Cathodal tDCS Research Articles

Alteration of hypnotic experience following transcranial electrical stimulation of the left prefrontal cortex

BackgroundRecent studies of neurostimulation reported alteration of hypnotizability and hypnotic phenomena after inhibition of the dorsolateral prefrontal cortex (DLPFC), but the different assessments of hypnosis and the stimulation parameters still left open many questions about the role of this brain region in hypnotizability. We aimed to administer inhibitory transcranial direct current stimulation (tDCS) over the left DLPFC to observe effects of stimulation on the hypnotic experience and the feeling of agency. Methodsa procedure of hypnotic induction with suggestions was repeated twice: before and after the unilateral cathodal tDCS over the left DLPFC. The experience was assessed through a phenomenological assessment of hypnosis and sense of agency in thirty-three participants randomly assigned to the sham or the active group. Resultsactive (inhibitory) tDCS enhanced the hypnotizability by 15.4% and altered a few dimensions of consciousness such as self-awareness and absorption. No changes emerged on the feeling of agency and pass rates for suggestions. ConclusionstDCS reflects a promising tool to alter the hypnotic phenomena and the responsiveness to hypnotic procedures. Neurocognitive implications are discussed for the construct of hypnotizability as well as for the role of the left DLPFC in the dimensions of consciousness such as self-awareness.

Neural correlates of spatial attention bias: Changes in functional connectivity in attention networks associated with tDCS

The prevailing theory concerning the pathophysiology of unilateral spatial neglect is that it is caused by an interhemispheric imbalance in attention networks. Previous studies have demonstrated that repetitive transcranial magnetic stimulation or transcranial direct current stimulation (tDCS) delivered over the right posterior parietal cortex can induce transitory neglect-like deficits in healthy individuals. We examined whether right cathodal and left anodal tDCS delivered over the posterior parietal cortex could produce neglect-like deficits and change the resting-state functional connectivity (rsFC) of attention networks. We found that the reaction time for targets in the left hemifield was significantly prolonged during two different types of visual search tasks, and rsFC of the attention networks was altered by tDCS. Furthermore, the change in the reaction times for the left visual target in the two different tasks significantly correlated with the change in the rsFC of either the right dorsal attention network (DAN) or right ventral attention network (VAN) based on the tasks. These results suggest that tDCS delivered to the posterior parietal cortex bilaterally induced neglect-like deficits by altering the connectivity of the attentional networks through excitability changes in the cortical area under the electrode. The results of this study are consistent with the hypothesis that the cause of neglect is the interhemispheric imbalance of attention networks. This is the first study to demonstrate that local cortical stimulation can induce changes not only in the local brain function but also in the cortical networks in healthy individuals.

Effects of transcranial direct current stimulation on neural activity and functional connectivity during fear extinction

Background/ObjectiveAnxiety disorders are highly prevalent and negatively impact daily functioning and quality of life. Transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex (dlPFC), especially in the right hemisphere impacts extinction learning; however, the underlying neural mechanisms are elusive. Therefore, we aimed to investigate the effects of cathodal tDCS stimulation to the right dlPFC on neural activity and connectivity patterns during delayed fear extinction in healthy participants. MethodsWe conducted a two-day fear conditioning and extinction procedure. On the first day, we collected fear-related self-reports, clinical questionnaires, and skin conductance responses during fear acquisition. On the second day, participants in the tDCS group (n = 16) received 20-min offline tDCS before fMRI and then completed the fear extinction session during fMRI. Participants in the control group (n = 18) skipped tDCS and directly underwent fMRI to complete the fear extinction procedure. Whole-brain searchlight classification and resting-state functional connectivity analyses were performed. ResultsWhole-brain searchlight classification during fear extinction showed higher classification accuracy of threat and safe cues in the left anterior dorsal and ventral insulae and hippocampus in the tDCS group than in the control group. Functional connectivity derived from the insula with the dlPFC, ventromedial prefrontal cortex, and inferior parietal lobule was increased after tDCS. ConclusiontDCS over the right dlPFC may function as a primer for information exchange among distally connected areas, thereby increasing stimulus discrimination. The current study did not include a sham group, and one participant of the control group was not randomized. Therefore, to address potential allocation bias, findings should be confirmed in the future with a fully randomized and sham controlled study.

Brain Perfusion Alterations Induced by Standalone and Combined Non-Invasive Brain Stimulation over the Dorsolateral Prefrontal Cortex.

Non-invasive brain stimulation (NIBS) interventions are promising for the treatment of psychiatric disorders. Notwithstanding, the NIBS mechanisms of action over the dorsolateral prefrontal cortex (DLPFC), a hub that modulates affective and cognitive processes, have not been completely mapped. We aimed to investigate regional cerebral blood flow (rCBF) changes over the DLPFC and the subgenual anterior cingulate cortex (sgACC) of different NIBS protocols using Single-Photon Emission Computed Tomography (SPECT). A factorial, within-subjects, double-blinded study was performed. Twenty-three healthy subjects randomly underwent four sessions of NIBS applied once a week: transcranial direct current stimulation (tDCS), intermittent theta-burst stimulation (iTBS), combined tDCS + iTBS and placebo. The radiotracer 99m-Technetium-ethylene-cysteine-dimer was injected intravenously during the NIBS session, and SPECT neuroimages were acquired after the session. Results revealed that the combination of tDCS + iTBS increased right sgACC rCBF. Cathodal and anodal tDCS increased and decreased DLPFC rCBF, respectively, while iTBS showed no significant changes compared to the placebo. Our findings suggest that the combined protocol might optimize the activity in the right sgACC and encourage future trials with neuropsychiatric populations. Moreover, mechanistic studies to investigate the effects of tDCS and iTBS over the DLPFC are required.

Transcranial-Direct-Current-Stimulation Accelerates Motor Recovery After Cortical Infarction in Mice: The Interplay of Structural Cellular Responses and Functional Recovery

Background Transcranial direct current stimulation (tDCS) promotes recovery after stroke in humans. The underlying mechanisms, however, remain to be elucidated. Animal models suggest tDCS effects on neuroinflammation, stem cell proliferation, neurogenesis, and neural plasticity. Objective In a longitudinal study, we employed tDCS in the subacute and chronic phase after experimental focal cerebral ischemia in mice to explore the relationship between functional recovery and cellular processes. Methods Mice received photothrombosis in the right motor cortex, verified by Magnetic Resonance Imaging. A composite neuroscore quantified subsequent functional deficits. Mice received tDCS daily: either 5 sessions from day 5 to 9, or 10 sessions with days 12 to 16 in addition. TDCS with anodal or cathodal polarity was compared to sham stimulation. Further imaging to assess proliferation and neuroinflammation was performed by immunohistochemistry at different time points and Positron Emission Tomography at the end of the observation time of 3 weeks. Results Cathodal tDCS at 198 kC/m2 (220 A/m2) between days 5 and 9 accelerated functional recovery, increased neurogenesis, decreased microglial activation, and mitigated CD16/32-expression associated with M1-phenotype. Anodal tDCS exerted similar effects on neurogenesis and microglial polarization but not on recovery of function or microglial activation. TDCS on days 12 to 16 after stroke did not induce any further effects, suggesting that the therapeutic time window was closed by then. Conclusion Overall, data suggest that non-invasive neuromodulation by tDCS impacts neurogenesis and microglial activation as critical cellular processes influencing functional recovery during the early phase of regeneration from focal cerebral ischemia.

Transcranial direct current stimulation in stroke – Motor excitability and motor function

ObjectiveTo characterize motor excitability changes and changes of motor performance induced by a single anodal and cathodal transcranial direct current stimulation (tDCS) session in stroke patients. MethodsTwenty subacute stroke patients participated. Motor performance was tested with the Box and Block Test [BBT]. Motor cortex excitability (short interval intracortical inhibition [SICI], intracortical facilitation [ICF], long interval intracortical inhibition [LICI]) was examined by paired pulse transcranial magnetic stimulation before and after a single tDCS session (20 minutes, 1,0 mA). On two different occasions, patients received anodal and cathodal tDCS over the affected hemisphere. TMS recordings were taken from both hands consecutively. ResultsAnodal tDCS significantly reduced SICI without changing ICF or LICI. Cathodal tDCS did not change motor excitability. Both types of tDCS did not alter motor performance. Even prior to anodal tDCS, SICI in the affected hemisphere was lower than in the unaffected hemisphere and was correlated with BBT changes after anodal tDCS. ConclusionsAnodal, but not cathodal tDCS specifically modulated intracortical inhibitory circuits, leading to a disinhibition. SignificanceThe results amplify our knowledge on excitability modulations of tDCS in stroke patients.

Effects of a short and intensive transcranial direct current stimulation treatment in children and adolescents with developmental dyslexia: A crossover clinical trial.

Developmental Dyslexia (DD) significantly interferes with children’s academic, personal, social, and emotional functioning. Nevertheless, therapeutic options need to be further validated and tested in randomized controlled clinical trials. The use of transcranial direct current stimulation (tDCS) has been gaining ground in recent years as a new intervention option for DD. However, there are still open questions regarding the most suitable tDCS protocol for young people with DD. The current crossover study tested the effectiveness of a short and intensive tDCS protocol, including the long-term effects, as well as the influence of age and neuropsychological processes at baseline on reading improvements. Twenty-four children and adolescents with DD were randomly assigned to receive active tDCS during the first slot and sham tDCS during the second slot or vice versa. Five consecutive daily sessions of left anodal/right cathodal tDCS set at 1 mA for 20 min were administered over the parieto-occipital regions. Reading measures (text, high frequency word, low frequency word, and non-word lists) and neuropsychological measures (visual-spatial and verbal working memory, phoneme blending, and rapid automatized naming tasks) were collected before, immediately after, 1 week and 1 month later the treatment. Our results showed that only the active tDCS condition improved non-word reading speed immediately after and 1 month later the end of the treatment compared with baseline. In addition, the improvement in non-word reading speed was significantly correlated with age and with neuropsychological measures (verbal working memory and phoneme blending) at baseline but only in the active tDCS condition. The current crossover study contributed to enforce previous effects of tDCS, including long-term effects, on non-word reading speed and to understand the effect of age and neuropsychological processes on reading outcomes. Our findings showed that tDCS could be a low-cost and easy-to-implement treatment option with long-term effects for children and adolescents with DD.

Repeated long sessions of transcranial direct current stimulation reduces seizure frequency in patients with refractory focal epilepsy: An open-label extension study

ObjectiveAlthough clinical trials have demonstrated that cathodal transcranial direct current stimulation (tDCS) is effective for seizure reduction, its long-term efficacy is unknown. This study aimed to determine the long-term effects of repeated cathodal long tDCS sessions on seizure suppression in patients with refractory epilepsy. MethodsPatients were recruited to participate in an extended phase of a previous randomized, double-blind, sham-controlled, three-arm, parallel, multicenter study on tDCS. The patients were divided into an active tDCS group (20 min of tDCS per day) and an intensified tDCS group (2 × 20 min of tDCS per day). Each tDCS session lasted 2 weeks and the patients underwent repeated sessions at intervals of 2 to 6 months. The cathode was placed over the epileptogenic focus with the current intensity set as 2 mA. Seizure frequency reduction from baseline was analyzed using the Wilcoxon signed-rank test for two related samples. A generalized estimating equation model was used to estimate group, time, and interaction effects. ResultsAmong the 19 patients who participated in the extended phase, 11 were in the active tDCS group and underwent 2–16 active tDCS sessions, and eight were in the intensified tDCS group and underwent 3–11 intensified tDCS sessions. Seizure reduction was significant from the first to the seventh follow-up, with a median seizure frequency reduction of 41.7%–83.3% (p < 0.05). Compared to the regular tDCS protocol, each intensified tDCS session substantially decreased seizure frequency by 0.3680 (p < 0.05). One patient experienced an increase of 8.5%–232.8% in the total number of seizures during three treatment sessions and follow-ups. ConclusionRepeated long cathodal tDCS sessions yielded significant and progressive long-term seizure reductions in patients with refractory focal epilepsy.

The impact of prefrontal transcranial direct current stimulation (tDCS) on theory of mind, emotion regulation and emotional-behavioral functions in children with autism disorder: A randomized, sham-controlled, and parallel-group study.

Advances in our knowledge about the neuropsychological mechanisms underlying core deficits in autism spectrum disorder (ASD) have produced several novel treatment modalities. One of these approaches is modulation of activity of the brain regions involved in ASD symptoms. This study examined the effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) on autism symptom severity, theory of mind, emotion regulation strategies, and emotional-behavioral functions in children with ASD. Thirty-two children (Mage =10.16, SD=1.93, range 7-12 years) diagnosed with ASD were randomly assigned to active (N=17) or sham stimulation (N=15) groups in a randomized, sham-controlled, parallel-group design. Participants underwent 10 sessions of active (1.5mA, 15 min, bilateral left anodal/right cathodal DLPFC, 2 sessions per week) or sham tDCS. Autism symptom severity, theory of mind, emotion regulation strategies, and emotional-behavioral functioning of the patients were assessed at baseline, immediately after the intervention, and 1 month after the intervention. A significant improvement of autism symptom severity (i.e., communication), theory of mind (i.e., ToM 3), and emotion regulation strategies was observed for the active as compared to the sham stimulation group at the end of the intervention, and these effects were maintained at the one-month follow-up. The results suggest that repeated tDCS with anodal stimulation of left and cathodal stimulation of right DLPFC improves autism symptom severity as well as social cognition and emotion regulation in ASD. LAY SUMMARY: Previous research has suggested that targeting core mechanisms underlying cognitive-emotional and behavioral deficits of autistic children might improve symptoms of ASD. Deficient social and behavioral functioning, impaired theory of mind, and emotional regulation deficits have been identified as core treatment targets for this group. Specific subregions of the prefrontal cortex are involved in these deficits, including hypoactivity of the dorsolateral prefrontal cortex (DLPFC). Upregulation of this area with non-invasive brain stimulation, namely anodal transcranial direct current stimulation (tDCS), results in improved social and behavioral functioning in children with ASD. Very few studies have however examined the effects of this intervention on theory of mind, emotional regulation, and emotional-behavioral problems. We examined the effects of anodal tDCS over the left DLPFC (F3), combined with cathodal tDCS over the right DLPFC (F4) on autism symptom severity as well as theory of mind, emotional regulation, and emotional-behavioral problems of children with ASD. This intervention improved autism symptom severity, specific domains of theory of mind, and emotion regulation. These findings have clinical implications for the treatment of ASD and suggest that targeting core mechanisms underlying socio-cognitive-emotional deficits of autistic children using tDCS might improve symptoms of ASD.

No robust online effects of transcranial direct current stimulation on corticospinal excitability

Transcranial direct current stimulation (tDCS) has been used for over twenty years to modulate cortical (particularly motor corticospinal) excitability both during (online) and outlasting (offline) the stimulation, with the former effects associated to the latter. However, tDCS effects are highly variable, partially because stimulation intensity is commonly not adjusted individually (in contrast to transcranial magnetic stimulation, TMS). In Experiment 1, we therefore explored an empirical approach of personalizing tDCS intensity for the primary motor cortex (M1) based on dose-response curves (DRCs), individually relating tDCS Intensity (in steps from 0.3 to 2.0 mA) and Polarity (anodal, cathodal) to the online modulation of concurrent TMS motor evoked potentials (MEP), assessing DRC reliability across two separate days. No robust DRCs could be observed, neither at the individual nor at the group level, with the only robust effect being a (paradoxical) MEP facilitation during cathodal tDCS at 2.0 mA, but no modulation at traditional intensities of or near 1 mA. In Experiment 2, we therefore attempted to replicate the classical bidirectional online MEP modulation during 1 mA tDCS that had been reported by several of the early seminal tDCS papers. We either closely recreated stimulation parameters and temporal protocol of these original studies (Experiment 2A) or slightly modernized them according to current standards (Experiment 2B). In neither experiment did we observed any significant online MEP modulation. We conclude that an empirical titration of individually effective tDCS intensities may not be feasible as online tDCS effects do not appear to be sufficiently robust.

High-definition transcranial direct current stimulation of the left middle temporal complex does not affect visual motion perception learning.

Visual perceptual learning (VPL) refers to the improvement in visual perceptual abilities through training and has potential implications for clinical populations. However, improvements in perceptual learning often require hundreds or thousands of trials over weeks to months to attain, limiting its practical application. Transcranial direct current stimulation (tDCS) could potentially facilitate perceptual learning, but the results are inconsistent thus far. Thus, this research investigated the effect of tDCS over the left human middle temporal complex (hMT+) on learning to discriminate visual motion direction. Twenty-seven participants were randomly assigned to the anodal, cathodal and sham tDCS groups. Before and after training, the thresholds of motion direction discrimination were assessed in one trained condition and three untrained conditions. Participants were trained over 5 consecutive days while receiving 4 × 1 ring high-definition tDCS (HD-tDCS) over the left hMT+. The results showed that the threshold of motion direction discrimination significantly decreased after training. However, no obvious differences in the indicators of perceptual learning, such as the magnitude of improvement, transfer indexes, and learning curves, were noted among the three groups. The current study did not provide evidence of a beneficial effect of tDCS on VPL. Further research should explore the impact of the learning task characteristics, number of training sessions and the sequence of stimulation.

TH-201. Transferability of cathodal tDCS effects from the primary motor to the dorsolateral prefrontal cortex: A multimodal TMS-EEG study

TH-201. Transferability of cathodal tDCS effects from the primary motor to the dorsolateral prefrontal cortex: A multimodal TMS-EEG study

TH-192. Age-dependent non-linear neuroplastic effects of cathodal tDCS in the elderly population; a titration study

TH-192. Age-dependent non-linear neuroplastic effects of cathodal tDCS in the elderly population; a titration study

Anodal and cathodal transcranial direct current stimulations of prefrontal cortex in a rodent model of Alzheimer's disease.

Alzheimer’s disease (AD) is a leading cause of dementia in the elderly, with no effective treatment currently available. Transcranial direct current stimulation (tDCS), a non-drug and non-invasive therapy, has been testified efficient in cognitive enhancement. This study aims to examine the effects of tDCS on brain function in a mouse model of AD. The amyloid precursor protein (APP) and presenilin 1 (PS1) transgenic mice (7–8 months old) were subjected to 20-min anodal and cathodal tDCS (atDCS and ctDCS; 300 μA, 3.12 mA/cm2) for continuous five days. tDCS was applied on the left frontal skull of the animals, targeting on their prefrontal cortex (PFC). Behavioral performances were assessed by open-field, Y-maze, Barnes maze and T-maze paradigms; and their PFC electroencephalogram (EEG) activities were recorded under spontaneous state and during Y-maze performance. Behaviorally, atDCS and ctDCS improved spatial learning and/or memory in AD mice without affecting their general locomotion and anxiety-like behaviors, but the effects depended on the testing paradigms. Interestingly, the memory improvements were accompanied by decreased PFC EEG delta (2–4 Hz) and increased EEG gamma (20–100 Hz) activities when the animals needed memory retrieval during task performance. The decreased EEG delta activities could also be observed in animals under spontaneous state. Specifically, atDCS increased PFC EEG activity in the alpha band (8–12 Hz) for spontaneous state, whereas ctDCS increased that in alpha-beta band (8–20 Hz) for task-related state. In addition, some EEG changes after ctDCS could be found in other cortical regions except PFC. These data indicate that tDCS can reverse the situation of slower brain activity in AD mice, which may further lead to cognitive improvement. Our work highlights the potential clinical use of tDCS to restore neural network activity and improve cognition in AD.

Transcranial direct current stimulation as a preventive treatment in multiple sclerosis? Preclinical evidence

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system, presenting with optic neuritis in about 20–30% of cases. Optic nerve demyelination, associated with delay of visual evoked potentials (VEPs), is also observed prior to motor signs in the preclinical MS model Experimental Autoimmune Encephalomyelitis (EAE). Transcranial direct current stimulation (tDCS), inducing polarity-dependent changes in neuronal excitability, is widely used to promote neuroplasticity in several neurological disorders. However, its potential effects on inflammation and demyelination are largely unknown. We tested the effectiveness of a preventive, 5-day tDCS treatment started 3 days post-immunization, in reducing the severity of VEP delays observed in early EAE. In mice undergoing cathodal tDCS (n = 6/26 eyes) VEPs were significantly less delayed compared with eyes from EAE-Sham (n = 24/32 eyes) and EAE-Anodal (n = 22/32 eyes). Optic nerve immunohistochemistry revealed a significantly lower cell density of microglia/macrophages, and less axonal loss in EAE-Cathodal vs EAE-Sham and EAE-Anodal, while the percent demyelination with Luxol-fast blue staining was comparable among EAE groups. Considering the latter result, immunofluorescence paranodal staining was performed, revealing a significantly higher number of complete paranode domains in EAE-Cathodal, closer to healthy mice, compared with EAE-Sham and EAE-Anodal groups. These results were reflected by the negative correlation between the number of complete paranode domains and VEP latency increase with respect to pre-immunization. Finally, cathodal tDCS was associated with a lower number, closer to healthy, of single paranodes in contrast to EAE-Sham. The effects of cathodal stimulation in preventing VEPs delays and optic nerve myelin damage were already observed in the pre-motor onset EAE stage, and were associated with a lower density of inflammatory cells. These findings suggest that tDCS may exert an anti-inflammatory effect with potential therapeutic application to be further explored in autoimmune demyelinating diseases.

The impact of cathodal tDCS on the GABAergic system in the epileptogenic zone: A multimodal imaging study.

ObjectivesWe aimed to investigate the antiepileptic effects of cathodal transcranial direct current stimulation (c-tDCS) and mechanisms of action based on its effects on the neurotransmitters responsible for the abnormal synchrony patterns seen in pharmacoresistant epilepsy. This is the first study to test the impact of neurostimulation on epileptiform interictal discharges (IEDs) and to measure brain metabolites in the epileptogenic zone (EZ) and control regions simultaneously in patients with pharmacoresistant epilepsy.MethodsThis is a hypothesis-driven pilot prospective single-blinded repeated measure design study in patients diagnosed with pharmacoresistant epilepsy of temporal lobe onset. We included seven patients who underwent two sessions of c-tDCS (sham followed by real). The real tDCS session was 20 min in duration and had a current intensity of 1.5 mA delivered via two surface electrodes that had dimensions of 3 × 4 cm. The cathode electrode was placed at FT7 in the center whereas the anode at Oz in the center. After each session, we performed electroencephalographic recording to count epileptiform IEDs over 30 min. We also performed magnetic resonance spectroscopy (MRS) to measure brain metabolite concentrations in the two areas of interest (EZ and occipital region), namely, gamma-aminobutyric acid (GABA), glutamate (Glx), and glutathione. We focused on a homogenous sample where the EZ and antiepileptic medications are shared among patients.ResultsReal tDCS decreased the number of epileptiform IEDs per min (from 9.46 ± 2.68 after sham tDCS to 5.37 ± 3.38 after real tDCS), p = 0.018, as compared to sham tDCS. GABA was decreased in the EZ after real c-tDCS stimulation as compared to sham tDCS (from 0.129 ± 0.019 to 0.096 ± 0.018, p = 0.02). The reduction in EZ GABA correlated with the reduction in the frequency of epileptiform IED per min (rho: 0.9, p = 0.003).ConclusionThese results provide a window into the antiepileptic mechanisms of action of tDCS, based on local and remote changes in GABA and neural oscillatory patterning responsible for the generation of interictal epileptiform discharges.

The effects of Single-Session Cathodal and Bihemispheric tDCS on Fluency in Stuttering

Developmental stuttering is a fluency disorder that adversely affect many aspects of a person's life. Recent transcranial direct current stimulation (tDCS) studies have shown promise to improve fluency in people who stutter. To date, bihemispheric tDCS has not been investigated in this population. In the present study, we aimed to investigate the effects of single-session bihemispheric and unihemispheric cathodal tDCS on fluency in adults who stutter. We predicted that bihemispheric tDCS with anodal stimulation to the left IFG and cathodal stimulation to the right IFG would improve fluency better than the sham and cathodal tDCS to the right IFG. Seventeen adults who stutter completed this single-blind, crossover, sham-controlled tDCS experiment. All participants received 20 min of tDCS alongside metronome-timed speech during intervention sessions. Three tDCS interventions were administered: bihemispheric tDCS with anodal stimulation to the left IFG and cathodal stimulation to the right IFG, unihemispheric tDCS with cathodal stimulation to the right IFG, and sham stimulation. Speech fluency during reading and conversation was assessed before, immediately after, and one week after each intervention session. There was no significant fluency improvement in conversation for any tDCS interventions. Reading fluency improved following both bihemispheric and cathodal tDCS interventions. tDCS montages were not significantly different in their effects on fluency.

Varied Response of EEG Rhythm to Different tDCS Protocols and Lesion Hemispheres in Stroke Subjects with Upper Limb Dysfunction.

Transcranial direct current stimulation (tDCS) provides a way to modulate the cortical activity and promote motor rehabilitation following stroke. However, evidence indicates that the response to tDCS is highly variable. This study was aimed at exploring rhythmic response of Electroencephalography (EEG) to three tDCS protocols in stroke subjects. We hypothesize that tDCS protocols may interact with stoke characteristics, and electrode placement may affect cortical activity which could be reflected by the EEG rhythm. 32 subjects with unilateral stroke were recruited to a single-blinded, randomized, and controlled crossover experiment. All of the subjects underwent four tDCS protocols (anodal (atDCS), cathodal (ctDCS), and bilateral tDCS (bi-tDCS) and sham) with an interval of at least 1 week. Resting-state EEG was acquired before and after the stimulation. We tested the change of EEG spectral power after tDCS and the difference of change among four protocols using the paired-sample t-test and repeated measures analysis of variance. Then, we investigated the clinical factors affecting the above changes using the linear and quadratic regression model. According to the results, EEG responded to atDCS and bi-tDCS protocols on alpha and beta rhythm and subjects with a left lesion had higher response than those with the right lesion. Besides that, the change of alpha and beta power after atDCS and of beta power after bi-tDCS showed association with clinical characteristics only in subjects with the left lesion. In conclusion, the study found varied EEG response with different protocols, lesion hemispheres, and other clinical characteristics supporting the individualized cortical oscillatory effect induced by tDCS.

Neural Mechanism Underlying Task-Specific Enhancement of Motor Learning by Concurrent Transcranial Direct Current Stimulation.

The optimal protocol for neuromodulation by transcranial direct current stimulation (tDCS) remains unclear. Using the rotarod paradigm, we found that mouse motor learning was enhanced by anodal tDCS (3.2 mA/cm2) during but not before or after the performance of a task. Dual-task experiments showed that motor learning enhancement was specific to the task accompanied by anodal tDCS. Studies using a mouse model of stroke induced by middle cerebral artery occlusion showed that concurrent anodal tDCS restored motor learning capability in a task-specific manner. Transcranial in vivo Ca2+ imaging further showed that anodal tDCS elevated and cathodal tDCS suppressed neuronal activity in the primary motor cortex (M1). Anodal tDCS specifically promoted the activity of task-related M1 neurons during task performance, suggesting that elevated Hebbian synaptic potentiation in task-activated circuits accounts for the motor learning enhancement. Thus, application of tDCS concurrent with the targeted behavioral dysfunction could be an effective approach to treating brain disorders.

Facilitation and inhibition effects of anodal and cathodal tDCS over areas MT+ on the flash-lag effect.

The perceived position of a moving object in vision entails an accumulation of neural signals over space and time. Due to neural signal transmission delays, the visual system cannot acquire immediate information about the moving object's position. Although physiological and psychophysical studies on the flash-lag effect (FLE), a moving object is perceived ahead of a flash even when they are aligned at the same location, have shown that the visual system develops the mechanisms of predicting the object's location to compensate for the neural delays, the neural mechanisms of motion-induced location prediction are not still understood well. Here, we investigated the role of neural activity changes in areas MT+ (specialized for motion processing) and the potential contralateral processing preference of MT+ in modulating the FLE. Using transcranial direct current stimulations (tDCS) over the left and right MT+ between pre- and posttests of the FLE in different motion directions, we measured the effects of tDCS on the FLE. The results found that anodal and cathodal tDCS enhanced and reduced the FLE with the moving object heading to but not deviating from the side of the brain stimulated, respectively, compared with sham tDCS. These findings suggest a causal role of area MT+ in motion-induced location prediction, which may involve the integration of position information.NEW & NOTEWORTHY Perceived positions of moving objects are related to neural activities in areas MT+. We demonstrate that tDCS over areas MT+ can modulate the FLE, and further anodal and cathodal tDCS facilitated and inhibited the FLE with a moving object heading to but not deviating from the side of the brain stimulated, respectively. These findings suggest a causal role of area MT+ in motion-induced location prediction and contribute to understanding the neural mechanism of the FLE.