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PubMed2006

Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation.

OBJECTIVE: Brain polarization in the form of transcranial direct current stimulation (tDCS), which influences motor function and learning processes, has been proposed as an adjuvant strategy to enhance training effects in Neurorehabilitation. Proper testing in Neurorehabilitation requires double-blind sham-controlled study designs. Here, we evaluated the effects of tDCS and sham stimulation (SHAM) on healthy subjects and stroke patients' self-report measures of attention, fatigue, duration of elicited sensations and discomfort. METHODS: tDCS or SHAM was in all cases applied over the motor cortex. Attention, fatigue, and discomfort were self rated by study participants using visual analog scales. Duration of perceived sensations and the ability to distinguish tDCS from Sham sessions were determined. Investigators questioning the patients were blind to the intervention type. RESULTS: tDCS and SHAM elicited comparably minimal discomfort and duration of sensations in the absence of differences in attention or fatigue, and could not be distinguished from SHAM by study participants nor investigators. CONCLUSIONS: Successful blinding of subjects and investigators and ease of application simultaneously with training protocols supports the feasibility of using tDCS in double-blind, sham-controlled randomized trials in clinical Neurorehabilitation. SIGNIFICANCE: tDCS could evolve into a useful tool, in addition to TMS, to modulate cortical activity in Neurorehabilitation.

Aged↗
PubMed2026

Dissociating behavioral, neural and experiential effects of prefrontal HD-tDCS during conflict resolution.

Inconsistent evidence regarding the cognitive effects of transcranial direct current stimulation (tDCS) highlights the need for more comprehensive approaches to assess its impact. This study aimed to investigate the effects of high-definition tDCS (HD-tDCS) on conflict resolution by combining behavioral, neural, and subjective experience measures. Sixty participants were randomly assigned to anodal, cathodal, or sham HD-tDCS groups and completed a 30-min flanker task. EEG was recorded during the first and last blocks (without stimulation), while stimulation was applied during the intermediate blocks of the task. Using a multidimensional methodological approach including Drift-Diffusion Modeling (DDM), EEG spectral analysis, Lempel-Ziv complexity, and Temporal Experience Tracing (TET), we assessed the cognitive, neural, and phenomenological effects of stimulation. Behavioral results indicated no significant improvements in reaction times or accuracy across the stimulation groups. Similarly, DDM parameters showed no effect of HD-tDCS on latent cognitive processes. However, EEG data revealed a significant reduction in neural complexity in the anodal group during resting-state, suggesting a stabilization or reorganization of neural dynamics. Subjective experience analysis identified two distinct clusters of task-related feelings, though time spent in these experiential states did not differ between groups. Interestingly, sensation of stimulation was significantly higher for anodal stimulation than sham when analyzed as a single dimension. Despite null behavioral effects, this study provides important insights into the neural and subjective responses to HD-tDCS and highlights the value of integrating complementary multidimensional approaches to better characterize brain stimulation effects. These findings contribute to the ongoing debate about the efficacy of tDCS in cognitive enhancement.

Humans↗
PubMed2026

Modulating sentence comprehension in people with aphasia through anodal tDCS: A double-blind randomized cross-over study.

This double-blind randomized cross-over study investigated the effects of perilesional anodal transcranial direct current stimulation (AtDCS) combined with speech-language therapy on sentence comprehension in eight individuals with chronic nonfluent agrammatic aphasia. The behavioral therapy consisted of an intensive comprehension treatment including drilling in sentence-to-picture matching and Mapping Therapy. Each participant underwent both the anodal tDCS and sham stimulation conditions (five received sham first followed by real stimulation, and the remaining three the reverse sequence), with each condition paired with the same behavioral treatment and separated by a four-month washout period. Stimulation was applied over the perilesional area (left BA6) for 20 min during daily 40-min therapy sessions over four consecutive weeks. Sentence comprehension was assessed with the RiComprendo battery and functional communication with the Communicative Effectiveness Index (CETI). Data were analyzed using paired t-tests, Bayesian analyses, and linear mixed-effects models to control for baseline performance and individual variability. Both stimulation conditions produced significant pre-to-post improvements in sentence comprehension, particularly for syntactically complex structures such as passives and center-embedded object relatives. However, gains were overall greater following AtDCS, as reflected in larger effect sizes, stronger Bayes factors, and a significant treatment effect in the mixed-effects models. Only the AtDCS condition yielded significant improvements in self-perceived comprehension abilities on the CETI. These findings suggest that AtDCS over perilesional cortical areas may boost the effects of traditional language therapy on sentence comprehension, supporting its feasibility and potential as an adjuvant intervention in post-stroke aphasia rehabilitation.

Humans↗
PubMed2004

Direct current stimulation over MT+/V5 modulates motion aftereffect in humans.

While there is strong evidence for the central role of the human MT+/V5 in motion processing, its involvement in motion adaptation is still the subject of debate. We used transcranial direct current stimulation (tDCS) to test whether MT+/V5 is part of the neural network involved in the long-term adaptation-induced motion after-effect in humans. It was found that both cathodal and anodal stimulation over MT+/V5 resulted in a significant reduction of the perceived motion after-effect duration, but had no effect on performance in a luminance-change-detection task used to determine attentional load during adaptation. Our control experiment excluded the possibility that the observed MT+/V5 stimulation effects were due to a diffused modulation of the early cortical areas, i.e. by the stimulation applied over MT+/V5. These results provide evidence that external modulation of neural excitability in human MT+/V5 affects the strength of perceived motion after-effect and support the involvement of MT+/V5 in motion adaptation processes.

Adaptation, Physiological↗
PubMed2005

How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain?

Transcranial direct current stimulation (tDCS) of the primary motor hand area (M1) can produce lasting polarity-specific effects on corticospinal excitability and motor learning in humans. In 16 healthy volunteers, O positron emission tomography (PET) of regional cerebral blood flow (rCBF) at rest and during finger movements was used to map lasting changes in regional synaptic activity following 10 min of tDCS (+/-1 mA). Bipolar tDCS was given through electrodes placed over the left M1 and right frontopolar cortex. Eight subjects received anodal or cathodal tDCS of the left M1, respectively. When compared to sham tDCS, anodal and cathodal tDCS induced widespread increases and decreases in rCBF in cortical and subcortical areas. These changes in rCBF were of the same magnitude as task-related rCBF changes during finger movements and remained stable throughout the 50-min period of PET scanning. Relative increases in rCBF after real tDCS compared to sham tDCS were found in the left M1, right frontal pole, right primary sensorimotor cortex and posterior brain regions irrespective of polarity. With the exception of some posterior and ventral areas, anodal tDCS increased rCBF in many cortical and subcortical regions compared to cathodal tDCS. Only the left dorsal premotor cortex demonstrated an increase in movement related activity after cathodal tDCS, however, modest compared with the relatively strong movement-independent effects of tDCS. Otherwise, movement related activity was unaffected by tDCS. Our results indicate that tDCS is an effective means of provoking sustained and widespread changes in regional neuronal activity. The extensive spatial and temporal effects of tDCS need to be taken into account when tDCS is used to modify brain function.

Adult↗
PubMed2004

Effect of transcranial DC sensorimotor cortex stimulation on somatosensory evoked potentials in humans.

OBJECTIVE: To study the after-effect of transcranial direct current stimulation (tDCS) over the sensorimotor cortex on the size of somatosensory evoked potentials (SEPs) in humans. METHODS: SEPs were elicited by electrical stimulation of right or left median nerve at the wrist before and after anodal or cathodal tDCS in 8 healthy subjects. tDCS was applied for 10 min to the left motor cortex at a current strength of 1 mA. RESULTS: Amplitudes of P25/N33, N33/P40 (parietal components) and P22/N30 (frontal component) following right median nerve stimulation were significantly increased for at least 60 min after the end of anodal tDCS, whereas P14/N20, N20/P25 (parietal components) and N18/P22 (frontal component) were unaffected. There was no effect on SEPs evoked by left median nerve stimulation. Cathodal tDCS had no effect on SEPs evoked from stimulation of either arm. CONCLUSIONS: Anodal tDCS over the sensorimotor cortex can induce a long-lasting increase in the size of ipsilateral cortical components of SEPs. SIGNIFICANCE: tDCS can modulate cortical somatosensory processing in humans and might be a useful tool to induce plasticity in cortical sensory processing.

Adult↗
PubMed2004

Direct current stimulation over V5 enhances visuomotor coordination by improving motion perception in humans.

The primary aim of this study was to determine the extent to which human MT+/V5, an extrastriate visual area known to mediate motion processing, is involved in visuomotor coordination. To pursue this we increased or decreased the excitability of MT+/V5, primary motor, and primary visual cortex by the application of 7 min of anodal and cathodal transcranial direct current stimulation (tDCS) in healthy human subjects while they were performing a visuomotor tracking task involving hand movements. The percentage of correct tracking movements increased specifically during and immediately after cathodal stimulation, which decreases cortical excitability, only when V5 was stimulated. None of the other stimulation conditions affected visuomotor performance. We propose that the improvement in performance caused by cathodal tDCS of V5 is due to a focusing effect on to the complex motion perception conditions involved in this task. This hypothesis was proven by additional experiments: Testing simple and complex motion perception in dot kinetograms, we found that a diminution in excitability induced by cathodal stimulation improved the subject's perception of the direction of the coherent motion only if this was presented among random dots (complex motion perception), and worsened it if only one motion direction was presented (simple movement perception). Our data suggest that area V5 is critically involved in complex motion perception and identification processes important for visuomotor coordination. The results also raise the possibility of the usefulness of tDCS in rehabilitation strategies for neurological patients with visuomotor disorders.

Adult↗
PubMed2004

Outlasting excitability shifts induced by direct current stimulation of the human brain.

tDCS appears to be a promising tool in neuroplasticity research with some perspectives in clinical neurophysiology. It is closely related to modulation of cortical excitability and activity which are key mechanisms for modulating neuroplasticity. Long-term potentiation and long-term depression-like effects have been shown to be involved in learning processes in animal studies so far. Stimulation with weak direct currents is capable of inducing stimulation-polarity-dependent, prolonged, diminutions or elevations of cortical activity and excitability, most probably elicited by a hyper- or depolarisation of resting membrane potentials. Moreover, these modulations are functionally important, since they affect learning processes and epileptic activity. Here excitability changes have been accomplished in the human by non-invasive transcranial direct current stimulation (tDCS). They share some important features with these well-known neuroplastic changes: The duration of the effects depends on stimulation duration and intensity, they are of intracortical origin, and the prolonged effects depend on NMDA-receptor activity. Thus, this technique is a promising method in the field of neuroplastic research in animals and humans and could evolve as a therapeutic tool in some neuro-psychiatric disorders which benefit from modulation of cortical excitability.

Brain↗
PubMed2006

Go-no-go task performance improvement after anodal transcranial DC stimulation of the left dorsolateral prefrontal cortex in major depression.

BACKGROUND: We recently showed that repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) can affect the performance in an affective go-no-go (AGN) task. We aimed to extend this previous investigation testing whether one session of anodal transcranial direct current stimulation (tDCS) of the left DLPFC, as compared with anodal occipital and sham tDCS, affects this AGN task performance. METHODS: Twenty-six patients with major depression were randomized to receive anodal tDCS of the left DLPFC, occipital cortex or sham tDCS (the cathode electrode was placed over the frontopolar area for the three conditions). An AGN task was performed immediately before and after treatment. Performance changes (pre and post-treatment) were compared across groups of treatment and correlated with Hamilton Depression Rating Scale (HDRS) score changes. RESULTS: The results show that anodal stimulation of the left DLPFC was the only condition that induced a significant improvement in task performance as shown by the increase in the number of correct responses. In addition, this effect was specific for figures with positive emotional content. This performance enhancement was not correlated with mood changes after 10 days of tDCS treatment. LIMITATIONS: Although the effects of tDCS are less focal than rTMS, it can induce a longer and stronger modulation of cortical excitability. CONCLUSIONS: Our findings suggest that left DLPFC activity is associated with positive emotional processing, confirming and extending results of previous studies that associated right DLPFC and orbito-frontal cortex activity with emotional processing. Furthermore the effects of tDCS on mood and cognition seem to be independent in major depression. These lines of evidence together shed light on the neural circuitry involved with emotional processing in major depression.

Adult↗
PubMed2005

Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke.

Stroke is a leading cause of adult motor disability. Despite recent progress, recovery of motor function after stroke is usually incomplete. This double blind, Sham-controlled, crossover study was designed to test the hypothesis that non-invasive stimulation of the motor cortex could improve motor function in the paretic hand of patients with chronic stroke. Hand function was measured using the Jebsen-Taylor Hand Function Test (JTT), a widely used, well validated test for functional motor assessment that reflects activities of daily living. JTT measured in the paretic hand improved significantly with non-invasive transcranial direct current stimulation (tDCS), but not with Sham, an effect that outlasted the stimulation period, was present in every single patient tested and that correlated with an increment in motor cortical excitability within the affected hemisphere, expressed as increased recruitment curves (RC) and reduced short-interval intracortical inhibition. These results document a beneficial effect of non-invasive cortical stimulation on a set of hand functions that mimic activities of daily living in the paretic hand of patients with chronic stroke, and suggest that this interventional strategy in combination with customary rehabilitative treatments may play an adjuvant role in neurorehabilitation.

Activities of Daily Living↗
PubMed2006

Dopaminergic modulation of long-lasting direct current-induced cortical excitability changes in the human motor cortex.

Dopaminergic mechanisms participate in N-methyl-D-aspartate (NMDA) receptor-dependent neuroplasticity, as animal experiments have shown. This may be similar in humans, where dopamine influences learning and memory. We tested the role of dopamine in human cortical neuroplasticity. Changes of excitability were induced by transcranial direct current stimulation (tDCS). D2 receptor blocking by sulpiride abolished the induction of after-effects nearly completely. D1 activation alone in the presence of D2 receptor blocking induced by co-administration of sulpiride and pergolide did not re-establish the excitability changes induced by tDCS. This suggests that D2 receptors play a major supporting role in inducing neuroplasticity in the human motor cortex. Enhancement of D2 and, to a lesser degree, D1 receptors by pergolide consolidated tDCS-generated excitability diminution until the morning after stimulation. The readiest explanation for this pattern of results is that D2 receptor activation has a consolidation-enhancing effect on tDCS-induced changes of excitability in the human cortex. The results of this study underscore the importance of the dopaminergic system for human neuroplasticity, suggest a first pharmacological add-on mechanism to prolong the excitability-diminishing effects of cathodal tDCS for up to 24 h after stimulation, and thus render the application of tDCS practicable in diseases displaying enhanced cortical excitability, e.g. migraine and epilepsy.

Adult↗
PubMed2026

The efficacy of non-invasive brain stimulation interventions in obsessive-compulsive disorder management: A network meta-analysis of randomized controlled trials.

Non-invasive brain stimulation (NIBS) has been widely used as an alternative treatment for obsessive compulsive disorder (OCD). However, the most effective NIBS parameters are unclear. To compare the efficacy of NIBS in OCD. We conducted a systematic review and network meta-analyses (NMA) to combine direct and indirect comparisons of NIBS.Systematic searches were conducted in Cochrane CENTRAL, EMBASE, PubMed, and Web of Science from inception to June 20, 2025. Forty-two randomized sham-controlled trials (n = 1456) were included. All statistical analyses were conducted with R statistical software. Bayesian NMAs mainly using the BUGSnet package and gemtc package. Five NIBS protocols produced statistically significant reductions in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores compared with sham stimulation: high-frequency rTMS over the FzFCz (Hf-rTMS-FzFCz; MD -11.77, 95% CrI -20.62 to -3.09), low-frequency rTMS over F3F4 (Lf-rTMS-F3F4; MD -9.93, 95% CrI -18.07 to -1.65), low-frequency rTMS over FCz (Lf-rTMS-FCz; MD -3.25, 95% CrI -6.06 to -0.40), high-frequency deep TMS over FzFC (Hf-dTMS-FzFC; MD -6.48, 95% CrI -12.32 to -0.50), and 2 mA anodal tDCS over F3 with cathodal over Fp2 (MD -9.34, 95% CrI -16.01 to -3.03).For secondary outcomes, high-frequency deep rTMS over FzFCz produced the largest reduction both in depressive symptoms (SMD -1.24, 95% CrI -1.92 to -0.55) and anxiety scores (SMD -1.88, 95% CrI -2.62 to -1.11), but had no effect on Clinical Global Impression-Severity (CGI-S) scores.Specific NIBS protocols are safe and effective adjunctive treatments for OCD, with promising yet inconclusive improvements in comorbid depressive symptoms. Further high-quality, head-to-head trials are needed.

Humans↗
PubMed2006

Visual evoked potentials modulation during direct current cortical polarization.

Transcranial direct current stimulation (tDCS) at low intensity induces changes in cortical excitability that persist after polarization ends. The effects of anodal and cathodal polarization remain controversial. We studied changes in visual evoked potentials (VEPs) during and after anodal and cathodal tDCS by applying, in healthy volunteers, 1 mA polarization through surface electrodes placed over the occipital scalp (polarizing) and over the anterior or posterior neck-base (reference). We compared tDCS applied at two durations, 3 and 10 min and both polarities. We assessed VEP-P100 latencies and amplitudes in response to pattern-reversal checkerboard stimuli before, during, and after polarization. Anodal polarization reduced VEP-P100 amplitude whereas cathodal polarization significantly increased amplitude but both polarities left latency statistically unchanged. These changes persisted for some minutes after polarization ended depending on the duration of tDCS and on the contrast level of visual stimuli. tDCS-induced changes in VEPs seem to depend on the duration of polarization and type of visual stimuli used. The effects induced on visual cortical neurones during polarization are more consistent than the aftereffects. Studying these changes during polarization may therefore improve our understanding of these phenomena.

Adult↗
PubMed2004

Catecholaminergic consolidation of motor cortical neuroplasticity in humans.

Amphetamine, a catecholaminergic re-uptake-blocker, is able to improve neuroplastic mechanisms in humans. However, so far not much is known about the underlying physiological mechanisms. Here, we study the impact of amphetamine on NMDA receptor-dependent long-lasting excitability modifications in the human motor cortex elicited by weak transcranial direct current stimulation (tDCS). Amphetamine significantly enhanced and prolonged increases in anodal, tDCS-induced, long-lasting excitability. Under amphetamine premedication, anodal tDCS resulted in an enhancement of excitability which lasted until the morning after tDCS, compared to approximately 1 h in the placebo condition. Prolongation of the excitability enhancement was most pronounced for long-term effects; the duration of short-term excitability enhancement was only slightly increased. Since the additional application of the NMDA receptor antagonist dextromethorphane blocked any enhancement of tDCS-driven excitability under amphetamine, we conclude that amphetamine consolidates the tDCS-induced neuroplastic effects, but does not initiate them. The fact that propanolol, a beta-adrenergic antagonist, diminished the duration of the tDCS-generated after-effects suggests that adrenergic receptors play a certain role in the consolidation of NMDA receptor-dependent motor cortical excitability modifications in humans. This result may enable researchers to optimize neuroplastic processes in the human brain on the rational basis of purpose-designed pharmacological interventions.

Adult↗
PubMed1996

The effect of current direction induced by transcranial magnetic stimulation on the corticospinal excitability in human brain.

Evoked spinal cord potentials (ESCPs) from the cervical epidural space and motor evoked potentials (MEPs) from the hand muscles were recorded simultaneously in 6 subjects following transcranial magnetic stimulation in two different coil orientations on motor cortex. The onset latency of the MEPs was approximately 1 ms shorter when the induced current flowed in a latero-medial direction (L-M stimulation) on the motor cortex as compared to a postero-anterior direction (P-A stimulation). Hence, L-M stimulation elicited an earlier component of the ESCPs than that induced by P-A stimulation. During general anesthesia with Sevoflurane, only the first component of the ESCPs could be elicited routinely following L-M stimulation. In contrast, all components of the ESCPs were dramatically attenuated following P-A stimulation. Moreover, first component latency of the ESCPs induced by L-M stimulation was almost the same as that induced by transcranial anodal electrical stimulation. These results suggest that if the induced current following transcranial magnetic stimulation flows in a latero-medial direction on motor cortex, it preferentially stimulates the corticospinal tract non-synaptically (producing a D-wave). However, if the induced current flows in a postero-anterior direction, it preferentially stimulates the corticospinal tract trans-synaptically (producing I-waves). Therefore, the direction of magnetically induced current is crucial in determining corticospinal excitability in the human brain.

Adult↗
PubMed1994

Differentiation of sensorimotor neuronal structures responsible for induction of motor evoked potentials, attenuation in detection of somatosensory stimuli, and induction of sensation of movement by mapping of optimal current directions.

Transcranial magnetic stimulation (TMS) of the sensorimotor cortex can evoke motor evoked potentials (MEPs), attenuation in detection of somatosensory stimuli (ADSS), and sensation of movement (SOM) referred to the same body part. In this study we tried to differentiate the substrates responsible for these effects. In 6 normal volunteers, TMS was applied with a nearly monopolar Dantec stimulator and a butterfly coil. Optimal scalp location and current direction were determined for induction of MEPs in abductor pollicis brevis (APB), first dorsal interosseous (FDI), and adductor digiti minimi (ADM); SOM in digits 2 and 5 in an ischemically paralyzed hand; and ADSS applied to digits 2 and 5. All 3 muscles' MEPs and SOM and ADSS in both digits were optimally activated from a single scalp position. In all subjects, optimal current directions for MEPs pointed anteriorly; those for ADSS and SOM pointed posteriorly. Optimal current directions showed the same progression in all subjects for MEPs (ADM, FDI, and APB from antero-lateral to antero-medial), ADSS (digit 5 postero-medial, 2 postero-lateral), and SOM (digit 1 through 5 postero-lateral to postero-medial). We conclude that neuronal networks targeting corticospinal neurons responsible for MEPs are different from those leading to SOM and ADSS (which could not be differentiated).

Adult↗
PubMed1999

Intracortical inhibition after paired transcranial magnetic stimulation depends on the current flow direction.

OBJECTIVES: To assess whether cortico-cortical inhibition (CCI) induced by paired-pulse transcranial magnetic stimulation (TMS) is influenced by 'preferential' or 'non-preferential' activation of the motor cortex. METHODS: Paired-pulse TMS (conditioning-test paradigm with interstimulus intervals of 2-5 ms) with a round coil centered over the vertex was performed in 10 normal subjects using opposite current flow directions. The amount of CCI in the opponens pollicis and first dorsal interosseus muscles was determined. RESULTS: When a clockwise current was induced in the brain (side A of the coil uppermost) a 'preferential' activation of the left hemisphere (right hand muscles) was observed, but the suppression of the test response by the conditioning stimulus (i.e. the CCI) was significantly greater in the left hand muscles. The situation was reversed when an anticlockwise current (side B of the coil uppermost) was induced in the brain. These effects occurred independently of the interstimulus interval, or of the absolute conditioning stimulus strength. CONCLUSIONS: CCI is more effective in the 'non-preferentially' stimulated hemisphere, and the neural elements generating the indirect I3 wave are more sensitive to intracortical inhibition than those generating the I1 wave.

Adult↗