Transcranial direct stimulation over left inferior frontal gyrus improves language production and comprehension in post-stroke aphasia: A double-blind randomized controlled study.

Transcranial direct current stimulation (tDCS) targeting Broca's area has shown promise for augmenting language production in post-stroke aphasia (PSA). However, previous research has been limited by small sample sizes and inconsistent outcomes. This study employed a double-blind, parallel, randomized, controlled design to evaluate the efficacy of anodal Broca's tDCS, paired with 20-minute speech and language therapy (SLT) focused primarily on expressive language, across 5 daily sessions in 45 chronic PSA patients. Utilizing the Western Aphasia Battery-Revised, which assesses a spectrum of linguistic abilities, we measured changes in both expressive and receptive language skills before and after intervention. The tDCS group demonstrated significant improvements over sham in aphasia quotient, auditory verbal comprehension, and spontaneous speech. Notably, tDCS improved both expressive and receptive domains, whereas sham only benefited expression. These results underscore the broader linguistic benefits of Broca's area stimulation and support the integration of tDCS with SLT to advance aphasia rehabilitation.

Repeated prefrontal tDCS for improving mental health and cognitive deficits in multiple sclerosis: a randomized, double-blind, parallel-group study.

BACKGROUND: Multiple Sclerosis (MS) is an autoimmune disease associated with physical disability, psychological impairment, and cognitive dysfunctions. Consequently, the disease burden is substantial, and treatment choices are limited. In this randomized, double-blind study, we conducted repeated prefrontal electrical stimulation in 40 patients with MS to evaluate mental health variables (quality of life, sleep difficulties, psychological distress) and cognitive dysfunctions (psychomotor speed, working memory, attention/vigilance), marking it as the third largest sample size tDCS research conducted in MS to date. METHODS: The patients were randomly assigned (block randomization method) to two groups of sham (n = 20), or 1.5-mA (n = 20) transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (F3) and right frontopolar cortex (Fp2) with anodal and cathodal stimulation respectively (electrode size: 25 cm2). The treatment included 10 sessions of 20 min of stimulation delivered every other day. Outcome measures were MS quality of life, sleep quality, psychological distress, and performance on a neuropsychological test battery dedicated to cognitive dysfunctions in MS (psychomotor speed, working memory, and attention). All outcome measures were evaluated at the pre-intervention and post-intervention assessments. Both patients and technicians delivering the stimulation were unaware of the type of stimulation being used. RESULTS: Repeated prefrontal real tDCS significantly improved quality of life and reduced sleep difficulties and psychological distress compared to the sham group. It, furthermore, improved psychomotor speed, attention, and vigilance compared to the sham protocol. Improvement in mental health outcome variables and cognitive outperformance were interrelated and could predict each other. CONCLUSIONS: Repeated prefrontal and frontopolar tDCS ameliorates secondary clinical symptoms related to mental health and results in beneficial cognitive effects in patients with MS. These results support applying prefrontal tDCS in larger trials for improving mental health and cognitive dysfunctions in MS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06401928.

Effects of treadmill training combined with transcranial direct current stimulation on mobility, motor performance, balance function, and other brain-related outcomes in stroke survivors: a systematic review and meta-analysis.

INTRODUCTION: Treadmill training (TT) is a gait training technique that has commonly been used in neurorehabilitation, and has positive effects on gait, mobility, and related outcomes in stroke survivors. Transcranial direct current stimulation (tDCS) is a non-invasive approach for modulating brain cortex excitability. AIM: To evaluate the available scientific evidence on the effects of TT combined with tDCS on mobility, motor performance, balance function, and brain-related outcomes in stroke survivors. METHODS: Five databases namely the Cochrane library, PEDro, Web of Science, PubMed, and EMBASE, were searched for relevant studies from inception to March, 2024. Only randomized controlled trials were included, and their methodological quality and risk of bias (ROB) were evaluated using the PEDro scale and Cochrane ROB assessment tool respectively. Qualitative and quantitative syntheses (using fixed effects meta-analysis) were employed to analyze the data. RESULTS: The results revealed that TT combined with active tDCS had significant beneficial effects on some mobility parameters, some gait spatiotemporal parameters, some gait kinematic parameters, gait endurance, gait ability, and corticomotor excitability in stroke survivors, but no significant difference on gait speed (P > 0.05), functional mobility (P > 0.05), motor performance (P > 0.05), or some balance functions (P > 0.05), compared with the control conditions. CONCLUSIONS: TT combined with active tDCS significantly improves some gait/mobility outcomes and corticomotor excitability in stroke survivors.

The effect of computerized cognitive training and transcranial direct current stimulation on working memory among post-stroke individuals: a systematic review with meta-analysis and meta-regression.

BACKGROUND: Working memory (WM) impairment is a common phenomenon after stroke; however, its management in rehabilitation is less researched. This systematic review and meta-analysis aimed to provide a quantitative synthesis of the impact of computerised cognitive training (CCT) and transcranial direct current stimulation (tDCS) on WM span in post-stroke individuals. METHODS: The literature search in PubMed, Embase, Scopus, and Cochrane Library focused on randomized controlled trials testing the effect of CCT and tDCS on treated stroke patients as compared to untreated controls. Neuropsychological instruments such as Digit Span Forward/Backward and Visual Span Forward Tests defined the outcome of WM span. After extracting study characteristics and quality assessment using the Cochrane Risk of Bias Tool, we conducted a meta-analysis and meta-regression using standardised mean differences. RESULTS: The search yielded 4142 articles, nine of which (N = 461) fulfilled the inclusion criteria. In the case of CCT, we found significant improvement in Digit Span Backward Test (Z = 2.65, P = 0.008; 95% CI [0.10, 0.67]) and Visual Span Forward Test performance (Z = 3.05, P = 0.002; 95% CI [0.15, 0.69]), while for tDCS, we could not find a sufficient number of studies for the analysis. Furthermore, no significant moderating factor was found in the meta-regression. CONCLUSIONS: In conclusion, CCT appears to be a suitable choice to enhance WM span performance after stroke. However, further research is needed to investigate the effect of tDCS due to the limited number of studies. TRIAL REGISTRATION: The meta-analysis was conducted according to PRISMA (Preferred Reporting of Systematic Reviews and Meta-Analyses) standards with a PROSPERO registration protocol (ID: CRD42023387182).

Effect of non-invasive brain stimulation in children with acquired brain injury-a scoping review.

Background: Children and young people (CYP) with acquired brain injury (ABI) require early and effective neurorehabilitation to improve long-term functional outcomes. Non-invasive brain stimulation (NIBS), including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have been used to improve motor and sensory skills for children with cerebral palsy. However, there is limited evidence supporting its use in CYP with ABI. Objective: To systematically review the TMS and tDCS intervention effects on motor, sensory and other functional issues in CYP with ABI as reported in the literature. Methods: A comprehensive online bibliographic databases search was performed in various databases using keywords related to NIBS and CYP with ABI. Studies that examine the effect of NIBS intervention on motor function and other functional difficulties either as a primary or secondary objective were included in this review. Results: Fourteen studies (10 single case reports, one retrospective analysis, one case series, one randomised and one quasi-randomised controlled trial) published between 2006 and 2023 were identified. These studies examined the use of NIBS to manage motor disorders, hearing, vision, headaches, speech and language and memory issues. Seventy-six children with mild to severe ABI had received NIBS. The session frequency (3-20), duration (10-45 min) was variable, and NIBS delivered between 3 and 28 days. Conclusion: The literature describing NIBS interventions in CYP with ABI is scarce. An insufficient number of studies, inadequate information reported in them, and small sample sizes limit the ability to conclude how effective NIBS is in improving motor function and other functional issues in this cohort. Further studies are therefore necessary to examine the therapeutic effects of NIBS to manage various functional problems in the CYP with ABI.

Transcranial direct current stimulation enhances the protective effect of isoflurane preconditioning on cerebral ischemia/reperfusion injury: A new mechanism associated with the nuclear protein Akirin2.

AIMS: Ischemic stroke is a major cause of disability and mortality worldwide. Transcranial direct current stimulation (tDCS) and isoflurane (ISO) preconditioning exhibit neuroprotective properties. However, it remains unclear whether tDCS enhances the protective effect of ISO preconditioning on ischemic stroke, and the underlying mechanisms are yet to be clarified. METHOD: A model of middle cerebral artery occlusion (MCAO), a rat ischemia-reperfusion (I/R) injury model, and an in vitro oxygen-glucose deprivation/re-oxygenation (O/R) model of ischemic injury were developed. ISO preconditioning and tDCS were administered daily for 7 days before MCAO modeling. Triphenyltetrazolium chloride staining, modified neurological severity score, and hanging-wire test were conducted to assess infarct volume and neurological outcomes. Untargeted metabolomic experiments, adeno-associated virus, lentiviral vectors, and small interfering RNA techniques were used to explore the underlying mechanisms. RESULTS: tDCS/DCS enhanced the protective effects of ISO pretreatment on I/R injury-induced brain damage. This was evidenced by reduced infarct volume and improved neurological outcomes in rats with MCAO, as well as decreased cortical neuronal death after O/R injury. Untargeted metabolomic experiments identified oxidative phosphorylation (OXPHOS) as a critical pathological process for ISO-mediated neuroprotection from I/R injury. The combination of tDCS/DCS with ISO preconditioning significantly inhibited I/R injury-induced OXPHOS. Mechanistically, Akirin2, a small nuclear protein that regulates cell proliferation and differentiation, was found to decrease in the cortex of rats with MCAO and in cortical primary neurons subjected to O/R injury. Akirin2 functions upstream of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). tDCS/DCS was able to further upregulate Akirin2 levels and activate the Akirin2/PTEN signaling pathway in vivo and in vitro, compared with ISO pretreatment alone, thereby contributing to the improvement of cerebral I/R injury. CONCLUSION: tDCS treatment enhances the neuroprotective effects of ISO preconditioning on ischemic stroke by inhibiting oxidative stress and activating Akirin2-PTEN signaling pathway, highlighting potential of combination therapy in ischemic stroke.

Effects of cerebellar transcranial direct current stimulation on the excitability of spinal motor neurons and vestibulospinal tract in healthy individuals.

Cerebellar transcranial direct current stimulation (ctDCS) modulates cerebellar cortical excitability in a polarity-dependent manner and affects inhibitory pathways from the cerebellum. The cerebellum modulates spinal reflex excitability via the vestibulospinal tract and other pathways projecting to the spinal motor neurons; however, the effects of ctDCS on the excitability of spinal motor neurons and vestibulospinal tract remain unclear. The experiment involved 13 healthy individuals. ctDCS (sham-ctDCS, anodal-ctDCS, and cathodal-ctDCS) was applied to the cerebellar vermis at 2 mA with an interval of at least 3 days between each condition. We measured the maximal M-wave (Mmax) and maximal H-reflex (Hmax) in the right soleus muscle to assess the excitability of spinal motor neurons. We applied galvanic vestibular stimulation (GVS) for 200 ms at 100 ms before tibial nerve stimulation to measure Hmax conditioned by GVS (GVS-Hmax) and calculated the change rate of Hmax by GVS as the excitability of vestibulospinal tract. We measured the Mmax, Hmax, and GVS-Hmax before, during, and after ctDCS in the sitting posture. No main effects of tDCS condition, main effects of time, or interaction effects were observed in Hmax/Mmax or the change rate of Hmax by GVS. It has been suggested that ctDCS does not affect the excitability of spinal motor neurons and vestibulospinal tract, as measured by neurophysiological methods, such as the H-reflex, in healthy individuals in a sitting posture. Effect of ctDCS on other descending pathways to spinal motor neurons, the neurological mechanism of tDCS and the cerebellar activity during the experiment may have contributed to these results. Therefore, we need to investigate the involvement of the cerebellum in Hmax/Mmax and the change rate of Hmax by GVS under different neuromodulation techniques and postural conditions.

Medial Prefrontal Cortex Stimulation Reduces Retrieval-Induced Forgetting via Fronto-parietal Beta Desynchronization.

The act of recalling memories can paradoxically lead to the forgetting of other associated memories, a phenomenon known as retrieval-induced forgetting (RIF). Inhibitory control mechanisms, primarily mediated by the prefrontal cortex, are thought to contribute to RIF. In this study, we examined whether stimulating the medial prefrontal cortex (mPFC) with transcranial direct current stimulation modulates RIF and investigated the associated electrophysiological correlates. In a randomized study, 50 participants (27 males and 23 females) received either real or sham stimulation before performing retrieval practice on target memories. After retrieval practice, a final memory test to assess RIF was administered. We found that stimulation selectively increased the retrieval accuracy of competing memories, thereby decreasing RIF, while the retrieval accuracy of target memories remained unchanged. The reduction in RIF was associated with a more pronounced beta desynchronization within the left dorsolateral prefrontal cortex (left-DLPFC), in an early time window (<500 ms) after cue onset during retrieval practice. This led to a stronger beta desynchronization within the parietal cortex in a later time window, an established marker for successful memory retrieval. Together, our results establish the causal involvement of the mPFC in actively suppressing competing memories and demonstrate that while forgetting arises as a consequence of retrieving specific memories, these two processes are functionally independent. Our findings suggest that stimulation potentially disrupted inhibitory control processes, as evidenced by reduced RIF and stronger beta desynchronization in fronto-parietal brain regions during memory retrieval, although further research is needed to elucidate the specific mechanisms underlying this effect.

Alignment of behaviour and tDCS stimulation site induces maximum response: evidence from online tDCS and ERP.

tDCS modulates the activity of the neuronal networks to induce the desired behavioural changes. Two factors determine its effectiveness- (1) whether the network being stimulated is relevant to the task, and (2) if there is a scope for improvement in behavioral performance. To explore this, both dorsal (sub-lexical) and ventral (lexical) reading networks were stimulated (20 min, 2 mA) in 25 healthy young volunteers. Participants performed two reading tasks with different levels of lexical involvement: word fragment completion tasks (WCT) and word association tasks (WAT), while event-related potentials (ERPs) were recorded simultaneously. The study used a within-subject design over three sessions, comparing various electrode montages targeting the dorsal pathway's left inferior parietal lobule or the ventral reading pathway's left middle temporal lobule, as well as sham stimulation. The impact of tDCS sessions (dorsal, ventral, & sham) and task type (WCT & WAT) on priming effects (primed vs. unprimed) of behavioral performance (accuracy and reaction times), and ERP parameters (N400 amplitudes and latencies) were statistically analyzed.It was found that tDCS modulated the performance of WAT only (a task with a lower priming effect). The failure to modulate WCT (larger priming effect) indicated that tDCS was effective for conditions with room for improvement compared to a task where performance has reached the ceiling. Ventral stimulation enhanced accuracy in the WAT condition and shortened the N400 latency of the priming effect. In contrast, dorsal stimulation delayed the priming effect reaction time in the WAT condition and enhanced the N400 amplitude. To conclude, enhancement in performance due to tDCS occurs when the network (ventral) being stimulated aligns with the cognitive demands of the task and there is a scope for improvement.

A systematic review and meta-analysis for the efficacy of transcranial direct current stimulation (tDCS) in OCD treatment: A non-pharmacological approach to clinical interventions.

Obsessive-compulsive disorder (OCD) is a prevalent mental condition characterized by recurrent, unwanted thoughts (obsessions) and repetitive behaviors (compulsions), significantly disrupting daily functioning and social interactions. Transcranial direct current stimulation (tDCS) presents a promising non-invasive treatment modality aimed at alleviating symptoms. However, the evidence regarding its effectiveness remains inconclusive. This study seeks to address this gap by conducting a systematic review and meta-analysis of clinical trials, offering improved guidance for clinical intervention. A comprehensive search strategy was implemented across multiple databases, including PubMed, Cochrane CENTRAL, Embase, Scopus, and Web of Science. This search focused strictly on randomized controlled trials (RCTs) involving 147 patients. These trials evaluated the efficacy of tDCS in OCD patients. Subsequent data extraction, risk of bias assessment, and statistical analysis using Review Manager software revealed the potential efficacy of tDCS in reducing OCD symptoms. The meta-analysis not only fails to demonstrate significant superiority of active tDCS over sham tDCS but also suggests that sham tDCS may be more effective than active tDCS in reducing OCD symptoms. This finding diminishes the promise of tDCS as an effective treatment for OCD. Larger trials are warranted to further elucidate these findings.

Direct current stimulation modulates prefrontal cell activity and behaviour without inducing seizure-like firing.

Transcranial direct current stimulation (tDCS) has garnered significant interest for its potential to enhance cognitive functions and as a therapeutic intervention in various cognitive disorders. However, the clinical application of tDCS has been hampered by significant variability in its cognitive outcomes. Furthermore, the widespread use of tDCS has raised concerns regarding its safety and efficacy, particularly due to our limited understanding of its underlying neural mechanisms at the cellular level. We still do not know 'where', 'when', and 'how' tDCS modulates information encoding by neurons, to lead to the observed changes in cognitive functions. Without elucidating these fundamental unknowns, the root causes of its outcome variability and long-term safety remain elusive, challenging the effective application of tDCS in clinical settings. Addressing this gap, our study investigates the effects of tDCS, applied over the dorsolateral prefrontal cortex (dlPFC), on cognitive abilities and individual neuron activity in macaque monkeys performing cognitive tasks. Like humans performing a Delayed Match-to-Sample task, monkeys exhibited practice-related slowing in their responses (within-session behavioural adaptation). Concurrently, there were practice-related changes in simultaneously recorded activity of prefrontal neurons (within-session neuronal adaptation). Anodal tDCS attenuated both these behavioural and neuronal adaptations when compared to sham. Furthermore, tDCS abolished the correlation between monkeys' response time and neuronal firing rate. At a single-cell level, we also found that following tDCS, neuronal firing rate was more likely to exhibit task-specific modulation than after sham stimulation. These tDCS-induced changes in both behaviour and neuronal activity persisted even after the end of tDCS stimulation. Importantly, multiple applications of tDCS did not alter burst-like firing rates of individual neurons when compared to sham stimulation. This suggests that tDCS modulates neural activity without enhancing susceptibility to epileptiform activity, confirming a potential for safe use in clinical settings. Our research contributes unprecedented insights into the 'where', 'when', and 'how' of tDCS effects on neuronal activity and cognitive functions by showing that modulation of monkeys' behaviour by the tDCS of the prefrontal cortex is accompanied by alterations in prefrontal cortical cell activity ('where') during distinct trial phases ('when'). Importantly, tDCS led to task-specific and state-dependent alterations in prefrontal cell activities ('how'). Our findings suggest a significant shift from the view that the tDCS effects are merely due to polarity-specific shifts in cortical excitability and instead, propose a more complex mechanism of action for tDCS that encompasses various aspects of cortical neuronal activity without increasing burst-like epileptiform susceptibility.

Enhancing response inhibition behavior through tDCS intervention in college students with smartphone addiction.

Smartphone addiction, emerging from excessive use of smartphones, poses a challenge to inhibitory control functions within society. This research employed transcranial direct current stimulation (tDCS) as an intervention alongside the stop signal task (SST) to explore behavioral distinctions between individuals with smartphone addiction and a non-addicted control group, focusing on the efficacy of tDCS intervention. The participant cohort comprised 80 individuals, divided into an addiction group (39 participants, with 19 receiving active tDCS and 20 receiving sham tDCS) and a control group (41 participants, with 20 receiving active tDCS and 21 receiving sham tDCS), with anodal stimulation applied over the right dorsolateral prefrontal cortex (dlPFC) and cathodal placement over the left arm. The findings indicate that university students struggling with smartphone addiction exhibit reduced inhibitory control compared to their non-addicted peers, while maintaining similar levels of general cognitive control. Remarkably, tDCS interventions were observed to enhance inhibitory control in both groups. Although the improvement in the addiction group appeared more pronounced numerically than in the control group, no significant interaction with group was noted. However, a higher percentage of participants in the smartphone addiction (SA) group exhibited enhanced response inhibition under active tDCS. This study demonstrates the inhibitory control deficits in individuals addicted to smartphones and underscores the potential of tDCS in enhancing response inhibition. It provides a valuable reference for future tDCS research targeting smartphone addiction and highlights the importance of developing healthier smartphone usage habits.

How does combining physical therapy with transcranial direct stimulation improve upper-limb motor functions in patients with stroke? A theory perspective.

More than half of stroke survivors suffer from upper-limb dysfunction that persists years after stroke, negatively impacting patients' independence and, therefore, affecting their quality of life. Intense motor rehabilitation is required after a stroke to facilitate motor recovery. More importantly, finding new ways to maximize patients' motor recovery is a core goal of stroke rehabilitation. Thus, researchers have explored the potential benefits of combining the effects of non-invasive brain stimulation with physical therapy rehabilitation. Specifically, combining transcranial direct stimulation (tDCS) with neurorehabilitation interventions can boost the brain's responses to interventions and maximize the effects of rehabilitation to improve upper-limb recovery post-stroke. However, it is still unclear which modes of tDCS are optimal for upper-limb motor recovery in patients with stroke when combined with physical therapy interventions. Here, the authors review the existing literature suggesting combining physical therapy rehabilitation with tDCS can maximize patients' motor recovery using the Interhemispheric Competition Model in Stroke. The authors focus on two main rehabilitation paradigms, which are constraint-induced movement therapy (CIMT) and Mirror therapy with and without tDCS. The authors also discuss potential studies to elucidate further the benefit of using tDCS adjunct with these upper-limb rehabilitation paradigms and its effectiveness in patients with stroke, with the ultimate goal of maximizing patients' motor recovery.

Eight sessions of transcranial electrical stimulation for postural response in people with Parkinson's disease: A randomized trial.

BACKGROUND: Impairments in postural responses to perturbation are common in people with Parkinson's disease (PwPD) and lack effective treatment. We recently showed that a single session of transcranial direct current stimulation (tDCS) promotes acute improvement of postural response to perturbation in PwPD. However, the effects of multiple tDCS sessions remain unclear. RESEARCH QUESTION: What is the efficacy of eight sessions of anodal tDCS on postural responses to external perturbation in PwPD? METHODS: Twenty-two PwPD participated in this randomized, double-blind, parallel-arm, and sham-controlled study. Participants were randomly distributed into active (a-tDCS; n=11) or sham stimulation (s-tDCS; n=11). Eight tDCS sessions were applied over the primary motor cortex (M1), with the a-tDCS group receiving 2 mA for 20 minutes. Postural responses to external perturbations were assessed before, 48 hours after, and one month after (follow-up) the completion of tDCS sessions. Primary outcome measures included the onset latency of medial gastrocnemius (MG) muscle and range of center of pressure. Secondary outcomes included electromyography and CoP parameters, and prefrontal cortex (PFC) activity. RESULTS: ANOVA revealed a trend for Group*Moment interaction for MG onset latency (p=0.058). a-tDCS tended to have shorter MG onset latency at post-test (p=0.040; SRM = -0.63) compared to pre-test. For the secondary outcomes, only a-tDCS decreased the time taken to recover balance after the perturbation at post-test and follow-up compared to pre-test (both p<0.001; SRM=-1.42 and -1.53, respectively). Also, only a-tDCS demonstrated lower PFC activity at post-test compared to pre-test (p=0.017; SRM = -0.82) and follow-up (p=0.001). SIGNIFICANCE: Eight sessions of tDCS over M1 improved postural response to perturbation in PwPD. Some benefits lasted for at least a month. Neuromuscular and behavioral changes observed after the intervention were accompanied by decreased PFC activity (executive-attentional control), suggesting that tDCS applied over M1 can improve movement automaticity.

Non-Invasive Brain Stimulation (NIBS), Hypnosis, and Hypnotizability: Literature Review and Future Directions.

Non-Invasive Brain Stimulation (NIBS) stands as an advanced technology embraced by researchers and clinicians to influence thoughts, emotions, and behaviors. The prevalent NIBS methods include transcranial Direct Current Stimulation (tDCS) and Transcranial Magnetic Stimulation (TMS), both proficient in either exciting or depressing neural activities in specific cortical regions. Recently, NIBS has been integrated into hypnosis research with the goal of enhancing hypnotizability. Specifically, the limited existing studies have predominantly focused on the dorsolateral prefrontal cortex (DLPFC) due to its significant role in neutral hypnosis. Overall, these studies suggest the fascinating potential to alter hypnotizability and hypnotic phenomena, although the impact on responsiveness to suggestions remains modest. In contrast to psychological and pharmacological methods, NIBS enables alterations in hypnotic experiences that are independent of operators and noninvasive. This grants researchers the chance to employ a causal approach in investigating the brain-behavior relationship associated with suggestibility. The present paper evaluates existing NIBS studies in this domain, delving into the neurocognitive mechanisms at play and their potential implications for hypnosis research and practice.

Multichannel tDCS with advanced targeting for major depressive disorder: a tele-supervised at-home pilot study.

Introduction: Proof-of-principle human studies suggest that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) may improve depression severity. This open-label multicenter study tested remotely supervised multichannel tDCS delivered at home in patients (N=35) with major depressive disorder (MDD). The primary aim was to assess the feasibility and safety of our protocol. As an exploratory aim, we evaluated therapeutic efficacy: the primary efficacy measure was the median percent change from baseline to the end of the 4-week post-treatment follow-up period in the observer-rated Montgomery-Asberg Depression Mood Rating Scale (MADRS). Methods: Participants received 37 at-home stimulation sessions (30 minutes each) of specifically designed multichannel tDCS targeting the left DLPFC administered over eight weeks (4 weeks of daily treatments plus 4 weeks of taper), with a follow-up period of 4 weeks following the final stimulation session. The stimulation montage (electrode positions and currents) was optimized by employing computational models of the electric field generated by multichannel tDCS using available structural data from a similar population (group optimization). Conducted entirely remotely, the study employed the MADRS for assessment at baseline, at weeks 4 and 8 during treatment, and at 4-week follow-up visits. Results: 34 patients (85.3% women) with a mean age of 59 years, a diagnosis of MDD according to DSM-5 criteria, and a MADRS score ≥20 at the time of study enrolment completed all study visits. At baseline, the mean time since MDD diagnosis was 24.0 (SD 19.1) months. Concerning compliance, 85% of the participants (n=29) completed the complete course of 37 stimulation sessions at home, while 97% completed at least 36 sessions. No detrimental effects were observed, including suicidal ideation and/or behavior. The study observed a median MADRS score reduction of 64.5% (48.6, 72.4) 4 weeks post-treatment (Hedge's g = -3.1). We observed a response rate (≥ 50% improvement in MADRS scores) of 72.7% (n=24) from baseline to the last visit 4 weeks post-treatment. Secondary measures reflected similar improvements. Conclusions: These results suggest that remotely supervised and supported multichannel home-based tDCS is safe and feasible, and antidepressant efficacy motivates further appropriately controlled clinical studies. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT05205915?tab=results, identifier NCT05205915.