Course Of tDCS Research Articles

The safety and feasibility of transcranial direct current stimulation for patients with chronic severe traumatic brain injury in Japan, a phase I study

BackgroundDespite evidence regarding the benefits of transcranial direct current stimulation (tDCS) in patients with severe traumatic brain injury, few trials have examined the treatment safety. Therefore, we created a phase I trial in Japan to investigate the safety of tDCS after severe brain injury. MethodsWe verified the safety of tDCS through constant left frontal anodal stimulation at 2 mA for 20 min for 5 consecutive days. Additionally, we added a variable stimuli period to explore the effects of stimulus intensity, location, and duration. We adapted a traditional 3 + 3 study design. We assessed the rate of adverse effects, including skin burns and clinical seizure. Changes in neurological symptoms were evaluated using the Glasgow Coma Scale, Coma Recovery Scale-Revised, and 4 states of consciousness (coma, unresponsive wakefulness syndrome, minimally conscious state, and severe disability). ResultsSix patients completed the study. No obvious adverse events were observed during the constant stimulation period or the variable stimulation period (right frontal anodal stimulation, stimulation frequency 2–4 mA, 1 or 5 times per week for a period of 4 weeks). Regarding the Coma Recovery Scale-Revised, patients in 4 out of 6 instances (66.7 %) improved by more than 1 point. ConclusionOur phase I safety study indicated that a single course of tDCS was safe in patients with severe traumatic brain injury. The next step is a phase II trial to investigate the preliminary efficacy and safety of tDCS at 2 mA (in comparison with sham stimulation).

Domiciliary tDCS in Geriatric Psychiatric Disorders: Opportunities and Challenges.

There is evidence to suggest improved efficacy with long-term tDCS.40,41 This stems from research supporting the efficacy via putative mechanisms related to long-term potentiation and neuroplasticity.42 Continuous and repeated tDCS may, therefore, hold the key to the treatment of chronic neurodegenerative illnesses. The possibility of domiciliary tDCS supported by technology for remote administration and telemonitoring provides the opportunity to continue research on tDCS for geriatric mental health conditions. Over recent years, tDCS (a type of tES) is evolving as a potential treatment modality for neurocognitive disorders and depression. There is a need to evaluate the effectiveness of the longer course of tDCS possibly delivered as domiciliary treatment with or without supervision (remotely supervised or preprogrammed).25 This becomes increasingly relevant for geriatric mental health conditions, particularly in the context of COVID-19, as there is a need for precautions to avoid high-risk exposure in hospital settings. [Extracted from the article] Copyright of Indian Journal of Psychological Medicine is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A Randomized, Double-Blind, Sham-Controlled Study of Transcranial Direct Current Stimulation as an Augmentation Intervention for the Attenuation of Motor Deficits in Patients With Stroke.

Most studies of transcranial direct current stimulation (tDCS) for motor deficits in patients with stroke administered few sessions of tDCS and with low current amplitude. During 2015 to 2019, we randomized 60 inpatients with ischemic/hemorrhagic stroke and motor deficits to true or sham tDCS. Transcranial direct current stimulation was administered at 2- to 3-mA current strength, twice daily, 6 days a week, for 2 weeks; anode and cathode were placed over ipsilesional and contralesional motor cortices, respectively. All patients received individualized motor and cognitive rehabilitation. Motor outcomes were assessed 1 day before and 1 day after the tDCS course using the Fugl-Meyer Assessment, the Jebson-Taylor Hand Function Test, and the Barthel index (all coprimary outcomes). Mood and cognition were also assessed. Motor outcomes were compared between groups using age, baseline scores, and latency to treatment as covariates. The study was prospectively registered (CTRI/2017/01/007733). The mean age of the patients was 46.9 years. The sample was 73.3% male. Six patients did not complete the study. The covariates were significantly related to motor outcomes. Although all patients showed motor improvements, after adjusting for covariates, tDCS was not superior to sham treatment on any motor, mood, or cognitive outcome. Laterality of hemispheric lesion influenced spatial but not motor outcomes with tDCS. One true tDCS patient developed blistering under the anode and was withdrawn from the study; 3 more reported transient itching during sessions. An intensive course of tDCS, as delivered in this study, does not improve motor, mood, and cognitive outcomes in ischemic/hemorrhagic stroke in patients undergoing individualized rehabilitation. The study provides important leads for directions for future research.

Transcranial Direct Current Stimulation in Poststroke Hemianopia

Introduction. Development of the new approaches to the rehabilitation of patients with poststroke hemianopia is of great importance, given the high prevalence of that disorder and its negative impact on patients’ quality of life. This study aimed to investigate the effect of transcranial direct current stimulation (tDCS) on the quality of life and the quality of visual perception in patients with poststroke hemianopia, as well as to study the safety and tolerability of this technique. Materials and methods. The study included ten patients with poststroke hemianopia. Patients underwent ten tDCS sessions (2 mA, 20 min with anode placed over Oz, cathode — over Cz for a unilateral lesion, and anode — over O1 and O2, cathode — over Fp1 and Fp2 for bilateral lesions). The tolerability of tDCS was evaluated after each session using a standardized questionnaire. Clinical assessment before and after tDCS was performed using the Visual Function Questionnaire (VFQ-25) and the 36-item Short Form Survey (SF-36). Functional MRI using a visual paradigm was performed in 5 patients before and after the course of tDCS. Results. Adverse effects were recorded during 9.9% of the sessions and had low severity in most cases. There was one withdrawal from the study because of increased pain in the hand and leg, in a patient with central post-stroke pain syndrome, which was likely unrelated to the biological effects of stimulation. Data of 9 patients were included in the analysis. There was a statistically significant increase in the overall score on the VFQ-25 (p = 0.02) after tDCS with improvements in the social activity (p = 0.02), mental health (p = 0.02), dependence on others (p = 0.04), and peripheral vision (p = 0.04) sections. A statistically significant improvement was also found in the psychological component of quality of life (p = 0.04), vitality (p = 0.03), social functioning (p = 0.02), role functioning due to physical health (p = 0.04), and general health (p = 0.008). In 3 cases, increased activation of the occipital cortex after tDCS was identified using functional MRI with a visual paradigm. Conclusion. tDCS is a safe, well-tolerated, and potentially effective method in patients with poststroke hemianopia. Larger, controlled, and randomized studies are needed to clarify the efficacy of this method in hemianopia.

Cumulative effect of transcranial direct current stimulation in patients with partial refractory epilepsy and its association with phase lag index-A preliminary study

There is an urgent need for alternative treatments for refractory epilepsy. We investigated the effect of two courses of cathodal transcranial direct current stimulation (tDCS) in nine patients with partial refractory epilepsy. A two-course treatment (1 month per course, with six sessions of stimulation per course within the first 2 weeks by 2-mA cathodal tDCS for 20 min) was administered to each patient. After the first course of tDCS, the average seizure frequency had decreased by 37.8 ± 21.9% compared with baseline (p = 0.001). After the second course, the average seizure frequency had decreased by 48.9 ± 31.2% compared with baseline (p = 0.002). Only seven of the nine patients maintained the same state of wakefulness in three electroencephalogram (EEG) recordings. We analyzed the EEG recordings of these seven patients on day 0 immediately posttreatment and on days 4 and 9 in the first course of tDCS. When compared with baseline, no significant change in the number of epileptiform discharges was observed. The day 9 phase lag index (PLI) decreased in five patients with seizure reduction after tDCS but increased in two patients without seizure reduction after tDCS. A significant negative correlation was observed between the day 9 PLI of alpha band and first-course seizure reduction (R2 = 0.6515) (p = 0.028). The results revealed that tDCS may be considered as an alternative treatment option for patients with refractory epilepsy, and its effect might be cumulative after repeated stimulations and associated with a decrease in PLI.

The adjunctive application of transcranial direct current stimulation in the management of de novo refractory epilepsia partialis continua in adolescent-onset POLG-related mitochondrial disease.

SummaryFocal status epilepticus in POLG‐related mitochondrial disease is highly refractory to pharmacological agents, including general anesthesia. We report the challenges in managing a previously healthy teenager who presented with de novo epilepsia partialis continua and metabolic stroke resulting from the homozygous p.Ala467Thr POLG mutation, the most common pathogenic variant identified in the Caucasian population. We applied transcranial direct current stimulation (tDCS; 2 mA; 20 min) daily as an adjunctive therapy because her focal seizures failed to respond to five antiepileptic drugs at maximal doses. The electrical and clinical seizures stopped after 3 days of tDCS. The second course of tDCS was administered for 14 days when the focal seizures re‐emerged a month later. The patient tolerated the procedure well. Following 4 months of hospitalization and prolonged community rehabilitation, our patient has now returned to full‐time education with support, and there is no report of cognitive deficit. We have demonstrated the safety and efficacy of tDCS in treating refractory focal motor seizures caused by mitochondrial disease.

The effect of combined treatment with transcranial direct current stimulation on cerebral blood flow in patients with cerebral palsy

There is a close link between the activity of the brain and cerebral blood supply. Transcranial direct current stimulation (tDCS) modulates the activity of the cerebral cortex and thus affects the cerebral blood flow. The aim of the study was to investigate the effect of combined treatment with tDCS on cerebral blood flow in patients with cerebral palsy (CP). Materials and Methods. 60 patients with various forms of cerebral palsy were examined and received the course of treatment. The comparison group was formed from 30 children who received the course of basic medical and rehabilitation procedures. The main group included 30 children who, in addition to the same therapy, received a course of tDCS. A transcranial Doppler ultrasound examination of head blood vessels was used for the study of cerebral hemodynamics in children with cerebral palsy before and after combined treatment with tDCS. Results. tDCS reduced asymmetry coefficient of blood flow velocity in the middle cerebral arteries (MCA) by 12.3 %, whereas in the comparison group only by 2.5 %; in the anterior cerebral artery (ACA) – 9.5 %, while in the comparison group – 0.8 %. tDCS significantly reduced the high mean blood flow velocity per cycle (MFV) in the basilar artery (BA), MCA and ACA (21.7 %, 18.3 % and 7.8 %, respectively); in the comparison group no statistically significant positive dynamics was observed. tDCS significantly increased the low MVF in the BA, MCA and ACA (29.7 %, 21.2 % and 9.7 % respectively); a statistically significant increase of MVF by 9.9 % was only in the CMA in the comparison group of patients. Conclusions. Our data indicate that the use of tDCS in the combined treatment of CP patients improves cerebral hemodynamics in 87 % of patients, in contrast to 52 % in the comparison group. The addition of transcranial direct current stimulation method to the complex treatment of patients with cerebral palsy improves the effectiveness of treatment and may also positively influence on the disease clinical course.

Treatment-resistant obsessive-compulsive disorder: Insights from an open trial of transcranial direct current stimulation (tDCS) to design a RCT

The present study collected preliminary data testing the hypothesis that a lengthy transcranial direct current stimulation (tDCS) protocol reduces obsessive-compulsive disorder symptoms and strengthens executive control. Five patients presenting with treatment-resistant obsessive-compulsive disorder (TR-OCD) underwent neurocognitive and clinical testing prior to (baseline assessment) and after completing three weeks of tDCS (post-treatment evaluation). Four TR-OCD patients participated in 15 daily tDCS sessions during the three-week trial. One patient participated in 13 sessions. Scalp electrodes were situated using the standard montage for DLPFC stimulation: anode over left DLPFC (F3) and cathode over right frontopolar region (Fp2). We gained significant insights with this extensive testing: (1) TR-OCD patients demonstrated significant OCD symptom reduction following the course of tDCS; however, gains were not maintained at 1-month follow-up; (2) there were changes in depressive and schizotypal (positive) symptoms following three weeks of tDCS; however, baseline/post-treatment differences did not reach significance; (3) TR-OCD patients significantly lowered their daily ratings of depressive and generalized anxiety symptoms; (4) TR-OCD patients obtained a significant and specific improvement in Trail Making Test-part B (TMT-B) performance; and (5) there was a significant and robust correlation between TMT-B improvement and OCD symptom reduction. Although practice and placebo effects cannot be ruled out, the specific effects found in the study support further testing in a randomized controlled trial. Our results provide data to design further randomized clinical trials as to test whether and how tDCS induces a relevant clinical benefit in OCD. We discuss important design considerations for such a trial.

Clinical Pilot Study and Computational Modeling of Bitemporal Transcranial Direct Current Stimulation, and Safety of Repeated Courses of Treatment, in Major Depression.

This study aimed to examine a bitemporal (BT) transcranial direct current stimulation (tDCS) electrode montage for the treatment of depression through a clinical pilot study and computational modeling. The safety of repeated courses of stimulation was also examined. Four participants with depression who had previously received multiple courses of tDCS received a 4-week course of BT tDCS. Mood and neuropsychological function were assessed. The results were compared with previous courses of tDCS given to the same participants using different electrode montages. Computational modeling examined the electric field maps produced by the different montages. Three participants showed clinical improvement with BT tDCS (mean [SD] improvement, 49.6% [33.7%]). There were no adverse neuropsychological effects. Computational modeling showed that the BT montage activates the anterior cingulate cortices and brainstem, which are deep brain regions that are important for depression. However, a fronto-extracephalic montage stimulated these areas more effectively. No adverse effects were found in participants receiving up to 6 courses of tDCS. Bitemporal tDCS was safe and led to clinically meaningful efficacy in 3 of 4 participants. However, computational modeling suggests that the BT montage may not activate key brain regions in depression more effectively than another novel montage--fronto-extracephalic tDCS. There is also preliminary evidence to support the safety of up to 6 repeated courses of tDCS.

Structural white matter changes in descending motor tracts correlate with improvements in motor impairment after undergoing a treatment course of tDCS and physical therapy.

Motor impairment after stroke has been related to the structural and functional integrity of corticospinal tracts including multisynaptic motor fibers and tracts such as the cortico-rubral-spinal and the cortico-tegmental-spinal tract. Furthermore, studies have shown that the concurrent use of transcranial direct current stimulation (tDCS) with peripheral sensorimotor activities can improve motor impairment. We examined microstructural effects of concurrent non-invasive bihemispheric stimulation and physical/occupational therapy for 10 days on the structural components of the CST as well as other descending motor tracts which will be referred to here as alternate motor fibers (aMF). In this pilot study, ten chronic patients with a uni-hemispheric stroke underwent Upper-Extremity Fugl-Meyer assessments (UE-FM) and diffusion tensor imaging (DTI) for determining diffusivity measures such as fractional anisotropy (FA) before and after treatment in a section of the CST and aMF that spanned between the lower end of the internal capsule (below each patient’s lesion) and the upper pons region on the affected and unaffected hemisphere. The treated group (tDCS + PT/OT) showed significant increases in the proportional UE-FM scores (+21%; SD 10%), while no significant changes were observed in an untreated comparison group. Significant increases in FA (+0.007; SD 0.0065) were found in the ipsilesional aMF in the treated group while no significant changes were found in the contralesional aMF, in either CST, or in any tracts in the untreated group. The FA changes in the ipsilesional aMF significantly correlated with the proportional change in the UE-FM (r = 0.65; p < 0.05). The increase in FA might indicate an increase in motor fiber alignment, myelination, and overall fiber integrity. Crossed and uncrossed fibers from multiple cortical regions might be one reason why the aMF fiber system showed more plastic structural changes that correlate with motor improvements than the CST.

Increase in PAS-induced neuroplasticity after a treatment courseof transcranial direct current stimulation for depression

BackgroundSeveral lines of evidence suggest that neuroplasticity is impaired in depression and improves with effective treatment. However until now, this evidence has largely involved measures such as learning and memory which can be influenced by subject effort and motivation. This pilot study aimed to objectively measure neuroplasticity in the motor cortex using paired associative stimulation (PAS), which induces short term neuroplastic changes. It is hypothesized that neuroplasticity would improve after effective treatment for depression. MethodsNeuroplasticity was measured in 18 depressed subjects before and after a course of anodal transcranial direct current stimulation (tDCS), given as treatment for depression. The relationships between PAS results, mood state and brain-derived neurotrophic factor (BDNF) serum levels were examined. ResultsNeuroplasticity (PAS-induced change) was increased after a course of tDCS (t(17)=−2.651, p=0.017). Treatment with tDCS also led to significant mood improvement, but this did not correlate with improved neuroplasticity. Serum BDNF levels did not change after tDCS, or correlate with change in neuroplasticity after tDCS treatment. LimitationsWhile this study showed evidence of improved neuroplasticity in the motor cortex after effective treatment, we are unable to present evidence that this change is generalized in the depressed brain. Also, the presence of antidepressant medications and the small sample of patients (n=18) meant the study could not definitively resolve the relationship between neuroplasticity, mood and BDNF. ConclusionThis novel preliminary study provides evidence that a treatment course of tDCS can improve neuroplasticity in depressed patients.

Spotlight on the April 1 Issue

Transcranial direct current stimulation (tDCS) was delivered in randomized order over the left dorsolateral prefrontal cortex for 20 minutes in patients in a vegetative state/unresponsive wakefulness syndrome or in a minimally conscious state (MCS). They were assessed at least 1 week after the acute traumatic or nontraumatic insult. tDCS may improve signs of consciousness in MCS following severe brain damage. See p. 1112 From editorialist John Whyte: “If a longer course of tDCS can accelerate recovery for a subgroup of the DOC population, perhaps a positive response to a single session of tDCS can identify …

Changes of electrophysiological parameters and neuropsychological characteristics in children with psychic development disorders after transcranial direct current stimulation (tDCS)

Abstract Introduction Recently, school maladjustment that is associated with the cognitive decline in children with minor central nervous system disorders has become one of the topical issues. Aim The aim of this research was a retrospective analysis of changes concerning neurophysiological and neuropsychological parameters in children with psychic development disorders after treatment employing the transcranial direct current stimulation (tDCS) technique. Materials and methods Study data of 128 children with learning disorders and 48 children with mild mental retardation, aged 8–12 years old, who had undergone a course of tDCS, were analyzed. The data of neuropsychological testing and electroencephalography (EEG) of 22 healthy children and 42 children with psychic development disorders who had undergone conventional treatment, aged 8–12 years old, were used as a control. For tDCS procedures 60–120 μA direct current was used, the stimulating electrodes area ranged from 2.5 cm2 to 6.25 cm2. Treatment session duration (ranging from 25 min to 45 min), as well as stimulating electrodes localization onto the scalp and the time of the procedure, depended on clinical goals, age, and the severity of disorders. The entire treatment course duration lasted 4–5 weeks: 5–9 procedures with 2–3 day intervals. Results A neuropsychological study revealed statistically significant improvement of higher mental functions in patients undergoing tDCS compared to control groups. Verbal functions improvement was observed in 80.0% of children with such disorders. In patients with dysgraphia, after tDCS the rate of mistakes in writing reduced 3-fold, the process of writing quickened. The ability to fulfill tasks requiring visual spatial analysis and synthesis also considerably improved. After the course of tDCS no cases of negative changes of EEG parameters were noted. On the contrary, the improvement of EEG parameters, showing their approaching the age norms, was observed. Discussion The study results indicate that tDCS enables one to not only change directionally the functional status of brain areas lying under electrodes, but also to influence actively the functional status of deep regulatory brain systems through the changing of modulatory cortical areas status. Conclusions Having practically no adverse effects, tDCS appears to be an effective correction technique with respect to higher psychic disorders for children with psychic development disorders.

Hypomania Induction in a Patient With Bipolar II Disorder by Transcranial Direct Current Stimulation (tDCS)

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. We report the case of a 33-year-old female with bipolar II disorder, on mood stabilizer medication, who had previously participated in a clinical trial of tDCS given with a bifrontal electrode montage for the treatment of major depression without incident, but became hypomanic when she received a later course of tDCS given with a frontoextracephalic configuration. Factors contributing to the development of hypomania in the second course of tDCS are examined. No substantial differences were found in the patient's clinical presentation between the 2 tDCS courses to explain the emergence of hypomania only after the second course. The different montage used in the second course appeared to be the main contributory factor in the induction of hypomania. The reported case suggests that frontoextracephalic tDCS has antidepressant properties and the potential to induce hypomanic symptoms. In particular, it raises the question of whether frontoextracephalic tDCS requires additional precautions when administered to bipolar patients compared to bifrontal tDCS.

Modulation of Event-related Desynchronization duringMotor Imagery with Transcranial Direct Current Stimulationin a Patient with Severe Hemiparetic Stroke: A Case Report

Recently, surface electroencephalogram (EEG)-based brain-machine interfaces (BMI) have been used for people with disabilities. As a BMI signal source, event-related desynchronization of alpha-band EEG (8-13 Hz) during motor imagery (mu ERD), which is interpreted as desynchronized activities of the activated neurons, is commonly used. However, it is often difficult for patients with severe hemiparesis to produce mu ERD of sufficient strength to activate BMI. Therefore, whether it is possible to modulate mu ERD during motor imagery with anodal transcranial direct-current stimulation (tDCS) was assessed in a severe left hemiparetic stroke patient. EEG was recorded over the primary motor cortex (M1), and mu ERD during finger flexion imagery was measured before and after a 5-day course of tDCS applied to M1. The ERD recorded over the affected M1 increased significantly after tDCS intervention. Anodal tDCS may increase motor cortex excitability and potentiate ERD during motor imagery in patients with severe hemiparetic stroke.