Transcranial Stimulation Research Articles

The safety and feasibility of transcranial direct current stimulation and exercise therapy for the treatment of cervicogenic headaches: A randomized pilot trial.

Our primary objective was to evaluate the safety and feasibility of transcranial direct current stimulation combined with exercise therapy for the treatment of cervicogenic headache. Our exploratory objectives compared symptoms of headache, mood, pain, and quality of life between active and sham transcranial direct stimulation combined with exercise therapy. Cervicogenic headache arises from injury to the cervical spine or degenerative diseases impacting cervical spine structure resulting in pain, reduced quality of life, and impaired function. Current standard-of-care treatments such as radiofrequency ablation, pharmacotherapy, manual therapy, and exercise therapy lack efficacy for some patients. Transcranial direct current stimulation is a neuromodulation technique that has shown promise in treating chronic pain conditions by positively altering neuronal activity but has not been evaluated as treatment for cervicogenic headache. This double-blind, sham-controlled, randomized, feasibility trial recruited 32 participants between the ages of 18 and 65 years that met the International Classification of Headache Disorders third edition criteria for cervicogenic headache. Participants were randomized to receive either active or sham transcranial direct current stimulation both combined with daily exercise therapy over 6 weeks. Transcranial direct current stimulation was applied over the primary motor cortex ipsilateral to worse pain for 20 min at 2 mA with a 30 s ramp up/down period. Recruitment, retention, and adherence were evaluated for feasibility. Safety was assessed through serious and minor adverse events and an adverse effect questionnaire. Clinical outcome measures assessed headache, pain, quality of life, and mood symptoms at pre-treatment, post-treatment, and 6- and 12-weeks post-treatment. A total of 97 participants were contacted to participate with 32 recruited, 16 randomized into each group, and 14 completing the treatment protocol in both groups. Within each group 12 (active) and nine (sham) completed treatment within the proposed 6 weeks (three sessions per week), others received 18 sessions but took longer. Exercise therapy was completed on an average of 87% of days for both groups. Transcranial direct current stimulation was safe, with no serious adverse events and one minor adverse event in the active group. Itching was a more common post-intervention complaint in the active group (64% active vs. 43% sham). Exploratory analysis revealed significant group × time interactions for average headache pain from pre- to post-treatment (β = -1.012, 95% confidence interval [CI] -1.751 to -0.273; p = 0.008), 6-weeks (β = -1.370, 95% CI -2.109 to -0.631; p < 0.001), and 12-weeks (β = -1.842, 95% CI -2.600 to -1.085; p < 0.001) post-treatment, and for neck pain from pre- to post-treatment (β = -1.184, 95% CI -2.076 to -0.292; p = 0.010) and 12-weeks (β = -1.029, 95% CI -1.944 to -0.114; p = 0.028) post-treatment favoring active vs. sham. There were no significant group × time interactions for quality of life or mood. The combination of transcranial direct stimulation and exercise therapy is safe and feasible for treating cervicogenic headache. While some promise has been shown for reducing headache and neck pain, larger scale trials with adequate power are needed to confirm these findings.

Transcranial random noise stimulation shifts time reproduction in opposite directions for ADHD and TD individuals.

Transcranial random noise stimulation shifts time reproduction in opposite directions for ADHD and TD individuals.

Biophysical effects and neuromodulatory dose of transcranial ultrasonic stimulation.

Biophysical effects and neuromodulatory dose of transcranial ultrasonic stimulation.

Boosting proactive motor control via statistical learning with brain stimulation.

Boosting proactive motor control via statistical learning with brain stimulation.

Lighting the Way to Seizure Cessation: Transcranial Optogenetic Therapies to Stop Seizures in Mouse Models.

Suppression of epileptic seizures by transcranial activation of K+-selective channelrhodopsin Duan X, Zhang C, Wu Y, Ju J, Xu Z, Li X, Ohdah S, Constantin OM, Pan Y, Lu Z, Wang C, Chen X, Gee CE, Nagel G, Hou S-T, Gao S, and Song K. 2025. Nature Commun . 16(1):559. PMID: 39780018. Optogenetics is a valuable tool for studying the mechanisms of neurological diseases and is now being developed for therapeutic applications. In rodents and macaques, improved channelrhodopsins have been applied to achieve transcranial optogenetic stimulation. While transcranial photoexcitation of neurons has been achieved, noninvasive optogenetic inhibition for treating hyperexcitability-induced neurological disorders has remained elusive. There is a critical need for effective inhibitory optogenetic tools that are highly light-sensitive and capable of suppressing neuronal activity in deep brain tissue. In this study, we developed a highly sensitive moderately K + -selective channelrhodopsin (HcKCR1-hs) by molecular engineering of the recently discovered Hyphochytrium catenoides kalium (potassium) channelrhodopsin 1. Transcranial activation of HcKCR1-hs significantly prolongs the time to the first seizure, increases survival, and decreases seizure activity in several status epilepticus mouse models. Our approach for transcranial optogenetic inhibition of neural hyperactivity may be adapted for cell type-specific neuromodulation in both basic and preclinical settings.

Quantitative analysis of transcranial temporal interference stimulation in rodents: A simulation study on electrode configurations

Transcranial temporal interference stimulation (tTIS) is a novel non-invasive transcranial electrical stimulation technique that achieves deep brain stimulation through multiple electrodes applying electric fields of different frequencies. Current studies on the mechanism of tTIS effects are primarily based on rodents, but experimental outcomes are often significantly influenced by electrode configurations. To enhance the performance of tTIS within the limited cranial space of rodents, we proposed various electrode configurations for tTIS and conducted finite element simulations using a realistic mouse model. Results demonstrated that ventral-dorsal, four-channel bipolar, and two-channel configurations performed best in terms of focality, diffusion of activated brain regions, and scalp impact, respectively. Compared to traditional transcranial direct current stimulation (tDCS), these configurations improved by 94.83%, 50.59%, and 3 514.58% in the respective evaluation metrics. This study provides a reference for selecting electrode configurations in future tTIS research on rodents.

Population-optimized electrode montage approximates individualized optimization in transcranial temporal interference stimulation.

Population-optimized electrode montage approximates individualized optimization in transcranial temporal interference stimulation.

Transcranial Pulsed Current Stimulation and Social Functioning in Children With Autism

Transcranial pulsed current stimulation (tPCS) may improve social functioning and sleep disorders in children with autism spectrum disorder (ASD). Prior trials have been limited by small sample sizes, single-center designs, and often a lack of sham controls. To examine the safety and efficacy of tPCS in improving social functioning and sleep disorders in children with ASD. This multicenter, double-blind, 2-armed, sham-controlled randomized clinical trial, conducted from May 1, 2022, through November 30, 2023, assessed children aged 3 to 14 years with ASD at 8 medical centers in China. Participants underwent daily 20-minute sessions of active tPCS (0.7 mA) or sham tPCS (brief 0.7 mA ramp-up and ramp-down) for 20 sessions over 4 weeks with anode over the right cerebellar hemisphere and cathode over the left dorsolateral prefrontal cortex (12.56-cm2-circular, 4-cm-diameter circular electrodes). Each day after tPCS, all participants received 1 hour of standard therapy. Social functioning was assessed using the Autism Treatment Evaluation Checklist as the primary outcome. Secondary outcomes included the Autism Behavior Checklist and the Childhood Sleep Habits Questionnaire. A total of 312 participants (155 in the active group and 157 in the sham group; 248 [79.5%] boys; mean [SD] age, 5.1 [1.6] years; 276 [88.5%] aged 3-6 years and 36 [11.5%] aged 7-14 years) completed the trial. After 20 sessions, the mean Autism Treatment Evaluation Checklist total score improved by 4.13 points (5.8%) in the sham tPCS group and 7.17 points (10.7%) in the active tPCS group. Analysis of covariance showed significantly greater improvement in the active tPCS group (difference, -3.50; 95% CI, -5.56 to -1.43; P < .001). Both treatments were well tolerated. In this randomized clinical trial of prefrontal-cerebellar tPCS in children aged 3 to 14 years with ASD, 20 sessions over 4 weeks improved social functioning and sleep. These findings suggest that tPCS may serve as a viable nonpharmacologic alternative for ASD. Chinese Clinical Trial Registry Identifier: ChiCTR2200059118.

Somatodendritic orientation determines tDCS-induced neuromodulation of Purkinje cell activity in awake mice

Transcranial direct-current stimulation (tDCS) of the cerebellum is a promising non-invasive neuromodulatory technique being proposed for the treatment of neurological and neuropsychiatric disorders. However, there is a lack of knowledge about how externally applied currents affect neuronal spiking activity in cerebellar circuits in vivo. We investigated how Cb-tDCS affects the firing rate of Purkinje cells (PC) and non-PC in the mouse cerebellar cortex to understand the underlying mechanisms behind the polarity-dependent modulation of neuronal activity induced by tDCS. Mice (n=9) were prepared for the chronic recording of local field potentials (LFPs) to assess the actual electric field gradient imposed by Cb-tDCS in our experimental design. Single-neuron extracellular recording of PCs in awake (n=24) and anesthetized (n=27) mice was combined with juxtacellular recordings and subsequent staining of PC with neurobiotin under anesthesia (n=8) to correlate their neuronal orientation with their response to Cb-tDCS. Finally, a high-density Neuropixels recording system was used to demonstrate the relevance of neuronal orientation during the application of Cb-tDCS in awake mice (n=6). In this study, we observe that Cb-tDCS induces a heterogeneous polarity-dependent modulation of the firing rate of PCs and non-PC in the mouse cerebellar cortex. We demonstrate that the apparently heterogeneous effects of tDCS on PC activity can be explained by taking into account the somatodendritic orientation relative to the electric field. Our findings highlight the need to consider neuronal orientation and morphology to improve tDCS computational models, enhance stimulation protocol reliability, and optimize effects in both basic and clinical applications.

Somatodendritic orientation determines tDCS-induced neuromodulation of Purkinje cell activity in awake mice.

Transcranial direct-current stimulation (tDCS) of the cerebellum is a promising non-invasive neuromodulatory technique being proposed for the treatment of neurological and neuropsychiatric disorders. However, there is a lack of knowledge about how externally applied currents affect neuronal spiking activity in cerebellar circuits in vivo. We investigated how Cb-tDCS affects the firing rate of Purkinje cells (PC) and non-PC in the mouse cerebellar cortex to understand the underlying mechanisms behind the polarity-dependent modulation of neuronal activity induced by tDCS. Mice (n=9) were prepared for the chronic recording of local field potentials (LFPs) to assess the actual electric field gradient imposed by Cb-tDCS in our experimental design. Single-neuron extracellular recording of PCs in awake (n=24) and anesthetized (n=27) mice was combined with juxtacellular recordings and subsequent staining of PC with neurobiotin under anesthesia (n=8) to correlate their neuronal orientation with their response to Cb-tDCS. Finally, a high-density Neuropixels recording system was used to demonstrate the relevance of neuronal orientation during the application of Cb-tDCS in awake mice (n=6). In this study, we observe that Cb-tDCS induces a heterogeneous polarity-dependent modulation of the firing rate of PCs and non-PC in the mouse cerebellar cortex. We demonstrate that the apparently heterogeneous effects of tDCS on PC activity can be explained by taking into account the somatodendritic orientation relative to the electric field. Our findings highlight the need to consider neuronal orientation and morphology to improve tDCS computational models, enhance stimulation protocol reliability, and optimize effects in both basic and clinical applications.

Transcranial temporal interference stimulation precisely targets deep brain regions to regulate eye movements.

Transcranial temporal interference stimulation (tTIS) is a novel non-invasive neuromodulation technique with the potential to precisely target deep brain structures. This study explores the neural and behavioral effects of tTIS on the superior colliculus (SC), a region involved in eye movement control, in mice. Computational modeling revealed that tTIS delivers more focused stimulation to the SC than traditional transcranial alternating current stimulation. In vivo experiments, including Ca2+ signal recordings and eye movement tracking, showed that tTIS effectively modulates SC neural activity and induces eye movements. A significant correlation was found between stimulation frequency and saccade frequency, suggesting direct tTIS-induced modulation of SC activity. These results demonstrate the precision of tTIS in targeting deep brain regions and regulating eye movements, highlighting its potential for neuroscientific research and therapeutic applications.

Efficacy and Safety of Coupled and Uncoupled Transcranial Brain Stimulations in Ischemic Stroke: A Randomised Clinical Trial (N5.003)

Efficacy and Safety of Coupled and Uncoupled Transcranial Brain Stimulations in Ischemic Stroke: A Randomised Clinical Trial (N5.003)

Effectiveness of Transcranial Stimulation on Cognitive Abilities of Older Adults with Mild Cognitive Impairment.

Background/Objectives: Aging leads to cognitive decline that may progress to dementia. Transcranial direct current stimulation (tDCS) has emerged as a strategy to improve cognitive functions in older adults with mild cognitive impairment (MCI). This study reviews the effectiveness of tDCS in these populations. Methods: A systematic review and meta-analysis was conducted following the PRISMA 2020 guidelines. Randomized controlled trials obtained from PubMed, Scopus, Cinahl, and Web of Science were included. Studies with tDCS intervention in older adults with MCI were selected, excluding those without a control group or that did not measure relevant cognitive variables. Methodological quality was analyzed with the PEDro scale and a meta-analysis was applied with random-effects models. Results: A total of 27 studies were included in this review, of which 13 were part of the meta-analysis. tDCS showed significant improvements in global cognitive function (p < 0.001) and selective attention (p = 0.044), but not in mental flexibility or visual attention. Positive effects on quality of life and depressive symptoms were also reported in some studies. Conclusions: tDCS may improve cognitive functions in older adults with MCI, but inconsistencies persist in its magnitude and duration. It is recommended to standardize protocols and conduct studies with greater methodological rigor and long-term follow-up.

Transcranial Pulse Stimulation for Alzheimer's Patients.

Transcranial pulse stimulation (TPS) is a noninvasive neuromodulation therapy with Conformité Européenne (CE) marking for the treatment of Alzheimer's disease (AD). Initial pilot studies have demonstrated promising effects on cognitive function. This article focuses on the procedure for treating patients with AD using an MRI-guided, neuro-navigated TPS device. The protocol to be followed for this is described in detail, including the necessary procedures and device settings. A brief overview of the representative clinical results published to date is also provided. In addition to significant clinical improvements in cognition and affect, adverse events (AE) and possible adverse device events (ADE) are presented to provide safety data. Finally, the method is critically discussed. In the future, randomized controlled trials should be conducted to rule out any placebo effects. There is also currently a lack of long-term studies with a larger number of patients. Despite these unresolved questions, TPS has the potential as an adjunct treatment for Alzheimer's patients when used in a controlled, scientifically guided setting.

Common and specific effects in brain oscillations and motor symptoms of tDCS and tACS in Parkinson's disease.

Common and specific effects in brain oscillations and motor symptoms of tDCS and tACS in Parkinson's disease.

Low-intensity transcranial ultrasound stimulation and its regulatory effect on pain.

Low-intensity transcranial ultrasound stimulation and its regulatory effect on pain.

Advancing network meta-analysis in non-invasive brain stimulation: Optimizing post-stroke mood through combined therapies.

Advancing network meta-analysis in non-invasive brain stimulation: Optimizing post-stroke mood through combined therapies.

Deep transcranial ultrasound stimulation using personalized acoustic metamaterials improves treatment-resistant depression in humans.

Deep transcranial ultrasound stimulation using personalized acoustic metamaterials improves treatment-resistant depression in humans.

Analgesic efficacy of non-invasive neuromodulation techniques in chronic cancer pain: a systematic review.

Chronic pain remains one of the most frequent and disabling symptoms of cancer, arising from tumors and/or treatments, and is poorly controlled in 40% of patients. Non-invasive brain stimulation (NIBS) is now widely recommended in drug-refractory neuropathic pain, but its effectiveness in chronic cancer-related pain remains unknown. A few observational studies and randomized controlled trials (RCTs) have assessed the effectiveness of NIBS on pain in this population. A systematic review of neuromodulation studies on patients with chronic cancer-related pain involving transcranial direct currents stimulation (tDCS) or repetitive transcranial magnetic stimulation (rTMS) was conducted to estimate the analgesic efficacy, safety and feasibility in clinical routine. Eleven publications (N = 298 patients) were included and analyzed. For tDCS, three RCT had a moderate effect size of 0.7 [0.6; 0.9] on a rating scale (0-10), and two case reports showed a significant decrease of pain intensity on average by -4.25 ± 0.36 points. The rTMS provided similar pain relief, with two RCTs showing a large effect size of 0.9 [0.7; 1.1], two observational study studies reporting a significant pooled effect on pain intensity (-0.9 [-1.6; -0.1] and -2.3 [-3.3; -1.3]), and two case reports where pain was reduced on average by -4.75 ± 0.36 points. None of these studies reported serious adverse events, and discontinuations of treatment were associated with cancer complications. NIBS appears to have an analgesic effect in cancer-related pain. However, due to the high heterogeneity of pain conditions, placebo-controlled trials with larger and homogeneous patient cohorts are required to confirm these promising results.

Low-intensity transcranial ultrasound stimulation modulates neurovascular coupling in mice under propofol anesthesia.

Low-intensity transcranial ultrasound stimulation modulates neurovascular coupling in mice under propofol anesthesia.