Sham tDCS Group Research Articles

P0159 Effects of Transcranial Direct Current Stimulation (tDCS) on enteric nervous system (ENS) gene expression and intestinal barrier in chronic DSS colitis

Abstract Background Chronic visceral pain is a clinical challenge in >50% of Inflammatory Bowel Disease (IBD) cases. A randomized controlled trial (RCT) revealed that transcranial direct current stimulation (tDCS) can modulate brain activity and effectively alleviate chronic abdominal pain associated with IBD. To elucidate the underlying mechanism of tDCS, we implemented this technique in a mouse model of inflammatory, chronic DSS colitis. Methods The tDCS protocol (10 stimulations) was deduced from human tDCS studies. We administered an anodal direct current (0.5 mA, 20 min) to both primary motor cortices over two separate periods (5 consecutive days of stimulation per period separated by a two-day break). The study was controlled by a sham-tDCS group. For determining mucosal barrier integrity murine intestinal mucosa was mounted to Ussing chambers. Histology was done (H&E staining of FFPE colon sections). Murine activity after tDCS was assessed by mouse tracking in home cages (RFID-chipped mice). Myenteric plexus (MP) cells from the murine terminal ileum, were isolated and cultivated for 10 days. Immunostaining and bulk-RNA sequencing (NovaSeq Xplus system, read length 150 bp, read depth 30 M copies/run) were performed. Results DSS caused an inflammation-driven thickening of the colon wall, resulting in an increased transmural resistance. This effect was ameliorated by tDCS (mean±SEM DSS+sham-tDCS: 72.2±8.2 Ω·cm²; DSS+tDCS: 48.1±2.1 Ω·cm²; MWU: p=0.007). Induction of a DSS colitis was associated with a reduced murine activity, which was partially recovered by tDCS (mean±SEM DSS+sham-tDCS: 70.7±15.2 rel.dist.U/day; DSS+tDCS: 205.9 ± 40.4 rel.dist.U/day; MWU: p=0.029). Neuronal cell identity was confirmed in isolated murine MP cells by immunostaining (b3-tubulin, S100B). Bulk-RNAseq significantly separated tDCS- from sham-tDCS treated DSS colitis mice as revealed by PCA. Consecutively, 739 differentially expressed genes were identified in tDCS-treated colitis mice compared to sham-tDCS-treated DSS colitic mice (622 upregulated, 117 downregulated genes; log2FC≥1.5, p-adj<0.05). KEGG and GO pathway analysis included neuroactive ligand-receptor interaction (p=7.94·10-3), gated channel activity (p=2.4·10-7), substrate-specific channel activity (p=1.99·10-7), leukocyte migration (p=3.99·10-7). Conclusion In colitis, tDCS has the capacity to modulate activity of DSS-treated mice and alters gene expression in MP cells. This reveals another layer of evidence for the impact of central pathways on the brain-gut-axis. References Neeb et al., Brain Stimulation, 2019

Efficacy of Transcranial Direct Current Stimulation on Cognitive Function in Dementia and Mild Cognitive Impairment Secondary to Neurodegenerative Etiology: A Systematic Review and Meta-Analysis

Background: Dementia is a chronic progressive illness with significant impairment in a person’s functioning ability. The currently available treatment options for dementia are limited in modifying disease progression. Non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) are emerging as potential treatment options for cognitive as well as behavioral symptoms in dementia. The objective of this systematic review and meta-analysis is to assess the efficacy of tDCS on cognitive function in mild cognitive impairment (MCI) and dementia due to neurodegenerative disorders to provide an update on the existing evidence considering an increasing number of trials using tDCS. Methods: The study was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines with a prespecified protocol registered in PROSPERO (CRD42024503852). The study selection was made through a search on databases such as PubMed, Ovid MEDLINE, APA PsycInfo, and Cochrane trials registry and a gray literature search on ClinicalTrials.gov. All randomized controlled trials that have used tDCS as a standalone intervention for cognitive impairment were included in the present study. Risk of bias (RoB) was assessed by the Cochrane RoB2 tool. Meta-analysis of outcomes was performed using RevMan software version 5.4. Pooled estimates of standardized mean difference (SMD) and 95% confidence interval (CI) were obtained for global cognition (primary outcome) and other domain-specific cognitive outcomes. Results: A total of 24 studies were finally included in the review. Most of the studies had “some concerns” with regard to the overall RoB. A total of 164 subjects in the true tDCS group and 151 subjects in the sham tDCS groups out of eight studies were analyzed for global cognitive outcome, giving a pooled SMD (95% CI) of 0.80 (0.35, 1.26), giving an overall effect of Z = 3.45 (P < 0.001), with I2 value of 72%, favoring true tDCS. On a sub-group analysis, a significant improvement was noted in the Alzheimer’s dementia group but not MCI. Discussion: The study findings suggest that tDCS is effective in improving global cognition in participants with Alzheimer’s dementia but not MCI. Owing to a smaller number of studies, the domain-specific cognitive outcomes could not be assessed effectively. There was a wide heterogeneity in the included studies in terms of tDCS stimulation protocols.

Non-invasive brain stimulation enhances the effect of physiotherapy for balance and mobility impairment in people with Multiple Sclerosis.

Impairment of balance and gait is common in Multiple Sclerosis (MS). Non-invasive Brain Stimulation techniques are promising adjuncts to physical therapy to improve disability. To determine if combining transcranial direct current stimulation (tDCS) with conventional exercise therapy enhances balance and mobility in people with multiple sclerosis (PwMS) compared to exercise alone. In a double-blind randomised controlled trial, PwMS were randomised into a real or sham tDCS group. All patients received individualized exercise treatment. Twelve sessions of real (intensity 2mA, bipolar) or sham tDCS was administered over the primary motor area for 20 minutes followed by one hour of physiotherapy focusing on balance, strength, and mobility, twice a week for six weeks. Outcome measures included balance (Berg Balance Score), mobility (10m Walk Test), fatigue (Fatigue Severity Scale) and quality of life (Multiple Sclerosis Quality of Life - 54) performed 1 week before intervention, at week 7 (1-week post-intervention), and at six months post-intervention. Falls questionnaire was completed 1 week before intervention and at 6 months post-intervention. Generalised linear mixed model analysis was used to compare outcomes at different time points within groups (before and after exercise treatment) and between groups (sham vs real stimulation groups). Forty participants (mean age 54 and mean EDSS 3.5) were randomly allocated to receive real (n=19) or sham (n=21) stimulation, with 36 completing the post-intervention (real 17, sham 19) and 32 completing the 6-month assessments (real 15, sham 17). All participants had significantly improved balance and mobility scores post exercise treatment (within groups comparison, p<0.05). Between groups comparison found a small but significant improvement in the Berg Balance Score (mean improvement 1.9 and 2 points, p <0.05) and 10-metre Walk Test (mean improvement of 0.09 and 0.11m/s, p <0.05) in the real tDCS group compared to the sham group after six weeks of training and at six months follow-up, respectively. There was no benefit in fatigue, falls and QOL scores in the real stimulation group compared to the control group. Our results suggest that the addition of tDCS prior to exercise treatment provides a significant improvement in walking speed and balance in people with MS which lasts longer, compared to exercise alone. Further study is needed to optimize the use of this relatively inexpensive and well tolerated device for rehabilitation. Australia and New Zealand Clinical Trial Registry (ACTRN12628001836224).

Combined Effect of tDCS and Motor or Cognitive Activity in Patients with Alzheimer's Disease: A Proof-of-Concept Pilot Study.

(1) Background: Alzheimer's disease (AD) accounts for 70% of dementia cases and with no effective pharmacological treatments, new rehabilitation methods are needed. Motor and cognitive activities and transcranial direct current stimulation (tDCS) have shown promise in stabilizing and enhancing cognitive functions. Objective: we want to investigate the effects of tDCS combined with motor or cognitive activity on cognitive functions in AD patients. (2) Methods: Patients with mild or moderate AD were randomized between anodic tDCS groups (MotA or CogA) and sham tDCS groups (MotS or CogS). They received two weeks of treatment (45 min, five days/week), with the first 15 min using tDCS stimulation on the dorsolateral prefrontal cortex. Cognitive assessments were conducted pre-treatment (T0), post-treatment (T1), and one week after (T2). (3) Results: Twenty-three patients were included. Statistical analysis showed significant differences between anodic tDCS groups (MotA + CogA) and sham tDCS groups (MotS + CogS) with advantages for the first in improving global cognitive status (p = 0.042), selective attention (p = 0.012), and sustained attention (p = 0.012). Further analysis indicated no differences between the two anodic tDCS groups between T0 and T1. (4) Conclusions: combined anodal tDCS with motor or cognitive activity could improve global cognitive state and attention, slowing cognitive decline in AD patients. The trial was registered on Clinical Trials: NCT06619795.

Comparing the effects of anodal and cathodal transcranial direct current stimulation of primary motor cortex at varying intensities on motor learning in healthy young adults.

Inconsistent results are observed in the effects of transcranial direct current stimulation (tDCS) with different montages on motor learning. This study aimed to compare the effects of anodal and cathodal tDCS (c-tDCS) over primary motor cortex (M1) at different intensities on motor learning in healthy young adults. The participants were randomly divided into: (1) 1mA M1 c-tDCS, (2) 1mA M1 anodal tDCS (a-tDCS), (3) 2mA M1 c-tDCS, (4) 2mA M1 a-tDCS and (5) M1 sham tDCS groups. The groups received 20-min stimulation with serial reaction time task (SRTT) incidentally, while the tDCS was turned off after 30 s in the sham tDCS group. Response time (RT) and error rate (ER) during SRTT were assessed prior, during and 72 h after the intervention. The results of the paired t-test indicated that online learning occurred in all groups (p< 0.05), except in M1 c-tDCS (1mA) (p> 0.05). One-way ANOVA analysis also indicated that there were differences in offline learning (RT (F(DF) =5.19(4); p< 0.001; and ER (F(DF) =9(4), p< 0.0001) among groups, with more offline learning in 1mA M1 a-tDCS, 2mA M1 c-tDCS and 2mA M1 a-tDCS groups (p< 0.05). On the other hand, the 1mA M1 c-tDCS group did not indicate any consolidation effect or even a trend toward negative offline learning. M1 a-tDCS with different intensities and also 2mA M1 c-tDCS may be helpful for the enhancement of motor learning in young healthy adults. This study enhances our understanding of tDCS intensity and polarity effects on motor learning, with potential for optimizing therapeutic protocols.

Comparison of short- and long-term effects of neurofeedback and transcranial electrical stimulation on the motor learning in healthy adults

Researchers are exploring non-invasive neuromodulation techniques like transcranial direct current stimulation (tDCS) and neurofeedback (NFB) for enhancing motor learning. While tDCS modulates brain excitability using exogenous electric fields, NFB is an endogenous brain stimulation technique that enables individuals to regulate brain excitability in a closed-loop system. Despite their differing mechanisms, a direct comparison of their effects on motor learning is lacking. This study aimed to compare tDCS and NFB on online learning, short-term offline learning, and long-term offline learning in healthy participants, seeking to identify the most effective method for motor learning enhancement. In this parallel, randomized, single-blinded, controlled trial, 100 healthy participants were randomly assigned to one of five groups: real tDCS, sham tDCS, real NFB, sham NFB, and passive control. Primary outcomes included normalized reaction time (NRT), normalized response accuracy (NRA), and normalized skill index (NSI), measured through a serial reaction time task. Secondary outcomes involved physical and mental fatigue, assessed using a visual analog scale. The study involved 14 blocks of 80 trials each. Online learning was assessed by changes in NRT, NRA, and NSI between Block 3 and Block 9. Short-term and long-term offline learning were evaluated by changes in these measures between Block 9 and Block 11, and between Block 9 and Block 13, respectively. Resultsshowed a significant decrease in NRA in the sham tDCS and passive control groups from block 3–9, with no changes in other groups. NRT significantly decreased in all intervention groups from block 9–11, with no change in the control group. The NSI significantly increased across all intervention groups between blocks 9 and 11, with large to very large effect sizes, while the passive control group saw a medium effect size increase. Furthermore, NRA significantly increased in the real NFB and real tDCS groups from block 9 to block 13. NRT also significantly decreased in all intervention groups when comparing block 13 to block 9, while the passive control group showed no significant changes. Notably, the reduction in NRT from block 9 to block 13 was significantly greater in the real tDCS group than in the control group, with a mean difference of 0.087 (95 % CI: 0.004–0.169, p = 0.031). Additionally, NSI significantly increased in all intervention groups except the control group from block 9 to block 13.In conclusion, neither NFB nor tDCS had a significant positive impact on online learning. However, both real and sham versions of tDCS and NFB resulted in notable improvements in short-term offline learning. The difference in improvement between NFB and tDCS, as well as between real and sham interventions, was not statistically significant, suggesting that the placebo effect may play a significant role in enhancing short-term offline learning. For long-term offline learning, both brain stimulation methods, particularly tDCS, showed positive effects, although the placebo effect also appeared to contribute.

Different montages of transcranial direct current stimulation on postural stability in chronic low back pain patients: A randomized sham-controlled study.

Impairment in both the motor and cognitive aspects of postural control is a critical issue in patients with chronic low back pain (CLBP) who experience high pain anxiety (HPA). This study aimed to compare the effects of cathodal and anodal transcranial direct current stimulation (c-tDCS and a-tDCS) over the dorsolateral prefrontal cortex (DLPFC) on postural control during cognitive postural tasks in CLBP patients with HPA. This study included 66 patients randomly assigned to three groups: DLPFC a-tDCS, DLPFC c-tDCS, and sham tDCS. All groups received 20 minutes of tDCS, but the stimulation was gradually turned off in the sham group. Postural stability indices were assessed using the Biodex Balance System. Both the a-tDCS and c-tDCS groups showed a significant reduction in most postural stability indices at static and dynamic levels after the interventions (immediately, 24 hours, and one-week follow-up) during the cognitive postural task (P< 0.01). Additionally, there was a significant improvement in postural balance in the a-tDCS and c-tDCS groups compared to the sham tDCS group (P< 0.01). Furthermore, the a-tDCS group showed significantly greater improvement than the c-tDCS group (P< 0.01). Based on the results, both a-tDCS and c-tDCS over the DLPFC had positive effects on postural control during cognitive postural tasks in CLBP patients with HPA.

Efficacy of Transcranial Direct Current Stimulation on the Dorsolateral Prefrontal Cortex in Reducing Craving, Depression, and Improving Working Memory in Patients with Cannabis Use Disorders: A Randomized, Double-blind, Sham-controlled

Background: The beneficial effect of transcranial direct current stimulation (tDCS) on substance use disorders, achieved by reducing craving, impulsivity, and risk-taking behavior, can be considered an effective therapeutic approach. Transcranial direct current stimulation can be considered an effective therapeutic approach for reducing cannabis craving, improving levels of depression, and enhancing working memory in cannabis users. Objectives: This study investigated the effectiveness of tDCS applied to the Dorsolateral prefrontal cortex (DLPFC) on craving, depression, and working memory in cannabis users. Methods: This was a randomized, sham-controlled, double-blind, parallel-group study. Fifty male participants who met the criteria for cannabis use disorder according to DSM-5 were randomly assigned to either the real tDCS group (25 participants) or the sham tDCS group (25 participants). Pretests, including marijuana urine tests, the Marijuana Craving Questionnaire-Short Form (MCQ-SF), the Hamilton Depression Rating Scale (HDRS), and the Wechsler Memory Scale, were conducted before the intervention. The real tDCS group underwent 20 sessions of tDCS stimulation, each lasting 20 minutes, with a current intensity of 2 milliamperes applied at the F3 and F4 positions for DLPFC stimulation. The sham tDCS group received only 30 seconds of initial electrical stimulation, with no further current delivered. Both groups also received standard psychological treatments alongside the tDCS interventions. After completing the interventions, the same tests were administered again to assess the outcomes. Results: Participants who received real tDCS showed significant improvement in levels of craving, depression, and working memory. This reduction in scores and levels was statistically significant compared to the sham group. Conclusions: Transcranial direct current stimulation can be considered an effective therapeutic approach for reducing cannabis craving, improving levels of depression, and enhancing working memory in cannabis users.

Effects of DLPFC tDCS Followed by Treadmill Training on Dual-Task Gait and Cortical Excitability in Parkinson’s Disease: A Randomized Controlled Trial

Background Gait disturbances are exacerbated in people with Parkinson’s disease (PD) during dual-task walking (DTW). Transcranial direct current stimulation (tDCS) has been shown to exert beneficial effects on gait performance and cortical excitability in PD; however, its combined effects with treadmill training (TT) remain undetermined. Objective To investigate the effects of tDCS followed by TT on DTW performance and cortical excitability in individuals with PD. Methods Thirty-four PD participants were randomized to dorsal lateral prefrontal cortex (DLPFC) tDCS and TT group (DLPFC tDCS + TT group) or sham tDCS and TT group (sham tDCS + TT group) for 50 minutes per session (20 minutes tDCS followed by 30 minutes TT), 12 sessions within 5 weeks (2-3 sessions each week). Outcome measures included cognitive dual-task walking (CDTW), motor dual-task walking (MDTW), usual walking performance, cortical excitability, functional mobility, cognitive function, and quality of life. Results The DLPFC tDCS + TT group exerted significantly greater improvement in CDTW velocity (P = .046), cadence (P = .043), and stride time (P = .041) compared to sham tDCS + TT group. In addition, DLPFC tDCS + TT group demonstrated a significant increase in resting motor threshold of stimulated hemisphere compared with sham tDCS + TT group (P = .026). However, no significant differences between groups were found in MDTW performance and other outcomes. Conclusion Twelve-session DLPFC tDCS followed by TT significantly improved CDTW performance and decreased cortical excitability more than TT alone in individuals with PD. Applying DLPFC tDCS prior to TT could be suggested for gait rehabilitation in individuals with PD. Clinical trial registration number: Australian New Zealand Clinical Trials Registry ACTRN12622000101785

Unraveling the temporal interplay of slow-paced breathing and prefrontal transcranial direct current stimulation on cardiac indices of autonomic activity.

The neurovisceral integration model proposes that information flows bidirectionally between the brain and the heart via the vagus nerve, indexed by vagally mediated heart rate variability (vmHRV). Voluntary reduction in breathing rate (slow-paced breathing, SPB, 5.5 Breathing Per Minute (BPM)) can enhance vmHRV. Additionally, prefrontal transcranial direct current stimulation (tDCS) can modulate the excitability of the prefrontal region and influence the vagus nerve. However, research on the combination of SPB and prefrontal tDCS to increase vmHRV and other cardiac (heart rate (HR) and blood pressure) and peripheral (skin conductance) indices is scarce. We hypothesized that the combination of 20 min of SPB and prefrontal tDCS would have a greater effect than each intervention in isolation. Hence, 200 participants were divided into four groups: active tDCS with SPB, active tDCS with 15 BPM breathing, sham tDCS with SPB, and sham tDCS with 15 BPM breathing. Regardless of the tDCS condition, the 5.5 BPM group showed a significant increase in vmHRV over 20 minutes and significant decreases in HR at the first and second 5-min epochs of the intervention. Regardless of breathing condition, the active tDCS group exhibited higher HR at the fourth 5-min epoch of the intervention than the sham tDCS group. No other effects were observed. Overall, SPB is a robust technique for increasing vmHRV, whereas prefrontal tDCS may produce effects that counteract those of SPB. More research is necessary to test whether and how SPB and neuromodulation approaches can be combined to improve cardiac vagal tone.

Effect of transcranial direct current stimulation with concurrent cognitive performance targeting posterior parietal cortex vs prefrontal cortex on working memory in schizophrenia: a randomized clinical trial

Working memory deficits are linked to irregularities in the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC) in schizophrenia, effective intervention strategies are lacking. We evaluated the differential efficacy and underlying neuromechanisms of targeting transcranial direct current stimulation (tDCS) at the DLPFC and the PPC with concurrent cognitive performance for working memory in schizophrenia. In a randomized and double-blind clinical trial, sixty clinically stable schizophrenic patients with below-average working memory were randomly assigned to active DLPFC, active PPC, and sham tDCS groups. Two sessions of tDCS during N-back task were delivered daily for five days. The primary outcome was changes in spatial span test scores from baseline to week 1. The secondary outcomes included changes in scores of color delay-estimation task, other cognitive tasks, and mismatch negativity (biomarker of N-methyl-d-aspartate receptor functioning). Compared with the active DLPFC group, the active PPC group demonstrated significantly greater improvement in spatial span test scores (p = 0.008, d = 0.94) and an augmentation in color delay-estimation task capacity at week 1; the latter sustained to week 2. Compared with the sham tDCS group, the active PPC group did not show a significant improvement in spatial span test scores at week 1 and 2; however, significant enhancement was observed in their color delay-estimation task capacity at week 2. Additionally, mismatch negativity amplitude was enhanced, and changes in theta band measures were positively correlated with working memory improvement in the active PPC group, while no such correlations were observed in the active DLPFC group or the sham tDCS group. Our results suggest that tDCS targeting the PPC relative to the DLPFC during concurrent cognitive performance may improve working memory in schizophrenia, meriting further investigation. The improvement in working memory appears to be linked to enhanced N-methyl-d-aspartate receptor functioning.

Effects of combined anodal transcranial direct current stimulation and motor control exercise on cortical topography and muscle activation in individuals with chronic low back pain: A randomized controlled study.

Aberrant movement in chronic low back pain (CLBP) is associated with a deficit in the lumbar multifidus (LM) and changes in cortical topography. Anodal transcranial direct current stimulation (a-tDCS) can be used to enhance cortical excitability by priming the neuromuscular system for motor control exercise (MCE), thereby enhancing LM activation and movement control. This study aimed to determine the effects of a 6-week MCE program combined with a-tDCS on cortical topography, LM activation, movement patterns, and clinical outcomes in individuals with CLBP. Twenty-two individuals with CLBP were randomly allocated to the a-tDCS group (a-tDCS; n=12) or sham-tDCS group (s-tDCS; n=10). Both groups received 20min of tDCS followed by 30min of MCE. The LM and erector spinae (ES) cortical topography, LM activation, movement control battery tests, and clinical outcomes (disability and quality of life) were measured pre- and post-intervention. Significant interaction (group×time; p<0.01) was found in the distance between LM and ES cortical locations. The a-tDCS group demonstrated significantly fewer discrete peaks (p<0.05) in both ES and LM and significant improvements (p<0.05) in clinical outcomes post-intervention. The s-tDCS group demonstrated a significant increase (p<0.05) in the number of discrete peaks in the LM cortical topography. No significant changes (p>0.05) in LM activation were observed in either group; however, both groups demonstrated improved movement patterns. Our findings suggest that combined a-tDCS with MCE can separate LM and ES locations over time while s-tDCS (MCE alone) reduces the distance. Our study did not find superior benefits of adding a-tDCS before MCE for LM activation, movement patterns, or clinical outcomes.

Effects of bilateral tDCS over DLPFC on response inhibition, craving, and brain functional connectivity in Internet gaming disorder: Arandomized, double-blind, sham-controlled trial with fMRI.

Impaired inhibitory control accompanied by enhanced craving is hallmark of addiction. This study investigated the effects of transcranial direct current stimulation (tDCS) on response inhibition and craving in Internet gaming disorder (IGD). We examined the brain changes after tDCS and their correlation with clinical variables. Twenty-four males with IGD were allocated randomly to an active or sham tDCS group, and data from 22 participants were included for analysis. Participants self-administered bilateral tDCS over the dorsolateral prefrontal cortex (DLPFC) for 10 sessions. Stop-signal tasks were conducted to measure response inhibition and participants were asked about their cravings for Internet gaming at baseline and post-tDCS. Functional magnetic resonance imaging data were collected at pre- and post-tDCS, and group differences in resting-state functional connectivity (rsFC) changes from the bilateral DLPFC and nucleus accumbens were examined. We explored the relationship between changes in the rsFC and behavioral variables in the active tDCS group. A significant group-by-time interaction was observed in response inhibition. After tDCS, only the active group showed a decrease in the stop-signal reaction time (SSRT). Although craving decreased, there were no significant group-by-time interactions or group main effects. The anterior cingulate cortex (ACC) showed group differences in post- versus pre-tDCS rsFC from the right DLPFC. The rsFC between the ACC and left middle frontal gyrus was negatively correlated with the SSRT. Our study provides preliminary evidence that bilateral tDCS over the DLPFC improves inhibitory control and could serve as a therapeutic approach for IGD.

Protocol for a home-based self-delivered prehabilitation intervention to proactively reduce fall risk in older adults: a pilot randomized controlled trial of transcranial direct current stimulation and motor imagery

BackgroundSeveral changes occur in the central nervous system with increasing age that contribute toward declines in mobility. Neurorehabilitation has proven effective in improving motor function though achieving sustained behavioral and neuroplastic adaptations is more challenging. While effective, rehabilitation usually follows adverse health outcomes, such as injurious falls. This reactive intervention approach may be less beneficial than prevention interventions. Therefore, we propose the development of a prehabilitation intervention approach to address mobility problems before they lead to adverse health outcomes. This protocol article describes a pilot study to examine the feasibility and acceptability of a home-based, self-delivered prehabilitation intervention that combines motor imagery (mentally rehearsing motor actions without physical movement) and neuromodulation (transcranial direct current stimulation, tDCS; to the frontal lobes). A secondary objective is to examine preliminary evidence of improved mobility following the intervention.MethodsThis pilot study has a double-blind randomized controlled design. Thirty-four participants aged 70–95 who self-report having experienced a fall within the prior 12 months or have a fear of falling will be recruited. Participants will be randomly assigned to either an active or sham tDCS group for the combined tDCS and motor imagery intervention. The intervention will include six 40-min sessions delivered every other day. Participants will simultaneously practice the motor imagery tasks while receiving tDCS. Those individuals assigned to the active group will receive 20 min of 2.0-mA direct current to frontal lobes, while those in the sham group will receive 30 s of stimulation to the frontal lobes. The motor imagery practice includes six instructional videos presenting different mobility tasks related to activities of daily living. Prior to and following the intervention, participants will undergo laboratory-based mobility and cognitive assessments, questionnaires, and free-living activity monitoring.DiscussionPrevious studies report that home-based, self-delivered tDCS is safe and feasible for various populations, including neurotypical older adults. Additionally, research indicates that motor imagery practice can augment motor learning and performance. By assessing the feasibility (specifically, screening rate (per month), recruitment rate (per month), randomization (screen eligible who enroll), retention rate, and compliance (percent of completed intervention sessions)) and acceptability of the home-based motor imagery and tDCS intervention, this study aims to provide preliminary data for planning larger studies.Trial registrationThis study is registered on ClinicalTrials.gov (NCT05583578). Registered October 13, 2022. https://www.clinicaltrials.gov/study/NCT05583578

Region-specific Effects of Transcranial Direct Current Stimulation Over Posterior Parietal Cortex and Cerebellum on Standing Postural Displacement After Prism Adaptation

Prism adaptation (PA) induces the after-effects of adapted tasks and transfers after-effects of non-adapted tasks, in which PA with pointing movements transfers to postural displacement during eyes-closed standing. However, the neural mechanisms underlying the transfer of PA after-effects on standing postural displacement remain unclear. The present study investigated the region-specific effects of transcranial direct current stimulation (tDCS) over the posterior parietal cortex (PPC) and cerebellum during prism exposure (PE) on standing postural displacement in healthy adults. Forty-two healthy young adults were grouped into pointing during PE with cathodal tDCS over the right PPC, anodal tDCS over the right cerebellum, and sham tDCS groups. They received 20 min of tDCS, during which they pointed to the visual targets while wearing prism lenses with a leftward visual shift (30 diopters) for 15 min. During the early PE, the pointing errors in the cerebellum group were significantly displaced more accurately toward the targets than those in the PPC group. However, after leftward PE, all groups had similar rightward displacements of the straight-ahead pointing with eyes closed. The PPC group only exhibited significant rightward center-of-pressure displacement during eyes-closed standing with feet-closed after leftward PE. The perception of longitudinal body axis rotation, as an indicator of the subjective body vertical axis, did not differ significantly between the pre- and post-evaluations in all groups. These results show that the PPC during PE could make an important neural contribution to inducing transfer of PA after-effect on standing postural displacement.

The effect of tDCS on inhibitory control and its transfer effect on sustained attention in children with autism spectrum disorder: An fNIRS study

BackgroundIndividuals with autism spectrum disorder (ASD) have inhibitory control deficits. The combination of transcranial direct current stimulation (tDCS) and inhibitory control training produces good transfer effects and improves neuroplasticity. However, no studies have explored whether applying tDCS over the dlPFC improves inhibitory control and produces transfer effects in children with ASD. ObjectiveTo explore whether multisession tDCS could enhance inhibitory control training (response inhibition), near-transfer (interference control) and far-transfer effects (sustained attention; stability of attention) in children with ASD and the generalizability of training effects in daily life and the class, as reflected by behavioral performance and neural activity measured by functional near-infrared spectroscopy (fNIRS). MethodsTwenty-eight autistic children were randomly assigned to either the true or sham tDCS group. The experimental group received bifrontal tDCS stimulation at 1.5 mA, administered for 15 min daily across eight consecutive days. tDCS was delivered during a computerized Go/No-go training task. Behavioral performance in terms of inhibitory control (Dog/Monkey and Day/Night Stroop tasks), sustained attention (Continuous Performance and Cancellation tests), prefrontal cortex (PFC) neural activity and inhibitory control and sustained attention in the class and at home were evaluated. ResultsTraining (response inhibition) and transfer effects (interference control; sustained attention) were significantly greater after receiving tDCS during the Go/No-go training task than after receiving sham tDCS. Changes in oxyhemoglobin (HbO) concentrations in the dlPFC and FPA associated with consistent conditions in the Day/Night Stroop and Continuous Performance test were observed after applying tDCS during the inhibitory control training task. Notably, transfer effects can be generalized to classroom environments. ConclusionInhibitory control training combined with tDCS may be a promising, safe, and effective method for improving inhibitory control and sustained attention in children with ASD.

Evidence and sources of placebo effects in transcranial direct current stimulation during a single session of visuospatial working memory practice

Transcranial direct current stimulation (tDCS) can be used to non-invasively augment cognitive training. However, the benefits of tDCS may be due in part to placebo effects, which have not been well-characterized. The purpose of this study was to determine whether tDCS can have a measurable placebo effect on cognitive training and to identify potential sources of this effect. Eighty-three right-handed adults were randomly assigned to one of three groups: control (no exposure to tDCS), sham tDCS, or active tDCS. The sham and active tDCS groups were double-blinded. Each group performed 20 min of an adapted Corsi Block Tapping Task (CBTT), a visuospatial working memory task. Anodal or sham tDCS was applied during CBTT training in a right parietal-left supraorbital montage. After training, active and sham tDCS groups were surveyed on expectations about tDCS efficacy. Linear mixed effects models showed that the tDCS groups (active and sham combined) improved more on the CBTT with training than the control group, suggesting a placebo effect of tDCS. Participants’ tDCS expectations were significantly related to the placebo effect, as was the belief of receiving active stimulation. This placebo effect shows that the benefits of tDCS on cognitive training can occur even in absence of active stimulation. Future tDCS studies should consider how treatment expectations may be a source of the placebo effect in tDCS research, and identify ways to potentially leverage them to maximize treatment benefit.

Transcranial Direct Current Stimulation for Anxiety During Laparoscopic Colorectal Cancer Surgery

Perioperative anxiety is prevalent among patients undergoing surgical treatment of cancer and often influences their prognosis. Transcranial direct current stimulation (tDCS) has shown potential in the treatment of various anxiety-related disorders, but data on the impact of tDCS on perioperative anxiety are limited. To evaluate the effect of tDCS in reducing perioperative anxiety among patients undergoing laparoscopic colorectal cancer (CRC) resection. This randomized clinical trial was conducted from March to August 2023 at the Affiliated Hospital of Xuzhou Medical University. Patients aged 18 years or older undergoing elective laparoscopic radical resection for CRC were randomly assigned to either the active tDCS group or the sham tDCS group. Intention-to-treat data analysis was performed in September 2023. Patients were randomly assigned to receive 2 sessions of either active tDCS or sham tDCS over the left dorsolateral prefrontal cortex on the afternoon of the day before the operation and in the morning of the day of operation. The main outcome was the incidence of perioperative anxiety from the day of the operation up to 3 days after the procedure, as measured using the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) subscale (range: 0-21, with higher scores indicating more anxiety). Secondary outcomes included postoperative delirium (assessed by the Confusion Assessment Method or Confusion Assessment Method intensive care unit scale); pain (assessed by the 10-point Numeric Rating Scale [NRS], with scores ranging from 0 [no pain] to 10 [worst pain]); frailty (assessed by the Fatigue, Resistance, Ambulation, Illness and Loss of Weight [FRAIL] Index, with scores ranging from 0 [most robust] to 5 [most frail]; and sleep quality (assessed by the Pittsburgh Sleep Quality Index [PSQI], with scores ranging from 0 to 21 and higher scores indicating worse sleep quality) after the 2 sessions of the tDCS intervention. A total of 196 patients (mean [SD] age, 63.5 [11.0] years; 124 [63.3%] men) were recruited and randomly assigned to the active tDCS group (98 patients) or the sham tDCS group (98 patients). After the second tDCS intervention on the day of the operation, the incidence of perioperative anxiety was 38.8% in the active tDCS group and 70.4% in the sham tDCS group (relative risk, 0.55 [95% CI, 0.42-0.73]; P < .001). Patients in the active tDCS group vs the sham tDCS group were less likely to have postoperative delirium (8.2% vs 25.5%) and, at 3 days after the operation, had lower median (IQR) pain scores (NRS, 1.0 [1.0-1.0] vs 2.0 [2.0-2.0]), better median (IQR) sleep quality scores (PSQI, 10.5 [10.0-11.0] vs 12.0 [11.0-13.0]), and lower median (IQR) FRAIL Index (2.0 [1.0-2.0] vs 2.0 [2.0-3.0]). Findings of this randomized clinical trial indicate that administration of 2 preoperative sessions of tDCS was associated with a decreased incidence of perioperative anxiety in patients undergoing elective CRC resection. Active tDCS was also associated with better anxiety scores, pain levels, and sleep quality as well as reduced postoperative delirium and frailty. The findings suggest that tDCS may be a novel strategy for improving perioperative anxiety in patients undergoing CRC resection. Chinese Clinical Trial Register Identifier: ChiCTR2300068859.

Safety and feasibility of optimized transcranial direct current stimulation in patients with mild cognitive impairment due to Alzheimer's disease: a multicenter study protocol for a randomized controlled trial.

Transcranial direct current stimulation (tDCS) may effectively preserve and improve cognitive function in patients with mild cognitive impairment (MCI). Research has shown that Individual brain characteristics can influence the effects of tDCS. Computer three-dimensional brain modeling based on magnetic resonance imaging (MRI) has been suggested as an alternative for determining the most accurate tDCS electrode position based on the patients' individual brain characteristics to enhance tDCS effects. Therefore, this study aims to determine the feasibility and safety of applying tDCS treatment using optimized and personalized tDCS electrode positions in patients with Alzheimer's disease (AD)-induced MCI using computer modeling and compare the results with those of a sham group to improve cognitive function. A prospective active-sham group feasibility study was set to recruit 40 participants, who will be randomized into Optimized-tDCS and Sham-tDCS groups. The parameters for tDCS will be 2 mA (disk electrodes R = 1.5 cm) for 30 min during two sets of 15 sessions (2 weeks of resting period in between), using two electrodes in pairs. Using computer modeling, the tDCS electrode positions of each participant will be personalized. Outcome measurements are going to be obtained at three points: baseline, first post-test, and second post-test. The AD assessment scale-cognitive subscale (ADAS-Cog) and the Korean version of Mini-Mental State Examination (K-MMSE), together with other secondary outcomes and safety tests will be used. For the present study, we hypothesize that compared to a sham group, the optimized personalized tDCS application would be effective in improving the cognitive function of patients with AD-induced MCI and the participants would tolerate the tDCS intervention without any significant adverse effects.Clinical trial registration: https://cris.nih.go.kr, identifier [KCT0008918].

Virtual Reality and Transcranial Direct Current Stimulation for Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) is a common psychiatric disorder that is particularly difficult to treat in military veterans. Noninvasive brain stimulation has significant potential as a novel treatment to reduce PTSD symptoms. To test whether active transcranial direct current stimulation (tDCS) plus virtual reality (VR) is superior to sham tDCS plus VR for warzone-related PTSD. This double-blind randomized clinical trial was conducted among US military veterans enrolled from April 2018 to May 2023 at a secondary care Department of Veterans Affairs hospital and included 1- and 3-month follow-up visits. Participants included US military veterans with chronic PTSD and warzone-related exposure, recruited via referral and advertisement. Patients in psychiatric treatment had to be on a stable regimen for at least 6 weeks to be eligible for enrollment. Data were analyzed from May to September 2023. Participants were randomly assigned to receive 2-mA anodal tDCS or sham tDCS targeted to the ventromedial prefrontal cortex, during six 25-minute sessions of standardized warzone VR exposure, delivered over 2 to 3 weeks. The co-primary outcomes were self-reported PTSD symptoms, measured via the PTSD checklist for DSM-5 (PCL-5), alongside quality of life. Other outcomes included psychophysiological arousal, clinician-assessed PTSD, depression, and social/occupational function. A total of 54 participants (mean [SD] age, 45.7 [10.5] years; 51 [94%] males) were assessed, including 26 in the active tDCS group and 28 in the sham tDCS group. Participants in the active tDCS group reported a superior reduction in self-reported PTSD symptom severity at 1 month (t = -2.27, P = .02; Cohen d = -0.82). There were no significant differences in quality of life between active and sham tDCS groups. Active tDCS significantly accelerated psychophysiological habituation to VR events between sessions compared with sham tDCS (F5,7689.8 = 4.65; P < .001). Adverse effects were consistent with the known safety profile of the corresponding interventions. These findings suggest that combined tDCS plus VR may be a promising strategy for PTSD reduction and underscore the innovative potential of these combined technologies. ClinicalTrials.gov Identifier: NCT03372460.