesthetics (EMLA) on tDCS-related discomfort.
Moreines JL, McClintock SM, Holtzheimer PE Neuropsychologic effects of neuromodulation techniques for treatment-resistant depression: a review. 2011 Brain Stimul
Electroconvulsive therapy (ECT) and ablative neurosurgical procedures are established interventions for treatment-resistant depression (TRD), but their use may be limited in part by neuropsychological adverse effects. Additional neuromodulation strategies are being developed that aim to match or exceed the efficacy of ECT/ablative surgery with a better neurocognitive side effect profile. In this review, we briefly discuss the neurocognitive effects of ECT and ablative neurosurgical procedures, then synthesize the available neurocognitive information for emerging neuromodulation therapies, including repetitive transcranial magnetic stimulation, magnetic seizure therapy, transcranial direct current stimulation, vagus nerve stimulation, and deep brain stimulation. The available evidence suggests these procedures may be more cognitively benign relative to ECT or ablative neurosurgical procedures, though further research is clearly needed to fully evaluate the neurocognitive effects, both positive and negative, of these novel neuromodulation interventions.
Fridriksson J, Richardson JD, Baker JM, Rorden C Transcranial direct current stimulation improves naming reaction time in fluent aphasia: a double-blind, sham-controlled study. 2011 Stroke
Previous evidence suggests that anodal transcranial direct current stimulation (A-tDCS) applied to the left hemisphere can improve aphasic participants' ability to name common objects. The current study further examined this issue in a more tightly controlled experiment in participants with fluent aphasia.
Hansen N, Obermann M, Poitz F, Holle D, Diener HC, Antal A, Paulus W, Katsarava Z Modulation of human trigeminal and extracranial nociceptive processing by transcranial direct current stimulation of the motor cortex. 2011 Cephalalgia
The study was conducted to investigate the after-effect of transcranial direct current stimulation (tDCS) applied over the human primary motor cortex (M1) on trigeminal and extracranial nociceptive processing.
Hamilton R, Messing S, Chatterjee A Rethinking the thinking cap: ethics of neural enhancement using noninvasive brain stimulation. 2011 Neurology
Although a growing body of evidence suggests that noninvasive brain stimulation techniques such as transcranial magnetic stimulation and transcranial direct current stimulation have the capacity to enhance neural function in both brain-injured and neurally intact individuals, the implications of their potential use for cosmetic self-enhancement have not been fully explored. We review 3 areas in which noninvasive brain stimulation has the potential to enhance neurologic function: cognitive skills, mood, and social cognition. We then characterize the ethical problems that affect the practice of cosmetic neurology, including safety, character, justice, and autonomy, and discuss how these problems may apply to the use of noninvasive brain stimulation for self-enhancement.
Takano Y, Yokawa T, Masuda A, Niimi J, Tanaka S, Hironaka N A rat model for measuring the effectiveness of transcranial direct current stimulation using fMRI. 2011 Neurosci. Lett.
Transcranial direct current stimulation (tDCS) is one of the noteworthy noninvasive brain stimulation techniques, but the mechanism of its action remains unclear. With the aim of clarifying the mechanism, we developed a rat model and measured its effectiveness using fMRI. Carbon fiber electrodes were placed on the top of the head over the frontal cortex as the anode and on the neck as the cathode. The stimulus was 400- or 40-μA current applied for 10 min after a baseline recording under an anesthetized condition. The 400-μA stimulation significantly increased signal intensities in the frontal cortex and nucleus accumbens. This suggests anodal tDCS over the frontal cortex induces neuronal activation in the frontal cortex and in its connected brain region.
Bueno VF, Brunoni AR, Boggio PS, Bensenor IM, Fregni F Mood and cognitive effects of transcranial direct current stimulation in post-stroke depression. 2011 Neurocase
Depression following stroke (PSD) affects up to 33% of patients and is associated with increased mortality. Antidepressant drugs have several side effects; therefore novel treatments are needed. Transcranial direct current stimulation (tDCS) has induced mood and cognitive gain in several neuropsychiatric conditions but has not been tested for PSD to date. Here, we report a patient with significant mood and cognitive impairment who showed marked amelioration of these symptoms following anodal stimulation (2 mA per 30 minutes per 10 days) over the left dorsolateral prefrontal cortex. We discuss the possible mechanisms of tDCS in improving PSD. This initial preliminary data is useful to encourage further controlled trials on the field.
Antal A, Polania R, Schmidt-Samoa C, Dechent P, Paulus W Transcranial direct current stimulation over the primary motor cortex during fMRI. 2011 Neuroimage
Measurements of motor evoked potentials (MEPs) have shown that anodal and cathodal transcranial direct current stimulations (tDCS) have facilitatory or inhibitory effects on corticospinal excitability in the stimulated area of the primary motor cortex (M1). Here, we investigated the online effects of short periods of anodal and cathodal tDCS on human brain activity of healthy subjects and associated hemodynamics by concurrent blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) at 3T. Using a block design, 20s periods of tDCS at 1 mA intensity over the left M1 altered with 20s periods without tDCS. In different fMRI runs, the effect of anodal or cathodal tDCS was assessed at rest or during finger tapping. A control experiment was also performed, in which the electrodes were placed over the left and right occipito-temporo-parietal junction. Neither anodal nor cathodal tDCS over the M1 for 20s stimulation duration induced a detectable BOLD signal change. However, in comparison to a voluntary finger tapping task without stimulation, anodal tDCS during finger tapping resulted in a decrease in the BOLD response in the supplementary motor area (SMA). Cathodal stimulation did not result in significant change in BOLD response in the SMA, however, a tendency toward decreased activity could be seen. In the control experiment neither cathodal nor anodal stimulation resulted in a significant change of BOLD signal during finger tapping in any brain area including SMA, PM, and M1. These findings demonstrate that the well-known polarity-dependent shifts in corticospinal excitability that have previously been demonstrated using measurements of MEPs after M1 stimulation are not paralleled by analogous changes in regional BOLD signal. This difference implies that the BOLD signal and measurements of MEPs probe diverse physiological mechanisms. The MEP amplitude reflects changes in transsynaptic excitability of large pyramidal neurons while the BOLD signal is a measure of net synaptic activity of all cortical neurons.
Zaehle T, Sandmann P, Thorne JD, Jancke L, Herrmann CS Transcranial direct current stimulation of the prefrontal cortex modulates working memory performance: combined behavioural and electrophysiological evidence. 2011 BMC Neurosci
Transcranial direct current stimulation (tDCS) is a technique that can systematically modify behaviour by inducing changes in the underlying brain function. In order to better understand the neuromodulatory effect of tDCS, the present study examined the impact of tDCS on performance in a working memory (WM) task and its underlying neural activity. In two experimental sessions, participants performed a letter two-back WM task after sham and either anodal or cathodal tDCS over the left dorsolateral prefrontal cortex (DLPFC).
Galvez V, Alonzo A, Martin D, Mitchell PB, Sachdev P, Loo CK Hypomania Induction in a Patient With Bipolar II Disorder by Transcranial Direct Current Stimulation (tDCS). 2011 J ECT
: To report a case of hypomania induced by transcranial direct current stimulation (tDCS) given with an extracephalic reference electrode. Transcranial direct current stimulation is a noninvasive brain stimulation technique in which a weak current is applied through the scalp to produce changes in neuronal excitability in the underlying cerebral tissue. Recent clinical trials have shown promising results with left anodal prefrontal tDCS in treating depression. When the reference cathodal electrode in tDCS is moved from the cranium to an extracephalic position, larger areas of both cerebral hemispheres are stimulated, with potential implications for both efficacy and safety.
Fricke K, Seeber AA, Thirugnanasambandam N, Paulus W, Nitsche MA, Rothwell JC Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex. 2011 J. Neurophysiol.
Several mechanisms have been proposed that control the amount of plasticity in neuronal circuits and guarantee dynamic stability of neuronal networks. Homeostatic plasticity suggests that the ease with which a synaptic connection is facilitated/suppressed depends on the previous amount of network activity. We describe how such homeostatic-like interactions depend on the time interval between two conditioning protocols and on the duration of the preconditioning protocol. We used transcranial direct current stimulation (tDCS) to produce short-lasting plasticity in the motor cortex of healthy humans. In the main experiment, we compared the aftereffect of a single 5-min session of anodal or cathodal tDCS with the effect of a 5-min tDCS session preceded by an identical 5-min conditioning session administered 30, 3, or 0 min beforehand. Five-minute anodal tDCS increases excitability for about 5 min. The same duration of cathodal tDCS reduces excitability. Increasing the duration of tDCS to 10 min prolongs the duration of the effects. If two 5-min periods of tDCS are applied with a 30-min break between them, the effect of the second period of tDCS is identical to that of 5-min stimulation alone. If the break is only 3 min, then the second session has the opposite effect to 5-min tDCS given alone. Control experiments show that these shifts in the direction of plasticity evolve during the 10 min after the first tDCS session and depend on the duration of the first tDCS but not on intracortical inhibition and facilitation. The results are compatible with a time-dependent "homeostatic-like" rule governing the response of the human motor cortex to plasticity probing protocols.
Madhavan S, Weber KA, Stinear JW Non-invasive brain stimulation enhances fine motor control of the hemiparetic ankle: implications for rehabilitation. 2011 Exp Brain Res
We set out to answer two questions with this study: 1. Can stroke patients improve voluntary control of their paretic ankle by practising a visuo-motor ankle-tracking task? 2. Are practice effects enhanced with non-invasive brain stimulation? A carefully selected sample of chronic stroke patients able to perform the experimental task attended three data collection sessions. Facilitatory transcranial direct current stimulation (tDCS) was applied in a random order over the lower limb primary motor cortex of the lesioned hemisphere or the non-lesioned hemisphere or sham stimulation was delivered over the lesioned hemisphere. In each session, tDCS was applied as patients practiced tracking a sinusoidal waveform for 15 min using dorsiflexion-plantarflexion movements of their paretic ankle. The difference in tracking error prior to, and after, the 15 min of practice was calculated. A practice effect was revealed following sham stimulation, and this effect was enhanced with tDCS applied over the lesioned hemisphere. The practice effect observed following sham stimulation was eliminated by tDCS applied over the non-lesioned hemisphere. The study provides the first evidence that non-invasive brain stimulation applied to the lesioned motor cortex of moderate- to well-recovered stroke patients enhances voluntary control of the paretic ankle. The results provide a basis for examining whether this enhanced ankle control can be induced in patients with greater impairments and whether enhanced control of a single or multiple lower limb joints improves hemiparetic gait patterns.
San-Juan D, Calcaneo Jde D, Gonzalez-Aragon MF, Bermudez Maldonado L, Avellan AM, Argumosa EV, Fregni F Transcranial direct current stimulation in adolescent and adult Rasmussen's encephalitis. 2011 Epilepsy Behav
Rasmussen's encephalitis is a rare, progressive inflammatory disease that typically affects one cerebral hemisphere and causes intractable partial-onset seizures. Currently, the only effective therapy is hemispherectomy; however, this procedure is associated with irreversible neurological deficits. Novel therapeutic approaches to this condition are therefore necessary. One possible option that has not yet been extensively studied is electrical cathodal transcranial direct current stimulation (cTDCS). We describe the cases of two patients with atypical-onset Rasmussen's encephalitis who underwent cTDCS at 1- and 2-mA intensity for 60 minutes in four sessions (on days 0, 7, 30, and 60). No complications were recorded during their therapy. At follow-up evaluations 6 and 12 months later, one patient had a significant reduction in seizure frequency and one was seizure free. Additionally, both patients had improved levels of alertness and language. This is the first time that cTDCS has been applied in serial sessions to treat Rasmussen's encephalitis to avoid or delay surgical treatment.
Thirugnanasambandam N, Grundey J, Adam K, Drees A, Skwirba AC, Lang N, Paulus W, Nitsche MA Nicotinergic impact on focal and non-focal neuroplasticity induced by non-invasive brain stimulation in non-smoking humans. 2011 Neuropsychopharmacology
Nicotine improves cognitive performance and modulates neuroplasticity in brain networks. The neurophysiological mechanisms underlying nicotine-induced behavioral changes have been sparsely studied, especially in humans. Global cholinergic activation focuses on plasticity in humans. However, the specific contribution of nicotinic receptors to these effects is unclear. Henceforth, we explored the impact of nicotine on non-focal neuroplasticity induced by transcranial direct current stimulation (tDCS) and focal, synapse-specific plasticity induced by paired associative stimulation (PAS) in healthy non-smoking individuals. Forty-eight subjects participated in the study. Each subject received placebo and nicotine patches combined with one of the stimulation protocols to the primary motor cortex in different sessions. Transcranial magnetic stimulation (TMS)-elicited motor-evoked potential (MEP) amplitudes were recorded as a measure of corticospinal excitability until the evening of the second day following the stimulation. Nicotine abolished or reduced both PAS- and tDCS-induced inhibitory neuroplasticity. Non-focal facilitatory plasticity was also abolished, whereas focal facilitatory plasticity was slightly prolonged by nicotine. Thus, nicotinergic influence on facilitatory, but not inhibitory plasticity mimics that of global cholinergic enhancement. Therefore, activating nicotinic receptors has clearly discernable effects from global cholinergic activation. These nicotine-generated plasticity alterations might be important for the effects of the drug on cognitive function.
Matsuo A, Maeoka H, Hiyamizu M, Shomoto K, Morioka S, Seki K Enhancement of precise hand movement by transcranial direct current stimulation. 2011 Neuroreport
The effect of transcranial direct current stimulation (tDCS) on the precise nondominant hand movement was investigated by applying anodal stimulation over the right primary motor cortex. We recruited 14 healthy participants for this single-blind, sham-controlled crossover trial. A circle-drawing task was performed before, immediately after, and at 30 min after 20 min of 1 mA anodal or sham tDCS. Anodal tDCS, compared with sham stimulation, significantly improved the circle-drawing task compared with sham stimulation. The deviation area and path length of the task were significantly decreased after anodal tDCS application and were further enhanced at 30 min after stimulation. These results suggest that anodal tDCS over the primary motor cortex enhances the precise movement of the nondominant hand for 30 min in healthy participants.
Wachter D, Wrede A, Schulz-Schaeffer W, Taghizadeh-Waghefi A, Nitsche MA, Kutschenko A, Rohde V, Liebetanz D Transcranial direct current stimulation induces polarity-specific changes of cortical blood perfusion in the rat. 2011 Exp. Neurol.
Transcranial direct current stimulation (tDCS) induces changes in cortical excitability and improves hand-motor function in chronic stroke. These effects depend on polarity, duration of stimulation and current intensity applied. Towards evaluating the therapeutic potential of tDCS in acute stroke, we investigated tDCS-effects on cerebral blood flow (CBF) in a tDCS rat model adapted for this purpose.
Keeser D, Padberg F, Reisinger E, Pogarell O, Kirsch V, Palm U, Karch S, Moller HJ, Nitsche MA, Mulert C Prefrontal direct current stimulation modulates resting EEG and event-related potentials in healthy subjects: a standardized low resolution tomography (sLORETA) study. 2011 Neuroimage
Prefrontal transcranial direct current stimulation (tDCS) with the anode placed on the left dorsolateral prefrontal cortex (DLPFC) has been reported to enhance working memory in healthy subjects and to improve mood in major depression. However, its putative antidepressant, cognitive and behavior action is not well understood. Here, we evaluated the distribution of neuronal electrical activity changes after anodal tDCS of the left DLPFC and cathodal tDCS of the right supraorbital region using spectral power analysis and standardized low resolution tomography (sLORETA). Ten healthy subjects underwent real and sham tDCS on separate days in a double-blind, placebo-controlled cross-over trial. Anodal tDCS was applied for 20 min at 2 mA intensity over the left DLPFC, while the cathode was positioned over the contralateral supraorbital region. After tDCS, EEG was recorded during an eyes-closed resting state followed by a working memory (n-back) task. Statistical non-parametric mapping showed reduced left frontal delta activity in the real tDCS condition. Specifically, a significant reduction of mean current densities (sLORETA) for the delta band was detected in the left subgenual PFC, the anterior cingulate and in the left medial frontal gyrus. Moreover, the effect was strongest for the first 5 min (p<0.01). The following n-back task revealed a positive impact of prefrontal tDCS on error rate, accuracy and reaction time. This was accompanied by increased P2- and P3- event-related potentials (ERP) component-amplitudes for the 2-back condition at the electrode Fz. A source localization using sLORETA for the time window 250-450 ms showed enhanced activity in the left parahippocampal gyrus for the 2-back condition. These results suggest that anodal tDCS of the left DLPFC and/or cathodal tDCS of the contralateral supraorbital region may modulate regional electrical activity in the prefrontal and anterior cingulate cortex in addition to improving working memory performance.
Galea JM, Vazquez A, Pasricha N, de Xivry JJ, Celnik P Dissociating the roles of the cerebellum and motor cortex during adaptive learning: the motor cortex retains what the cerebellum learns. 2011 Cereb. Cortex
Adaptation to a novel visuomotor transformation has revealed important principles regarding learning and memory. Computational and behavioral studies have suggested that acquisition and retention of a new visuomotor transformation are distinct processes. However, this dissociation has never been clearly shown. Here, participants made fast reaching movements while unexpectedly a 30-degree visuomotor transformation was introduced. During visuomotor adaptation, subjects received cerebellar, primary motor cortex (M1) or sham anodal transcranial direct current stimulation (tDCS), a noninvasive form of brain stimulation known to increase excitability. We found that cerebellar tDCS caused faster adaptation to the visuomotor transformation, as shown by a rapid reduction of movement errors. These findings were not present with similar modulation of visual cortex excitability. In contrast, tDCS over M1 did not affect adaptation, but resulted in a marked increase in retention of the newly learnt visuomotor transformation. These results show a clear dissociation in the processes of acquisition and retention during adaptive motor learning and demonstrate that the cerebellum and primary motor cortex have distinct functional roles. Furthermore, they show that is possible to enhance cerebellar function using tDCS.
Mahmoudi H, Borhani Haghighi A, Petramfar P, Jahanshahi S, Salehi Z, Fregni F Transcranial direct current stimulation: electrode montage in stroke. 2011 Disabil Rehabil
Neurophysiological and computer modelling studies have shown that electrode montage is a critical parameter to determine the neuromodulatory effects of transcranial direct current stimulation (tDCS). We tested these results clinically by systematically investigating optimal tDCS electrode montage in stroke. Ten patients received in a counterbalanced and randomised order the following conditions of stimulation (i) anodal stimulation of affected M1 (primary motor cortex) and cathodal stimulation of unaffected M1 ('bilateral tDCS'); (ii) anodal stimulation of affected M1 and cathodal stimulation of contralateral supraorbital area ('anodal tDCS'); (iii) cathodal stimulation of unaffected M1 and anodal stimulation of contralateral supraorbital area ('cathodal tDCS'); (iv) anodal stimulation of affected M1 and cathodal stimulation of contralateral deltoid muscle ('extra-cephalic tDCS') and (v) sham stimulation. We used the Jebsen-Taylor Test (JTT) as a widely accepted measure of upper limb function. Bilateral tDCS, anodal tDCS and cathodal tDCS were shown to be associated with significant improvements on the JTT. Placing the reference electrode in an extracephalic position and use of sham stimulation did not induce any significant effects. This small sham controlled cross-over clinical trial is important to provide additional data on the clinical effects of tDCS in stroke and for planning and designing future large tDCS trials in patients with stroke.
Kirimoto H, Ogata K, Onishi H, Oyama M, Goto Y, Tobimatsu S Transcranial direct current stimulation over the motor association cortex induces plastic changes in ipsilateral primary motor and somatosensory cortices. 2011 Clin Neurophysiol
This study was performed to elucidate whether transcranial direct current stimulation (tDCS) over the motor association cortex modifies the excitability of primary motor (M1) and somatosensory (S1) cortices via neuronal connectivity.
Ambrus GG, Antal A, Paulus W Comparing cutaneous perception induced by electrical stimulation using rectangular and round shaped electrodes. 2011 Clin Neurophysiol
We have investigated the cutaneous perception differences for anodal and cathodal transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS) between two electrode configurations: a standard, rectangle-shaped, and a circle-shaped, round geometry with the same surface area, and thus, same nominal current distribution. We have aimed to find whether a smaller perimeter length and the absence of corners in the case of the round configuration would lead to altered skin perception characteristics when compared to the rectangular geometry.
May A, Jurgens TP [Therapeutic neuromodulation in primary headaches]. 2011 Nervenarzt
Neuromodulatory techniques have developed rapidly in the therapeutic management of refractory headaches. Invasive procedures comprise peripheral nerve stimulation (particularly occipital nerve stimulation), vagus nerve stimulation, cervical spinal cord stimulation and hypothalamic deep brain stimulation. Transcutaneous electrical nerve stimulation, repetitive transcranial magnetic stimulation and transcranial direct current stimulation are noninvasive variants. Based on current neuroimaging, neurophysiological and clinical studies occipital nerve stimulation and hypothalamic deep brain stimulation are recommended for patients with chronic cluster headache. Less convincing evidence can be found for their use in other refractory headaches such as chronic migraine. No clear recommendation can be given for the other neuromodulatory techniques. The emerging concept of intermittent stimulation of the sphenopalatine ganglion is nonetheless promising. Robust randomized and sham-controlled multicenter studies are needed before these therapeutic approaches are widely implemented. Due to the experimental nature all patients should be treated in clinical studies. It is essential to confirm the correct headache diagnosis and the refractory nature before an invasive approach is considered. Patients should generally be referred to specialized interdisciplinary outpatient departments which closely collaborate with neurosurgeons who are experienced in the implantation of neuromodulatory devices. It is crucial to ensure a competent postoperative follow-up with optimization of stimulation parameters and adjustment of medication.
Fiori V, Coccia M, Marinelli CV, Vecchi V, Bonifazi S, Ceravolo MG, Provinciali L, Tomaiuolo F, Marangolo P Transcranial direct current stimulation improves word retrieval in healthy and nonfluent aphasic subjects. 2011 J Cogn Neurosci
A number of studies have shown that modulating cortical activity by means of transcranial direct current stimulation (tDCS) affects performances of both healthy and brain-damaged subjects. In this study, we investigated the potential of tDCS to enhance associative verbal learning in 10 healthy individuals and to improve word retrieval deficits in three patients with stroke-induced aphasia. In healthy individuals, tDCS (20 min, 1 mA) was applied over Wernicke's area (position CP5 of the International 10-20 EEG System) while they learned 20 new "words" (legal nonwords arbitrarily assigned to 20 different pictures). The healthy subjects participated in a randomized counterbalanced double-blind procedure in which they were subjected to one session of anodic tDCS over left Wernicke's area, one sham session over this location and one session of anodic tDCS stimulating the right occipito-parietal area. Each experimental session was performed during a different week (over three consecutive weeks) with 6 days of intersession interval. Over 2 weeks, three aphasic subjects participated in a randomized double-blind experiment involving intensive language training for their anomic difficulties in two tDCS conditions. Each subject participated in five consecutive daily sessions of anodic tDCS (20 min, 1 mA) and sham stimulation over Wernicke's area while they performed a picture-naming task. By the end of each week, anodic tDCS had significantly improved their accuracy on the picture-naming task. Both normal subjects and aphasic patients also had shorter naming latencies during anodic tDCS than during sham condition. At two follow-ups (1 and 3 weeks after the end of treatment), performed only in two aphasic subjects, response accuracy and reaction times were still significantly better in the anodic than in the sham condition, suggesting a long-term effect on recovery of their anomic disturbances.
Polania R, Paulus W, Antal A, Nitsche MA Introducing graph theory to track for neuroplastic alterations in the resting human brain: a transcranial direct current stimulation study. 2011 Neuroimage
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that alters cortical excitability and activity in a polarity-dependent way. Stimulation for a few minutes has been shown to induce plastic alterations of cortical excitability and to improve cognitive performance. These effects might be related to stimulation-induced alterations of functional cortical network connectivity. We aimed to investigate the impact of tDCS on cortical network function by functional connectivity and graph theoretical analysis of the BOLD fMRI spontaneous activity. fMRI resting-state datasets were acquired immediately before and after 10-min bipolar tDCS during rest, with the anode placed over the left primary motor cortex (M1) and the cathode over the contralateral frontopolar cortex. For each dataset, grey matter voxel-based synchronization matrices were calculated and thresholded to construct undirected graphs. Nodal connectivity degree and minimum path length maps were calculated and compared before and after tDCS. Nodal minimum path lengths significantly increased in the left somatomotor (SM1) cortex after anodal tDCS, which means that the number of direct functional connections from the left SM1 to topologically distant grey matter voxels significantly decreased. In contrast, functional coupling between premotor and superior parietal areas with the left SM1 significantly increased. Additionally, the nodal connectivity degree in the left posterior cingulate cortex (PCC) area as well as in the right dorsolateral prefrontal cortex (right DLPFC) significantly increased. In summary, we provide initial support that tDCS-induced neuroplastic alterations might be related to functional connectivity changes in the human brain. Additionally, we propose our approach as a powerful method to track for neuroplastic changes in the human brain.
Loo CK, Martin DM, Alonzo A, Gandevia S, Mitchell PB, Sachdev P Avoiding skin burns with transcranial direct current stimulation: preliminary considerations. 2011 Int. J. Neuropsychopharmacol.
Loo C, Katalinic N, Mitchell PB, Greenberg B Physical treatments for bipolar disorder: a review of electroconvulsive therapy, stereotactic surgery and other brain stimulation techniques. 2011 J Affect Disord
Despite pharmacological advances, bipolar disorder continues to be difficult to treat. This article reviews the evidence base for the use of electroconvulsive therapy (ECT) and other brain stimulation therapies in bipolar disorder.
Brunoni AR, Valiengo L, Baccaro A, Zanao TA, de Oliveira JF, Vieira GP, Bueno VF, Goulart AC, Boggio PS, Lotufo PA, Bensenor IM, Fregni F Sertraline vs. ELectrical Current Therapy for Treating Depression Clinical Trial--SELECT TDCS: design, rationale and objectives. 2011 Contemp Clin Trials
Despite significant advancements in psychopharmacology, treating major depressive disorder (MDD) is still a challenge considering the efficacy, tolerability, safety, and economical costs of most antidepressant drugs. One approach that has been increasingly investigated is modulation of cortical activity with tools of non-invasive brain stimulation - such as transcranial magnetic stimulation and transcranial direct current stimulation (tDCS). Due to its profile, tDCS seems to be a safe and affordable approach.
Brunoni AR, Ferrucci R, Bortolomasi M, Vergari M, Tadini L, Boggio PS, Giacopuzzi M, Barbieri S, Priori A Transcranial direct current stimulation (tDCS) in unipolar vs. bipolar depressive disorder. 2011 Prog. Neuropsychopharmacol. Biol. Psychiatry
Transcranial direct current stimulation (tDCS) is a non-invasive method for brain stimulation. Although pilot trials have shown that tDCS yields promising results for major depressive disorder (MDD), its efficacy for bipolar depressive disorder (BDD), a condition with high prevalence and poor treatment outcomes, is unknown. In a previous study we explored the effectiveness of tDCS for MDD. Here, we expanded our research, recruiting patients with MDD and BDD. We enrolled 31 hospitalized patients (24 women) aged 30-70 years 17 with MDD and 14 with BDD (n = 14). All patients received stable drug regimens for at least two weeks before enrollment and drug dosages remained unchanged throughout the study. We applied tDCS over the dorsolateral prefrontal cortex (anodal electrode on the left and cathodal on the right) using a 2 mA-current for 20 min, twice-daily, for 5 consecutive days. Depression was measured at baseline, after 5 tDCS sessions, one week later, and one month after treatment onset. We used the scales of Beck (BDI) and Hamilton-21 items (HDRS). All patients tolerated treatment well without adverse effects. After the fifth tDCS session, depressive symptoms in both study groups diminished, and the beneficial effect persisted at one week and one month. In conclusion, our preliminary study suggests that tDCS is a promising treatment for patients with MDD and BDD.2.
Kamida T, Kong S, Eshima N, Abe T, Fujiki M, Kobayashi H Transcranial direct current stimulation decreases convulsions and spatial memory deficits following pilocarpine-induced status epilepticus in immature rats. 2011 Behav. Brain Res.
Transcranial direct current stimulation (tDCS) is a recently available, noninvasive brain stimulation technique. The effects of cathodal tDCS on convulsions and spatial memory after status epilepticus (SE) in immature animals were investigated.
Polania R, Nitsche MA, Paulus W Modulating functional connectivity patterns and topological functional organization of the human brain with transcranial direct current stimulation. 2011 Hum Brain Mapp
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that alters cortical excitability and activity in a polarity-dependent way. Stimulation for few minutes has been shown to induce plastic alterations of cortical excitability and to improve cognitive performance. These effects might be caused by stimulation-induced alterations of functional cortical network connectivity. We aimed to investigate the impact of tDCS on cortical network function through functional connectivity and graph theoretical analysis. Single recordings in healthy volunteers with 62 electroencephalography channels were acquired before and after 10 min of facilitatory anodal tDCS over the primary motor cortex (M1), combined with inhibitory cathodal tDCS of the contralateral frontopolar cortex, in resting state and during voluntary hand movements. Correlation matrices containing all 62 pairwise electrode combinations were calculated with the synchronization likelihood (SL) method and thresholded to construct undirected graphs for the θ, α, β, low-γ and high-γ frequency bands. SL matrices and undirected graphs were compared before and after tDCS. Functional connectivity patterns significantly increased within premotor, motor, and sensorimotor areas of the stimulated hemisphere during motor activity in the 60-90 Hz frequency range. Additionally, tDCS-induced significant intrahemispheric and interhemispheric connectivity changes in all the studied frequency bands. In summary, we show for the first time evidence for tDCS-induced changes in brain synchronization and topological functional organization.
Mathys C, Loui P, Zheng X, Schlaug G Non-invasive brain stimulation applied to Heschl's gyrus modulates pitch discrimination. 2010 Frontiers in psychology
The neural basis of the human brain's ability to discriminate pitch has been investigated by functional neuroimaging and the study of lesioned brains, indicating the critical importance of right and left Heschl's gyrus (HG) in pitch perception. Nonetheless, there remains some uncertainty with regard to localization and lateralization of pitch discrimination, partly because neuroimaging results do not allow us to draw inferences about the causality. To address the problem of causality in pitch discrimination functions, we used transcranial direct current stimulation to downregulate (via cathodal stimulation) and upregulate (via anodal stimulation) excitability in either left or right auditory cortex and measured the effect on performance in a pitch discrimination task in comparison with sham stimulation. Cathodal stimulation of HG on the left and on the right hemispheres adversely affected pitch discrimination in comparison to sham stimulation, with the effect on the right being significantly stronger than on the left. Anodal stimulation on either side had no effect on performance in comparison to sham. Our results indicate that both left and right HG are causally involved in pitch discrimination, although the right auditory cortex might be a stronger contributor.
Harvey RL, Stinear JW Cortical stimulation as an adjuvant to upper limb rehabilitation after stroke. 2010 PM R
Recovery of upper limb function after stroke remains a clinical challenge in rehabilitation. New insights into the role of activity-dependent motor recovery have guided clinicians to develop novel task-oriented therapies that are effective in reducing functional limitations in hand use after stroke. A number of brain-stimulation techniques have been examined as therapeutic adjuvants applied to enhance functional outcomes. Cortical stimulation with the use of either noninvasive techniques or implanted technology has shown some promise as an adjuvant therapy but has yet to be supported in well-designed clinical trials. In this article, we review the physiology of neural plasticity and of cortical stimulation. Laboratory studies and early clinical trials of repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and epidural cortical stimulation are reported. Cortical stimulation may have a role in facilitating motor recovery after stroke, but a better understanding of the physics of cortical stimulation, biological response to stimulation, effective stimulation protocols, and proper patient selection is needed.
Clark VP, Coffman BA, Mayer AR, Weisend MP, Lane TD, Calhoun VD, Raybourn EM, Garcia CM, Wassermann EM TDCS guided using fMRI significantly accelerates learning to identify concealed objects. 2010 NeuroImage
The accurate identification of obscured and concealed objects in complex environments was an important skill required for survival during human evolution, and is required today for many forms of expertise. Here we used transcranial direct current stimulation (tDCS) guided using neuroimaging to increase learning rate in a novel, minimally guided discovery-learning paradigm. Ninety-six subjects identified threat-related objects concealed in naturalistic virtual surroundings used in real-world training. A variety of brain networks were found using functional magnetic resonance imaging (fMRI) data collected at different stages of learning, with two of these networks focused in right inferior frontal and right parietal cortex. Anodal 2.0mA tDCS performed for 30min over these regions in a series of single-blind, randomized studies resulted in significant improvements in learning and performance compared with 0.1mA tDCS. This difference in performance increased to a factor of two after a one-hour delay. A dose-response effect of current strength on learning was also found. Taken together, these brain imaging and stimulation studies suggest that right frontal and parietal cortex are involved in learning to identify concealed objects in naturalistic surroundings. Furthermore, they suggest that the application of anodal tDCS over these regions can greatly increase learning, resulting in one of the largest effects on learning yet reported. The methods developed here may be useful to decrease the time required to attain expertise in a variety of settings.
Lepage JF, Theoret H Numerical processing: stimulating numbers. 2010 Curr. Biol.
A new study using transcranial direct current stimulation shows that modulating parietal cortex activity during the learning of abstract numerical material can enhance numerical competency for up to six months.
Sharma N, Cohen LG Recovery of motor function after stroke. 2010 Dev Psychobiol
The human brain possesses a remarkable ability to adapt in response to changing anatomical (e.g., aging) or environmental modifications. This form of neuroplasticity is important at all stages of life but is critical in neurological disorders such as amblyopia and stroke. This review focuses upon our new understanding of possible mechanisms underlying functional deficits evidenced after adult-onset stroke. We review the functional interactions between different brain regions that may contribute to motor disability after stroke and, based on this information, possible interventional approaches to motor stroke disability. New information now points to the involvement of non-primary motor areas and their interaction with the primary motor cortex as areas of interest. The emergence of this new information is likely to impact new efforts to develop more effective neurorehabilitative interventions using transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) that may be relevant to other neurological disorders such as amblyopia. © 2010 Wiley Periodicals, Inc. Dev Psychobiol.
Zaehle T, Rach S, Herrmann CS Transcranial alternating current stimulation enhances individual alpha activity in human EEG. 2010 PLoS ONE
Non-invasive electrical stimulation of the human cortex by means of transcranial direct current stimulation (tDCS) has been instrumental in a number of important discoveries in the field of human cortical function and has become a well-established method for evaluating brain function in healthy human participants. Recently, transcranial alternating current stimulation (tACS) has been introduced to directly modulate the ongoing rhythmic brain activity by the application of oscillatory currents on the human scalp. Until now the efficiency of tACS in modulating rhythmic brain activity has been indicated only by inference from perceptual and behavioural consequences of electrical stimulation. No direct electrophysiological evidence of tACS has been reported. We delivered tACS over the occipital cortex of 10 healthy participants to entrain the neuronal oscillatory activity in their individual alpha frequency range and compared results with those from a separate group of participants receiving sham stimulation. The tACS but not the sham stimulation elevated the endogenous alpha power in parieto-central electrodes of the electroencephalogram. Additionally, in a network of spiking neurons, we simulated how tACS can be affected even after the end of stimulation. The results show that spike-timing-dependent plasticity (STDP) selectively modulates synapses depending on the resonance frequencies of the neural circuits that they belong to. Thus, tACS influences STDP which in turn results in aftereffects upon neural activity.The present findings are the first direct electrophysiological evidence of an interaction of tACS and ongoing oscillatory activity in the human cortex. The data demonstrate the ability of tACS to specifically modulate oscillatory brain activity and show its potential both at fostering knowledge on the functional significance of brain oscillations and for therapeutic application.
Lindenberg R, Renga V, Zhu LL, Nair D, Schlaug G Bihemispheric brain stimulation facilitates motor recovery in chronic stroke patients. 2010 Neurology
Motor recovery after stroke depends on the integrity of ipsilesional motor circuits and interactions between the ipsilesional and contralesional hemispheres. In this sham-controlled randomized trial, we investigated whether noninvasive modulation of regional excitability of bilateral motor cortices in combination with physical and occupational therapy improves motor outcome after stroke.
Cohen Kadosh R, Soskic S, Iuculano T, Kanai R, Walsh V Modulating neuronal activity produces specific and long-lasting changes in numerical competence. 2010 Curr. Biol.
Around 20% of the population exhibits moderate to severe numerical disabilities [1-3], and a further percentage loses its numerical competence during the lifespan as a result of stroke or degenerative diseases [4]. In this work, we investigated the feasibility of using noninvasive stimulation to the parietal lobe during numerical learning to selectively improve numerical abilities. We used transcranial direct current stimulation (TDCS), a method that can selectively inhibit or excitate neuronal populations by modulating GABAergic (anodal stimulation) and glutamatergic (cathodal stimulation) activity [5, 6]. We trained subjects for 6 days with artificial numerical symbols, during which we applied concurrent TDCS to the parietal lobes. The polarity of the brain stimulation specifically enhanced or impaired the acquisition of automatic number processing and the mapping of number into space, both important indices of numerical proficiency [7-9]. The improvement was still present 6 months after the training. Control tasks revealed that the effect of brain stimulation was specific to the representation of artificial numerical symbols. The specificity and longevity of TDCS on numerical abilities establishes TDCS as a realistic tool for intervention in cases of atypical numerical development or loss of numerical abilities because of stroke or degenerative illnesses.
Kraft A, Roehmel J, Olma MC, Schmidt S, Irlbacher K, Brandt SA Transcranial direct current stimulation affects visual perception measured by threshold perimetry. 2010 Exp Brain Res
In this study, we aimed to characterize the effect of anodal and cathodal direct current stimulation (tDCS) on contrast sensitivity inside the central 10 degrees of the visual field in healthy subjects. Distinct eccentricities were investigated separately, since at the cortical level, more central regions of the visual field are represented closer to the occipital pole, i.e. closer to the polarizing electrodes, than are the more peripheral regions. Using a double-blind and sham-controlled within-subject design, we measured the effect of stimulation and potential learning effect separately across testing days. Anodal stimulation of the visual cortex compared to sham stimulation yielded a significant increase in contrast sensitivity within 8° of the visual field. A significant increase in contrast sensitivity between the conditions "pre" and "post" anodal stimulation was only obtained for the central positions at eccentricities smaller than 2°. Cathodal stimulation of the visual cortex did not affect contrast sensitivity at either eccentricity. Perceptual learning across testing days was only observed for threshold perimetry before stimulation. Measuring contrast sensitivity changes after tDCS with a standard clinical tool such as threshold perimetry may provide an interesting perspective in assessing therapeutic effects of tDCS in ophthalmological or neurological defects (e.g. with foveal sparing vs. foveal splitting).
Kim DY, Lim JY, Kang EK, You DS, Oh MK, Oh BM, Paik NJ Effect of transcranial direct current stimulation on motor recovery in patients with subacute stroke. 2010 Am J Phys Med Rehabil
To test the hypothesis that 10 sessions of transcranial direct current stimulation combined with occupational therapy elicit more improvement in motor function of the paretic upper limb than sham stimulation in patients with subacute stroke.
Kim SJ, Kim BK, Ko YJ, Bang MS, Kim MH, Han TR Functional and histologic changes after repeated transcranial direct current stimulation in rat stroke model. 2010 J. Korean Med. Sci.
Transcranial direct current stimulation (tDCS) is associated with enhancement or weakening of the NMDA receptor activity and change of the cortical blood flow. Therefore, repeated tDCS of the brain with cerebrovascular injury will induce the functional and histologic changes. Sixty-one Sprague-Dawley rats with cerebrovascular injury were used. Twenty rats died during the experimental course. The 41 rats that survived were allocated to the exercise group, the anodal stimulation group, the cathodal stimulation group, or the control group according to the initial motor function. Two-week treatment schedules started from 2 days postoperatively. Garcia, modified foot fault, and rota-rod performance scores were checked at 2, 9, and 16 days postoperatively. After the experiments, rats were sacrificed for the evaluation of histologic changes (changes of the white matter axon and infarct volume). The anodal stimulation and exercise groups showed improvement of Garcia's and modified foot fault scores at 16 days postoperatively. No significant change of the infarct volume happened after exercise and tDCS. Neuronal axons at the internal capsule of infarct hemispheres showed better preserved axons in the anodal stimulation group. From these results, repeated tDCS might have a neuroprotective effect on neuronal axons in rat stroke model.
Liuzzi G, Freundlieb N, Ridder V, Hoppe J, Heise K, Zimerman M, Dobel C, Enriquez-Geppert S, Gerloff C, Zwitserlood P, Hummel FC The involvement of the left motor cortex in learning of a novel action word lexicon. 2010 Curr. Biol.
Current theoretical positions assume that action-related word meanings are established by functional connections between perisylvian language areas and the motor cortex (MC) according to Hebb's associative learning principle. To test this assumption, we probed the functional relevance of the left MC for learning of a novel action word vocabulary by disturbing neural plasticity in the MC with transcranial direct current stimulation (tDCS). In combination with tDCS, subjects learned a novel vocabulary of 76 concrete, body-related actions by means of an associative learning paradigm. Compared with a control condition with "sham" stimulation, cathodal tDCS reduced success rates in vocabulary acquisition, as shown by tests of novel action word translation into the native language. The analysis of learning behavior revealed a specific effect of cathodal tDCS on the ability to associatively couple actions with novel words. In contrast, we did not find these effects in control experiments, when tDCS was applied to the prefrontal cortex or when subjects learned object-related words. The present study lends direct evidence to the proposition that the left MC is causally involved in the acquisition of novel action-related words.
Benninger DH, Lomarev M, Lopez G, Wassermann EM, Li X, Considine E, Hallett M Transcranial direct current stimulation for the treatment of Parkinson's disease. 2010 J. Neurol. Neurosurg. Psychiatr.
Progression of Parkinson's disease (PD) is characterised by motor deficits which eventually respond less to dopaminergic therapy and thus pose a therapeutic challenge. Deep brain stimulation has proven efficacy but carries risks and is not possible in all patients. Non-invasive brain stimulation has shown promising results and may provide a therapeutic alternative.
O'Connell NE, Wand BM, Marston L, Spencer S, Desouza LH Non-invasive brain stimulation techniques for chronic pain. 2010 Cochrane Database Syst Rev
Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES) and transcranial direct current stimulation (tDCS).
Boggio PS, Zaghi S, Villani AB, Fecteau S, Pascual-Leone A, Fregni F Modulation of risk-taking in marijuana users by transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC). 2010 Drug Alcohol Depend
Cognitive deficits that are reported in heavy marijuana users (attention, memory, affect perception, decision-making) appear to be completely reversible after a prolonged abstinence period of about 28 days. However, it remains unclear whether the reversibility of these cognitive deficits indicates that (1) chronic marijuana use is not associated with long-lasting changes in cortical networks or (2) that such changes occur but the brain adapts to and compensates for the drug-induced changes. Therefore, we examined whether chronic marijuana smokers would demonstrate a differential pattern of response in comparison to healthy volunteers on a decision-making paradigm (Risk Task) while undergoing sham or active transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC). Twenty-five chronic marijuana users who were abstinent for at least 24h were randomly assigned to receive left anodal/right cathodal tDCS of DLPFC (n=8), right anodal/left cathodal tDCS of DLPFC (n=9), or sham stimulation (n=8); results on Risk Task during sham/active tDCS were compared to healthy volunteers from a previously published dataset. Chronic marijuana users demonstrated more conservative (i.e. less risky) decision-making during sham stimulation. While right anodal stimulation of the DLPFC enhanced conservative decision-making in healthy volunteers, both right anodal and left anodal DLPFC stimulation increased the propensity for risk-taking in marijuana users. These findings reveal alterations in the decision-making neural networks among chronic marijuana users. Finally, we also assessed the effects of tDCS on marijuana craving and observed that right anodal/left cathodal tDCS of DLPFC is significantly associated with a diminished craving for marijuana.
Loui P, Hohmann A, Schlaug G Inducing Disorders in Pitch Perception and Production: a Reverse-Engineering Approach. 2010 Proc Meet Acoust
To perceive and produce music accurately, the brain must represent, categorize, plan, and execute pitched information in response to environmental stimuli. Convergent methods from psychophysics, voxel-based morphometry, and diffusion tensor imaging with normal and tone-deaf (TD) subjects have shown that neural networks controlling pitch perception and production systems include bilateral frontotemporal networks. Although psychophysical and neuroimaging results are suggestive of a superior temporal and inferior frontal network responsible for pitch perception and production, active intervention of these areas is necessary to establish a causal connection between superior temporal and inferior frontal areas and pitch production ability. We sought to reverse-engineer the pitch perception-production network by noninvasive brain stimulation. Transcranial direct current stimulation (tDCS), a noninvasive brain-stimulation technique that is optimal for auditory research, was applied over superior temporal and inferior frontal regions. Pitch matching ability was assessed using an individually optimized pitch matching task administered after each stimulation session. Results showed diminished accuracy in pitch matching after cathodal stimulation over inferior frontal and superior temporal areas compared to sham control. Results demonstrate that intact function and connectivity of a distributed cortical network, centered around bilateral superior temporal and inferior frontal regions, are required for efficient neural interactions with musical sounds.
Soler MD, Kumru H, Pelayo R, Vidal J, Tormos JM, Fregni F, Navarro X, Pascual-Leone A Effectiveness of transcranial direct current stimulation and visual illusion on neuropathic pain in spinal cord injury. 2010 Brain
The aim of this study was to evaluate the analgesic effect of transcranial direct current stimulation of the motor cortex and techniques of visual illusion, applied isolated or combined, in patients with neuropathic pain following spinal cord injury. In a sham controlled, double-blind, parallel group design, 39 patients were randomized into four groups receiving transcranial direct current stimulation with walking visual illusion or with control illusion and sham stimulation with visual illusion or with control illusion. For transcranial direct current stimulation, the anode was placed over the primary motor cortex. Each patient received ten treatment sessions during two consecutive weeks. Clinical assessment was performed before, after the last day of treatment, after 2 and 4 weeks follow-up and after 12 weeks. Clinical assessment included overall pain intensity perception, Neuropathic Pain Symptom Inventory and Brief Pain Inventory. The combination of transcranial direct current stimulation and visual illusion reduced the intensity of neuropathic pain significantly more than any of the single interventions. Patients receiving transcranial direct current stimulation and visual illusion experienced a significant improvement in all pain subtypes, while patients in the transcranial direct current stimulation group showed improvement in continuous and paroxysmal pain, and those in the visual illusion group improved only in continuous pain and dysaesthesias. At 12 weeks after treatment, the combined treatment group still presented significant improvement on the overall pain intensity perception, whereas no improvements were reported in the other three groups. Our results demonstrate that transcranial direct current stimulation and visual illusion can be effective in the management of neuropathic pain following spinal cord injury, with minimal side effects and with good tolerability.
Chi RP, Fregni F, Snyder AW Visual memory improved by non-invasive brain stimulation. 2010 Brain Res.
Our visual memories are susceptible to errors, but less so in people who have a more literal cognitive style. This inspired us to attempt to improve visual memory with non-invasive brain stimulation. We applied 13 min of bilateral transcranial direct current stimulation (tDCS) to the anterior temporal lobes. Our stimulation protocol included 3 conditions, each with 12 neurotypical participants: (i) left cathodal stimulation together with right anodal stimulation, (ii) left anodal stimulation together with right cathodal stimulation, and (iii) sham (control) stimulation. Only participants who received left cathodal stimulation (decrease in excitability) together with right anodal stimulation (increase in excitability) showed an improvement in visual memory. This 110% improvement in visual memory was similar to the advantage people with autism, who are known to be more literal, show over normal people in the identical visual task. Importantly, participants receiving stimulation of the opposite polarity (left anodal together with right cathodal stimulation) failed to show any change in memory performance. This is the first demonstration that visual memory can be enhanced in healthy people using non-invasive brain stimulation.
Vernieri F, Assenza G, Maggio P, Tibuzzi F, Zappasodi F, Altamura C, Corbetto M, Trotta L, Palazzo P, Ercolani M, Tecchio F, Rossini PM Cortical neuromodulation modifies cerebral vasomotor reactivity. 2010 Stroke
Cerebral vasomotor reactivity (VMR) is a capability of cerebral vessels to dilate in response to hypercapnia. Transcranial direct current stimulation (tDCS) effects on cerebral hemodynamics have been poorly studied.
Ross LA, McCoy D, Wolk DA, Coslett HB, Olson IR Improved proper name recall by electrical stimulation of the anterior temporal lobes. 2010 Neuropsychologia
People's names have an embarrassing propensity to be forgotten. This problem is exacerbated by normal aging and by some kinds of dementia. As evidence from neuroimaging and neuropsychology suggest that portions of the anterior temporal lobes play a role in proper name retrieval, we hypothesized that transcranial direct current stimulation (tDCS), a technique that modulates neural transmission, to the anterior temporal lobes would alter the retrieval of proper names. Fifteen young adults received left anodal, right anodal, or sham stimulation of the anterior temporal lobes while naming pictures of famous individuals and landmarks. Right anterior temporal lobe stimulation significantly improved naming for people but not landmarks. These findings are consistent with the notion that the anterior temporal lobes are critically involved in the retrieval of people's names.
Buttkus F, Baur V, Jabusch HC, Paulus W, Nitsche MA, Altenmuller E Retraining and transcranial direct current stimulation in musician's dystonia - a case report. 2010 Mov. Disord.
Frank E, Wilfurth S, Landgrebe M, Eichhammer P, Hajak G, Langguth B Anodal skin lesions after treatment with transcranial direct current stimulation. 2010 Brain Stimul
Brunoni AR, Teng CT, Correa C, Imamura M, Brasil-Neto JP, Boechat R, Rosa M, Caramelli P, Cohen R, Del Porto JA, Boggio PS, Fregni F Neuromodulation approaches for the treatment of major depression: challenges and recommendations from a working group meeting. 2010 Arq Neuropsiquiatr
The use of neuromodulation as a treatment for major depressive disorder (MDD) has recently attracted renewed interest due to development of other non-pharmacological therapies besides electroconvulsive therapy (ECT) such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS).
Bolognini N, Fregni F, Casati C, Olgiati E, Vallar G Brain polarization of parietal cortex augments training-induced improvement of visual exploratory and attentional skills. 2010 Brain Res.
Recent evidence suggests that behavioural gains induced by behavioural training are maximized when combined with techniques of cortical neuromodulation, such as transcranial Direct Current Stimulation (tDCS). Here we address the validity of this appealing approach by investigating the effect of coupling a multisensory visual field exploration training with tDCS of the posterior parietal cortex (PPC). The multisensory visual field exploration training consisted in the practice of visual search through the systematic audio-visual stimulation of the visual field. Neurologically unimpaired participants performed a bimodal exploration training for 30 min, while simultaneously receiving anodal-excitatory PPC tDCS or sham tDCS. In two different experiments, the left and the right hemisphere were stimulated. Outcome measures included visual exploration speed at different time intervals during the training, and the post-training effects on tests assessing visual scanning and visuo-spatial orienting. Results show that PPC tDCS applied to the right, but not to the left, hemisphere increases the training-induced behavioural improvement of visual exploration, as compared to sham tDCS. In addition, right PPC tDCS brings about an improvement of covert visual orienting, in a task different from the visual search practice. In an additional experiment, we confirm that right parietal tDCS by itself, even without the associated training, can lead to enhancement of visual search. Overall, anodal PPC tDCS is a promising technique to enhance visuo-spatial abilities, when combined to a visual field exploration training task.
Fecteau S, Fregni F, Boggio PS, Camprodon JA, Pascual-Leone A Neuromodulation of decision-making in the addictive brain. 2010 Subst Use Misuse
Noninvasive brain stimulation of the dorsolateral prefrontal cortex with repetitive transcranial magnetic stimulation and transcranial direct current stimulation can modify decision-making behaviors in healthy subjects. The same type of noninvasive brain stimulation can suppress drug craving in substance user patients, who often display impaired decision-making behaviors. We discuss the implications of these studies for the cognitive neurosciences and their translational applications to the treatment of addictions. We propose a neurocognitive model that can account for our findings and suggests a promising therapeutic role of brain stimulation in the treatment of substance abuse and addictive behavior disorders.
Bolognini N, Olgiati E, Rossetti A, Maravita A Enhancing multisensory spatial orienting by brain polarization of the parietal cortex. 2010 Eur. J. Neurosci.
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that induces polarity-specific excitability changes in the human brain, therefore altering physiological, perceptual and higher-order cognitive processes. Here we investigated the possibility of enhancing attentional orienting within and across different sensory modalities, namely visual and auditory, by polarization of the posterior parietal cortex (PPC), given the putative involvement of this area in both unisensory and multisensory spatial processing. In different experiments, we applied anodal or sham tDCS to the right PPC and, for control, anodal stimulation of the right occipital cortex. Using a redundant signal effect (RSE) task, we found that anodal tDCS over the right PPC significantly speeded up responses to contralateral targets, regardless of the stimulus modality. Furthermore, the effect was dependant on the nature of the audiovisual enhancement, being stronger when subserved by a probabilistic mechanism induced by blue visual stimuli, which probably involves processing in the PPC. Hence, up-regulating the level of excitability in the PPC by tDCS appears a successful approach for enhancing spatial orienting to unisensory and crossmodal stimuli. Moreover, audiovisual interactions mostly occurring at a cortical level can be selectively enhanced by anodal PPC tDCS, whereas multisensory integration of stimuli, which is also largely mediated at a subcortical level, appears less susceptible to polarization of the cortex.
Berryhill ME, Wencil EB, Branch Coslett H, Olson IR A selective working memory impairment after transcranial direct current stimulation to the right parietal lobe. 2010 Neurosci. Lett.
The role of the posterior parietal cortex in working memory (WM) is poorly understood. We previously found that patients with parietal lobe damage exhibited a selective WM impairment on recognition but not recall tasks. We hypothesized that this dissociation reflected strategic differences in the utilization of attention. One concern was that these findings, and our subsequent interpretation, would not generalize to normal populations because of the patients' older age, progressive disease processes, and/or possible brain reorganization following injury. To test whether our findings extended to a normal population we applied transcranial direct current stimulation (tDCS) to right inferior parietal cortex. tDCS is a technique by which low electric current applied to the scalp modulates the resting potentials of underlying neural populations and can be used to test structure-function relationships. Eleven normal young adults received cathodal, anodal, or sham stimulation over right inferior posterior parietal cortex and then performed separate blocks of an object WM task probed by recall or recognition. The results showed that cathodal stimulation selectively impaired WM on recognition trials. These data replicate and extend our previous findings of preserved WM recall and impaired WM recognition in patients with parietal lobe lesions.
Bachmann CG, Muschinsky S, Nitsche MA, Rolke R, Magerl W, Treede RD, Paulus W, Happe S Transcranial direct current stimulation of the motor cortex induces distinct changes in thermal and mechanical sensory percepts. 2010 Clin Neurophysiol
The aim of this single-blinded, complete crossover study was to evaluate the effects of tDCS on thermal and mechanical perception, as assessed by quantitative sensory testing (QST).
Chen R Transcranial direct current stimulation as a treatment for Parkinson's disease--interesting, but not ready for prime time. 2010 J. Neurol. Neurosurg. Psychiatr.
Utz KS, Dimova V, Oppenlander K, Kerkhoff G Electrified minds: transcranial direct current stimulation (tDCS) and galvanic vestibular stimulation (GVS) as methods of non-invasive brain stimulation in neuropsychology--a review of current data and future implications. 2010 Neuropsychologia
Transcranial direct current stimulation (tDCS) is a noninvasive, low-cost and easy-to-use technique that can be applied to modify cerebral excitability. This is achieved by weak direct currents to shift the resting potential of cortical neurons. These currents are applied by attaching two electrodes (usually one anode and one cathode) to distinct areas of the skull. Galvanic Vestibular Stimulation (GVS) is a variant of tDCS where the electrodes are attached to the mastoids behind the ears in order to stimulate the vestibular system. tDCS and GVS are safe when standard procedures are used. We describe the basic physiological mechanisms and application of these procedures. We also review current data on the effects of tDCS and GVS in healthy subjects as well as clinical populations. Significant effects of such stimulation have been reported for motor, visual, somatosensory, attentional, vestibular and cognitive/emotional function as well as for a range of neurological and psychiatric disorders. Moreover, both techniques may induce neuroplastic changes which make them promising techniques in the field of neurorehabilitation. A number of open research questions that could be addressed with tDCS or GVS are formulated in the domains of sensory and motor processing, spatial and nonspatial attention including neglect, spatial cognition and body cognition disorders, as well as novel treatments for various neuropsychological disorders. We conclude that the literature suggests that tDCS and GVS are exciting and easily applicable research tools for neuropsychological as well as clinical-therapeutic investigations.
Matsumoto J, Fujiwara T, Takahashi O, Liu M, Kimura A, Ushiba J Modulation of mu rhythm desynchronization during motor imagery by transcranial direct current stimulation. 2010 J Neuroeng Rehabil
The mu event-related desynchronization (ERD) is supposed to reflect motor preparation and appear during motor imagery. The aim of this study is to examine the modulation of ERD with transcranial direct current stimulation (tDCS).
Tecchio F, Zappasodi F, Assenza G, Tombini M, Vollaro S, Barbati G, Rossini PM Anodal transcranial direct current stimulation enhances procedural consolidation. 2010 J. Neurophysiol.
The primary motor cortex (M1) area recruitment enlarges while learning a finger tapping sequence. Also M1 excitability increases during procedural consolidation. Our aim was to investigate whether increasing M1 excitability by anodal transcranial DC stimulation (AtDCS) when procedural consolidation occurs was able to induce an early consolidation improvement. Forty-seven right-handed healthy participants were trained in a nine-element serial finger tapping task (SFTT) executed with the left hand. Random series blocks were interspersed with training series blocks. Anodal or sham tDCS was administered over the right M1 after the end of the training session. After stimulation, the motor skills of both trained and a new untrained sequential series blocks were tested again. For each block, performance was estimated as the median execution time of correct series. Early consolidation of the trained series, assessed by the performance difference between the first block after and the last block before stimulation normalized by the random, was enhanced by anodal and not by sham tDCS. Stimulation did not affect random series execution. No stimulation effect was found on the on-line learning of the trained and new untrained series. Our results suggest that AtDCS applied on M1 soon after training improves early consolidation of procedural learning. Our data highlight the importance of neuromodulation procedures for understanding learning processes and support their use in the motor rehabilitation setting, focusing on the timing of the application.
Penolazzi B, Di Domenico A, Marzoli D, Mammarella N, Fairfield B, Franciotti R, Brancucci A, Tommasi L Effects of Transcranial Direct Current Stimulation on episodic memory related to emotional visual stimuli. 2010 PLoS ONE
The present study investigated emotional memory following bilateral transcranial electrical stimulation (direct current of 1 mA, for 20 minutes) over fronto-temporal cortical areas of healthy participants during the encoding of images that differed in affective arousal and valence. The main result was a significant interaction between the side of anodal stimulation and image emotional valence. Specifically, right anodal/left cathodal stimulation selectively facilitated the recall of pleasant images with respect to both unpleasant and neutral images whereas left anodal/right cathodal stimulation selectively facilitated the recall of unpleasant images with respect to both pleasant and neutral images. From a theoretical perspective, this double dissociation between the side of anodal stimulation and the advantage in the memory performance for a specific type of stimulus depending on its pleasantness supported the specific-valence hypothesis of emotional processes, which assumes a specialization of the right hemisphere in processing unpleasant stimuli and a specialization of the left hemisphere in processing pleasant stimuli. From a methodological point of view, first we found tDCS effects strictly dependent on the stimulus category, and second a pattern of results in line with an interfering and inhibitory account of anodal stimulation on memory performance. These findings need to be carefully considered in applied contexts, such as the rehabilitation of altered emotional processing or eye-witness memory, and deserve to be further investigated in order to understand their underlying mechanisms of action.
Minhas P, Bansal V, Patel J, Ho JS, Diaz J, Datta A, Bikson M Electrodes for high-definition transcutaneous DC stimulation for applications in drug delivery and electrotherapy, including tDCS. 2010 J. Neurosci. Methods
Transcutaneous electrical stimulation is applied in a range of biomedical applications including transcranial direct current stimulation (tDCS). tDCS is a non-invasive procedure where a weak direct current (<2 mA) is applied across the scalp to modulate brain function. High-definition tDCS (HD-tDCS) is a technique used to increase the spatial focality of tDCS by passing current across the scalp using <12 mm diameter electrodes. The purpose of this study was to design and optimize "high-definition" electrode-gel parameters for electrode durability, skin safety and subjective pain. Anode and cathode electrode potential, temperature, pH and subjective sensation over time were assessed during application of 2 mA direct current, for up to 22 min on agar gel or subject forearms. A selection of five types of solid-conductors (Ag pellet, Ag/AgCl pellet, rubber pellet, Ag/AgCl ring and Ag/AgCl disc) and seven conductive gels (Signa, Spectra, Tensive, Redux, BioGel, Lectron and CCNY-4) were investigated. The Ag/AgCl ring in combination with CCNY-4 gel resulted in the most favorable outcomes. Under anode stimulations, electrode potential and temperature rises were generally observed in all electrode-gel combinations except for Ag/AgCl ring and disc electrodes. pH remained constant for all solid-conductors except for both Ag and rubber pellet electrodes with Signa and CCNY-4 gels. Sensation ratings were independent of stimulation polarity. Ag/AgCl ring electrodes were found to be the most comfortable followed by Ag, rubber and Ag/AgCl pellet electrodes across all gels.
Antal A, Terney D, Kuhnl S, Paulus W Anodal transcranial direct current stimulation of the motor cortex ameliorates chronic pain and reduces short intracortical inhibition. 2010 J Pain Symptom Manage
Consecutive sessions of transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) may be a suitable therapy to treat chronic pain, as it can modulate neural activities in the stimulated and interconnected regions.
Ambrus GG, Paulus W, Antal A Cutaneous perception thresholds of electrical stimulation methods: comparison of tDCS and tRNS. 2010 Clin Neurophysiol
Controlled blinded studies using transcranial electrical stimulation (tES) paradigms need a validated sham stimulation paradigm since an itching or tingling sensation on the skin surface under the electrode can be associated with current flow.
Rothwell JC Plasticity in the human motor system. 2010 Folia Phoniatr Logop
It is well recognized that the number and effectiveness of synapses in the adult brain change in response to learning and that similar processes contribute to the restoration of function after central nervous system damage. It is possible to use non-invasive methods of brain stimulation in humans (transcranial magnetic stimulation or transcranial direct current stimulation) to study and even manipulate these processes. Initial studies are now underway to test whether modification of synaptic plasticity by neurostimulation can improve the recovery of motor function in patients after stroke.
Datta A, Bikson M, Fregni F Transcranial direct current stimulation in patients with skull defects and skull plates: high-resolution computational FEM study of factors altering cortical current flow. 2010 Neuroimage
Preliminary positive results of transcranial direct current stimulation (tDCS) in enhancing the effects of cognitive and motor training indicate that this technique might also be beneficial in traumatic brain injury or patients who had decompressive craniectomy for trauma and cerebrovascular disease. One perceived hurdle is the presence of skull defects or skull plates in these patients that would hypothetically alter the intensity and location of current flow through the brain. We aimed to model tDCS using a magnetic resonance imaging (MRI)-derived finite element head model with several conceptualized skull injuries. Cortical electric field (current density) peak intensities and distributions were compared with the healthy (skull intact) case. The factors of electrode position (C3-supraorbital or O1-supraorbital), electrode size skull defect size, skull defect state (acute and chronic) or skull plate (titanium and acrylic) were analyzed. If and how electric current through the brain was modulated by defects was found to depend on a specific combination of factors. For example, the condition that led to largest increase in peak cortical electric field was when one electrode was placed directly over a moderate sized skull defect. In contrast, small defects midway between electrodes did not significantly change cortical currents. As the conductivity of large skull defects/plates was increased (chronic to acute to titanium), current was shunted away from directly underlying cortex and concentrated in cortex underlying the defect perimeter. The predictions of this study are the first step to assess safety of transcranial electrical therapy in subjects with skull injuries and skull plates.
Fritsch B, Reis J, Martinowich K, Schambra HM, Ji Y, Cohen LG, Lu B Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning. 2010 Neuron
Despite its increasing use in experimental and clinical settings, the cellular and molecular mechanisms underlying transcranial direct current stimulation (tDCS) remain unknown. Anodal tDCS applied to the human motor cortex (M1) improves motor skill learning. Here, we demonstrate in mouse M1 slices that DCS induces a long-lasting synaptic potentiation (DCS-LTP), which is polarity specific, NMDA receptor dependent, and requires coupling of DCS with repetitive low-frequency synaptic activation (LFS). Combined DCS and LFS enhance BDNF-secretion and TrkB activation, and DCS-LTP is absent in BDNF and TrkB mutant mice, suggesting that BDNF is a key mediator of this phenomenon. Moreover, the BDNF val66met polymorphism known to partially affect activity-dependent BDNF secretion impairs motor skill acquisition in humans and mice. Motor learning is enhanced by anodal tDCS, as long as activity-dependent BDNF secretion is in place. We propose that tDCS may improve motor skill learning through augmentation of synaptic plasticity that requires BDNF secretion and TrkB activation within M1.
Baker JM, Rorden C, Fridriksson J Using transcranial direct-current stimulation to treat stroke patients with aphasia. 2010 Stroke
Recent research suggests that increased left hemisphere cortical activity, primarily of the left frontal cortex, is associated with improved naming performance in stroke patients with aphasia. Our aim was to determine whether anodal transcranial direct-current stimulation (tDCS), a method thought to increase cortical excitability, would improve naming accuracy in stroke patients with aphasia when applied to the scalp overlying the left frontal cortex.
Antal A, Paulus W [Transcranial magnetic and direct current stimulation in the therapy of pain]. 2010 Schmerz
Neuroplasticity is the ability of the central nervous system to induce functional and microstructural changes in order to adapt to a new environment. However, so-called maladaptive neuroplasticity can also bring disadvantages, such as reduced inhibition of input signals, one of the suspected causes of chronic pain. With the method of repetitive transcranial magnetic stimulation (rTMS) a technique has been developed that makes it possible to study cortical excitability changes in the human brain non-invasively over a long time. Electrophysiological studies have shown that the application of rTMS over the primary motor cortex induces a facilitatory or inhibitory effect on the corticospinal and cortico-cortical excitability depending on the protocol used. The results of the clinical studies published suggest that rTMS can inhibit pain perception with regard to chronic pain and in experimentally induced pain conditions. An alternative method to induce neuroplastic changes is transcranial direct current stimulation (tDCS). tDCS acts primarily on the membrane potential, by hyper- or depolarizing it. The induced after-effects are NMDA receptor dependent. The effectiveness of tDCS is currently being explored in migraine research as well as experimentally induced and chronic pain conditions. In phase II trials its efficacy has been demonstrated. Ongoing studies are focusing on management of the placebo effect; however, it is easier to control this effect in tDCS compared to rTMS. Phase III trials are currently in preparation.
Sadleir RJ, Vannorsdall TD, Schretlen DJ, Gordon B Transcranial direct current stimulation (tDCS) in a realistic head model. 2010 Neuroimage
Distributions of current produced by transcranial direct current stimulation (tDCS) in humans were predicted by a finite-element model representing several individual and collective refinements over prior efforts. A model of the entire human head and brain was made using a finely meshed (1.1x1.1x1.4mm(3) voxel) tissue dataset derived from the MRI data set of a normal human brain. The conductivities of ten tissues were simulated (bone, scalp, blood, CSF, muscle, white matter, gray matter, sclera, fat, and cartilage). We then modeled the effect of placing a "stimulating" electrode with a saline-like conductivity over F3, and a similar "reference" electrode over a right supraorbital (RS) location, as well as the complements of these locations, to compare expectations derived from the simulation with experimental data also using these locations in terms of the presence or absence of subjective and objective effects. The sensitivity of the results to changes in conductivity values were examined by varying white matter conductivity over a factor of ten. Our simulations established that high current densities were found directly under the stimulating and reference electrodes, but values of the same order of magnitude occurred in other structures, and many areas of the brain that might be behaviorally active were also subjected to what may be substantial amounts of current. The modeling also suggests that more targeted stimulations might be achieved by different electrode topologies.
Knotkova H, Cruciani RA Non-invasive transcranial direct current stimulation for the study and treatment of neuropathic pain. 2010 Methods Mol. Biol.
In the last decade, radiological neuroimaging techniques have enhanced the study of mechanisms involved in the development and maintenance of neuropathic pain. Recent findings suggest that neuropathic pain in certain pain syndromes (e.g., complex regional pain syndrome/reflex sympathic dystrophy, phantom-limb pain) is associated with a functional reorganization and hyperexitability of the somatosensory and motor cortex. Studies showing that the reversal of cortical reorganization in patients with spontaneous or provoked pain is accompanied by pain relief stimulated the search for novel alternatives how to modulate the cortical excitability as a strategy to relieve pain. Recently, non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) were proposed as suitable methods for modulation of cortical excitability. Both techniques (TMS and tDCS) have been clinically investigated in healthy volunteers as well as in patients with various clinical pathologies and variety of pain syndromes. Although there is less evidence on tDCS as compared with TMS, the findings on tDCS in patients with pain are promising, showing an analgesic effect of tDCS, and observations up to date justify the use of tDCS for the treatment of pain in selected patient populations. tDCS has been shown to be very safe if utilized within the current protocols. In addition, tDCS has been proven to be easy to apply, portable and not expensive, which further enhances great clinical potential of this technique.
Hecht D, Walsh V, Lavidor M Transcranial direct current stimulation facilitates decision making in a probabilistic guessing task. 2010 J. Neurosci.
In a random sequence of binary events where one alternative occurs more often than the other, humans tend to guess which of the two alternatives will occur next by trying to match the frequencies of previous occurrences. Based on split-brain and unilaterally damaged patients' performances, it has been proposed that the left hemisphere (LH) tends to match the frequencies, while the right hemisphere (RH) tends toward maximizing and always choosing the most frequent alternative. The current study used transcranial direct current stimulation (tDCS) to test this hemispheric asymmetry hypothesis by stimulating the dorsolateral prefrontal cortex of each hemisphere and simultaneously inhibiting the corresponding region in the homotopic hemisphere, while participants were engaged in a probabilistic guessing task. Results showed no difference in strategy between the three groups (RH anodal/LH cathodal, LH anodal/RH cathodal, no stimulation) as participants predominantly matched the frequencies of the two alternatives. However, when anodal tDCS was applied to the LH and cathodal tDCS applied to the RH, participants became quicker to select the most frequent alternative. This finding is in line with previous evidence on the involvement of the LH in probabilistic learning and reasoning and adds to a number of demonstrations of anodal tDCS leading to some behavioral enhancement or change in bias.
Mameli F, Mrakic-Sposta S, Vergari M, Fumagalli M, Macis M, Ferrucci R, Nordio F, Consonni D, Sartori G, Priori A Dorsolateral prefrontal cortex specifically processes general - but not personal - knowledge deception: Multiple brain networks for lying. 2010 Behav. Brain Res.
Despite intensive research into ways of detecting deception in legal, moral and clinical contexts, few experimental data are available on the neural substrate for the different types of lies. We used transcranial direct current stimulation (tDCS) to modulate dorsolateral prefrontal cortex (DLPFC) function and to assess its influence on various types of lies. Twenty healthy volunteers were tested before and after tDCS (anodal and sham). In each session the Guilty Knowledge Task and Visual Attention Task were administered at baseline and immediately after tDCS ended. A computer-controlled task was used to evaluate truthful responses and lie responses to questions referring to personal information and general knowledge. Dependent variables collected were reaction times (RTs) and accuracy. At baseline the RTs were significantly longer for lies than for truthful responses. After sham stimulation, lie responses remained unchanged (p = 0.24) but after anodal tDCS, RTs decreased significantly only for lies involving general knowledge (p = 0.02). tDCS left the Visual Attention Task unaffected. These findings show that manipulating DLPFC function with tDCS specifically modulates deceptive responses for general information leaving those on personal information unaffected. Multiple cortical networks intervene in deception involving general and personal knowledge. Deception referring to general and personal knowledge probably involves multiple cortical networks.
Vandermeeren Y, Jamart J, Ossemann M Effect of tDCS with an extracephalic reference electrode on cardio-respiratory and autonomic functions. 2010 BMC Neurosci
Transcranial direct current stimulation (tDCS) is used in human physiological studies and for therapeutic trials in patients with abnormalities of cortical excitability. Its safety profile places tDCS in the pole-position for translating in real-world therapeutic application. However, an episode of transient respiratory depression in a subject receiving tDCS with an extracephalic electrode led to the suggestion that such an electrode montage could modulate the brainstem autonomic centres. We investigated whether tDCS applied over the midline frontal cortex in 30 healthy volunteers (sham n = 10, cathodal n = 10, anodal n = 10) with an extracephalic reference electrode would modulate brainstem activity as reflected by the monitoring and stringent analysis of vital parameters: heart rate (variability), respiratory rate, blood pressure and sympatho-vagal balance. We reasoned that this study could lead to two opposite but equally interesting outcomes: 1) If tDCS with an extracephalic electrode modulated vital parameters, it could be used as a new tool to explore the autonomic nervous system and, even, to modulate its activity for therapeutic purposes. 2) On the opposite, if applying tDCS with an extracephalic electrode had no effect, it could thus be used safely in healthy human subjects. This outcome would significantly impact the field of non-invasive brain stimulation with tDCS. Indeed, on the one hand, using an extracephalic electrode as a genuine neutral reference (as opposed to the classical "bi-cephalic" tDCS montages which deliver bi-polar stimulation of the brain) would help to comfort the conclusions of several modern studies regarding the spatial location and polarity of tDCS. On the other hand, using an extracephalic reference electrode may impact differently on a given cortical target due to the change of direct current flow direction; this may enlarge the potential interventions with tDCS.
Bradnam LV, Stinear CM, Lewis GN, Byblow WD Task-dependent modulation of inputs to proximal upper limb following transcranial direct current stimulation of primary motor cortex. 2010 J. Neurophysiol.
Cathodal transcranial DC stimulation (c-tDCS) suppresses excitability of primary motor cortex (M1) controlling contralateral hand muscles. This study assessed whether c-tDCS would have similar effects on ipsi- and contralateral M1 projections to a proximal upper limb muscle. Transcranial magnetic stimulation (TMS) of left M1 was used to elicit motor evoked potentials (MEPs) in the left and right infraspinatus (INF) muscle immediately before and after c-tDCS of left M1, and at 20 and 40 min, post-c-tDCS. TMS was delivered as participants preactivated each INF in isolation (left, right) or both INF together (bilateral). After c-tDCS, ipsilateral MEPs in left INF and contralateral MEPs in right INF were suppressed in the left task but not in the bilateral or right tasks, indicative of task-dependent modulation. Ipsilateral silent period duration in the left INF was reduced after c-tDCS, indicative of altered transcallosal inhibition. These findings may have implications for the use of tDCS as an adjunct to therapy for the proximal upper limb after stroke.
Vanneste S, Plazier M, Ost J, van der Loo E, Van de Heyning P, De Ridder D Bilateral dorsolateral prefrontal cortex modulation for tinnitus by transcranial direct current stimulation: a preliminary clinical study. 2010 Exp Brain Res
Tinnitus is considered as an auditory phantom percept. Preliminary evidence indicates that transcranial direct current stimulation (tDCS) of the temporo-parietal area might reduce tinnitus. tDCS studies of the prefrontal cortex have been successful in reducing depression, impulsiveness and pain. Recently, it was shown that the prefrontal cortex is important for the integration of sensory and emotional aspects of tinnitus. As such, frontal tDCS might suppress tinnitus as well. In an open label study, a total of 478 tinnitus patients received bilateral tDCS on dorsolateral prefrontal cortex (448 patients anode right, cathode left and 30 anode left, cathode right) for 20 min. Treatment effects were assessed with visual analogue scale for tinnitus intensity and distress. No tinnitus-suppressing effect was found for tDCS with left anode and right cathode. Analyses show that tDCS with right anode and left cathode modulates tinnitus perception in 29.9% of the tinnitus patients. For these responders a significant reduction was found for both tinnitus-related distress and tinnitus intensity. In addition, the amount of suppression for tinnitus-related distress is moderated by an interaction between tinnitus type and tinnitus laterality. This was, however, not the case for tinnitus intensity. Our study supports the involvement of the prefrontal cortex in the pathophysiology of tinnitus.
Madhavan S, Stinear JW Focal and bi-directional modulation of lower limb motor cortex using anodal transcranial direct current stimulation. 2010 Brain Stimul
Because we are interested in non-invasive transcranial brain stimulation as an adjuvant to post-stroke walking therapy, we applied direct current stimulation (tDCS) preferentially to either the left or right lower limb motor cortex (M1) in two separate sessions and assessed the resulting modulation in both cortices.
Winkler T, Hering P, Straube A Spinal DC stimulation in humans modulates post-activation depression of the H-reflex depending on current polarity. 2010 Clin Neurophysiol
Transcranial direct current stimulation induces long-lasting changes in cortical excitability in humans depending on the current used. Further, transcutaneous spinal application of direct current (tsDCS) induces plastic changes in spinal conduction properties, tested by somatosensory evoked potentials. To verify this thesis on plastic changes in spinal circuitry, we investigated the effects of tsDCS on H-reflex size and post-activation depression.
Cambiaghi M, Velikova S, Gonzalez-Rosa JJ, Cursi M, Comi G, Leocani L Brain transcranial direct current stimulation modulates motor excitability in mice. 2010 Eur. J. Neurosci.
Shortly after the application of weak transcranial direct current stimulation (tDCS) to the animal and human brain, changes in corticospinal excitability, which mainly depend on polarity, duration and current density of the stimulation protocol, have been reported. In humans, anodal tDCS has been reported to enhance motor-evoked potentials (MEPs) elicited by transcranial brain stimulation while cathodal tDCS has been shown to decrease them. Here we investigated the effects produced by tDCS on mice motor cortex. MEPs evoked by transcranial electric stimulation were recorded from forelimbs of 12 C57BL/6 mice, under sevofluorane anaesthesia, before and after (0, 5 and 10 min) anodal and cathodal tDCS (tDCS duration 10 min). With respect to sham condition stimulation (anaesthesia), MEP size was significantly increased immediately after anodal tDCS, and was reduced after cathodal tDCS (approximately 20% vs. sham). Both effects declined towards basal levels in the following 10 min. Although the site and mechanisms of action of tDCS need to be more clearly identified, the directionality of effects of tDCS on mice MEPs is consistent with previous findings in humans. The feasibility of tDCS in mice suggests the potential applicability of this technique to assess the potential therapeutic options of brain polarization in animal models of neurological and neuropsychiatric diseases.
Fumagalli M, Vergari M, Pasqualetti P, Marceglia S, Mameli F, Ferrucci R, Mrakic-Sposta S, Zago S, Sartori G, Pravettoni G, Barbieri S, Cappa S, Priori A Brain switches utilitarian behavior: does gender make the difference? 2010 PLoS ONE
Decision often implies a utilitarian choice based on personal gain, even at the expense of damaging others. Despite the social implications of utilitarian behavior, its neurophysiological bases remain largely unknown. To assess how the human brain controls utilitarian behavior, we delivered transcranial direct current stimulation (tDCS) over the ventral prefrontal cortex (VPC) and over the occipital cortex (OC) in 78 healthy subjects. Utilitarian judgment was assessed with the moral judgment task before and after tDCS. At baseline, females provided fewer utilitarian answers than males for personal moral dilemmas (p = .007). In males, VPC-tDCS failed to induce changes and in both genders OC-tDCS left utilitarian judgments unchanged. In females, cathodal VPC-tDCS tended to decrease whereas anodal VPC-tDCS significantly increased utilitarian responses (p = .005). In males and females, reaction times for utilitarian responses significantly decreased after cathodal (p<.001) but not after anodal (p = .735) VPC-tDCS. We conclude that ventral prefrontal tDCS interferes with utilitarian decisions, influencing the evaluation of the advantages and disadvantages of each option in both sexes, but does so more strongly in females. Whereas cathodal tDCS alters the time for utilitarian reasoning in both sexes, anodal stimulation interferes more incisively in women, modifying utilitarian reasoning and the possible consequent actions. The gender-related tDCS-induced changes suggest that the VPC differentially controls utilitarian reasoning in females and in males. The gender-specific functional organization of the brain areas involved in utilitarian behavior could be a correlate of the moral and social behavioral differences between the two sexes.
Williams JA, Pascual-Leone A, Fregni F Interhemispheric modulation induced by cortical stimulation and motor training. 2010 Phys Ther
Interhemispheric inhibition might be a beneficial cortico-cortical interaction, but also might be maladaptive in people with neurological disorders. One recently revisited technique that has been shown to be effective in improving motor function in people with stroke using interhemispheric modulation is transcranial direct current stimulation (tDCS).
Monte-Silva K, Kuo MF, Liebetanz D, Paulus W, Nitsche MA Shaping the optimal repetition interval for cathodal transcranial direct current stimulation (tDCS). 2010 J. Neurophysiol.
Transcranial DC stimulation (tDCS) is a plasticity-inducing noninvasive brain stimulation tool with various potential therapeutic applications in neurological and psychiatric diseases. Currently, the duration of the aftereffects of stimulation is restricted. For future clinical applications, stimulation protocols are required that produce aftereffects lasting for days or weeks. Options to prolong the effects of tDCS are further prolongation or repetition of tDCS. Nothing is known thus far about optimal protocols in this behalf, although repetitive stimulation is already performed in clinical applications. Thus we explored the effects of different break durations on cathodal tDCS-induced cortical excitability alterations. In 12 subjects, two identical periods of cathodal tDCS (9-min duration; 1 mA) with an interstimulation interval of 0 (no break), 3, or 20 min or 3 or 24 h were performed. The results indicate that doubling stimulation duration without a break prolongs the aftereffects from 60 to 90 min after tDCS. When the second stimulation was performed during the aftereffects of the first, a prolongation and enhancement of tDCS-induced effects for ≤ 120 min after stimulation was observed. In contrast, when the second stimulation followed the first one after 3 or 24 h, the aftereffects were initially attenuated, or abolished, but afterwards re-established for up to 120 min after tDCS in the 24-h condition. These results suggest that, for prolonging the aftereffects of cathodal tDCS, stimulation interval might be important.
Boggio PS, Campanha C, Valasek CA, Fecteau S, Pascual-Leone A, Fregni F Modulation of decision-making in a gambling task in older adults with transcranial direct current stimulation. 2010 Eur. J. Neurosci.
Cognitive performance usually declines in older adults as a result of neurodegenerative processes. One of the cognitive domains usually affected is decision-making. Based on our recent findings suggesting that non-invasive brain stimulation can improve decision-making in young participants, we studied whether bifrontal transcranial direct current stimulation (tDCS) applied over the right and left prefrontal cortex of older adult subjects can change balance of risky and safe responses as it can in younger individuals. Twenty-eight subjects (age range from 50 to 85 years) performed a gambling risk task while receiving either anodal tDCS over the right and cathodal tDCS over the left dorsolateral prefrontal cortex (DLPFC), anodal tDCS over the left with cathodal tDCS over the right DLPFC, or sham stimulation. Our main finding was a significant group effect showing that participants receiving left anodal/right cathodal stimulation chose more often high-risk prospects as compared with participants receiving sham or those receiving right anodal/left cathodal stimulation. This result is contrary to previous findings in young subjects, suggesting that modulation of cortical activity in young and elderly results in opposite behavioral effects; thus supporting fundamental changes in cognitive processing in the elderly.
Hecht D Transcranial direct current stimulation in the treatment of anorexia. 2010 Med. Hypotheses
Transcranial direct current stimulation (tDCS) is a non-invasive technique for brain stimulation and it increasingly being used in the treatments of some neurological/psychiatric conditions (e.g. chronic pain, epilepsy, depression, motor rehabilitation after stroke and Parkinson's disease). With tDCS, cortical neurons excitability increases in the vicinity of the anodal electrode and suppressed near the cathodal electrode. There is evidence that anorexia is associated with hyperactivity in right-hemisphere frontal regions. tDCS, therefore has a promising potential in facilitating inter-hemispheric balance. A tDCS protocol is proposed: the anode electrode placed over the left prefrontal cortex and the cathode electrode located, either on the right homotopic region for non-SSRI-medicated anorexics, or on a non-cephalic site for SSRI-medicated anorexics. Together with nutritional supplements, psychotherapy and other treatments, tDCS have a good potential, as a complementary tool, in the treatment of anorexia.
Groppa S, Bergmann TO, Siems C, Molle M, Marshall L, Siebner HR Slow-oscillatory transcranial direct current stimulation can induce bidirectional shifts in motor cortical excitability in awake humans. 2010 Neuroscience
Constant transcranial direct stimulation (c-tDCS) of the primary motor hand area (M1(HAND)) can induce bidirectional shifts in motor cortical excitability depending on the polarity of tDCS. Recently, anodal slow oscillation stimulation at a frequency of 0.75 Hz has been shown to augment intrinsic slow oscillations during sleep and theta oscillations during wakefulness. To embed this new type of stimulation into the existing tDCS literature, we aimed to characterize the after effects of slowly oscillating stimulation (so-tDCS) on M1(HAND) excitability and to compare them to those of c-tDCS. Here we show that so-tDCS at 0.8 Hz can also induce lasting changes in corticospinal excitability during wakefulness. Experiment 1. In 10 healthy awake individuals, we applied c-tDCS or so-tDCS to left M1(HAND) on separate days. Each tDCS protocol lasted for 10 min. Measurements of motor evoked potentials (MEPs) confirmed previous work showing that anodal c-tDCS at an intensity of 0.75 mA (maximal current density 0.0625 mA/cm2) enhanced corticospinal excitability, while cathodal c-tDCS at 0.75 mA reduced it. The polarity-specific shifts in excitability persisted for at least 20 min after c-tDCS. Using a peak current intensity of 0.75 mA, neither anodal nor cathodal so-tDCS had consistent effects on corticospinal excitability. Experiment 2. In a separate group of ten individuals, peak current intensity of so-tDCS was raised to 1.5 mA (maximal current density 0.125 mA/cm2) to match the total amount of current applied with so-tDCS to the amount of current that had been applied with c-tDCS at 0.75 mA in Experiment 1. At peak intensity of 1.5 mA, anodal and cathodal so-tDCS produced bidirectional changes in corticospinal excitability comparable to the after effects that had been observed after c-tDCS at 0.75 mA in Experiment 1. The results show that so-tDCS can induce bidirectional shifts in corticospinal excitability in a similar fashion as c-tDCS if the total amount of applied current during the tDCS session is matched.
Buttkus F, Weidenmuller M, Schneider S, Jabusch HC, Nitsche MA, Paulus W, Altenmuller E Failure of cathodal direct current stimulation to improve fine motor control in musician's dystonia. 2010 Mov. Disord.
Musician's dystonia (MD) is a task-specific movement disorder with a loss of voluntary motor control in highly trained movements. Defective inhibition on different levels of the central nervous system is involved in its pathophysiology. Cathodal transcranial direct current stimulation (ctDCS) diminishes excitability of the motor cortex and improves performance in overlearned tasks in healthy subjects. The aim of this study was to investigate whether ctDCS improves fine motor control in MD. Professional guitarists (n = 10) with MD played exercises before, directly after ctDCS, and 60 min after ctDCS. ctDCS (2 mA, 20 min) was applied on the primary motor cortex contralateral to the affected hand. Guitar exercises were video-documented and symptoms were evaluated by three independent experts. No beneficial effect of ctDCS on fine motor control was found for the entire group. However, motor control of one guitarist improved after stimulation. This patient suffered from arm dystonia, whereas the other guitarists suffered from hand dystonia.
Edelmuth RC, Nitsche MA, Battistella L, Fregni F Why do some promising brain-stimulation devices fail the next steps of clinical development? 2010 Expert Rev Med Devices
Interest in techniques of noninvasive brain stimulation (NIBS) has been growing exponentially in the last decade. Recent studies have shown that some of these techniques induce significant neurophysiological and clinical effects. Although recent results are promising, there are several techniques that have been abandoned despite positive initial results. In this study, we performed a systematic review to identify NIBS methods with promising preliminary clinical results that were not fully developed and adopted into clinical practice, and discuss its clinical, research and device characteristics. We identified five devices (transmeatal cochlear laser stimulation, transcranial micropolarization, transcranial electrostimulation, cranial electric stimulation and stimulation with weak electromagnetic fields) and compared them with two established NIBS devices (transcranial magnetic stimulation and transcranial direct current stimulation) and with well-known drugs used in neuropsychiatry (pramipexole and escitalopram) in order to understand the reasons why they failed to reach clinical practice and further steps of research development. Finally, we also discuss novel NIBS devices that have recently showed promising results: brain ultrasound and transcranial high-frequency random noise stimulation. Our results show that some of the reasons for the failure of NIBS devices with promising clinical findings are the difficulty to disseminate results, lack of controlled studies, duration of research development, mixed results and lack of standardization.
Mori F, Codeca C, Kusayanagi H, Monteleone F, Buttari F, Fiore S, Bernardi G, Koch G, Centonze D Effects of anodal transcranial direct current stimulation on chronic neuropathic pain in patients with multiple sclerosis. 2010 J Pain
Neuropathic pain in patients with MS is frequent and is associated with a great interference with daily life activities. In the present study, we investigated whether anodal transcranial direct current stimulation (tDCS) may be effective in reducing central chronic pain in MS patients. Patients received sham tDCS or real tDCS in a 5-day period of treatment in a randomized, double blind, sham-controlled study. Pain was measured using visual analog scale (VAS) for pain and the short form McGill questionnaire (SF-MPQ). Quality of life was measured using the Multiple Sclerosis Quality of Life-54 scale (MSQoL-54). Depressive symptoms and anxiety were also evaluated as confounding factors using the Beck Depression Inventory (BDI) and VAS for anxiety. Evaluations were performed at baseline, immediately after the end of treatment, and once a week during a 3-week follow-up period. Following anodal but not sham tDCS over the motor cortex, there was a significant pain improvement as assessed by VAS for pain and McGill questionnaire, and of overall quality of life. No depression or anxiety changes were observed. Our results show that anodal tDCS is able to reduce pain-scale scores in MS patients with central chronic pain and that this effect outlasts the period of stimulation, leading to long-lasting clinical effects. PERSPECTIVE: This article presents a new, noninvasive therapeutic approach to chronic, central neuropathic pain in multiple sclerosis, poorly responsive to current conventional medications. tDCS is known to cause long-lasting changes of neuronal excitability at the site of stimulation and in the connected areas in healthy subjects. This led us to hypothesize that pain decrease may be the result of functional plastic changes in brain structures involved in the pathogenesis of chronic neuropathic pain.
de Vries MH, Barth AC, Maiworm S, Knecht S, Zwitserlood P, Floel A Electrical stimulation of Broca's area enhances implicit learning of an artificial grammar. 2010 J Cogn Neurosci
Artificial grammar learning constitutes a well-established model for the acquisition of grammatical knowledge in a natural setting. Previous neuroimaging studies demonstrated that Broca's area (left BA 44/45) is similarly activated by natural syntactic processing and artificial grammar learning. The current study was conducted to investigate the causal relationship between Broca's area and learning of an artificial grammar by means of transcranial direct current stimulation (tDCS). Thirty-eight healthy subjects participated in a between-subject design, with either anodal tDCS (20 min, 1 mA) or sham stimulation, over Broca's area during the acquisition of an artificial grammar. Performance during the acquisition phase, presented as a working memory task, was comparable between groups. In the subsequent classification task, detecting syntactic violations, and specifically, those where no cues to superficial similarity were available, improved significantly after anodal tDCS, resulting in an overall better performance. A control experiment where 10 subjects received anodal tDCS over an area unrelated to artificial grammar learning further supported the specificity of these effects to Broca's area. We conclude that Broca's area is specifically involved in rule-based knowledge, and here, in an improved ability to detect syntactic violations. The results cannot be explained by better tDCS-induced working memory performance during the acquisition phase. This is the first study that demonstrates that tDCS may facilitate acquisition of grammatical knowledge, a finding of potential interest for rehabilitation of aphasia.
Feil J, Zangen A Brain stimulation in the study and treatment of addiction. 2010 Neurosci Biobehav Rev
Addiction is a devastating and chronically relapsing disorder. Repeated drug administration induces neuroadaptations associated with abnormal dopaminergic activity in the mesocorticolimbic circuitry, resulting in altered cortical neurotransmission and excitability. Electrical stimulation of specific brain regions can be used in animal models and humans to induce local activation or disruption of specific circuitries or alter neuronal excitability and cause neuroadaptations. Non-surgical stimulation of specific brain regions in human addicts can be achieved by transcranial magnetic stimulation (TMS). TMS is used for transient stimulation or disruption of neural activity in specific cortical regions, which can be used to assess cortical excitability, and to induce changes in cortical excitability. Moreover, it is suggested that repeated stimulation can cause long-lasting neuroadaptations. Therefore, TMS paradigms were used in some studies to assess the presence of altered cortical excitability associated with chronic drug consumption, while other studies have begun to assess the therapeutic potential of repetitive TMS. Similarly, transcranial direct current stimulation (tDCS) is used to modulate neuronal resting membrane potential in humans and alter cortical excitability. The current review describes how these brain stimulation techniques have recently been used for the study and treatment of addiction in animal models and humans.
Fertonani A, Rosini S, Cotelli M, Rossini PM, Miniussi C Naming facilitation induced by transcranial direct current stimulation. 2010 Behav. Brain Res.
Transcranial direct current stimulation (tDCS) is able to generate a long-term increase or decrease in the neuronal excitability that can modulate cognitive tasks, similar to repetitive transcranial magnetic stimulation. The aim of this study was to explore the effects of tDCS on a language task in young healthy subjects. Anodal, cathodal and sham tDCS were applied to the left dorsolateral prefrontal cortex (DLPFC) before two picture naming experiments, a preliminary study (i.e., experiment 1) and a main study (i.e., experiment 2). The results show that anodal tDCS of the left DLPFC improves naming performance, speeding up verbal reaction times after the end of the stimulation, whereas cathodal stimulation had no effect. We hypothesize that the cerebral network dedicated to lexical retrieval processing is facilitated by anodal tDCS to the left DLPFC. Although the mechanisms responsible for facilitation are not yet clear, the results presented herein implicate a facilitation lasting beyond the end of the stimulation that imply cortical plasticity mechanisms. The opportunity to non-invasively interact with the functioning of these plasticity mechanisms will surely open new and promising scenarios in language studies in basic and clinical neuroscience fields.
Merzagora AC, Foffani G, Panyavin I, Mordillo-Mateos L, Aguilar J, Onaral B, Oliviero A Prefrontal hemodynamic changes produced by anodal direct current stimulation. 2010 Neuroimage
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that has been investigated for the treatment of many neurological or neuropsychiatric disorders. Its main effect is to modulate the cortical excitability depending on the polarity of the current applied. However, understanding the mechanisms by which these modulations are induced and persist is still an open question. A possible marker indicating a change in cortical activity is the subsequent variation in regional blood flow and metabolism. These variations can be effectively monitored using functional near-infrared spectroscopy (fNIRS), which offers a noninvasive and portable measure of regional blood oxygenation state in cortical tissue. We studied healthy volunteers at rest and evaluated the changes in cortical oxygenation related to tDCS using fNIRS. Subjects were tested after active stimulation (12 subjects) and sham stimulation (10 subjects). Electrodes were applied at two prefrontal locations; stimulation lasted 10 min and fNIRS data were then collected for 20 min. The anodal stimulation induced a significant increase in oxyhemoglobin (HbO(2)) concentration compared to sham stimulation. Additionally, the effect of active 10-min tDCS was localized in time and lasted up to 8-10 min after the end of the stimulation. The cathodal stimulation manifested instead a negligible effect. The changes induced by tDCS on HbO(2), as captured by fNIRS, agreed with the results of previous studies. Taken together, these results help clarify the mechanisms underlying the regional alterations induced by tDCS and validate the use of fNIRS as a possible noninvasive method to monitor the neuromodulation effect of tDCS.
Cogiamanian F, Brunoni AR, Boggio PS, Fregni F, Ciocca M, Priori A Non-invasive brain stimulation for the management of arterial hypertension. 2010 Med. Hypotheses
The neural control of the cardiovascular system is a complex process that involves many structures at different levels of nervous system. Several cortical areas are involved in the control of systemic blood pressure, such as the sensorimotor cortex, the medial prefrontal cortex and the insular cortex. Non-invasive brain stimulation techniques - repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) - induce sustained and prolonged functional changes of the human cerebral cortex. rTMS and tDCS has led to positive results in the treatment of some neurological and psychiatric disorders. Because experiments in animals show that cortical modulation can be an effective method to regulate the cardiovascular system, non-invasive brain stimulation might be a novel tool in the therapeutics of human arterial hypertension. We here review the experimental evidence that non-invasive brain stimulation can influence the autonomic nervous system and discuss the hypothesis that focal modulation of cortical excitability by rTMS or tDCS can influence sympathetic outflow and, eventually, blood pressure, thus providing a novel therapeutic tool for human arterial hypertension.
George MS, Aston-Jones G Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). 2010 Neuropsychopharmacology
Although the preceding chapters discuss much of the new knowledge of neurocircuitry of neuropsychiatric diseases, and an invasive approach to treatment, this chapter describes and reviews the noninvasive methods of testing circuit-based theories and treating neuropsychiatric diseases that do not involve implanting electrodes into the brain or on its surface. These techniques are transcranial magnetic stimulation, vagus nerve stimulation, and transcranial direct current stimulation. Two of these approaches have FDA approval as therapies.
Loo CK, Sachdev P, Martin D, Pigot M, Alonzo A, Malhi GS, Lagopoulos J, Mitchell P A double-blind, sham-controlled trial of transcranial direct current stimulation for the treatment of depression. 2010 Int. J. Neuropsychopharmacol.
Two recent sham-controlled studies found that transcranial direct current stimulation (tDCS) was an effective treatment for depression. As tDCS is painless, relatively safe and inexpensive, its efficacy in treating depression warrants further investigation. This double-blind, randomized study tested tDCS at the same stimulation parameters as a previous positive study (1 mA current strength, five treatment sessions, active or sham, given on alternate days) in 40 depressed participants. Anodal stimulation was centred over the left dorsolateral prefrontal cortex, with the cathode placed on the lateral aspect of the contralateral orbit. tDCS was continued up to a total of ten active sessions per participant. Mood outcomes were measured by psychiatrist raters blind to treatment condition using the Montgomery-Asberg and other depression rating scales. Psychomotor speed was assessed immediately before and after a single tDCS session and attention, frontal executive function, working memory and verbal learning were assessed after each group of five sessions. Overall depression scores improved significantly over ten tDCS treatments, but there was no between-group difference in the five-session, sham-controlled phase. tDCS was found to be safe, with no adverse effects on neuropsychological function, and only minor side-effects. It is recommended that the efficacy of tDCS in depression be further evaluated over a longer treatment period, using enhanced stimulation parameters.
Arul-Anandam AP, Loo C, Mitchell P Induction of hypomanic episode with transcranial direct current stimulation. 2010 J ECT
We report on the case of a 57-year-old man who experienced an episode of hypomania while participating in a clinical trial of transcranial direct current stimulation for the treatment of major depressive disorder. Although hypomania and mania have been reported after transcranial magnetic stimulation to the dorsolateral prefrontal cortex in the past, to our knowledge, this is the first report of mania after transcranial direct current stimulation to the dorsolateral prefrontal cortex.
Karim AA, Schneider M, Lotze M, Veit R, Sauseng P, Braun C, Birbaumer N The truth about lying: inhibition of the anterior prefrontal cortex improves deceptive behavior. 2010 Cereb. Cortex
Recent neuroimaging studies have indicated a predominant role of the anterior prefrontal cortex (aPFC) in deception and moral cognition, yet the functional contribution of the aPFC to deceptive behavior remains unknown. We hypothesized that modulating the excitability of the aPFC by transcranial direct current stimulation (tDCS) could reveal its functional contribution in generating deceitful responses. Forty-four healthy volunteers participated in a thief role-play in which they were supposed to steal money and then to attend an interrogation with the Guilty Knowledge Test. During the interrogation, participants received cathodal, anodal, or sham tDCS. Remarkably, inhibition of the aPFC by cathodal tDCS did not lead to an impairment of deceptive behavior but rather to a significant improvement. This effect manifested in faster reaction times in telling lies, but not in telling the truth, a decrease in sympathetic skin-conductance response and feelings of guilt while deceiving the interrogator and a significantly higher lying quotient reflecting skillful lying. Increasing the excitability of the aPFC by anodal tDCS did not affect deceptive behavior, confirming the specificity of the stimulation polarity. These findings give causal support to recent correlative data obtained by functional magnetic resonance imaging studies indicating a pivotal role of the aPFC in deception.
Borckardt JJ, Reeves S, George MS The potential role of brain stimulation in the management of postoperative pain. 2009 Journal of pain management
There is limited evidence to date of the effectiveness of minimally-invasive brain stimulation in controlling postoperative pain. Two studies have provided preliminary evidence that transcranial magnetic stimulation (TMS) can significantly reduce post-operative pain, and no studies have been published on the effects of transcranial direct current stimulation (tDCS) on postoperative pain. The evidence supporting the role of brain stimulation in producing general anesthetic effects is also limited but there is a possibility that appropriately targeted electrical stimulation might have a role in the future if the technology permits such stimulation in a non-invasive manner. The present article provides a brief overview of the available evidence supporting the role of minimally invasive brain stimulation technology in perioperative medicine. More studies and well-controlled trials are needed to establish a clear role for minimally-invasive brain stimulation technologies in the perioperative arena.
Short B, Borckardt JJ, George M, Beam W, Reeves ST Non-invasive brain stimulation approaches to fibromyalgia pain. 2009 Journal of pain management
Fibromyalgia is a poorly understood disorder that likely involves central nervous system sensory hypersensitivity. There are a host of genetic, neuroendocrine and environmental abnormalities associated with the disease, and recent research findings suggest enhanced sensory processing, and abnormalities in central monoamines and cytokines expression in patients with fibromyalgia. The morbidity and financial costs associated with fibromyalgia are quite high despite conventional treatments with antidepressants, anticonvulsants, low-impact aerobic exercise and psychotherapy. Noninvasive brain stimulation techniques, such as transcranial direct current stimulation, transcranial magnetic stimulation, and electroconvulsive therapy are beginning to be studied as possible treatments for fibromyalgia pain. Early studies appear promising but more work is needed. Future directions in clinical care may include innovative combinations of noninvasive brain stimulation, pharmacological augmentation, and behavior therapies.
Valle A, Roizenblatt S, Botte S, Zaghi S, Riberto M, Tufik S, Boggio PS, Fregni F Efficacy of anodal transcranial direct current stimulation (tDCS) for the treatment of fibromyalgia: results of a randomized, sham-controlled longitudinal clinical trial. 2009 Journal of pain management
Fibromyalgia has been recognized as a central pain disorder with evidence of neuroanatomic and neurophysiologic alterations. Previous studies with techniques of noninvasive brain stimulation--transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS)--have shown that these methods are associated with a significant alleviation of fibromyalgia-associated pain and sleep dysfunction. Here we sought to determine whether a longer treatment protocol involving 10 sessions of 2 mA, 20 min tDCS of the left primary motor (M1) or dorsolateral prefrontal cortex (DLPFC) could offer additional, more long-lasting clinical benefits in the management of pain from fibromyalgia. METHODS: Forty-one women with chronic, medically refractory fibromyalgia were randomized to receive 10 daily sessions of M1, DLPFC, or sham tDCS. RESULTS: Our results show that M1 and DLPFC stimulation both display improvements in pain scores (VAS) and quality of life (FIQ) at the end of the treatment protocol, but only M1 stimulation resulted in long-lasting clinical benefits as assessed at 30 and 60 days after the end of treatment. CONCLUSIONS: This study demonstrates the importance of the duration of the treatment period, suggesting that 10 daily sessions of tDCS result in more long lasting outcomes than only five sessions. Furthermore, this study supports the findings of a similarly designed rTMS trial as both induce pain reductions that are equally long-lasting.
Kim DY, Ohn SH, Yang EJ, Park CI, Jung KJ Enhancing motor performance by anodal transcranial direct current stimulation in subacute stroke patients. 2009 Am J Phys Med Rehabil
To investigate whether anodal transcranial direct current stimulation enhances motor performance in the paretic hand of subacute poststroke patients and how long the improvement persisted after the session.
Arul-Anandam AP, Loo C, Sachdev P Transcranial direct current stimulation - what is the evidence for its efficacy and safety? 2009 F1000 Med Rep
Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, has emerged in the past decade as a useful investigative and therapeutic technique. A number of recent studies suggest that tDCS is safe and may be efficacious in the treatment of a variety of psychiatric and neurological disorders, including major depressive disorder, chronic neuropathic pain, and stroke. More evidence is necessary, however, before it can be recommended for general clinical application.
Datta A, Bansal V, Diaz J, Patel J, Reato D, Bikson M Gyri-precise head model of transcranial direct current stimulation: improved spatial focality using a ring electrode versus conventional rectangular pad. 2009 Brain Stimul
The spatial resolution of conventional transcranial direct current stimulation (tDCS) is considered to be relatively diffuse owing to skull dispersion. However, we show that electric fields may be clustered at distinct gyri/sulci sites because of details in tissue architecture/conductivity, notably cerebrospinal fluid (CSF). We calculated the cortical electric field/current density magnitude induced during tDCS using a high spatial resolution (1 mm3) magnetic resonance imaging (MRI)-derived finite element human head model; cortical gyri/sulci were resolved. The spatial focality of conventional rectangular-pad (7 x 5 cm2) and the ring (4 x 1) electrode configurations were compared. The rectangular-pad configuration resulted in diffuse (unfocal) modulation, with discrete clusters of electric field magnitude maxima. Peak-induced electric field magnitude was not observed directly underneath the pads, but at an intermediate lobe. The 4 x 1 ring resulted in enhanced spatial focality, with peak-induced electric field magnitude at the sulcus and adjacent gyri directly underneath the active electrode. Cortical structures may be focally targeted by using ring configurations. Anatomically accurate high-resolution MRI-based forward-models may guide the "rational" clinical design and optimization of tDCS.
Priori A, Hallett M, Rothwell JC Repetitive transcranial magnetic stimulation or transcranial direct current stimulation? 2009 Brain Stimul
In recent years two techniques have become available to stimulate the human brain noninvasively through the scalp: repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). Prolonged application of either method (eg, several hundred TMS pulses [rTMS] or several minutes of tDCS) leads to changes in excitability of the cortex that outlast the period of stimulation. Because of this, besides the implications for experimental neuroscientists, there is increasing interest in the potential for applying either method as a therapy in neurology, psychiatry, rehabilitation, and pain. Given that both techniques lead to the same final result, this article discusses in theory several issues that can help an investigator to decide whether rTMS or tDCS would be more suitable for the scope of the planned work.
Arul-Anandam AP, Loo C, Martin D, Mitchell PB Chronic neuropathic pain alleviation after transcranial direct current stimulation to the dorsolateral prefrontal cortex. 2009 Brain Stimul
Fenton BW, Palmieri PA, Boggio P, Fanning J, Fregni F A preliminary study of transcranial direct current stimulation for the treatment of refractory chronic pelvic pain. 2009 Brain Stimul
The modulatory effects of transcranial direct current stimulation (tDCS) appear beneficial for different chronic pain syndromes; however, it is unclear whether this method can be used to treat refractory chronic pelvic pain.
George MS, Padberg F, Schlaepfer TE, O'Reardon JP, Fitzgerald PB, Nahas ZH, Marcolin MA Controversy: Repetitive transcranial magnetic stimulation or transcranial direct current stimulation shows efficacy in treating psychiatric diseases (depression, mania, schizophrenia, obsessive-complusive disorder, panic, posttraumatic stress disorder). 2009 Brain Stimul
Brain imaging studies performed over the past 20 years have generated new knowledge about the specific brain regions involved in the brain diseases that have been classically labeled as psychiatric. These include the mood and anxiety disorders, and the schizophrenias. As a natural next step, clinical researchers have investigated whether the minimally invasive brain stimulation technologies (transcranial magnetic stimulation [TMS] or transcranial direct current stimulation [tDCS]) might potentially treat these disorders. In this review, we critically review the research studies that have examined TMS or tDCS as putative treatments for depression, mania, obsessive-complusive disorder, posttraumatic stress disorder, panic disorder, or schizophrenia. (Separate controversy articles deal with using TMS or tDCS to treat pain or tinnitus. We will not review here the large number of studies using TMS or tDCS as research probes to understand disease mechanisms of psychiatric disorders.) Although there is an extensive body of randomized controlled trials showing antidepressant effects of daily prefrontal repetitive TMS, the magnitude or durability of this effect remains controversial. US Food and Drug Administration approval of TMS for depression was recently granted. There is much less data in all other diseases, and therapeutic effects in other psychiatric conditions, if any, are still controversial. Several issues and problems extend across all psychiatric TMS studies, including the optimal method for a sham control, appropriate coil location, best device parameters (intensity, frequency, dosage, and dosing schedule) and refining what subjects should be doing during treatment (activating pathologic circuits or not). In general, TMS or tDCS as a treatment for most psychiatric disorders remains exciting but controversial, other than prefrontal TMS for depression.
Zaghi S, Heine N, Fregni F Brain stimulation for the treatment of pain: A review of costs, clinical effects, and mechanisms of treatment for three different central neuromodulatory approaches. 2009 J Pain Manag
Methods of cortical stimulation including epidural motor cortex stimulation (MCS), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS) are emerging as alternatives in the management of pain in patients with chronic medically-refractory pain disorders. Here we consider the three methods of brain stimulation that have been investigated for the treatment of central pain: MCS, rTMS, and tDCS. While all three treatment modalities appear to induce significant clinical gains in patients with chronic pain, tDCS is revealed as the most cost-effective approach (compared to rTMS and MCS) when considering a single year of treatment. However, if a 5-year treatment is considered, MCS is revealed as the most cost-effective modality (as compared to rTMS and tDCS) for the neuromodulatory treatment of chronic pain. We discuss the theory behind the application of each modality as well as efficacy, cost, safety, and practical considerations.
Datta A, Bansal V, Diaz J, Patel J, Reato D, Bikson M Gyri -precise head model of transcranial DC stimulation: Improved spatial focality using a ring electrode versus conventional rectangular pad. 2009 Brain Stimul
The spatial resolution of conventional transcranial direct current stimulation (tDCS) is considered to be relatively diffuse owing to skull dispersion. However, here we show that electric fields may be clustered at distinct gyri/sulci sites due to details in tissue architecture/conductivity notably cerebrospinal fluid (CSF). We calculated the cortical electric field/current density magnitude induced during tDCS using a high spatial resolution (1 mm(3)) MRI-derived finite element human head model; cortical gyri/sulci were resolved. The spatial focality of conventional rectangular-pad (7 x 5 cm(2)) and the ring (4 x 1) electrode configurations were compared. The rectangular-pad configuration resulted in diffuse (un-focal) modulation, with discrete clusters of electric field magnitude maxima. Peak induced electric field magnitude was not observed directly underneath the pads, but at an intermediate lobe. The 4 x 1 ring resulted in enhanced spatial focality, with peak induced electric field magnitude at the sulcus and adjacent gyri directly underneath the active electrode. Cortical structures may be focally targeted using ring configurations. Anatomically accurate high resolution MRI-based forward-models may guide the 'rational' clinical design and optimization of tDCS.
Kang EK, Baek MJ, Kim S, Paik NJ Non-invasive cortical stimulation improves post-stroke attention decline. 2009 Restor. Neurol. Neurosci.
Attention decline after stroke is common and hampers the rehabilitation process, and non-invasive transcranial direct current stimulation (tDCS) has the potential to elicit behavioral changes by modulating cortical excitability. The authors tested the hypothesis that a single session of non-invasive cortical stimulation with excitatory anodal tDCS applied to the left dorsolateral prefrontal cortex (DLPFC) can improve attention in stroke patients.
Kranz G, Shamim EA, Lin PT, Kranz GS, Voller B, Hallett M Blepharospasm and the modulation of cortical excitability in primary and secondary motor areas. 2009 Neurology
Traditionally, benign essential blepharospasm (BEB) is considered a disorder caused by basal ganglia dysfunction. Electrophysiologic and brain imaging studies suggest pathologic changes in excitability in the primary motor cortex (MC), anterior cingulate (AC), and secondary motor areas, such as premotor (PMC) and supplementary motor cortices (SMA).
Palm U, Keeser D, Schiller C, Fintescu Z, Reisinger E, Baghai TC, Mulert C, Padberg F Transcranial direct current stimulation in a patient with therapy-resistant major depression. 2009 World J. Biol. Psychiatry
Transcranial direct current stimulation (tDCS) of the prefrontal cortex (PFC) has been reported to exert significant antidepressant effects in patients with major depression. Several recent studies found an improvement of depressive symptoms in drug-free patients. Here we report the case of a 66-year-old female patient suffering from recurrent major depressive episodes who underwent anodal tDCS of the left dorsolateral PFC over 4 weeks as an add-on treatment to a stable antidepressant medication. Only a modest improvement of depressive symptoms was observed after tDCS, i.e. reduction of the baseline scores in the Hamilton Depression Rating Scale from 23 to 19 and in the Beck Depression Inventory from 27 to 20. However, there was an increase from 52 to 90% in the Regensburg Verbal Fluency Test. In addition, EEG was used to assess the acute effects of tDCS. Low resolution brain electromagnetic tomography (LORETA) showed a left unilateral focal effect (25-40% reduced power) in the delta, theta and alpha frequency bands. The same effect appeared in the surface analysis of the EEG. The absolute, as well as the relative power decreased significantly in the delta, theta and alpha bands after a comparison of the spectral analysis. Though tDCS over 4 weeks did not exert clinically meaningful antidepressant effects in this case of therapy-resistant depression, the findings for cognitive measures and EEG suggest that beneficial effects may occur in depressed subjects and future studies need to further explore this approach also in therapy-resistant major depression.
Faria P, Leal A, Miranda PC Comparing different electrode configurations using the 10-10 international system in tDCS: a finite element model analysis. 2009 Conf Proc IEEE Eng Med Biol Soc
For the past few years, the potential of transcranial direct current stimulation (tDCS) for the treatment of several pathologies has been investigated. Knowledge of the current density distribution is an important factor in optimizing such applications of tDCS. We use the finite element method to compare three different models in tDCS, where the stimulation electrodes (EEG electrodes) are placed in the 10-10 international system coordinates. We studied the focality and the distribution of the current density in depth and at the surface of the brain for three different electrode configurations. We show that the use of EEG electrodes increases the focality of tDCS, especially when one cathode and several anodes are used. Additionally, these electrodes need less injected current, can be placed at scalp positions whose relationship with the underlying cerebral cortex are known and allow the use of tDCS and EEG recording concomitantly.
Datta A, Elwassif M, Bikson M Bio-heat transfer model of transcranial DC stimulation: comparison of conventional pad versus ring electrode. 2009 Conf Proc IEEE Eng Med Biol Soc
Transcranial Direct Current Stimulation (tDCS) is a non-invasive procedure where a weak electrical current is applied across the scalp to modulate brain function. The proliferation of this therapy has been accompanied by isolated reports regarding concern about their safety namely skin irritation. The potential cause of skin irritation has sometimes been attributed to increased scalp temperature during stimulation. We have developed novel technology for tDCS that improves spatial focality at the cost of increased stimulation electrode current density; high density tDCS (HD-tDCS). The goal of this paper was to provide information on the thermal effects of tDCS using a MRI-derived finite element human head model. The tissue temperature increases of tDCS using conventional rectangular-pad (7 x 5 cm(2)) and HD-tDCS using the ring (4 x 1) electrode configurations were compared using a bio-heat model. Our results indicate that clinical tDCS do not increase tissue temperature and 4 x 1 ring configurations leads to a negligible increase in scalp temperature.
Suh HS, Kim SH, Lee WH, Kim TS Realistic simulation of transcranial direct current stimulation via 3-d high-resolution finite element analysis: Effect of tissue anisotropy. 2009 Conf Proc IEEE Eng Med Biol Soc
Recently, transcranial direct current stimulation (tDCS) is getting an attentions as a promising technique with a capability of noninvasive and nonconvulsive stimulation to treat ill conditions of the brain such as depression. However, knowledge on how exactly tDCS affects the activity of neurons in the brain is still not sufficient. Precise analysis on the electromagnetic effect of tDCS on the brain requires finite element analysis (FEA) with realistic head models including anisotropy of the white matter and the skull. In this paper, we have simulated tDCS via 3-D high-resolution FEA and investigated the effect of tissue anisotropy on tDCS. The results show that the skull anisotropy induces a strong shunting effect, causing a shift of the stimulated areas, and the white matter anisotropy affects strongly the current flow directions, changing the current field distribution inside the human brain. Our presented methodology and results should be useful for more effective guiding and treatment using tDCS.
Brunoni AR, Fraguas R, Fregni F Pharmacological and combined interventions for the acute depressive episode: focus on efficacy and tolerability. 2009 Ther Clin Risk Manag
Use of antidepressants is the gold standard therapy for major depression. However, despite the large number of commercially available antidepressant drugs there are several differences among them in efficacy, tolerability, and cost-effectiveness. In addition the optimal augmentation strategy is still not clear when dealing with treatment-resistant depression, a condition that affects 15% to 40% of depressed patients.
Boggio PS, Amancio EJ, Correa CF, Cecilio S, Valasek C, Bajwa Z, Freedman SD, Pascual-Leone A, Edwards DJ, Fregni F Transcranial DC stimulation coupled with TENS for the treatment of chronic pain: a preliminary study. 2009 Clin J Pain
Based on evidence showing that electrical stimulation of the nervous system is an effective method to decrease chronic neurogenic pain, we aimed to investigate whether the combination of 2 methods of electrical stimulation-a method of peripheral stimulation [transcutaneous electrical nerve stimulation (TENS)] and a method of noninvasive brain stimulation [transcranial direct current stimulation (tDCS)]-induces greater pain reduction as compared with tDCS alone and sham stimulation.
Smith DV, Clithero JA Manipulating executive function with transcranial direct current stimulation. 2009 Front Integr Neurosci
Jefferson S, Mistry S, Singh S, Rothwell J, Hamdy S Characterizing the application of transcranial direct current stimulation in human pharyngeal motor cortex. 2009 Am. J. Physiol. Gastrointest. Liver Physiol.
Transcranial direct current stimulation (tDCS) is a novel intervention that can modulate brain excitability in health and disease; however, little is known about its effects on bilaterally innervated systems such as pharyngeal motor cortex. Here, we assess the effects of differing doses of tDCS on the physiology of healthy human pharyngeal motor cortex as a prelude to designing a therapeutic intervention in dysphagic patients. Healthy subjects (n = 17) underwent seven regimens of tDCS (anodal 10 min 1 mA, cathodal 10 min 1 mA, anodal 10 min 1.5 mA, cathodal 10 min 1.5 mA, anodal 20 min 1 mA, cathodal 20 min 1 mA, Sham) on separate days, in a double blind randomized order. Bihemispheric motor evoked potential (MEP) responses to single-pulse transcranial magnetic stimulation (TMS) as well as intracortical facilitation (ICF) and inhibition (ICI) were recorded using a swallowed pharyngeal catheter before and up to 60 min following the tDCS. Compared with sham, both 10 min 1.5 mA and 20 min 1 mA anodal stimulation induced increases in cortical excitability in the stimulated hemisphere (+44 +/- 17% and +59 +/- 16%, respectively; P < 0.005) whereas only 10 min 1.5 mA cathodal stimulation induced inhibition (-26 +/- 4%, P = 0.02). There were neither contralateral hemisphere changes nor any evidence for ICI or ICF in driving the ipsilateral effects. In conclusion, anodal tDCS can alter pharyngeal motor cortex excitability in an intensity-dependent manner, with little evidence for transcallosal spread. Anodal stimulation may therefore provide a useful means of stimulating pharyngeal cortex and promoting recovery in dysphagic patients.
Roche N, Lackmy A, Achache V, Bussel B, Katz R Impact of transcranial direct current stimulation on spinal network excitability in humans. 2009 J. Physiol. (Lond.)
Transcranial direct current stimulation (tDCS) when applied over the motor cortex, modulates excitability dependent on the current polarity. The impact of this cortical modulation on spinal cord network excitability has rarely been studied. In this series of experiments, performed in healthy subjects, we show that anodal tDCS increases disynaptic inhibition directed from extensor carpi radialis (ECR) to flexor carpi radialis (FCR) with no modification of presynaptic inhibition of FCR Ia terminals and FCR H-reflex recruitment curves. We also show that cathodal tDCS does not modify spinal network excitability. Our results suggest that the increase of disynaptic inhibition observed during anodal tDCS relies on an increase of disynaptic interneuron excitability and that tDCS over the motor cortex in human subjects induces effects on spinal network excitability. Our results highlight the fact that the effects of tDCS should be considered in regard to spinal motor circuits and not only to cortical circuits.
Stagg CJ, O'Shea J, Kincses ZT, Woolrich M, Matthews PM, Johansen-Berg H Modulation of movement-associated cortical activation by transcranial direct current stimulation. 2009 Eur. J. Neurosci.
Transcranial direct current stimulation (tDCS) is currently attracting increasing interest as a tool for neurorehabilitation. However, local and distant effects of tDCS on motor-related cortical activation patterns remain poorly defined, limiting the rationale for its use. Here we describe the results of a functional magnetic resonance imaging (MRI) experiment designed to characterize local and distant effects on cortical motor activity following excitatory anodal stimulation and inhibitory cathodal stimulation. Fifteen right-handed subjects performed a visually cued serial reaction time task with their right hand in a 3-T MRI scanner both before and after 10 min of 1-mA tDCS applied to the left primary motor cortex (M1). Relative to sham stimulation, anodal tDCS led to short-lived activation increases in the M1 and the supplementary motor area (SMA) within the stimulated hemisphere. The increase in activation in the SMA with anodal stimulation was found also when directly comparing anodal with cathodal stimulation. Relative to sham stimulation, cathodal tDCS led to an increase in activation in the contralateral M1 and dorsal premotor cortex (PMd), as well as an increase in functional connectivity between these areas and the stimulated left M1. These increases were also found when directly comparing cathodal with anodal stimulation. Significant within-session linear decreases in activation occurred in all scan sessions. The after-effects of anodal tDCS arose primarily from a change in the slope of these decreases. In addition, following sham stimulation compared with baseline, a between-session decrease in task-related activity was found. The effects of cathodal tDCS arose primarily from a reduction of this normal decrease.
Abe N The neurobiology of deception: evidence from neuroimaging and loss-of-function studies. 2009 Curr. Opin. Neurol.
Visualization of how the brain generates a lie is now possible because of recent conceptual and technical advances in functional neuroimaging; this has led to a rapid increase in studies related to the cognitive neuroscience of deception. The present review summarizes recent work on the neural substrates that underlie human deceptive behavior.
Jancke L, Cheetham M, Baumgartner T Virtual reality and the role of the prefrontal cortex in adults and children. 2009 Front Neurosci
In this review, the neural underpinnings of the experience of presence are outlined. Firstly, it is shown that presence is associated with activation of a distributed network, which includes the dorsal and ventral visual stream, the parietal cortex, the premotor cortex, mesial temporal areas, the brainstem and the thalamus. Secondly, the dorsolateral prefrontal cortex (DLPFC) is identified as a key node of the network as it modulates the activity of the network and the associated experience of presence. Thirdly, children lack the strong modulatory influence of the DLPFC on the network due to their unmatured frontal cortex. Fourthly, it is shown that presence-related measures are influenced by manipulating the activation in the DLPFC using transcranial direct current stimulation (tDCS) while participants are exposed to the virtual roller coaster ride. Finally, the findings are discussed in the context of current models explaining the experience of presence, the rubber hand illusion, and out-of-body experiences.
Bergmann TO, Groppa S, Seeger M, Molle M, Marshall L, Siebner HR Acute changes in motor cortical excitability during slow oscillatory and constant anodal transcranial direct current stimulation. 2009 J. Neurophysiol.
Transcranial oscillatory current stimulation has recently emerged as a noninvasive technique that can interact with ongoing endogenous rhythms of the human brain. Yet, there is still little knowledge on how time-varied exogenous currents acutely modulate cortical excitability. In ten healthy individuals we used on-line single-pulse transcranial magnetic stimulation (TMS) to search for systematic shifts in corticospinal excitability during anodal sleeplike 0.8-Hz slow oscillatory transcranial direct current stimulation (so-tDCS). In separate sessions, we repeatedly applied 30-s trials (two blocks at 20 min) of either anodal so-tDCS or constant tDCS (c-tDCS) to the primary motor hand area during quiet wakefulness. Simultaneously and time-locked to different phase angles of the slow oscillation, motor-evoked potentials (MEPs) as an index of corticospinal excitability were obtained in the contralateral hand muscles 10, 20, and 30 s after the onset of tDCS. MEPs were also measured off-line before, between, and after both stimulation blocks to detect any lasting excitability shifts. Both tDCS modes increased MEP amplitudes during stimulation with an attenuation of the facilitatory effect toward the end of a 30-s tDCS trial. No phase-locking of corticospinal excitability to the exogenous oscillation was observed during so-tDCS. Off-line TMS revealed that both c-tDCS and so-tDCS resulted in a lasting excitability increase. The individual magnitude of MEP facilitation during the first tDCS trials predicted the lasting MEP facilitation found after tDCS. We conclude that sleep slow oscillation-like excitability changes cannot be actively imposed on the awake cortex with so-tDCS, but phase-independent on-line as well as off-line facilitation can reliably be induced.
Jo JM, Kim YH, Ko MH, Ohn SH, Joen B, Lee KH Enhancing the working memory of stroke patients using tDCS. 2009 Am J Phys Med Rehabil
We investigated whether anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex affected the working memory performance of patients after a stroke.
Boggio PS, Liguori P, Sultani N, Rezende L, Fecteau S, Fregni F Cumulative priming effects of cortical stimulation on smoking cue-induced craving. 2009 Neurosci. Lett.
Smoking cue-provoked craving is an intricate behavior associated with strong changes in neural networks. Craving is one of the main reasons subjects continue to smoke; therefore interventions that can modify activity in neural networks associated with craving can be useful tools in future research investigating novel treatments for smoking cessation. The goal of this study was to use a neuromodulatory technique associated with a powerful effect on spontaneous neuronal firing - transcranial direct current stimulation (tDCS) - to modify cue-provoked smoking craving. Based on preliminary data showing that craving can be modified after a single tDCS session, here we investigated the effects of repeated tDCS sessions on craving behavior. Twenty-seven subjects were randomized to receive sham or active tDCS (anodal tDCS of the left DLPFC). Our results show a significant cumulative effect of tDCS on modifying smoking cue-provoked craving. In fact, in the group of active stimulation, smoking cues had an opposite effect on craving after stimulation - it decreased craving - as compared to sham stimulation in which there was a small decrease or increase on craving. In addition, during these 5 days of stimulation there was a small but significant decrease in the number of cigarettes smoked in the active as compared to sham tDCS group. Our findings extend the results of our previous study as they confirm the notion that tDCS has a specific effect on craving behavior and that the effects of several sessions can increase the magnitude of its effect. These results open avenues for the exploration of this method as a therapeutic alternative for smoking cessation and also as a mean to change stimulus-induced behavior.
Galea JM, Jayaram G, Ajagbe L, Celnik P Modulation of cerebellar excitability by polarity-specific noninvasive direct current stimulation. 2009 J. Neurosci.
The cerebellum is a crucial structure involved in movement control and cognitive processing. Noninvasive stimulation of the cerebellum results in neurophysiological and behavioral changes, an effect that has been attributed to modulation of cerebello-brain connectivity. At rest, the cerebellum exerts an overall inhibitory tone over the primary motor cortex (M1), cerebello-brain inhibition (CBI), likely through dentate-thalamo-cortical connections. The level of excitability of this pathway before and after stimulation of the cerebellum, however, has not been directly investigated. In this study, we used transcranial magnetic stimulation to determine changes in M1, brainstem, and CBI before and after 25 min of anodal, cathodal, or sham transcranial direct current stimulation (tDCS) applied over the right cerebellar cortex. We hypothesized that anodal tDCS would result in an enhancement of CBI and cathodal would decrease it, relative to sham stimulation. We found that cathodal tDCS resulted in a clear decrease of CBI, whereas anodal tDCS increased it, in the absence of changes after sham stimulation. These effects were specific to the cerebello-cortical connections with no changes in other M1 or brainstem excitability measures. The cathodal effect on CBI was found to be dependent on stimulation intensity and lasted up to 30 min after the cessation of tDCS. These results suggest that tDCS can modulate in a focal and polarity-specific manner cerebellar excitability, likely through changes in Purkinje cell activity. Therefore, direct current stimulation of the cerebellum may have significant potential implications for patients with cerebellar dysfunction as well as to motor control studies.
Elmer S, Burkard M, Renz B, Meyer M, Jancke L Direct current induced short-term modulation of the left dorsolateral prefrontal cortex while learning auditory presented nouns. 2009 Behav Brain Funct
Stone DB, Tesche CD Transcranial direct current stimulation modulates shifts in global/local attention. 2009 Neuroreport
The effects of transcranial direct current stimulation on global/local attentional switching and feature processing were assessed. Direct current stimulation was applied to the left posterior parietal cortex in 14 healthy participants. A compound letter task was used to probe the feature processing and the switching of attention between global and local features. Results indicate that cathodal stimulation acutely degraded attentional switches during stimulation, and anodal stimulation persistently degraded local-to-global attentional switching for at least 20 min after stimulation. Direct current stimulation had no significant effects on global/local feature processing. These results support the functionality of left parietal cortex in attentional switch and represent the first successful modulation of global/local switching using exogenous brain stimulation.
Jayaram G, Stinear JW The effects of transcranial stimulation on paretic lower limb motor excitability during walking. 2009 J Clin Neurophysiol
Balanced transcallosal inhibition sustains symmetrical corticomotor excitability and assists the performance of bimanual voluntary movements. After stroke, transcallosal inhibition becomes asymmetric. This finding raised the notion that reducing poststroke asymmetry in transcallosal inhibition might prime the motor system before training and lead to improvements in walking recovery. In this study, we examined three neuromodulatory protocols applied during walking to determine if they could increase ipsilesional and decrease contralesional motor excitability in patients with chronic stroke. Inhibitory repetitive transcranial magnetic stimulation and inhibitory paired associative stimulation were applied to the contralesional motor system, and facilitatory anodal transcranial direct current stimulation was applied to the ipsilesional motor system. We tested the bilateral modulatory effects of each stimulation protocol on the tibialis anterior, medial gastrocnemius, medial hamstrings, and vastus lateralis of nine patients with chronic stroke. All stimulation protocols increased paretic limb and decreased nonparetic limb motor excitability. There was no statistical difference in the extent of modulation between these stimulation protocols. This result suggests these three protocols are promising candidate priming mechanisms for testing the hypothesis in a future study that reducing the poststroke asymmetry of between-hemisphere motor excitability will enhance the effect of gait therapy.
Berlim MT, Dias Neto V, Turecki G [Transcranial direct current stimulation: a promising alternative for the treatment of major depression?]. 2009 Rev Bras Psiquiatr
In recent years, a number of new somatic (non-pharmacological treatments) have been developed for the treatment of major depression and other neuropsychiatric disorders. Among these, one of the most promising is transcranial direct current stimulation.
Edwards DJ, Krebs HI, Rykman A, Zipse J, Thickbroom GW, Mastaglia FL, Pascual-Leone A, Volpe BT Raised corticomotor excitability of M1 forearm area following anodal tDCS is sustained during robotic wrist therapy in chronic stroke. 2009 Restor. Neurol. Neurosci.
Anodal transcranial direct current stimulation (tDCS) can transiently increase corticomotor excitability of intrinsic hand muscles and improve upper limb function in patients with chronic stroke. As a preliminary study, we tested whether increased corticomotor excitability would be similarly observed in muscles acting about the wrist, and remain present during robotic training involving active wrist movements, in six chronic stroke patients with residual motor deficit.
Nowak DA, Grefkes C, Ameli M, Fink GR Interhemispheric competition after stroke: brain stimulation to enhance recovery of function of the affected hand. 2009 Neurorehabil Neural Repair
Within the concept of interhemispheric competition, technical modulation of the excitability of motor areas in the contralesional and ipsilesional hemisphere has been applied in an attempt to enhance recovery of hand function following stroke. This review critically summarizes the data supporting the use of novel electrophysiological concepts in the rehabilitation of hand function after stroke.
Sparing R, Thimm M, Hesse MD, Kust J, Karbe H, Fink GR Bidirectional alterations of interhemispheric parietal balance by non-invasive cortical stimulation. 2009 Brain
Transcranial direct current stimulation is a painless, non-invasive brain stimulation technique that allows one to induce polarity-specific excitability changes in the human brain. Here, we investigated, for the first time in a 'proof of principle' study, the behavioural effect of transcranial direct current stimulation on visuospatial attention in both healthy controls and stroke patients suffering from left visuospatial neglect. We applied anodal, cathoP:dal or sham transcranial direct current stimulation (57 microA/cm(2), 10 min) to the left or right posterior parietal cortex. Using a visual detection task in a group of right-handed healthy individuals (n = 20), we observed that transcranial direct current stimulation enhanced or impaired performance depending on stimulation parameters (i.e. current polarity) and stimulated hemisphere. These results are in good accordance with classic models of reciprocal interhemispheric competition ('rivalry'). In a second experiment, we investigated the potential of transcranial direct current stimulation to ameliorate left visuospatial neglect (n = 10). Interestingly, both the inhibitory effect of cathodal transcranial direct current stimulation applied over the unlesioned posterior parietal cortex and the facilitatory effect of anodal transcranial direct current stimulation applied over the lesioned posterior parietal cortex reduced symptoms of visuospatial neglect. Taken together, our findings suggest that transcranial direct current stimulation applied over the posterior parietal cortex can be used to modulate visuospatial processing and that this effect is exerted by influencing interhemispheric reciprocal networks. These novel findings also suggest that a transcranial direct current stimulation-induced modulation of interhemispheric parietal balance may be used clinically to ameliorate visuospatial attention deficits in neglect patients.
Rosenberg O, Shoenfeld N, Kotler M, Dannon PN Mood disorders in elderly population: neurostimulative treatment possibilities. 2009 Recent Pat CNS Drug Discov
Treatment of mood disorders is one of the most challenging territories in elderly. Effectiveness of different treatment strategies could be related to age, sex and physical conditions. The side effect profile in this population also affects pharmacological interventions. Our review includes the neurostimulative treatment strategies in elderly. However, possible treatment strategies such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS) and deep brain stimulation (DBS) were less studied in elderly. ECT was found to be an effective treatment procedure in mood disorders. Few double-blind sham controlled studies were conducted and demonstrated effectiveness of TMS. DBS has lack of double-blind studies. ECT seems to be the golden standard for the treatment resistant elderly patients, yet side effect profile of ECT in elderly will be discussed. Double -blind sham controlled studies with larger samples are necessary to confirm preliminary results with transcranial direct current stimulation (tDCS), magnetic seizure therapy (MST) and VNS, DBS.
Rakofsky JJ, Holtzheimer PE, Nemeroff CB Emerging targets for antidepressant therapies. 2009 Curr Opin Chem Biol
Despite adequate antidepressant monotherapy, the majority of depressed patients do not achieve remission. Even optimal and aggressive therapy leads to a substantial number of patients who show minimal and often only transient improvement. In order to address this substantial problem of treatment-resistant depression, a number of novel targets for antidepressant therapy have emerged as a consequence of major advances in the neurobiology of depression. Three major approaches to uncover novel therapeutic interventions are: first, optimizing the modulation of monoaminergic neurotransmission; second, developing medications that act upon neurotransmitter systems other than monoaminergic circuits; and third, using focal brain stimulation to directly modulate neuronal activity. We review the most recent data on novel therapeutic compounds and their antidepressant potential. These include triple monoamine reuptake inhibitors, atypical antipsychotic augmentation, and dopamine receptor agonists. Compounds affecting extra-monoamine neurotransmitter systems include CRF(1) receptor antagonists, glucocorticoid receptor antagonists, substance P receptor antagonists, NMDA receptor antagonists, nemifitide, omega-3 fatty acids, and melatonin receptor agonists. Focal brain stimulation therapies include vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS).
Dockery CA, Hueckel-Weng R, Birbaumer N, Plewnia C Enhancement of planning ability by transcranial direct current stimulation. 2009 J. Neurosci.
The functional neuroanatomy of executive function critically involves the dorsolateral prefrontal cortex. Transcranial direct current stimulation (tDCS) has been established as a noninvasive tool for transient modulation of cortical function. Here, we examined the effects of tDCS of the left dorsolateral prefrontal cortex on planning function by using the Tower of London task to evaluate performance during and after anodal, cathodal (1 mA, 15 min), and sham tDCS in 24 healthy volunteers. The key finding was a double dissociation of polarity and training phase: improved performance was found with cathodal tDCS applied during acquisition and early consolidation, when preceding anodal tDCS, but not in the later training session. In contrast, anodal tDCS enhanced performance when applied in the later sessions following cathodal tDCS. Our results indicate that both anodal and cathodal tDCS can improve planning performance as quantified by the Tower of London test. Most importantly, these data demonstrate training-phase-specific effects of tDCS. We propose that excitability decreasing cathodal tDCS mediates its early beneficial effect through noise reduction of neuronal activity, whereas a further adaptive configuration of specific neuronal connections is supported by excitability enhancing anodal tDCS in the later training phase by enhanced efficacy of active connections. This gain of function was sustained in a follow-up 6 and 12 months after training. In conclusion, the specific coupling of stimulation and training phase interventions may support the treatment of cognitive disorders involving frontal lobe functions.
Tanaka S, Hanakawa T, Honda M, Watanabe K Enhancement of pinch force in the lower leg by anodal transcranial direct current stimulation. 2009 Exp Brain Res
Transcranial direct current stimulation (tDCS) is a procedure to polarize human brain. It has been reported that tDCS over the hand motor cortex transiently improves the performance of hand motor tasks. Here, we investigated whether tDCS could also improve leg motor functions. Ten healthy subjects performed pinch force (PF) and reaction time (RT) tasks using the left leg before, during and after anodal, cathodal or sham tDCS over the leg motor cortex. The anodal tDCS transiently enhanced the maximal leg PF but not RT during its application. Neither cathodal nor sham stimulation changed the performance. None of the interventions affected hand PF or RT, showing the spatial specificity of the effect of tDCS. These results indicate that motor performance of not only the hands but also the legs can be enhanced by anodal tDCS. tDCS may be applicable to the neuro-rehabilitation of patients with leg motor disability.
Jang SH, Ahn SH, Byun WM, Kim CS, Lee MY, Kwon YH The effect of transcranial direct current stimulation on the cortical activation by motor task in the human brain: an fMRI study. 2009 Neurosci. Lett.
We attempted to evaluate whether cortical activation resulting from hand movements is changed by transcranial direct current stimulation (tDCS) applied on the primary motor cortex for the hand in the human brain, using functional MRI (fMRI).
Loo C, Martin D, Pigot M, Arul-Anandam P, Mitchell P, Sachdev P Transcranial direct current stimulation priming of therapeutic repetitive transcranial magnetic stimulation: a pilot study. 2009 J ECT
Repetitive transcranial magnetic stimulation (rTMS) has been shown to be a safe treatment of depression, and research efforts are now largely focused on strategies to enhance its efficacy. Motor cortex experiments suggest that the effects of rTMS can be enhanced by first priming the same cortical area with transcranial direct current stimulation (tDCS). We explored this approach in depressed subjects.
Monte-Silva K, Kuo MF, Thirugnanasambandam N, Liebetanz D, Paulus W, Nitsche MA Dose-dependent inverted U-shaped effect of dopamine (D2-like) receptor activation on focal and nonfocal plasticity in humans. 2009 J. Neurosci.
The neuromodulator dopamine (DA) has multiple modes of action on neuroplasticity induction and modulation, depending on subreceptor specificity, concentration level, and the kind of stimulation-induced plasticity. To determine the dosage-dependent effects of D(2)-like receptor activation on nonfocal and focal neuroplasticity in the human motor cortex, different doses of ropinirole (0.125, 0.25, 0.5, and 1.0 mg), a D(2)/D(3) dopamine agonist, or placebo medication were combined with anodal and cathodal transcranial direct current stimulation (tDCS) protocols, which induce nonfocal plasticity, or paired associative stimulation (PAS, ISI of 10 or 25 ms), which generates focal plasticity, in healthy volunteers. D(2)-like receptor activation produced an inverted "U"-shaped dose-response curve on plasticity for facilitatory tDCS and PAS and for inhibitory tDCS. Here, high or low dosages of ropinirole impaired plasticity. However, no dose-dependent response effect of D(2)-like receptor activation was evident for focal inhibitory plasticity. In general, our study supports the assumption that modulation of D(2)-like receptor activity exerts dose-dependent inhibitory or facilitatory effects on neuroplasticity in the human motor cortex depending on the topographic specificity of plasticity.
Nitsche MA, Kuo MF, Karrasch R, Wachter B, Liebetanz D, Paulus W Serotonin affects transcranial direct current-induced neuroplasticity in humans. 2009 Biol. Psychiatry
Modulation of the serotonergic system affects long-term potentiation (LTP) and long-term depression (LTD), the likely neurophysiologic derivates of learning and memory formation, in animals and slice preparations. Serotonin-dependent modulation of plasticity has been proposed as an underlying mechanism for depression. However, direct knowledge about the impact of serotonin on neuroplasticity in humans is missing. Here we explore the impact of the serotonin reuptake blocker citalopram on plasticity induced by transcranial direct current stimulation (tDCS) in humans in a single-blinded, placebo-controlled, randomized crossover study.
Miranda PC, Faria P, Hallett M What does the ratio of injected current to electrode area tell us about current density in the brain during tDCS? 2009 Clin Neurophysiol
To examine the relationship between the ratio of injected current to electrode area (I/A) and the current density at a fixed target point in the brain under the electrode during transcranial direct current stimulation (tDCS).
Boggio PS, de Macedo EC, Schwartzman JS, Brunoni D, Teixeira MC, Fregni F Transcranial direct current stimulation: a novel approach to control hyperphagia in Prader-Willi syndrome. 2009 J. Child Neurol.
Hunter T, Sacco P, Nitsche MA, Turner DL Modulation of internal model formation during force field-induced motor learning by anodal transcranial direct current stimulation of primary motor cortex. 2009 J. Physiol. (Lond.)
Human subjects can quickly adapt and maintain performance of arm reaching when experiencing novel physical environments such as robot-induced velocity-dependent force fields. Using anodal transcranial direct current stimulation (tDCS) this study showed that the primary motor cortex may play a role in motor adaptation of this sort. Subjects performed arm reaching movement trials in three phases: in a null force field (baseline), in a velocity-dependent force field (adaptation; 25 N s m(-1)) and once again in a null force field (de-adaptation). Active or sham tDCS was directed to the motor cortex representation of biceps brachii muscle during the adaptation phase of the motor learning protocol. During the adaptation phase, the global error in arm reaching (summed error from an ideal trajectory) was similar in both tDCS conditions. However, active tDCS induced a significantly greater global reaching (overshoot) error during the early stage of de-adaptation compared to the sham tDCS condition. The overshoot error may be representative of the development of a greater predictive movement to overcome the expected imposed force. An estimate of the predictive, initial movement trajectory (signed error in the first 150 ms of movement) was significantly augmented during the adaptation phase with active tDCS compared to sham tDCS. Furthermore, this increase was linearly related to the change of the overshoot summed error in the de-adaptation process. Together the results suggest that anodal tDCS augments the development of an internal model of the novel adapted movement and suggests that the primary motor cortex is involved in adaptation of reaching movements of healthy human subjects.
Liebetanz D, Koch R, Mayenfels S, Konig F, Paulus W, Nitsche MA Safety limits of cathodal transcranial direct current stimulation in rats. 2009 Clin Neurophysiol
The aim of this rat study was to investigate the safety limits of extended transcranial direct current stimulation (tDCS). tDCS may be of therapeutic value in several neuro-psychiatric disorders. For its clinical applicability, however, more stable effects are required, which may be induced by intensified stimulations.
Bikson M, Datta A, Elwassif M Establishing safety limits for transcranial direct current stimulation. 2009 Clin Neurophysiol
Ben Taib NO, Manto M Trains of transcranial direct current stimulation antagonize motor cortex hypoexcitability induced by acute hemicerebellectomy. 2009 J. Neurosurg.
The cerebellum is a key modulator of motor cortex activity, allowing both the maintenance and fine-tuning of motor cortex discharges. One elemental defect associated with acute cerebellar lesions is decreased excitability of the contralateral motor cortex, which is assumed to participate in deficits in skilled movements and considered a major defect in motor cortex properties. In the present study, the authors assessed the effect of trains of anodal transcranial direct current stimulation (tDCS), which elicits polarity-dependent shifts in resting membrane potentials.
Stagg CJ, Best JG, Stephenson MC, O'Shea J, Wylezinska M, Kincses ZT, Morris PG, Matthews PM, Johansen-Berg H Polarity-sensitive modulation of cortical neurotransmitters by transcranial stimulation. 2009 J. Neurosci.
Transcranial direct current stimulation (tDCS) modulates cortical excitability and is being used for human studies more frequently. Here we probe the underlying neuronal mechanisms by measuring polarity-specific changes in neurotransmitter concentrations using magnetic resonance spectroscopy (MRS). MRS provides evidence that excitatory (anodal) tDCS causes locally reduced GABA while inhibitory (cathodal) stimulation causes reduced glutamatergic neuronal activity with a highly correlated reduction in GABA, presumably due to the close biochemical relationship between the two neurotransmitters.
Williams JA, Imamura M, Fregni F Updates on the use of non-invasive brain stimulation in physical and rehabilitation medicine. 2009 J Rehabil Med
Brain stimulation for the treatment of neuropsychiatric diseases has been used for more than 50 years. Although its development has been slow, current advances in the techniques of brain stimulation have improved its clinical efficacy. The use of non-invasive brain stimulation has significant advantages, such as not involving surgical procedures and having relatively mild adverse effects. In this paper we briefly review the use of 2 non-invasive brain stimulation techniques, repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), as therapeutic approaches in physical and rehabilitation medicine. We also compare the effects of non-invasive central nervous system stimulation with techniques of non-invasive peripheral electrical stimulation, in order to provide new insights for future developments. Although the outcomes of these initial trials include some conflicting results, the evidence supports that rTMS and tDCS might have a therapeutic value in different neurological conditions. Studies published within the last year have examined new approaches of stimulation, such as longer intensities of stimulation, new electrode sizes for tDCS, novel coils for stimulation of deeper areas, and new frequencies of stimulation for rTMS. These new approaches need to be tested in larger clinical trials in order to determine whether they offer significant clinical effects.
Nitsche MA, Boggio PS, Fregni F, Pascual-Leone A Treatment of depression with transcranial direct current stimulation (tDCS): a review. 2009 Exp. Neurol.
Major Depression Disorder (MDD) is usually accompanied by alterations of cortical activity and excitability, especially in prefrontal areas. These are reflections of a dysfunction in a distributed cortico-subcortical, bihemispheric network. Therefore it is reasonable to hypothesize that altering this pathological state with techniques of brain stimulation may offer a therapeutic target. Besides repetitive transcranial magnetic stimulation, tonic stimulation with weak direct currents (tDCS) modulates cortical excitability for hours after the end of stimulation, thus, it is a promising non-invasive therapeutic option. Early studies from the 1960s suggested some efficacy of DC stimulation to reduce symptoms in depression, but mixed results and development of psychotropic drugs resulted in an early abandonment of this technique. In the last years tDCS protocols have been optimized. Application of the newly developed stimulation protocols in patients with major depression has shown promise in few pilot studies. Further studies are needed to identify the optimal parameters of stimulation and the clinical and patient characteristics that may condition response to tDCS.
Murphy DN, Boggio P, Fregni F Transcranial direct current stimulation as a therapeutic tool for the treatment of major depression: insights from past and recent clinical studies. 2009 Curr Opin Psychiatry
Transcranial direct current stimulation (tDCS) is a noninvasive method of brain stimulation that has been increasingly tested for the treatment of neuropsychiatric disorders. It has useful characteristics, such as low cost, ease of use, reliable sham methodology, and relatively powerful effects on cortical excitability. Because of its potential to modulate cortical excitability noninvasively, tDCS has been tested for the treatment of depression for several decades. Therefore, we reviewed evidence on the use of tDCS for major depression examining evidence from past and recent tDCS studies. We also briefly compared tDCS with other techniques of neuromodulation, namely deep brain stimulation, vagal nerve stimulation, and transcranial magnetic stimulation; and suggest future directions for the use of tDCS in major depression.
Nitsche MA, Paulus W Noninvasive brain stimulation protocols in the treatment of epilepsy: current state and perspectives. 2009 Neurotherapeutics
In epileptic seizures, there is an enhanced probability of neuronal networks to fire synchronously at high frequency, initiated by a paroxysmal depolarisation shift. Reducing neuronal excitability is a common target of antiepileptic therapies. Beyond or in addition to pharmacological interventions, excitability-reducing brain stimulation is pursued as an alternative therapeutic approach. Hereby, noninvasive brain stimulation tools, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have gained increased interest as efficient tools to modulate cortical excitability and activity. In animal models, stimulation-induced cortical excitability diminution has been shown to be suited to reduce seizures. Clinical studies conducted to date, however, have shown mixed results. Reasons for this, as well as possible optimization strategies that might lead to more efficient future stimulation protocols, will be discussed.
Boggio PS, Fregni F, Valasek C, Ellwood S, Chi R, Gallate J, Pascual-Leone A, Snyder A Temporal lobe cortical electrical stimulation during the encoding and retrieval phase reduces false memories. 2009 PLoS ONE
A recent study found that false memories were reduced by 36% when low frequency repetitive transcranial magnetic stimulation (rTMS) was applied to the left anterior temporal lobe after the encoding (study) phase. Here we were interested in the consequences on a false memory task of brain stimulation throughout the encoding and retrieval task phases. We used transcranial direct current stimulation (tDCS) because it has been shown to be a useful tool to enhance cognition. Specifically, we examined whether tDCS can induce changes in a task assessing false memories. Based on our preliminary results, three conditions of stimulation were chosen: anodal left/cathodal right anterior temporal lobe (ATL) stimulation ("bilateral stimulation"); anodal left ATL stimulation (with a large contralateral cathodal electrode--referred as "unilateral stimulation") and sham stimulation. Our results showed that false memories were reduced significantly after the two active conditions (unilateral and bilateral stimulation) as compared with sham stimulation. There were no significant changes in veridical memories. Our findings show that false memories are reduced by 73% when anodal tDCS is applied to the anterior temporal lobes throughout the encoding and retrieval stages, suggesting a possible strategy for improving certain aspects of learning.
Bolognini N, Pascual-Leone A, Fregni F Using non-invasive brain stimulation to augment motor training-induced plasticity. 2009 J Neuroeng Rehabil
Therapies for motor recovery after stroke or traumatic brain injury are still not satisfactory. To date the best approach seems to be the intensive physical therapy. However the results are limited and functional gains are often minimal. The goal of motor training is to minimize functional disability and optimize functional motor recovery. This is thought to be achieved by modulation of plastic changes in the brain. Therefore, adjunct interventions that can augment the response of the motor system to the behavioural training might be useful to enhance the therapy-induced recovery in neurological populations. In this context, noninvasive brain stimulation appears to be an interesting option as an add-on intervention to standard physical therapies. Two non-invasive methods of inducing electrical currents into the brain have proved to be promising for inducing long-lasting plastic changes in motor systems: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). These techniques represent powerful methods for priming cortical excitability for a subsequent motor task, demand, or stimulation. Thus, their mutual use can optimize the plastic changes induced by motor practice, leading to more remarkable and outlasting clinical gains in rehabilitation. In this review we discuss how these techniques can enhance the effects of a behavioural intervention and the clinical evidence to date.
Ferrucci R, Bortolomasi M, Vergari M, Tadini L, Salvoro B, Giacopuzzi M, Barbieri S, Priori A Transcranial direct current stimulation in severe, drug-resistant major depression. 2009 J Affect Disord
Though antidepressant drugs are the treatment of choice for severe major depression, a number of patients do not improve with pharmacologic treatment. This study aimed to assess the effects of transcranial direct current stimulation (tDCS) in patients with severe, drug-resistant depression.
Nitsche MA, Kuo MF, Grosch J, Bergner C, Monte-Silva K, Paulus W D1-receptor impact on neuroplasticity in humans. 2009 J. Neurosci.
Dopamine improves learning and memory formation. The neurophysiological basis for these effects might be a focusing effect of dopamine on neuroplasticity: Accordingly, in humans L-dopa prolongs focal facilitatory plasticity, but turns nonfocal facilitatory plasticity into inhibition. Here we explore the impact of D(1) receptors on plasticity. Nonfocal plasticity was induced by transcranial direct current stimulation (tDCS), and focal plasticity by paired associative stimulation (PAS). Subjects received sulpiride, a D(2) antagonist, to increase the relative contribution of D(1) receptors to dopaminergic activity, combined sulpiride and L-dopa, to increase the relation of D(1)/D(2) activity further, or placebo medication. Under placebo, anodal tDCS and excitatory PAS (ePAS) increased motor cortex excitability. Cathodal tDCS and inhibitory PAS (iPAS) reduced it. Sulpiride abolished iPAS-induced inhibition, but not ePAS-generated facilitation, underlining the importance of D(1)-receptor activity for focal facilitatory neuroplasticity. Combining sulpiride with L-dopa reestablished iPAS-induced inhibition, but did not affect ePAS-induced plasticity. tDCS-induced plasticity, which was abolished by sulpiride in a former study, also recovered. Thus enhancing D(1) activity further relative to D(2) activity is relevant for facilitatory and inhibitory plasticity. However, comparison with former results show that an appropriate balance of D(1) and D(2) activity seems necessary to (1) consolidate the respective excitability modifications and (2) to elicit a focusing effect.
Brighina F, Palermo A, Fierro B Cortical inhibition and habituation to evoked potentials: relevance for pathophysiology of migraine. 2009 J Headache Pain
Dysfunction of neuronal cortical excitability has been supposed to play an important role in etiopathogenesis of migraine. Neurophysiological techniques like evoked potentials (EP) and in the last years non-invasive brain stimulation techniques like transcranial magnetic stimulation (TMS) and transcranial direct current stimulation gave important contribution to understanding of such issue highlighting possible mechanisms of cortical dysfunctions in migraine. EP studies showed impaired habituation to repeated sensorial stimulation and this abnormality was confirmed across all sensorial modalities, making defective habituation a neurophysiological hallmark of the disease. TMS was employed to test more directly cortical excitability in visual cortex and then also in motor cortex. Contradictory results have been reported pointing towards hyperexcitability or on the contrary to reduced preactivation of sensory cortex in migraine. Other experimental evidence speaks in favour of impairment of inhibitory circuits and analogies have been proposed between migraine and conditions of sensory deafferentation in which down-regulation of GABA circuits is considered the more relevant pathophysiological mechanism. Whatever the mechanism involved, it has been found that repeated sessions of high-frequency rTMS trains that have been shown to up-regulate inhibitory circuits could persistently normalize habituation in migraine. This could give interesting insight into pathophysiology establishing a link between cortical inhibition and habituation and opening also new treatment strategies in migraine.
Arul-Anandam AP, Loo C Transcranial direct current stimulation: a new tool for the treatment of depression? 2009 J Affect Disord
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that applies mild (typically 1-2 mA) direct currents via the scalp to enhance or diminish neuronal excitability. The technique has a dual function: on the one hand, it has been used to investigate the functions of various cortical regions; on the other, it has been used as an experimental treatment modality, most notably for Major Depressive Disorder (MDD). With the growing utility of tDCS in psychiatry, it is important from the vantage of safety and effectiveness to understand its underlying neurobiological mechanisms. In this respect, researchers have made significant progress in recent years, highlighting changes in resting membrane potential, spontaneous neuronal firing rates, synaptic strength, cerebral blood flow and metabolism subsequent to tDCS. We briefly review tDCS clinical trials for MDD, and then consider its mechanisms of action, identifying potential avenues for future research.
Tanaka S, Watanabe K [Transcranial direct current stimulation--a new tool for human cognitive neuroscience]. 2009 Brain Nerve
Transcranial direct current stimulation (tDCS) is a non-invasive procedure of cortical stimulation, in which weak direct currents are used to polarize target brain regions. Depending on the polarity of the stimulation, tDCS can increase (anodal tDCS) or decrease (cathodal tDCS) cortical excitability in the stimulated brain regions and thereby enable the investigation of the causal relationships between brain activity and behavior. Recently, tDCS has been increasingly used to investigate human cognitive and motor functions in both healthy volunteers and neurological patients. Although tDCS generally produces diffuse cortical stimulation over a period of time, it has several advantages over other brain-stimulation tools such as transcranial magnetic stimulation (TMS). First, since tDCS produces less artifacts such as acoustic noise and muscle twitching, it is more suitable for double-blind, sham-controlled studies and clinical applications. Second, tDCS is not very expensive and can be performed with compact equipment, it can be easily combined with ongoing projects in neuroscience and psychology laboratories. Third, the facilitation of motor and cognitive functions by anodal tDCS may have great potential for cognitive and motor enhancement, for example, to support learning in healthy volunteers and to expedite the rehabilitation process in neurological patients. Finally, thus far, seizure incidents have not been reported in tDCS studies, tDCS has thus become a complementary tool to TMS and occupies a unique position in current cognitive neuroscience.
Reis J, Schambra HM, Cohen LG, Buch ER, Fritsch B, Zarahn E, Celnik PA, Krakauer JW Noninvasive cortical stimulation enhances motor skill acquisition over multiple days through an effect on consolidation. 2009 Proc. Natl. Acad. Sci. U.S.A.
Motor skills can take weeks to months to acquire and can diminish over time in the absence of continued practice. Thus, strategies that enhance skill acquisition or retention are of great scientific and practical interest. Here we investigated the effect of noninvasive cortical stimulation on the extended time course of learning a novel and challenging motor skill task. A skill measure was chosen to reflect shifts in the task's speed-accuracy tradeoff function (SAF), which prevented us from falsely interpreting variations in position along an unchanged SAF as a change in skill. Subjects practiced over 5 consecutive days while receiving transcranial direct current stimulation (tDCS) over the primary motor cortex (M1). Using the skill measure, we assessed the impact of anodal (relative to sham) tDCS on both within-day (online) and between-day (offline) effects and on the rate of forgetting during a 3-month follow-up (long-term retention). There was greater total (online plus offline) skill acquisition with anodal tDCS compared to sham, which was mediated through a selective enhancement of offline effects. Anodal tDCS did not change the rate of forgetting relative to sham across the 3-month follow-up period, and consequently the skill measure remained greater with anodal tDCS at 3 months. This prolonged enhancement may hold promise for the rehabilitation of brain injury. Furthermore, these findings support the existence of a consolidation mechanism, susceptible to anodal tDCS, which contributes to offline effects but not to online effects or long-term retention.
Rosen AC, Ramkumar M, Nguyen T, Hoeft F Noninvasive transcranial brain stimulation and pain. 2009 Curr Pain Headache Rep
Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are two noninvasive brain stimulation techniques that can modulate activity in specific regions of the cortex. At this point, their use in brain stimulation is primarily investigational; however, there is clear evidence that these tools can reduce pain and modify neurophysiologic correlates of the pain experience. TMS has also been used to predict response to surgically implanted stimulation for the treatment of chronic pain. Furthermore, TMS and tDCS can be applied with other techniques, such as event-related potentials and pharmacologic manipulation, to illuminate the underlying physiologic mechanisms of normal and pathological pain. This review presents a description and overview of the uses of two major brain stimulation techniques and a listing of useful references for further study.
Koenigs M, Ukueberuwa D, Campion P, Grafman J, Wassermann E Bilateral frontal transcranial direct current stimulation: Failure to replicate classic findings in healthy subjects. 2009 Clin Neurophysiol
There has been no modern effort to replicate, further characterize, or quantify the dramatic effects on affect described in controlled studies from the 1960s using bilateral frontal electrodes with an extra-cephalic reference in a mixed group composed primarily of mildly depressed individuals. We performed a comprehensive, quantitative assessment of the effects of bifrontal TDCS on emotion in 21 healthy subjects.
Boggio PS, Khoury LP, Martins DC, Martins OE, de Macedo EC, Fregni F Temporal cortex direct current stimulation enhances performance on a visual recognition memory task in Alzheimer disease. 2009 J. Neurol. Neurosurg. Psychiatr.