Transcranial direct current stimulation for post-COVID fatigue: a randomized, double-blind, controlled pilot study

Effects of transcranial direct current stimulation on pain and function in patients with knee osteoarthritis: A systematic review and meta-analysis.

Transcranial direct current stimulation can be effective in reducing the craving for food, alcohol, and methamphetamine. Because its effects have not been tested on patients with opium use disorder, we investigated its efficacy when it is combined with a standard methadone maintenance therapy protocol. We carried out a pretest-posttest control group method to evaluate the effect of transcranial direct current stimulation at the dorsolateral prefrontal cortex (right anodal/left cathodal) on opium craving, depression, and anxiety symptoms. We considered opium craving as a primary outcome as well as depression and anxiety symptoms as secondary outcomes. Sixty participants with opium use disorder were randomly assigned into 3 groups (n = 20 for each group): (1) an active transcranial direct current stimulation with methadone maintenance treatment (active tDCS group), (2) sham transcranial direct current stimulation with methadone maintenance treatment (sham tDCS group), and (3) only methadone maintenance treatment (methadone maintenance treatment group). All participants completed the Desire for Drug Questionnaire, Obsessive-Compulsive Drug Use Scale, Beck Depression Inventory II, and Beck Anxiety Inventory a week before and a week after the treatment. The outcomes were assessed by independent assessors who were blind to the treatment conditions. The active tDCS group had a significant reduction in opium craving, depression, and anxiety symptoms compared with the other 2 groups. Our results provide a preliminary support for using the transcranial direct current stimulation along with methadone maintenance therapy in the treatment of patients with opium use disorder.

Short-term memory refers to the capacity for holding information in mind for a short period of time with conscious memorization. It is an important ability for daily life and is impaired in several neurological and psychiatric disorders. Anodal transcranial direct current stimulation (tDCS) applied to the dorsolateral prefrontal cortex (DLPFC) was reported to enhance the capability of short-term memory in healthy subjects. However, results were not consistent and what is the possible impact factor is not known. One important factor that may significantly influence the effect of tDCS is the timing of tDCS administration. In order to explore whether tDCS impact short-term memory and the optimal timing of tDCS administration, we applied anodal tDCS to the left DLPFC to explore the modulatory effect of online and off-line tDCS on digit span as well as visual short-term memory performance in healthy subjects. Results showed tDCS of the left DLPFC did not influence intentional digit span memory performance, whether before the task or during the task. In addition, tDCS of the DLPFC administered before the task showed no effect on visual short-term memory, while there was a trend of increase in false alarm when tDCS of the DLPFC administered during the task. These results did not provide evidence for the enhancement of short-term memory by tDCS of the left DLPFC in healthy subjects, but it suggested an importance of administration time for visual short-term memory. Further studies are required to taking into account the baseline performance of subjects and time-dependence feature of tDCS.

Preliminary evidence showed additional effects of anodal transcranial direct current stimulation over the damaged cerebral hemisphere combined with cathodal transcutaneous spinal direct current stimulation during robot-assisted gait training in chronic stroke patients. This is consistent with the neural organization of locomotion involving cortical and spinal control. The cerebellum is crucial for locomotor control, in particular for avoidance of obstacles, and adaptation to novel conditions during walking. Despite its key role in gait control, to date the effects of transcranial direct current stimulation of the cerebellum have not been investigated on brain stroke patients treated with robot-assisted gait training. To evaluate the effects of cerebellar transcranial direct current stimulation combined with transcutaneous spinal direct current stimulation on robot-assisted gait training in patients with chronic brain stroke. After balanced randomization, 20 chronic stroke patients received ten, 20-minute robot-assisted gait training sessions (five days a week, for two consecutive weeks) combined with central nervous system stimulation. Group 1 underwent on-line cathodal transcranial direct current stimulation over the contralesional cerebellar hemisphere + cathodal transcutaneous spinal direct current stimulation. Group 2 received on-line anodal transcranial direct current stimulation over the damaged cerebral hemisphere + cathodal transcutaneous spinal direct current stimulation. The primary outcome was the 6-minute walk test performed before, after, and at follow-up at 2 and 4 weeks post-treatment. The significant differences in the 6-minute walk test noted between groups at the first post-treatment evaluation (p = 0.041) were not maintained at either the 2-week (P = 0.650) or the 4-week (P = 0.545) follow-up evaluations. Our preliminary findings support the hypothesis that cathodal transcranial direct current stimulation over the contralesional cerebellar hemisphere in combination with cathodal transcutaneous spinal direct current stimulation might be useful to boost the effects of robot-assisted gait training in chronic brain stroke patients with walking impairment.

Background: Burnout is characterized by deficiencies in attention and several components of the working memory. It has been shown that cognitive behavioral therapy can have a positive effect on burnout and depressive symptoms, however, the lingering effects of impaired attention and executive functions are the most frustrating. We hypothesized that anodal transcranial direct current stimulation (atDCS) over the left dorsolateral prefrontal cortex (DLPFC) can improve the executive control of attention and possibly several other components of working memory in patients with burnout. Methods: This was a randomized double-blind sham-controlled pilot study with two groups. Patients with burnout received three weeks of daily sessions (15 sessions in total) of atDCS or sham stimulation in addition to three weekly sessions of standard behavioral therapy. The primary outcome measure was attention and the central executive of the working memory. Secondary, the effect of atDCS was measured on other components of working memory, on burnout and depression scores, and on quality of life (QoL). Results: We enrolled and randomly assigned 16 patients to a sham or real stimulation group, 15 (7 sham, 8 real) were included in the analysis. atDCS had a significant impact on attention. Post-hoc comparisons also revealed a trend towards more improvement after real tDCS for inhibition and shifting, updating and control, and encoding. Both groups improved on burnout and depression scores. Conclusion: These data provide preliminary evidence for the value of atDCS over the left DLPFC in rehabilitating attention deficits, and possibly also central executive and encoding deficits, in burnout. However, the current study has some limitations, including the sample size and heterogeneous patient population. More elaborate studies are needed to elucidate the specific impact of atDCS over the left DLPFC on burnout. Trial registration: ISRCTN.com ( ISRCTN94275121) 17/11/19.

Transcranial direct current stimulation (TDCS) of primary motor cortex (M1) can transiently improve paretic hand function in chronic stroke. However, responses are variable so there is incentive to try to improve efficacy and or to predict response in individual patients. Both excitatory (Anodal) stimulation of ipsilesional M1 and inhibitory (Cathodal) stimulation of contralesional M1 can speed simple reaction time. Here we tested whether combining these two effects simultaneously, by using a bilateral M1–M1 electrode montage, would improve efficacy. We tested the physiological efficacy of Bilateral, Anodal or Cathodal TDCS in changing motor evoked potentials (MEPs) in the healthy brain and their behavioural efficacy in changing reaction times with the paretic hand in chronic stroke. In addition, we aimed to identify clinical or neurochemical predictors of patients' behavioural response to TDCS. There were three main findings: 1) unlike Anodal and Cathodal TDCS, Bilateral M1–M1 TDCS (1mA, 20min) had no significant effect on MEPs in the healthy brain or on reaction time with the paretic hand in chronic stroke patients; 2) GABA levels in ipsilesional M1 predicted patients' behavioural gains from Anodal TDCS; and 3) although patients were in the chronic phase, time since stroke (and its combination with Fugl–Meyer score) was a positive predictor of behavioural gain from Cathodal TDCS. These findings indicate the superiority of Anodal or Cathodal over Bilateral TDCS in changing motor cortico-spinal excitability in the healthy brain and in speeding reaction time in chronic stroke. The identified clinical and neurochemical markers of behavioural response should help to inform the optimization of TDCS delivery and to predict patient outcome variability in future TDCS intervention studies in chronic motor stroke.

Modulation of risk-taking in marijuana users by transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC)

A growing body of literature has implicated the left dorsolateral prefrontal cortex (DLPFC) in the online monitoring of vocal production through auditory feedback. Specifically, disruption of or damage to the left DLPFC leads to exaggerated compensatory vocal responses to altered auditory feedback. It is conceivable that enhancing the cortical excitability of the left DLPFC may produce inhibitory influences on vocal feedback control by reducing vocal compensations. We used anodal transcranial direct current stimulation (a-tDCS) to modulate cortical excitability of the left DLPFC and examined its effects on auditory-motor integration for vocal pitch regulation. Seventeen healthy young adults vocalized vowel sounds while hearing their voice pseudo-randomly pitch-shifted by ±50 or ±200 cents, either during (online) or after (offline) receiving active or sham a-tDCS over the left DLPFC. Active a-tDCS over the left DLPFC led to significantly smaller peak magnitudes and shorter peak times of vocal compensations for pitch perturbations than sham stimulation. In addition, this effect was consistent regardless of the timing of a-tDCS (online or offline stimulation) and the size and direction of the pitch perturbation. These findings provide the first causal evidence that a-tDCS over the left DLPFC can facilitate auditory-motor integration for compensatory adjustment to errors in vocal output. Reduced and accelerated vocal compensations caused by a-tDCS over left DLPFC support the hypothesis of a top-down neural mechanism that exerts inhibitory control over vocal motor behavior through auditory feedback.

Effects of transcranial direct current stimulation on working memory in patients with Parkinson's disease

Balance and gait impairments are major motor deficits in stroke patients that require intensive neuro-rehabilitation. Anodal transcranial direct current stimulation is a neuro-modulatory technique recently used in stroke patients for balance and gait improvement. Majority of studies focusing on tDCS have assessed its effects on cerebral motor cortex and more recently cerebellum as well but to our best knowledge the comparison of stimulating these two regions in stroke patients is not investigated so far. The current study aimed to compare the effect of anodal transcranial direct current stimulation on cerebellar and cerebral motor cortex M1 in stroke patients. This double-blinded, parallel, randomized, sham controlled trial included 66 patients with a first-ever ischemic stroke were recruited into three groups; Cerebellar stimulation group (CbSG), M1 Stimulation Group (MSG), and Sham stimulation group (SSG). A total of three sessions of anodal transcranial direct current stimulation were given on consecutive days in addition to non-immersive virtual reality using Xbox 360 with kinect. Anodal tDCS with an intensity of 2 mA was applied for a duration of 20 min. Primary outcome measures berg balance scale (BBS), timed up and go test (TUG), BESTest Balance Evaluation-Systems Test (BESTest) and secondary outcomes measures montreal cognitive assessment (MoCA), mini mental state examination (MMSE), Johns Hopkins Fall Risk Assessment Tool (JHFRAT), twenty five feet walk test (25FWT), six minute walk test (6MWT), and tDCS Adverse Effects was assessed before initiation of treatment (T0) and at the end of third session of stimulation (T1). The results of between group's analysis using mean difference showed a significant difference with p-value <0.05 for balance (BBS, TUG, BESTest), walking ability (6MWT, 25FWT), risk of fall (JHFRAT). Cognitive function did not show any significant change among the groups for MoCA with p-value >0.05 but MMSE was improved having significant p-value (p = 0.013). However, 6MWT and 25FWT showed non-significant results for both between group and within group analysis. In pairwise comparison both the cerebellar and cerebral stimulation groups showed Significant difference with p-value <0.05 in comparison to sham stimulation; BBS (cerebellar vs. sham p ≤ 0.001, cerebral vs. sham p = 0.011), TUG (cerebellar vs. sham p = 0.001, cerebral vs. sham p = 0.041), Bestest (cerebellar vs. sham p = 0.007, cerebral vs. sham p = 0.003). Whereas for JHFRAT only cerebellar stimulation in comparison to sham and motor cortex stimulation showed significant improvements (cerebellar vs. M1 p = 0.037, cerebellar vs. sham p = 0.037). MMSE showed significant improvement in M1 stimulation (M1 vs. cerebellar p = 0.036, M1 vs. sham p = 0.011). Findings of the study suggest anodal tDCS stimulation of the cerebellum and cerebral motor cortex both improves gait, balance and risk of fall in stroke patients. However, both stimulation sites do not induce any notable improvement in cognitive function. Effects of both stimulation sites have similar effects on mobility in stroke patients.

Previously, transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has resulted in improved performance in simple motor tasks. For a complex bimanual movement, studies using functional magnetic resonance imaging and transcranial magnetic stimulation indicated the involvement of the left dorsolateral prefrontal cortex (DLPFC) as well as left M1. Here we investigated the relative effect of up-regulating the cortical function in left DLPFC and left M1 with tDCS. Participants practised a complex bimanual task over four days while receiving either of five stimulation protocols: anodal tDCS applied over M1, anodal tDCS over DLPFC, sham tDCS over M1, sham tDCS over DLPFC, or no stimulation. Performance was measured at the start and end of each training day to make a distinction between acquisition and consolidation. Although task performance improved over days, no significant difference between stimulation protocols was observed, suggesting that anodal tDCS had little effect on learning the bimanual task regardless of the stimulation sites and learning phase (acquisition or consolidation). Interestingly, cognitive performance as well as corticomotor excitability did not change following stimulation. Accordingly, we found no evidence for behavioural or neurophysiological changes following tDCS over left M1 or left DLPFC in learning a complex bimanual task.

Background: Studies have demonstrated that fear memories can be modified using non-invasive methods. Recently, we demonstrated that anodal transcranial direct current stimulation (tDCS) of the right dorsolateral prefrontal cortex is capable of enhancing fear memories. Here, we examined the effects of cathodal tDCS of the right dorsolateral prefrontal cortex during fear reconsolidation in humans. Methods: Seventeen young, healthy subjects were randomly assigned to two groups, which underwent fear conditioning with mild electric stimuli paired with a visual stimulus. Twenty-four hours later, both groups were shown a reminder of the conditioned fearful stimulus. Shortly thereafter, they received either tDCS (right prefrontal—cathodal, left supraorbital—anodal) for 20 min at 1 mA, or sham stimulation. A day later, fear responses of both groups were compared. Results: On Day 3, during fear response assessment, there were no significant differences between the tDCS and sham group (p > 0.05). Conclusion: We conclude that cathodal tDCS of the right dorsolateral prefrontal cortex (right prefrontal—cathodal, left supraorbital—anodal) did not influence fear memories.

Objective: To improve gait and balance in patients with Parkinson’s disease by combining anodal transcranial direct current stimulation with physical training. Design: In a double-blind design, one group (physical training; n = 8) underwent gait and balance training during transcranial direct current stimulation (tDCS; real/sham). Real stimulation consisted of 15 minutes of 2 mA transcranial direct current stimulation over primary motor and premotor cortex. For sham, the current was switched off after 30 seconds. Patients received the opposite stimulation (sham/real) with physical training one week later; the second group (No physical training; n = 8) received stimulation (real/sham) but no training, and also repeated a sequential transcranial direct current stimulation session one week later (sham/real). Setting: Hospital Srio Libanes, Buenos Aires, Argentina. Subjects: Sixteen community-dwelling patients with Parkinson’s disease. Interventions: Transcranial direct current stimulation with and without concomitant physical training. Main measures: Gait velocity (primary gait outcome), stride length, timed 6-minute walk test, Timed Up and Go Test (secondary outcomes), and performance on the pull test (primary balance outcome). Results: Transcranial direct current stimulation with physical training increased gait velocity (mean = 29.5%, SD = 13; p < 0.01) and improved balance (pull test: mean = 50.9%, SD = 37; p = 0.01) compared with transcranial direct current stimulation alone. There was no isolated benefit of transcranial direct current stimulation alone. Although physical training improved gait velocity (mean = 15.5%, SD = 12.3; p = 0.03), these effects were comparatively less than with combined tDCS + physical therapy (p < 0.025). Greater stimulation-related improvements were seen in patients with more advanced disease. Conclusions: Anodal transcranial direct current stimulation during physical training improves gait and balance in patients with Parkinson’s disease. Power calculations revealed that 14 patients per treatment arm (α = 0.05; power = 0.8) are required for a definitive trial.

Transcranial Direct Current Brain Stimulation Increases Ability to Resist Smoking.

Sports fatigue in soccer athletes has been shown to decrease neural activity, impairing cognitive function and negatively affecting motor performance. Transcranial direct current stimulation (tDCS) can alter cortical excitability, augment synaptic plasticity, and enhance cognitive function. However, its potential to ameliorate cognitive impairment during sports fatigue remains largely unexplored. This study investigated the effect of dual-site tDCS targeting the dorsolateral prefrontal cortex (DLPFC) or primary motor cortex (M1) on attention, decision-making, and working memory in elite soccer athletes during sports fatigue. Sports fatigue was induced in 23 (non-goalkeeper) elite soccer athletes, who then participated in three counterbalanced intervention sessions: dual-site tDCS over the M1, dual-site tDCS over the DLPFC, and sham tDCS. Following tDCS, participants completed the Stroop, Iowa Gambling, and 2-back tasks. We found a significant improvement in Stroop task accuracy following dual-site anodal tDCS over the M1 compared with the sham intervention in the incongruent condition (p = 0.036). Net scores in the Iowa Gambling task during blocks 4 (p = 0.019) and 5 (p = 0.014) significantly decreased under dual-site tDCS targeting the DLPFC compared with the sham intervention. No differences in 2-back task performance were observed between sessions (all p > 0.05). We conclude that dual-site anodal tDCS applied to the M1 enhanced attention performance while tDCS targeting the DLPFC increased risk propensity in a decision-making task during sports fatigue in elite soccer athletes. However, dual-site anodal tDCS targeting either the M1 or DLPFC did not significantly influence working memory performance during sports fatigue in this population. These preliminary findings suggest that dual-site tDCS targeting the M1 has beneficial effects on attention performance, potentially informing future research on sports fatigue in athletes. No: NCT06594978. Registered 09 September, 2024; https://clinicaltrials.gov/search?cond=NCT06594978.