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PubMed2026

A single session of high-definition transcranial direct current stimulation does not modulate effects of knee two-point discrimination training or sensorimotor function in healthy adults: Double-blind randomised controlled trial.

BACKGROUND: Benefits of sensory-training interventions on sensorimotor outcomes are inconsistent, and it is unclear whether transcranial direct current stimulation (tDCS) can enhance proprioception, which is fundamental to neuromuscular control. Existing evidence is dominated by upper-limb studies, so transferability to the knee is unclear. This study investigated whether a single session of anodal high-definition (HD)-tDCS, alone or combined with brief two-point discrimination (TPD) training, enhances knee sensorimotor function and performance in healthy adults. METHODS: In a double-blind randomised-controlled trial, 57 healthy participants received (1) 20-min, 1 mA anodal HD-tDCS over the knee primary somatosensory (S1) map or sham stimulation, and (2) 15-min knee TPD training or no training. Knee somatosensory, sensorimotor, and functional performance measures were assessed pre- and immediately post-intervention. Three-way mixed-design ANOVAs, equivalence testing (smallest effect size of interest η2 = 0.02), Bayes factors, and linear mixed-effects models quantified effects. RESULTS: HD-tDCS, TPD training, and their sequential combination had no effect on any outcome measure (p ≥ 0.05; η2 ≤ 0.015). Confidence intervals spanned equivalence bounds, and equivalence testing results were non-significant (p ≥ 0.05). Bayes factors (<0.33) showed moderate evidence for the null (no effect). Mixed-effects modelling attributed ≤8% of total variance to intervention fixed effects, with the remainder captured by participant-level random effects. CONCLUSION: A single 20-minute session of 1 mA HD-tDCS, with or without brief TPD training, does not acutely modify knee somatosensory, sensorimotor, or functional performance in healthy adults. Existing evidence at the hand may not translate to the lower limb. Future work should investigate higher-dose, multi-session, task-concurrent, or network-targeted strategies in clinical populations.

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PubMed2026

Reducing state anxiety with alpha-frequency transcranial alternating current stimulation.

BACKGROUND: Anxiety reactivity to acute stress is a transdiagnostic vulnerability factor. We tested whether a single session of alpha-frequency transcranial alternating current stimulation (tACS) targeting the frontoparietal control network reduces stress-evoked state anxiety in healthy adults. METHODS: In a randomized, blinded, sham-controlled study, 42 participants (mean age 58.9 years) completed an acute stress task before and after stimulation. The task was an adapted moving-circles paradigm in which circle collisions triggered a brief aversive event (mild electric shock plus unpleasant noise and a white flash). Active stimulation consisted of 20 min of 10-Hz tACS (2.0 mA/channel; 30-s ramp up/down) delivered via electrodes at F3, P3, Cz, and T7 (0° phase at F3/P3; 180° at Cz/T7). Sham stimulation used the same montage and ramp periods but no sustained current. RESULTS: State anxiety showed a significant Time × Protocol interaction (F(1,35) = 4.22, p = .047): STAI-S decreased after active tACS (Δ = -3.16) but increased slightly after sham (Δ = +1.17). Perceived stress appraisal (SAAS) did not change. Resting-state alpha power at F3/P3 showed no reliable pre-post effects. During the task, left-frontal relative alpha differed by protocol and showed a trend toward larger increases following active tACS. Electrodermal and pupil indices changed across sessions in both groups, with no differential stimulation effects. CONCLUSIONS: A single alpha-tACS session produced a modest, selective reduction in stress-evoked state anxiety, supporting oscillatory neuromodulation as a scalable approach to dampen anxiety reactivity.

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PubMed2026

Dissociating behavioral, neural and experiential effects of prefrontal HD-tDCS during conflict resolution.

Inconsistent evidence regarding the cognitive effects of transcranial direct current stimulation (tDCS) highlights the need for more comprehensive approaches to assess its impact. This study aimed to investigate the effects of high-definition tDCS (HD-tDCS) on conflict resolution by combining behavioral, neural, and subjective experience measures. Sixty participants were randomly assigned to anodal, cathodal, or sham HD-tDCS groups and completed a 30-min flanker task. EEG was recorded during the first and last blocks (without stimulation), while stimulation was applied during the intermediate blocks of the task. Using a multidimensional methodological approach including Drift-Diffusion Modeling (DDM), EEG spectral analysis, Lempel-Ziv complexity, and Temporal Experience Tracing (TET), we assessed the cognitive, neural, and phenomenological effects of stimulation. Behavioral results indicated no significant improvements in reaction times or accuracy across the stimulation groups. Similarly, DDM parameters showed no effect of HD-tDCS on latent cognitive processes. However, EEG data revealed a significant reduction in neural complexity in the anodal group during resting-state, suggesting a stabilization or reorganization of neural dynamics. Subjective experience analysis identified two distinct clusters of task-related feelings, though time spent in these experiential states did not differ between groups. Interestingly, sensation of stimulation was significantly higher for anodal stimulation than sham when analyzed as a single dimension. Despite null behavioral effects, this study provides important insights into the neural and subjective responses to HD-tDCS and highlights the value of integrating complementary multidimensional approaches to better characterize brain stimulation effects. These findings contribute to the ongoing debate about the efficacy of tDCS in cognitive enhancement.

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PubMed2026

Deep brain stimulation for Tourette syndrome: a systematic review and meta-analysis.

Deep brain stimulation (DBS) has emerged as a promising neuromodulatory therapy for patients with refractory Tourette syndrome (TS). Various brain targets-including the globus pallidus internus (GPi) and several thalamic nuclei-have been explored, yet the comparative efficacy of DBS in different targets remain unclear. This meta-analysis aims to evaluate the clinical efficacy of DBS in TS and assess symptom improvements across different stimulation targets. A systematic search of PubMed, Embase, and Web of Science identified studies published between October 2014 and September 2025. Study quality was assessed using the French and Gronseth classification system. Outcomes of interest included pre- and postoperative scores on the Yale Global Tic Severity Scale (YGTSS) and Yale-Brown Obsessive Compulsive Scale (YBOCS). A total of 22 studies involving 358 patients were included in this meta-analysis. Mean YGTSS scores decreased from 69.19 ± 18.04 preoperatively to 35.88 ± 17.23 postoperatively. There was an average 48% reduction in YGTSS scores. DBS led to a substantial reduction in tic severity (YGTSS: GPi, SMD = 2.29, P < 0.00001; thalamus, SMD = 2.33, P < 0.0001). Within the GPi subgroup, stimulation of the anteromedial GPi (amGPi) resulted in significantly better benefits (SMD = 3.01, P < 0.00001) compared to the posterior-ventrolateral GPi (pvlGPi), which did not reach statistical significance (SMD = 1.23, P = 0.05). YBOCS scores decreased from a mean of 17.38 ± 6.15 preoperatively to 9.16 ± 4.12 postoperatively. The average reduction in YBOCS scores was 47%. Obsessive-compulsive disorder (OCD) symptoms also showed significant improvement following DBS (overall YBOCS, SMD = 0.94, P < 0.00001; amGPi, SMD = 1.49, P = 0.004; pvlGPi, SMD = 0.72; P = 0.006). DBS is an effective and target-sensitive intervention for TS, alleviating both motor tics and obsessive-compulsive symptoms. Compared to therapies such as pvlGPi and thalamic-DBS, amGPi-DBS may demonstrate greater therapeutic potential compared with pvlGPi-DBS, suggesting its potential advantage in modulating the associated circuits involved in the pathophysiology of TS.

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PubMed2026

Dual Transcranial Direct Current Stimulation Modulates Hierarchical Functional Network Organization in Post-Stroke Cognitive Impairment: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the clinical efficacy of dual transcranial direct current stimulation (tDCS) in patients with post-stroke cognitive impairment (PSCI) and to explore the effects on the hierarchical organization of functional brain networks, ranging from regional synchronization to inter-regional connectivity and global network topology. METHODS: In this randomized, double-blind, sham-controlled trial, 74 PSCI patients received conventional therapy alongside either active dual-tDCS (n = 38) or sham stimulation (n = 36). Active tDCS targeted the dorsolateral prefrontal cortex (DLPFC) via anodal-left/cathodal-right nodes (2.0 mA, 20 min/day, 20 sessions). The primary outcome was the Montreal Cognitive Assessment (MoCA). Secondary outcomes included the Mini-Mental Status Examination (MMSE), Stroop Test (ST), Trail Making Test (TMT), Wechsler Memory Scale (WMS), and Barthel Index (BI). A subgroup of 36 participants (18 per group) underwent resting-state functional magnetic resonance imaging (rs-fMRI) to analyze regional homogeneity (ReHo), functional connectivity (FC), and network topology. Partial correlations assessed the association between neuroimaging alterations and clinical improvements. RESULTS: The tDCS group showed significantly greater improvements in MoCA scores (tDCS: 5.74 ± 2.76 vs. sham: 2.69 ± 2.69; t = 4.799, p < 0.001) as well as in attention and memory domains compared to the sham group. The rs-fMRI changes included increased ReHo in the right middle temporal gyrus (MTG) and the left inferior frontal gyrus (IFG), and reduced FC between the right MTG-left superior frontal gyrus and left IFG-cerebellum (p < 0.05, FWE-corrected). Additionally, small-worldness and global efficiency increased (p < 0.05) with these alterations correlating with clinical recovery. Adverse events were rare and self-limiting. CONCLUSION: Dual-tDCS over bilateral DLPFC safely improves cognitive recovery in PSCI. These clinical gains are associated with rs-fMRI alterations, specifically in regional synchronization, inter-regional connectivity, and global topology, which suggest a potential biomarker for monitoring tDCS efficacy, offering a rationale for precision neuromodulation in stroke rehabilitation.

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PubMed2026

Remotely Supervised, Home-Based Transcranial Direct Current Stimulation for Major Depressive Disorder: Systematic Review and Meta-Analysis.

BACKGROUND: Major depressive disorder affects over 280 million people worldwide, and access to effective treatment remains limited. Transcranial direct current stimulation (tDCS) is a noninvasive option, and portable devices now allow for home-based delivery under varying degrees of remote supervision. OBJECTIVE: This study aimed to systematically review and meta-analyze the efficacy, safety, feasibility, and acceptability of home-based and remotely supervised tDCS for depressive disorders. METHODS: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 and PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses literature search extension) guidelines, we searched MEDLINE, Embase, Web of Science, the Cochrane databases, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform up to July 2025, with backward and forward citation searching. Two reviewers independently screened records, extracted data, and assessed risk of bias (version 2 of the Cochrane risk-of-bias tool for randomized trials, Newcastle-Ottawa Scale for observational studies, and Critical Appraisal Skills Programme for qualitative studies) and certainty of evidence (Grading of Recommendations Assessment, Development, and Evaluation; GRADE). RESULTS: This review included 12 distinct studies (16 reports), of which 6 (50%) were randomized sham-controlled trials forming the meta-analytic pool. Active home-based tDCS produced a small, statistically significant improvement over sham (pooled Hedges g=0.36, 95% CI 0.06-0.66; P=.03; I2=34.3%). The effect was not robust to removal of the single largest positive trial (omitting the one study from 2025: g=0.39, 95% CI -0.12 to 0.91), and trial-level results were mixed: the 2 largest trials (one unsupervised [n=210] and one self-administered [n=141]) were negative on their primary depression outcomes, whereas the largest real-time supervised trial (n=174) was positive (between-group 95% CI 0.51-4.01; P=.01). This estimate was concordant in direction with an independent peer-reviewed meta-analysis of overlapping trials, which reported a pooled Montgomery-Åsberg Depression Rating Scale reduction (weighted mean difference -2.74, 95% CI -4.19 to -1.29) and Hamilton Depression Rating Scale reduction (weighted mean difference -2.24, 95% CI -4.16 to -1.49), attenuating to nonsignificance (P>.05) in major depressive disorder without comorbid cognitive impairment. The pooled effect fell at or near the minimal clinically important difference. GRADE certainty was moderate. Adverse events were predominantly mild: one pilot study was terminated early for skin lesions, and one nonfatal suicide attempt occurred in an unsupervised trial. CONCLUSIONS: Home-based and remotely supervised tDCS produces a small, statistically significant but clinically modest antidepressant effect that is sensitive to the inclusion of the largest positive trial, with the 2 largest trials being negative. The available controlled evidence does not establish supervision intensity as a determinant of efficacy. Current data are insufficient to recommend routine clinical adoption; adequately powered trials with standardized supervision and longer follow-up are needed.

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PubMed2026

[Efficacy and safety of acute-phase transcutaneous auricular vagus nerve stimulation for herpes zoster-related pain in middle-aged and elderly patients with comorbid depression and anxiety].

Objective: To evaluate the efficacy and safety of transcutaneous auricular vagus nerve stimulation (taVNS) during the acute phase in middle-aged and elderly patients with herpes zoster (HZ) comorbid depressive and anxiety states. Methods: This was a randomized controlled trial. Forty middle-aged and elderly patients with acute-phase HZ who attended the Department of Dermatology at Xuanwu Hospital, Capital Medical University, from June 2024 to June 2025 were enrolled and randomly assigned in a 1∶1 ratio using a random number table to receive either taVNS (n=20) or sham stimulation (n=20) for 5 consecutive days. Both groups received antiviral therapy and on-demand rescue analgesia. Pain, anxiety/depression, and sleep quality were evaluated using the Visual Analog Scale (VAS), the 4-item Patient Health Questionnaire (PHQ-4), and the Insomnia Severity Index (ISI), respectively. The primary outcome was the incidence of subacute pain at 30 days post-rash onset. Secondary outcomes included cumulative analgesic consumption at 1 and 2 weeks after treatment, the changes from baseline (Δ values) in PHQ-4 and ISI scores at 2 weeks, and the incidence of postherpetic neuralgia (PHN) at 90 days post-rash onset. Results: In the taVNS group, 7 patients (35%) were female, with a mean age of (64.1±9.7) years; in the sham group, 10 patients (50%) were female, with a mean age of (61.5±8.5) years. There were no statistically significant differences between the two groups in baseline VAS, PHQ-4, or ISI scores (all P>0.05). The incidence of subacute pain was significantly lower in the taVNS group than in the sham group [5% (1/20) vs 35% (7/20), RD=-30.0% (95%CI:-52.1%--4.9%); RR=0.14 (95%CI: 0.02-1.06); P=0.044]. At 2 weeks after treatment, the Δ values of PHQ-4 and ISI in the taVNS group were significantly greater than those in the sham group. The proportion of patients taking Lofentadine and the cumulative Lofentadine consumption at weeks 1 and 2 were both lower in the taVNS group than in the sham group (all P<0.05). No serious adverse events occurred in either group, and the difference in PHN incidence between groups was not statistically significant (P>0.05). Conclusions: Acute-phase taVNS appears to be feasible and safe in middle-aged and elderly patients with HZ and comorbid depressive and anxiety, effectively reducing subacute pain and improving emotional and sleep outcomes.

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PubMed2026

Choice of Anesthesia in Microelectrode Recording-guided Deep Brain Stimulation Surgery for Parkinson's Disease (CHAMPION): A Noninferiority Randomized Controlled Trial.

BACKGROUND: Deep brain stimulation for Parkinson's disease is often performed under conscious sedation or general anesthesia. However, anesthetic agents may influence intraoperative microelectrode recording, and the optimal anesthesia method for microelectrode recording remains unclear. This study compared general anesthesia and conscious sedation in preserving microelectrode recording signal intensity during deep brain stimulation. METHODS: In this prospective, noninferiority randomized controlled trial, patients with Parkinson's disease (United Kingdom Brain Bank criteria) undergoing elective bilateral surgery were randomized 1:1 to the conscious sedation or the general anesthesia group. During surgery, a desflurane anesthetic titrated against the quality of the electrophysiologic signal was applied in the general anesthesia group, whereas patients in the conscious sedation group received dexmedetomidine anesthesia. The primary outcome was the proportion of patients with high-quality microelectrode recording (normalized root mean square greater than 2.0), assessed postoperatively off-line. Secondary outcomes included operation and recording duration, 6-month clinical efficacy, and complication rates. RESULTS: Of 188 randomized patients (94 general anesthesia, 93 conscious sedation), desflurane anesthesia was noninferior for high normalized root mean square proportion (89.4% vs . 90.3%; difference, -0.96%; 95% CI, -9.62 to 7.70). The general anesthesia group had shorter operative time (difference, -9.07 min; 95% CI, -13.99 to -4.14; P < 0.001). At 6 months, changes in Unified Parkinson's Disease Rating Scale score (difference, -2.50; 95% CI, -7.20 to 2.20; P = 0.297), levodopa equivalent daily dose (difference, -58.4 mg; 95% CI, -133.56 to 16.75; P = 0.128), and complication rates (general anesthesia: 10.9% vs . conscious sedation: 8.9%; P = 0.655) were comparable between the groups. CONCLUSIONS: General anesthesia is noninferior to conscious sedation for microelectrode-guided subthalamic nucleus deep brain stimulation, providing equivalent signal intensity and clinical outcomes while improving procedural efficiency, supporting its use as a valid clinical option.

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PubMed2026

Modulating sentence comprehension in people with aphasia through anodal tDCS: A double-blind randomized cross-over study.

This double-blind randomized cross-over study investigated the effects of perilesional anodal transcranial direct current stimulation (AtDCS) combined with speech-language therapy on sentence comprehension in eight individuals with chronic nonfluent agrammatic aphasia. The behavioral therapy consisted of an intensive comprehension treatment including drilling in sentence-to-picture matching and Mapping Therapy. Each participant underwent both the anodal tDCS and sham stimulation conditions (five received sham first followed by real stimulation, and the remaining three the reverse sequence), with each condition paired with the same behavioral treatment and separated by a four-month washout period. Stimulation was applied over the perilesional area (left BA6) for 20 min during daily 40-min therapy sessions over four consecutive weeks. Sentence comprehension was assessed with the RiComprendo battery and functional communication with the Communicative Effectiveness Index (CETI). Data were analyzed using paired t-tests, Bayesian analyses, and linear mixed-effects models to control for baseline performance and individual variability. Both stimulation conditions produced significant pre-to-post improvements in sentence comprehension, particularly for syntactically complex structures such as passives and center-embedded object relatives. However, gains were overall greater following AtDCS, as reflected in larger effect sizes, stronger Bayes factors, and a significant treatment effect in the mixed-effects models. Only the AtDCS condition yielded significant improvements in self-perceived comprehension abilities on the CETI. These findings suggest that AtDCS over perilesional cortical areas may boost the effects of traditional language therapy on sentence comprehension, supporting its feasibility and potential as an adjuvant intervention in post-stroke aphasia rehabilitation.

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PubMed2026

Effectiveness of transcranial direct current stimulation with and without positive mood induction on worry and transdiagnostic cognitive-emotional processes: A randomized controlled trial.

The present study investigated the effectiveness of transcranial direct current stimulation (tDCS), with and without positive mood induction, on worry and key transdiagnostic cognitive-emotional processes, including attentional bias, working memory, problem solving, and emotion regulation, in individuals with high levels of worry. This single-blind randomized controlled trial included 45 individuals with high levels of worry. After a structured clinical interview, participants were randomly assigned, with gender balancing, to one of three groups: (1) tDCS alone, (2) tDCS combined with positive mood induction, or (3) a sham control group. Outcome measures were administered at three time points (pretest, posttest, and one-month follow-up) and assessed attentional bias (Dot Probe Task), working memory (1-back task), problem solving (Tower of London task), emotion regulation (Gross's Emotion Regulation Questionnaire), and worry severity (Penn State Worry Questionnaire; PSWQ). Repeated-measures ANOVA showed that both active groups (tDCS alone and tDCS + positive mood induction) significantly improved attentional bias, worry, working memory, problem solving, and emotion regulation compared to controls (p < 0.05). The combined intervention produced significantly greater gains than tDCS alone in working memory, problem solving, emotion regulation (p < 0.05), and reductions in attentional bias and worry (p < 0.001). All effects persisted at one-month follow-up (p < 0.05). tDCS reduces worry and attentional bias and enhances cognition and emotion regulation in individuals with high levels of worry. The combined intervention produced larger and more sustained improvements than tDCS alone across the assessed behavioral outcomes. These findings support further investigation of combining tDCS with structured positive mood induction while the mechanisms underlying the additional benefits remain to be established.

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PubMed2026

Effects of transcutaneous electrical acupoint stimulation versus acupressure on the trajectories of multidimensional adverse reactions to chemotherapy in breast cancer patients: a secondary analysis of a randomized controlled trial.

BACKGROUND: Chemotherapy for breast cancer often induces multidimensional adverse reactions such as nausea and vomiting, anxiety, depression, and sleep disturbances. These symptoms are interrelated and may evolve dynamically, impacting patients' treatment outcomes and quality of life. As non-pharmacological interventions, transcutaneous electrical acupoint stimulation (TEAS) and self-acupressure (SA) have shown potential in alleviating symptoms. However, their long-term effects on the joint developmental trajectories of these multidimensional symptoms (nausea and vomiting, anxiety, depression, and sleep disturbances) remain unclear. OBJECTIVE: This study aimed to identify potential trajectory class of multidimensional adverse reactions in breast cancer patients undergoing chemotherapy and to explore the differential effects of TEAS and SA on different trajectory subgroups. METHODS: This was a secondary analysis of a randomized controlled trial. A total of 189 breast cancer patients receiving chemotherapy were included. The Group-Based Multi-Trajectory Model (GBMTM) was employed to identify joint developmental trajectories of acute/delayed chemotherapy-induced nausea and vomiting (CINV), anxiety, depression, and sleep quality during chemotherapy. Subsequently, causal forest was used to analyze the average treatment effects (ATE) of TEAS (vs. control group) and SA (vs. control group) on patients' symptom trajectory. RESULTS: Multidimensional adverse reactions were classified into two heterogeneous trajectories: a "High Symptom Burden-Persistent (HSBP)" type (n = 101) and a "Low Symptom Burden-Relieving (LSBR)" type (n = 88). The persistent high incidence of acute CINV contrasted sharply with the comprehensive relief of other symptoms in the latter group. Causal forest suggested that both TEAS and SA significantly increased the probability of patients being classified into the "LSBR" trajectory. The ATE was 0.147 (95% CI: 0.143, 0.151) for TEAS, slightly lower (P < 0.05) than 0.176 (95% CI: 0.162, 0.190) for SA.  CONCLUSION: Multidimensional adverse reactions in breast cancer patients undergoing chemotherapy exhibit heterogeneity in their trajectories. Both TEAS and SA were associated with a higher probability of patients being classified into a more favorable symptom trajectory-LSBR. The multidimensional trajectory identification with treatment effect estimation may serve as a useful analytical strategy for future longitudinal research in cancer chemotherapy-induced adverse reactions symptom management. CLINICAL TRIAL REGISTRATION: ChiCTR2300077667 (Chinese Clinical Trial Registry, https://www.chictr.org.cn/ ), Registered 15 November 2023.

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PubMed2026

Effects of Transcranial Direct Current Stimulation and Individualized Physical Therapy on Pain and Function in Individuals With Chronic Knee Pain: A Pilot Study.

BACKGROUND AND PURPOSE: Noninvasive brain stimulation is a promising neuromodulatory intervention for chronic pain. This study aimed to determine the impact that transcranial direct current stimulation (tDCS) in combination with individualized physical therapy (PT) has on pain and function in individuals with chronic knee pain. METHODS: This study was a preliminary pragmatic, triple-blinded, randomized, and sham-controlled clinical trial performed in an outpatient orthopedic physical therapy clinic. Participants participated in 5 sessions of active or sham tDCS followed by individualized PT intervention. Pain outcomes included the Numeric Pain Rating Scale, Movement-Evoked Pain, pressure pain thresholds (PPT), and the Central Sensitization Inventory. Functional outcomes included the 2-minute walk test, 5-time sit-to-stand test, quadriceps strength, knee range of motion, Patient Specific Functional Scale, and the Lower Extremity Functional Scale. RESULTS: Thirty participants with chronic knee pain completed the study. There were no significant differences observed for primary patient-centered pain and functional outcomes. For secondary outcomes, the active tDCS group had a significant effect (p < 0.05) on percent change in lateral joint line PPT and a significant multivariate effect of group on PPT change scores for 3-site and 5-site clusters (p < 0.05). Exploratory responder analyses demonstrated that the active tDCS group was 12.8 times more likely to achieve the minimum detectable change in quadriceps strength improvement compared with the sham tDCS group (p < 0.05). DISCUSSION: There were no significant between-group differences for primary pain and functional outcomes. However, the active tDCS group showed improvements in pain sensitivity, as measured by PPT, and quadriceps strength, which were superior to those seen in the sham tDCS group. These preliminary findings provide insight into possible mechanisms of tDCS in addressing pain as opposed to efficacy. Given that there were no clear between-group differences in patient-centered outcomes, there is insufficient evidence for routine tDCS use for chronic knee pain. TRIAL REGISTRATION: NCT06132412.

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PubMed2026

Post-intervention effectiveness of a computerized personalized cognitive stimulation program adapted according to cognitive reserve in older adults without cognitive impairment in Primary Care: A randomized clinical trial.

BACKGROUND: Cognitive reserve may influence responsiveness to cognitive interventions, yet it is rarely used to tailor computerized stimulation. OBJECTIVE: To evaluate the effectiveness of a computerized cognitive stimulation program personalized according to cognitive reserve on cognition, reserve-related activities, and digital competence in community-dwelling older adults without cognitive impairment in Primary Care. METHODS: In this randomized clinical trial, 102 adults aged ≥65 years with normal cognitive performance were recruited from three primary care centers in Zaragoza, Spain, and stratified by cognitive reserve level before random allocation to intervention or control. The intervention comprised digital literacy sessions followed by 8 weeks of home-based computerized cognitive stimulation tailored to participants' cognitive reserve profiles and life history. Controls received a single group-based health education session focused on maintaining everyday cognitive activity. Outcomes were assessed at baseline and post-intervention using global cognition (MEC-35), the Cognitive Reserve Questionnaire, the Mobile Device Proficiency Questionnaire-16, and domain-specific neuropsychological tests. A total of 100 participants completed the final evaluation and were included in complete-case analyses. RESULTS: Compared with controls, the intervention group showed greater adjusted post-intervention improvements in global cognition (MEC-35 between-group difference: 1.8 points) and several cognitive measures, including temporal orientation, calculation, attention, praxis, verbal fluency, processing speed, executive functions, and verbal learning. CRQ scores and digital competence also improved, with small-to-large effect sizes. CONCLUSIONS: A computerized cognitive stimulation program adapted according to cognitive reserve appears feasible in Primary Care and may improve cognition, engagement in reserve-related activities, and digital competence in older adults without cognitive impairment.

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PubMed2026

Transcranial Magnetic Stimulation for Patients with Exposure Therapy Resistant Obsessive-Compulsive Disorder (TETRO): Study Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling mental disorder, characterized by obsessions, compulsions, and substantial morbidity. Approximately 50% of adults with OCD fail to achieve satisfactory outcomes from first-line treatments, such as exposure therapy with response prevention (ERP), with or without medication. This leads to chronic social, educational, and occupational impairment. While invasive procedures such as deep brain stimulation are available for severe, treatment-refractory cases, a need remains for less invasive alternatives. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive intervention, shows promise in reducing OCD symptoms. Unlike in depression, rTMS is not yet reimbursed for OCD in the Dutch healthcare system. OBJECTIVE: This study examines the efficacy and cost-effectiveness of low-frequency (1Hz) rTMS targeting the presupplementary motor area (pre-SMA) compared to sham rTMS as an adjuvant treatment to ERP in adults with OCD with inadequate response to first-line treatment. METHODS: A total of 250 adults with OCD will be enrolled in this multicenter randomized controlled trial. Participants will be randomly assigned to ERP combined with either active or sham 1Hz rTMS over the pre-SMA. Treatment is administered 4 times weekly for at least 5 weeks (20 rTMS-ERP sessions), with optional extension of 1 to 2 weeks, up to 28 rTMS-ERP sessions. Clinical assessments occur at baseline, weekly during treatment, posttreatment, and at 3, 6, and 12 months follow-up. Participants undergo pre- and posttreatment (functional) (MRI) scans, including a symptom provocation task. Blood sampling takes place pre- and posttreatment and at 3-month follow-up. The primary outcome is OCD severity at posttreatment, as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Secondary outcomes include functional improvement, quality of life, and societal costs. Pretreatment symptom profiles, genotype, and brain network topology will be analyzed as predictors of response and relapse risk. Pre-to-post treatment change in blood-based and magnetic resonance (MR)-based neuroplasticity markers will help explore differential mechanisms between ERP alone and combined rTMS-ERP. We expect that the verum rTMS protocol will be cost-effective compared to sham-rTMS. RESULTS: Recruitment started in April 2022, and as of February 2026, 201 participants have been enrolled. Posttreatment assessments are projected to be completed in December 2026, with final one-year follow-up evaluations anticipated by the end of 2027. CONCLUSIONS: To our knowledge, this study is the first adequately powered randomized controlled trial examining efficacy, cost-effectiveness, and mechanism of action of rTMS for OCD as adjuvant therapy to ERP. In case of efficacy and/or cost-effectiveness, it will pave the way for rTMS as insured health care for adults with OCD in the Netherlands, and possibly other European countries. Furthermore, this trial will provide insight into the mechanisms of treatment response to intensive ERP, with and without adjunctive rTMS, as well as potential side effects, individual variability, and long-term outcomes in adults with OCD.

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PubMed2026

Effects of adjunctive bifrontal tDCS on depressive symptoms and cognitive performance in major depressive disorder: A randomized, double-blind, sham-controlled crossover pilot study.

BACKGROUND: Evidence for antidepressant effects of transcranial direct current stimulation (tDCS) in major depressive disorder (MDD) is heterogeneous, and cognitive effects remain uncertain. We compared depressive symptoms and DSST performance during active and sham bifrontal tDCS in medicated outpatients with MDD and baseline HAMD-17 ≥ 15. METHODS: In this randomized, double-blind, sham-controlled crossover pilot trial, adults with MDD and inadequate response to an adequate antidepressant trial were assigned to active→sham or sham→active tDCS sequences while continuing antidepressants. Each period comprised 10 sessions over 2 weeks. Active stimulation was delivered at 2 mA for 20 min (anode F3, cathode F4); sham used the same montage with brief ramping only. No washout interval was used. No washout interval was used. The primary outcome was HAMD-17; secondary outcomes were DSST and CGI ratings. RESULTS: Of 38 randomized participants, 32 completed both periods and were analyzed per protocol. HAMD-17 scores were lower during active than sham stimulation (mean difference -3.63, 95% CI -5.86 to -1.40; p = 0.002), but the condition-by-sequence interaction was significant (p = 0.026). No condition effect was observed for DSST (p = 0.261) or CGI-Severity (p = 1.000); CGI-Improvement was strongly sequence-dependent (p < 0.001). In an exploratory first-period analysis, adjusted T1 HAMD-17 scores were lower in the active-first group (adjusted difference -4.90, 95% CI -7.92 to -1.87; p = 0.003). Adverse effects were mild and transient. CONCLUSIONS: Active tDCS was associated with lower HAMD-17 scores, but the pooled contrast was order-dependent and cannot be interpreted as a definitive treatment effect. No DSST benefit was observed.

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PubMed2026

The effect of tDCS on emotion-related risk-taking behavior and delay discounting in adults with ADHD.

INTRODUCTION: Adults with Attention Deficit Hyperactivity Disorder (ADHD) often engage in risky behaviors due to impaired decision-making processes. This study aims to investigate the effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) on emotion-related risk-taking behavior and delay discounting in adults with ADHD. METHODS: Thirty adults with ADHD underwent three tDCS conditions, administered in a randomized order with at least one week between sessions: (1) left dlPFC anode/right vmPFC cathode, (2) left dlPFC cathode/right vmPFC anode, and (3) sham stimulation. In each session, participants completed the Delay Discounting Task (DDT) and the Modified Balloon Analogue Risk Task (mBART) under three emotional conditions (neutral, positive, and negative) which were induced using emotionally congruent photographs and sounds. Galvanic skin responses (GSR) were also recorded. In the DDT, both area under the curve (AUC) values and log-transformed discounting rates (log k) were calculated for small, medium, and large reward magnitudes (RM). Exploratory electric field modeling was also performed to characterize current distribution. RESULTS: The findings demonstrated task-specific effects of tDCS on decision-making. Although no overall tDCS effect was observed on DDT performance, significant tDCS × RM interactions emerged, particularly for smaller rewards. In contrast, exploratory analyses suggested that tDCS affected all mBART scores. Emotional condition did not influence consistently behavioral performance in either task, whereas both emotional stimulation and tDCS significantly affected GSR responses. However, exploratory electric field modeling indicated a broad prefrontal current distribution extending beyond the intended cortical targets. CONCLUSIONS: These findings suggest preliminary evidence that prefrontal tDCS can influence risk-related decision-making and autonomic responses in adults with ADHD. However, its effects on delay discounting appear to be context-dependent and limited to specific RMs. Future studies combining neuroimaging with individualized electric field modeling are needed to clarify the neural mechanisms underlying the observed effects of tDCS and to optimize stimulation protocols in adults with ADHD.

Humans↗

PubMed2026

Efficacy of a high-frequency repetitive transcranial magnetic stimulation for craving reduction in adolescents with gaming disorder: a 4-week randomized control trial with 24-week follow-up.

BACKGROUND: With the widespread popularity of online gaming, gaming addiction has come under scrutiny. While there is ongoing research on the diagnosis and treatment of gaming disorder among adolescents, the clinical robustness and reliability of intervention strategies remain uncertain. METHODS: A 4-week, double-blind, randomized, sham-controlled clinical trial was conducted to evaluate the efficacy of noninvasive, high-frequency repetitive transcranial magnetic stimulation (rTMS) in alleviating psychological craving in adolescents diagnosed with gaming disorder. Sham rTMS was administered to the control group using the tilted-coil method. Both groups of participants were treated with SSRI medications. A total of 80 adolescents with gaming disorder participated in this study, and 73 ultimately completed the 24-week follow-up. The primary outcome was the change in craving levels before and after the rTMS intervention, as assessed by the Visual Analogue Scale (VAS). Secondary outcomes included changes in anxiety and depression levels before and after the intervention, as assessed by the HAMA and HAMD. RESULTS: We assessed levels of psychological craving, anxiety, and depression among adolescents with gaming disorder at baseline, after completing a 4-week intervention, and at a 24-week follow-up post-intervention. Our repeated-measures MANOVA results, adjusted for course variables, revealed a significant main effect of rTMS intervention on psychological craving levels in adolescents addicted to online games (F(11, 781) = 11.238, P < 0.001, partial η² = 0.142), as well as significant main effects on time (F(11, 781) = 6.809; P < 0.001, partial η² = 0.091) and group effects (F(1, 71) = 26.707, P < 0.001, partial η² = 0.282). In addition, repeated-measures ANOVA results showed significant time effects for anxiety (F(2, 142) = 20.747, P < 0.001, partial η² = 0.234) and depression levels (F(2, 142) = 22.277, P < 0.001, partial η² = 0.285) among adolescents with gaming disorder, with nonsignificant between-group effects and no intergroup interaction. In the active stimulation group, changes in psychological craving levels after 4 weeks of treatment were significantly and positively correlated with changes in anxiety levels after 4 weeks of treatment in adolescents addicted to online games (r = 0.335, P < 0.05). CONCLUSION: Our findings indicate that high-frequency rTMS targeting the left dorsolateral prefrontal cortex may be a promising approach for reducing psychological craving in adolescents with gaming disorder. TRIAL REGISTRATION: ChiCTR2500102979 in chictr.org.cn, registered on May 22, 2025.

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PubMed2026

High-frequency contralesional dorsal premotor cortex and low-frequency contralesional primary motor cortex rTMS in subacute stroke with severe upper limb impairment: comparable motor outcomes and differential regional degree centrality changes.

BACKGROUND: The contralesional dorsal premotor cortex has been proposed as a potential neuromodulatory target for patients with severe upper limb impairment due to subacute ischemic stroke. This proof-of-concept study aimed to compare behavioral outcomes and resting-state neuroimaging findings between high-frequency repetitive transcranial magnetic stimulation (rTMS) over the contralesional dorsal premotor cortex and guideline-supported low-frequency stimulation over the contralesional primary motor cortex. METHODS: In this randomized trial, 46 patients with severe upper limb impairment in the subacute stage after ischemic stroke were randomly assigned to receive either high-frequency rTMS over the contralesional dorsal premotor cortex or low-frequency rTMS over the contralesional primary motor cortex. Low-frequency stimulation over the contralesional primary motor cortex served as an evidence-supported active comparator for poststroke upper limb motor recovery. Stimulation was administered five times per week for two weeks using magnetic resonance imaging-guided neuronavigation. All participants received concurrent standard rehabilitation therapy. The primary outcome was the Fugl-Meyer Assessment for Upper Extremity. Secondary outcomes included the Arm Subscore of the Motricity Index, the Hong Kong version of the Functional Test for the Hemiplegic Upper Extremity, the Modified Barthel Index, and resting-state functional magnetic resonance imaging-derived degree centrality. RESULTS: Both groups showed significant improvements in the primary and secondary behavioral measures (p < 0.01), with no significant between-group differences in the magnitude of change (p > 0.05). In neuroimaging analyses, patients receiving high-frequency rTMS over the contralesional dorsal premotor cortex showed significantly greater degree centrality changes in the ipsilesional middle occipital gyrus, contralesional medial superior frontal gyrus, and contralesional middle frontal gyrus than those receiving low-frequency rTMS over the contralesional primary motor cortex (p < 0.05). Within the high-frequency stimulation group, degree centrality changes in the ipsilesional middle occipital gyrus were positively correlated with improvements in the Fugl-Meyer Assessment for Upper Extremity (r = 0.619, false discovery rate-corrected p = 0.018). CONCLUSIONS: High-frequency rTMS over the contralesional dorsal premotor cortex produced behavioral improvements comparable to guideline-supported low-frequency rTMS over the contralesional primary motor cortex, without establishing superiority or formal non-inferiority. Exploratory neuroimaging analyses showed greater degree centrality changes in the ipsilesional middle occipital gyrus after high-frequency premotor stimulation, and these changes correlated with upper-limb motor improvement. These findings support further investigation of contralesional dorsal premotor cortex-targeted high-frequency rTMS for severe subacute post-stroke upper limb impairment. REGISTRATION: URL: http://www.chictr.org.cn; Unique identifier: ChiCTR2000038049.

Humans↗