Contralateral and ipsilateral motor effects after transcranial direct current stimulation

Transcranial direct current stimulation over the left motor area influenced both contralateral and ipsilateral finger sequence movements in seven healthy adults. Effects for the two hands were reversed: anodal stimulation improved right-hand performance significantly more than cathodal stimulation, whereas cathodal stimulation improved left-hand performance significantly more than anodal stimulation. The results show that stimulating a motor region directly, or indirectly by modulating activity in the homologous region on the opposite hemisphere, can affect motor skill acquisition, presumably by facilitating effective synaptic connectivity. This outcome provides evidence for the role of interhemispheric inhibition in corticomotor functioning, and also has implications for treatment methods aimed at facilitating motor recovery after stroke.     

Failure of cathodal direct current stimulation to improve fine motor control in musician's dystonia

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. © 2009 Movement Disorder Society     

Parietal transcranial direct current stimulation modulates primary motor cortex excitability

The posterior parietal cortex is part of the cortical network involved in motor learning and is structurally and functionally connected with the primary motor cortex (M1). Neuroplastic alterations of neuronal connectivity might be an important basis for learning processes. These have however not been explored for parieto‐motor connections in humans by transcranial direct current stimulation (tDCS). Exploring tDCS effects on parieto‐motor cortical connectivity might be functionally relevant, because tDCS has been shown to improve motor learning. We aimed to explore plastic alterations of parieto‐motor cortical connections by tDCS in healthy humans. We measured neuroplastic changes of corticospinal excitability via motor evoked potentials (MEP) elicited by single‐pulse transcranial magnetic stimulation (TMS) before and after tDCS over the left posterior parietal cortex (P3), and 3 cm posterior or lateral to P3, to explore the spatial specificity of the effects. Furthermore, short‐interval intracortical inhibition/intracortical facilitation (SICI/ICF) over M1, and parieto‐motor cortical connectivity were obtained before and after P3 tDCS. The results show polarity‐dependent M1 excitability alterations primarily after P3 tDCS. Single‐pulse TMS‐elicited MEPs, M1 SICI/ICF at 5 and 7 ms and 10 and 15 ms interstimulus intervals (ISIs), and parieto‐motor connectivity at 10 and 15 ms ISIs were all enhanced by anodal stimulation. Single pulse‐TMS‐elicited MEPs, and parieto‐motor connectivity at 10 and 15 ms ISIs were reduced by cathodal tDCS. The respective corticospinal excitability alterations lasted for at least 120 min after stimulation. These results show an effect of remote stimulation of parietal areas on M1 excitability. The spatial specificity of the effects and the impact on parietal cortex–motor cortex connections suggest a relevant connectivity‐driven effect.     

Acute effects of spaced cathodal transcranial direct current stimulation in drug resistant focal epilepsies

ObjectiveTo evaluate the safety and temporal dynamic of the antiepileptic effect of spaced transcranial direct current stimulation (tDCS) in different focal epilepsies.MethodsCathodal tDCS with individual electrode placement was performed in 15 adults with drug resistant focal epilepsy. An amplitude of 2 mA was applied twice for 9 minutes, with an interstimulation interval of 20 minutes. Tolerability was assessed via the Comfort Rating Questionnaire and the frequency of interictal epileptiform discharges (IEDs) was sequentially compared between the 24 hours before and after tDCS.ResultsTDCS led to a significant reduction in the total number of IEDs/24 h by up to 68% (mean ± SD: −30.4 ± 21.1%, p = 0.001) as well as in seizure frequency (p = 0.041). The maximum IED reduction was observed between the 3rd and 21st hour after stimulation. Favorable clinical response was associated with structural etiology and clearly circumscribed epileptogenic foci but did not differ between frontal and temporal epilepsies. Overall, the tDCS treatment was well tolerated and did not lead to severe adverse events.ConclusionsThe spaced stimulation approach proved to be safe and well-tolerated in patients with drug-resistant unifocal epilepsies, leading to sustained IED and seizure frequency reduction.SignificanceSpaced tDCS induces mediate antiepileptic effects with promising therapeutic potential.     

Safety limits of cathodal transcranial direct current stimulation in rats

ObjectiveThe 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.MethodsFifty-eight rats received single cathodal stimulations at 1–1000 μA for up to 270 min through an epicranial electrode (3.5 mm²). Histological evaluation (H&E) was performed 48 h later. A threshold estimate was calculated from volumes of DC-induced lesions.ResultsBrain lesions occurred at a current density of 142.9 A/m² for durations greater than 10 min. For current densities between 142.9 and 285.7 A/m², lesion size increased linearly with charge density; with a calculated zero lesion size intercept of 52400 C/m². Brains stimulated below either this current density or charge density threshold, including stimulations over 5 consecutive days, were morphologically intact.ConclusionThe experimentally determined threshold estimate is two orders of magnitude higher than the charge density currently applied in humans (171–480 C/m²). In relation to transcranial DC stimulation in humans the rat epicranial electrode montage may provide for an additional safety margin.SignificanceAlthough these results cannot be directly transferred to humans, they encourage the development intensified tDCS protocols. Further animal studies are required, before such protocols can be applied in humans.     

Meta-analysis of the effects of transcranial direct current stimulation on inhibitory control

BackgroundInhibitory control refers to a central cognitive capacity involved in the interruption and correction of actions. Dysfunctions in these cognitive control processes have been identified as major maintaining mechanisms in a range of mental disorders such as ADHD, binge eating disorder, obesity, and addiction. Improving inhibitory control by transcranial direct current stimulation (tDCS) could ameliorate symptoms in a broad range of mental disorders.ObjectiveThe primary aim of this pre-registered meta-analysis was to investigate whether inhibitory control can be improved by tDCS in healthy and clinical samples. Additionally, several moderator variables were investigated.MethodsA comprehensive literature search was performed on PubMed/MEDLINE database, Web of Science, and Scopus. To achieve a homogenous sample, only studies that assessed inhibitory control in the go-/no-go (GNG) or stop-signal task (SST) were included, yielding a total of 75 effect sizes from 45 studies.ResultsResults of the meta-analysis indicate a small but significant overall effect of tDCS on inhibitory control (g = 0.21) which was moderated by target and return electrode placement as well as by the task. The small effect size was further reduced after correction for publication bias.ConclusionBased on the studies included, our meta-analytic approach substantiates previously observed differences between brain regions, i.e., involvement of the right inferior frontal gyrus (rIFG) vs. the right dorsolateral prefrontal cortex (rDLPFC) in inhibitory control. Results indicate a small moderating effect of tDCS on inhibitory control in single-session studies and highlight the relevance of technical and behavioral parameters.     

Influence of pulse configuration and direction of coil current on excitatory effects of magnetic motor cortex and nerve stimulation.

This paper describes the influence of pulse configuration and current direction on the excitation of the hand-associated motor cortex and the median nerve by magnetic stimulation. Monophasic and biphasic current pulses with the same peak rise time of 80 micros and a maximum rate of current change (dI/dt) were discharged through an eight-shaped coil of the stimulator used (Dantec MagPro). Two current directions with opposite orientation in the coil axis were studied. FINDINGS: (1) for both, cortex and nerve stimulation, biphasic stimuli were more effective and elicited compound muscle action potentials (CMAPs) with lower thresholds and larger amplitudes. (2) Using biphasic pulses the direction of the currents in the first phase of the pulse did not influence the CMAP amplitude. (3) Using monophasic pulses induced currents oriented postero-anteriorly in the motor cortex or orthodromically along the nerve axis elicited larger CMAPs than currents in the opposite orientation. (4) Pulse configuration did not influence the CMAP-latencies and by this the stimulation site (cortex, nerve). CONCLUSION: Monophasic stimuli are useful to investigate excitation effects which are dependent on the current direction. The application of biphasic stimuli with their stronger excitation effects might be advantageous when patients with high cortical thresholds or deep lying nerves shall be investigated.     

Unihemispheric concurrent dual‐site cathodal transcranial direct current stimulation: the effects on corticospinal excitability

We aimed to assess the effects of concurrent cathodal transcranial direct current stimulation (c‐tDCS) of two targets in a hemisphere, termed unihemispheric concurrent dual‐site cathodal tDCS (c‐tDCS_UHCDS), on the size of M1 corticospinal excitability and its lasting effect. Secondary aims were to identify the mechanisms behind the efficacy of c‐tDCS_UHCDS and to evaluate the side effects of this new technique. Twelve healthy volunteers received 20 min c‐tDCS under five conditions in a random order: M1 c‐tDCS, c‐tDCS_UHCDS of M1–dorsolateral prefrontal cortex (DLPFC), M1–primary sensory cortex (S1), M1–primary visual cortex (V1) and sham. The M1 corticospinal excitability of the first dorsal interossei muscle was assessed before, immediately after, and 30 min, 60 min and 24 h after the interventions. Short‐interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were also assessed, using a paired‐pulse paradigm. Compared to conventional M1 c‐tDCS, corticospinal excitability significantly increased following c‐tDCS_UHCDS of M1‐DLPFC and M1‐V1 for up to 24 h (P = 0.001). Significant increases in ICF were observed following c‐tDCS_UHCDS of M1‐DLPFC (P = 0.005) and M1‐V1 (P = 0.002). Compared to baseline values, ICF and SICI increased significantly at T₆₀ (P < 0.001) and T_24 h (P < 0.001) following the concurrent c‐tDCS of M1 and V1. Sham c‐tDCS_UHCDS did not induce any significant alteration. The corticospinal excitability increase was mainly accompanied by ICF increase, which indirectly indicates the activity of glutamergic mechanisms. The findings may help us to more fully understand the brain function and develop future motor learning studies. No significant excitability change induced by sham c‐tDCS_UHCDS suggests that there is no placebo effect associated with this new tDCS technique.     

Long lasting effects of transcranial direct current stimulation on motor imagery

Transcranial magnetic stimulation (TMS) was employed to probe the modulatory effects of transcranial direct current stimulation of motor cortex on motor evoked responses (MEPs) produced during motor imagery. MEP amplitudes at rest and during motor imagery were assessed before and for a period of 60 min after transcranial direct current stimulation (tDCS) applied over the primary motor cortex at 1 mA for 5 min. Cathodal stimulation induced a decrease of about 30% of MEP amplitude at rest and a 50% reduction of MEP size during imagery. Ten minutes after tDCS, MEPs at rest returned to baseline values while MEPs during motor imagery were suppressed for up to 30 min. No changes in MEP amplitude during imagery were found after anodal stimulation. tDCS could represent a powerful tool to modulate the excitability of motor areas involved in mental practice and motor imagery.     

Maturation of inhibitory and excitatory motor cortex pathways in children

Objective

To study intracortical inhibition and facilitation with paired-pulse transcranial magnetic stimulation in children, adolescents and adults. Methods: Paired-pulse transcranial magnetic stimulation (interstimulus intervals (ISI): 1, 3, 5, 10 and 20 ms) was applied over the primary motor cortex (M1) in 30 healthy subjects (range 6–30 years, median age 15 years and 8 months, SD 7,9) divided in three groups: adults (? 18 years), adolescents (> 10 and < 18 years) and children (? 10 years). Results: We observed significantly less intracortical inhibition (SICI) in children’s M1 compared to that of adults. Adolescents showed significantly less SICI at the 5 ms interval than did adults. No significant differences were apparent in intracortical facilitation (ICF). Conclusion: We postulate that, as in adults, the maturing M1 possesses horizontal glutamatergic cross-links that represent the neuronal substrate of excitatory intracortical pathways. GABAergic interneurons, the neuronal substrate of inhibitory intracortical pathways, mature between childhood and adulthood. Reduced GABAergic inhibition may facilitate neuronal plasticity and motor learning in children.     

Somatosensory and transcranial direct current stimulation effects on manual dexterity and motor cortex function: A metaplasticity study

BackgroundNon-invasive neuromodulation may provide treatment strategies for neurological deficits affecting movement, such as stroke. For example, weak electrical stimulation applied to the hand by wearing a “mesh glove” (MGS) can transiently increase primary motor cortex (M1) excitability. Conversely, transcranial direct current stimulation with the cathode over M1 (c-tDCS) can decrease corticomotor excitability.Objective/Hypothesis: We applied M1 c-tDCS as a priming adjuvant to MGS and hypothesised metaplastic effects would be apparent in improved motor performance and modulation of M1 inhibitory and facilitatory circuits.MethodsSixteen right-handed neurologically healthy individuals participated in a repeated measures cross-over study; nine minutes of sham- or c-tDCS followed by 30 min of suprasensory threshold MGS. Dexterity of the non-dominant (left) hand was assessed using the grooved pegboard task, and measures of corticomotor excitability, intracortical facilitation, short-latency afferent inhibition (SAI), short-interval intracortical inhibition (SICI), and SAI in the presence of SICI (SAIxSICI), were obtained at baseline, post-tDCS, and 0, 30 and 60 min post-MGS.ResultsThere was a greater improvement in grooved pegboard completion times with c-tDCS primed MGS than sham + MGS. There was also more pronounced disinhibition of SAI. However, disinhibition of SAI in the presence of SICI was less and rest motor threshold higher compared to sham + MGS.ConclusionsThe results indicate a metaplastic modulation of corticomotor excitability with c-tDCS primed MGS. Further studies are warranted to determine how various stimulation approaches can induce metaplastic effects on M1 neuronal circuits to boost functional gains obtained with motor practice.     

Task-specific facilitation of cognition by cathodal transcranial direct current stimulation of the cerebellum

A role for the cerebellum in cognition is controversial, but it is a view that is becoming increasingly popular. The aim of the current study was to investigate this issue using transcranial Direct Current Stimulation (tDCS) during two cognitive tasks that require comparable motor skills, but different levels of working memory and attention. Three groups of twenty-two participants each performed the Paced Auditory Serial Addition Task (PASAT) and a novel variant of this task called the Paced Auditory Serial Subtraction Task (PASST), together with a verb generation task and its two controls, before and after the modulation of cortico-cerebellar connectivity using anodal or cathodal tDCS over the cerebellum. Participants' performance in the difficult PASST task significantly improved after cathodal stimulation compared to sham or anodal stimulation. Improvement in the easier PASAT was equal across all three stimulation conditions. Improvement in verbal response latencies were also greatest during the PASST task after cathodal stimulation, compared to sham and anodal stimulation, and became less variable. Results for the verb generation task complimented those for the PASST, such that the rate and consistency of participants' verbal responses were facilitated by cathodal stimulation, compared to sham and anodal stimulation. These findings suggest that DC stimulation over the right cerebellum affects working memory and attention differently depending on task difficulty. They support a role for the cerebellum in cognitive aspects of behaviour, whereby activity in the prefrontal cortex is likely dis-inhibited by cathodal tDCS stimulation over the right cerebellar cortex, which normally exerts an overall inhibitory tone on the cerebral cortex. We speculate that the cerebellum is capable of releasing cognitive resources by dis-inhibition of prefrontal regions of cerebral cortex, enhancing performance when tasks become demanding.     

Anodal vs cathodal stimulation of motor cortex: a modeling study.

OBJECTIVE: To explore the effects of electrical stimulation performed by an anode, a cathode or a bipole positioned over the motor cortex for chronic pain management. METHODS: A realistic 3D volume conductor model of the human precentral gyrus (motor cortex) was used to calculate the stimulus-induced electrical field. The subsequent response of neural elements in the precentral gyrus and in the anterior wall and lip of the central sulcus was simulated using compartmental neuron models including the axon, soma and dendritic trunk. RESULTS: While neural elements perpendicular to the electrode surface are preferentially excited by anodal stimulation, cathodal stimulation excites those with a direction component parallel to its surface. When stimulating bipolarly, the excitation of neural elements parallel to the bipole axis is additionally facilitated. The polarity of the contact over the precentral gyrus determines the predominant response. Inclusion of the soma-dendritic model generally reduces the excitation threshold as compared to simple axon model. CONCLUSIONS: Electrode polarity and electrode position over the precentral gyrus and central sulcus have a large and distinct influence on the response of cortical neural elements to stimuli. SIGNIFICANCE: Modeling studies like this can help to identify the effects of electrical stimulation on cortical neural tissue, elucidate mechanisms of action and ultimately to optimize the therapy.     

Effect of fatiguing maximal voluntary contraction on excitatory and inhibitory responses elicited by transcranial magnetic motor cortex stimulation

Vertex transcranial magnetic stimulation (TMS) elicited tibialis anterior motor evoked potentials (MEPs) and silent periods (SPs) that were recorded during and following isometric maximal volitional contraction (MVC). During MVC in 6 healthy subjects, MEP amplitudes in the exercised muscle showed an increasing trend from an initial value of 4539 ± 809 μV (mean ± SE) to 550 ± 908 μV (P < 0.13) while force and EMG decreased (P < 0.01). Also, SP duration increased from 165 ± 37 ms to 231 ± 32 ms (P < 0.01). Thus, during a fatiguing MVC both excitatory and inhibitory TMS-induced responses increased. TMS delivered during repeated brief 10% MVC contractions before and after a fatiguing MVC in 5 subjects, showed no change in MEP amplitude but SP duration was prolonged after MVC. This SP prolongation was focal to the exercised muscle. Silent periods recorded after pyramidal tract stimulation were unchanged following the MVC. These results suggest that MEP and SP might have common sources of facilitation during an MVC and that inhibitory mechanisms remain focally augmented following a fatiguing MVC. © 1996 John Wiley & Sons, Inc.     

Transcranial direct current stimulation and the visual cortex

Neuroplastic changes are defined as enduring changes in the organization of the central nervous system, such as the strength of connections, representational patterns, or neuronal properties, either morphological or functional. In recent years, new tools have emerged to induce and manipulate ongoing neuroplastic changes by external stimulation, either by modification of synchronized neuronal activity or modulation of the spontaneous firing rate. The first is performed by transcranial magnetic stimulation (TMS), the latter by direct current stimulation (tDCS). tDCS as a tool aims to induce prolonged neuronal excitability and activity alterations in the human brain via alterations of the neuronal membrane potential and results in prolonged synaptic efficacy changes. Apart from its impressive persistent excitability effects, it is a non-invasive method and can be applied painlessly. Most likely that up- or downregulation of different cortical areas by tDCS will open a new branch in the area of visual psychophysics.     

Corticospinal excitability enhancement with simultaneous transcranial near-infrared stimulation and anodal direct current stimulation of motor cortex

ObjectivesNon-invasive brain stimulation (NIBS) is beneficial to many neurological and psychiatric disorders by modulating neuroplasticity and cortical excitability. However, recent studies evidence that single type of NIBS such as transcranial direct current stimulation (tDCS) does not have meaningful clinical therapeutic responses due to their small effect size. Transcranial near-infrared stimulation (tNIRS) is a novel form of NIBS. Both tNIRS and tDCS implement its therapeutic effects by modulating cortical excitability but with different mechanisms. We hypothesized that simultaneous tNIRS and tDCS is superior to single stimulation, leading to a greater cortical excitability.MethodsSixteen healthy subjects participated in a double-blind, sham-controlled, cross-over designed study. Motor evoked potentials (MEPs) were used to measure motor cortex excitability. The changes of MEP were calculated and compared in the sham condition, tDCS stimulation condition, tNIRS condition and the simultaneous tNIRS and anodal tDCS condition.ResultstDCS alone and tNIRS alone both elicited higher MEP after stimulation, while the MEP amplitude in the simultaneous tNIRS and tDCS condition was significantly higher than either tNIRS alone or tDCS alone. The enhancement lasted up to at least 30 minutes after stimulation, indicating simultaneous 820 nm tNIRS with 2 mA anodal tDCS have a synergistic effect on cortical plasticity.ConclusionsSimultaneous application of tNIRS with tDCS produces a stronger cortical excitability effect.SignificanceThe simultaneous tNIRS and tDCS is a promising technology with exciting potential as a means of treatment, neuro-enhancement, or neuro-protection.     

Exploring and optimizing the neuroplastic effects of anodal transcranial direct current stimulation over the primary motor cortex of older humans

BackgroundtDCS modulates cortical plasticity and has shown potential to improve cognitive/motor functions in healthy young humans. However, age-related alterations of brain structure and functions might require an adaptation of tDCS-parameters to achieve a targeted plasticity effect in older humans and conclusions obtained from young adults might not be directly transferable to older adults. Thus, our study aimed to systematically explore the association between tDCS-parameters and induced aftereffects on motor cortical excitability to determine optimal stimulation protocols for older individuals, as well as to investigate age-related differences of motor cortex plasticity in two different age groups of older adults.Methods32 healthy, volunteers from two different age groups of Young-Old (50–65 years, n = 16) and Old-Old (66–80 years, n = 16) participated in this study. Anodal tDCS was applied over the primary motor cortex, with respective combinations of three intensities (1, 2, and 3 mA) and durations (15, 20, and 30 min), in a sham-controlled cross-over design. Cortical excitability alterations were monitored by single-pulse TMS-induced MEPs until the next day morning after stimulation.ResultsAll active stimulation conditions resulted in a significant enhancement of motor cortical excitability in both age groups. The facilitatory aftereffects of anodal tDCS did not significantly differ between age groups. We observed prolonged plasticity in the late-phase range for two protocols with the highest stimulation intensity (i.e., 3 mA-20 min, 3 mA-30 min).ConclusionsOur study highlights the role of stimulation dosage in tDCS-induced neuroplastic aftereffects in the motor cortex of healthy older adults and delivers crucial information about optimized tDCS protocols in the domain of the primary motor cortex. Our findings might set the grounds for the development of optimal stimulation protocols to reinstate neuroplasticity in different cortical areas and induce long-lasting, functionally relevant plasticity in normal aging and in pathological conditions, which would require however systematic tDCS titration studies over respective target areas.     

Regional specificity of cathodal transcranial direct current stimulation (tDCS) effects on spatial-numerical associations: Comparison of four stimulation sites

Based on a theory of impulsive and reflective human behavior, we test the effects of transcranial direct current stimulation (tDCS) targeting either prefrontal or parietal cortex in either hemisphere. In a confirmatory registered report, cathodal tDCS is administered to conceptually reproduce tDCS modulations of implicit spatial-numerical associations, numerical distance effects, and response inhibition. Those cognitive operations are hypothesized to draw on left prefrontal, parietal, and right prefrontal activations, respectively, thereby susceptible to inhibitory, cathodal tDCS across those regions. Vice versa, the mutual regional and behavioral specificity of tDCS effects on these behavioral indices is examined and expected to produce double dissociations. In a mixed within-subjects (baseline, during tDCS, post-tDCS) and between-subjects (target electrode: left/right prefrontal cortex/posterior parietal cortex, or sham tDCS) design, we collect (a) confirmatory data on the robustness of cathodal tDCS effects on three behavioral effects and (b) differential data on the specificity of regional targets in male and female human participants. Results will provide crucial tests of theories of cortical organization implied by implicit associations and explicit regulation, which can direct future brain stimulation studies.