Pub Date : 2025-11-01DOI: 10.1016/j.brs.2025.11.002
Sophia H. Blyth , Rabee Haq , Sahit Menon , Benson King , Gabriela Torres Quesada , Darara Borodge , Benjamin Johnson , J. Mason Harding , Simon Vandekar , Heather Burrell Ward
Objective
Transcranial magnetic stimulation (TMS) is an exciting novel treatment for substance use disorders (SUDs). While TMS is safe and effective in the general population, there have been concerns about its safety with concurrent substance use. To date, guidelines on managing substance use during TMS have been vague – recommending caution and weighing risks and benefits – and solely based on expert opinion, rather than based on quantitative data on the prevalence of TMS side effects with concurrent substance use.
Methods
We performed a systematic review with meta-analysis of TMS studies for a SUD – a clinically impairing level of substance use where we would be more likely to detect adverse effects – to quantify the safety of TMS in the setting of substance use. We searched PubMed, Embase, PsycINFO, and the Cochrane Library for TMS studies for SUDs that reported adverse effects. We extracted adverse effects and tested the difference between the prevalence of events in the active and sham conditions.
Results
Forty-seven studies comprising 2865 participants with a SUD were included. The prevalence of neck pain and cognitive impairment was higher for sham compared to active TMS (p < .05). The prevalence of all other adverse effects, including seizure, was not significantly different between active and sham TMS.
Conclusions
TMS is safe and well-tolerated for people with SUDs. The prevalence of side effects from TMS in people with SUDs is comparable to that in the general population. TMS can be just as safely administered for SUDs as for any other psychiatric disorder.
{"title":"Evidence for safety and tolerability of transcranial magnetic stimulation for substance use disorders","authors":"Sophia H. Blyth , Rabee Haq , Sahit Menon , Benson King , Gabriela Torres Quesada , Darara Borodge , Benjamin Johnson , J. Mason Harding , Simon Vandekar , Heather Burrell Ward","doi":"10.1016/j.brs.2025.11.002","DOIUrl":"10.1016/j.brs.2025.11.002","url":null,"abstract":"<div><h3>Objective</h3><div>Transcranial magnetic stimulation (TMS) is an exciting novel treatment for substance use disorders (SUDs). While TMS is safe and effective in the general population, there have been concerns about its safety with concurrent substance use. To date, guidelines on managing substance use during TMS have been vague – recommending caution and weighing risks and benefits – and solely based on expert opinion, rather than based on quantitative data on the prevalence of TMS side effects with concurrent substance use.</div></div><div><h3>Methods</h3><div>We performed a systematic review with meta-analysis of TMS studies for a SUD – a clinically impairing level of substance use where we would be more likely to detect adverse effects – to quantify the safety of TMS in the setting of substance use. We searched PubMed, Embase, PsycINFO, and the Cochrane Library for TMS studies for SUDs that reported adverse effects. We extracted adverse effects and tested the difference between the prevalence of events in the active and sham conditions.</div></div><div><h3>Results</h3><div>Forty-seven studies comprising 2865 participants with a SUD were included. The prevalence of neck pain and cognitive impairment was higher for sham compared to active TMS (p < .05). The prevalence of all other adverse effects, including seizure, was not significantly different between active and sham TMS.</div></div><div><h3>Conclusions</h3><div>TMS is safe and well-tolerated for people with SUDs. The prevalence of side effects from TMS in people with SUDs is comparable to that in the general population. TMS can be just as safely administered for SUDs as for any other psychiatric disorder.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 6","pages":"Pages 2043-2049"},"PeriodicalIF":8.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.brs.2025.10.023
Ilya Demchenko , Ishaan Tailor , Sina Chegini , Haochen Yu , Fatemeh Gholamali Nezhad , Alice Rueda , Anne Kever , Sridhar Krishnan , Abhishek Datta , Jed A. Meltzer , Simon J. Graham , Tom A. Schweizer , Sumientra Rampersad , Edward S. Boyden , Ines R. Violante , Robert Chen , Andres M. Lozano , Venkat Bhat
Background
Many neurological and psychiatric disorders involve dysregulation of subcortical structures. Transcranial temporal interference stimulation (tTIS) is a novel, non-invasive method developed to selectively modulate deep brain regions and associated neural circuits.
Methods
A systematic review was conducted to evaluate human applications of tTIS (PROSPERO ID: CRD42024559678). MEDLINE, Embase, APA PsycINFO, CENTRAL, ClinicalTrials.gov, and WHO ICTRP were searched up to December 12, 2024. Studies involving human applications of tTIS were eligible. Methodological quality was appraised using the National Institutes of Health and modified Oxford Centre for Evidence-Based Medicine tools.
Results
Forty-eight records were reviewed (20 published studies, 28 ongoing trials). Of published studies, 16 single-session and 4 multi-session studies assessed safety, mechanistic outcomes, or therapeutic effects of tTIS in 820 participants. Stimulation was most commonly delivered at beta (20 Hz) or gamma (30–130 Hz) envelope frequencies. Neuroimaging studies support target engagement of the motor cortex, basal ganglia, and hippocampus in humans, particularly when stimulation is paired with behavioural tasks. Preliminary clinical findings in small samples demonstrated acute symptom improvements in bradykinesia and tremor within 60 min following a single tTIS session in Parkinson's disease and essential tremor. Reported adverse events across studies were mild (e.g., tingling, itching). Emerging trials increasingly utilize multi-session protocols (2–40 sessions) and are extending tTIS to patients with neurological and psychiatric disorders, particularly epilepsy and depression.
Conclusions
Phase 1 studies demonstrate that tTIS is safe, well-tolerated, and capable of engaging deep brain targets in humans. Well-controlled Phase 2 trials are needed to assess its therapeutic potential in patient populations.
背景：许多神经和精神疾病涉及皮质下结构的失调。经颅颞叶干扰刺激（tTIS）是一种新的、非侵入性的方法，可以选择性地调节脑深部区域和相关的神经回路。方法：对tTIS （PROSPERO ID: CRD42024559678）的临床应用进行系统评价。MEDLINE, Embase, APA PsycINFO， CENTRAL, ClinicalTrials.gov和WHO ICTRP被检索到2024年12月12日。涉及tTIS人体应用的研究是合格的。采用美国国立卫生研究院和改良的牛津循证医学中心工具对方法学质量进行评价。结果：回顾了48项记录（20项已发表的研究，28项正在进行的试验）。在已发表的研究中，有16项单期研究和4项多期研究评估了820名参与者的tTIS的安全性、机制结局或治疗效果。刺激最常见的是在β（20赫兹）或γ（30-130赫兹）包络频率下进行。神经影像学研究支持人类运动皮层、基底神经节和海马体的目标参与，特别是当刺激与行为任务配对时。在小样本中的初步临床结果显示，帕金森病和原发性震颤患者在单次tTIS治疗后60分钟内，运动迟缓和震颤的急性症状得到改善。所有研究报告的不良事件都是轻微的（例如，刺痛，瘙痒）。新兴试验越来越多地采用多期治疗方案（2-40期），并将tTIS扩展到神经和精神疾病患者，特别是癫痫和抑郁症患者。结论：i期研究表明，tTIS是安全的，耐受性良好，并且能够作用于人类深部脑靶点。需要进行控制良好的2期试验来评估其在患者群体中的治疗潜力。
{"title":"Human applications of transcranial temporal interference stimulation: A systematic review","authors":"Ilya Demchenko , Ishaan Tailor , Sina Chegini , Haochen Yu , Fatemeh Gholamali Nezhad , Alice Rueda , Anne Kever , Sridhar Krishnan , Abhishek Datta , Jed A. Meltzer , Simon J. Graham , Tom A. Schweizer , Sumientra Rampersad , Edward S. Boyden , Ines R. Violante , Robert Chen , Andres M. Lozano , Venkat Bhat","doi":"10.1016/j.brs.2025.10.023","DOIUrl":"10.1016/j.brs.2025.10.023","url":null,"abstract":"<div><h3>Background</h3><div>Many neurological and psychiatric disorders involve dysregulation of subcortical structures. Transcranial temporal interference stimulation (tTIS) is a novel, non-invasive method developed to selectively modulate deep brain regions and associated neural circuits.</div></div><div><h3>Methods</h3><div>A systematic review was conducted to evaluate human applications of tTIS (PROSPERO ID: CRD42024559678). MEDLINE, Embase, APA PsycINFO, CENTRAL, <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, and WHO ICTRP were searched up to December 12, 2024. Studies involving human applications of tTIS were eligible. Methodological quality was appraised using the National Institutes of Health and modified Oxford Centre for Evidence-Based Medicine tools.</div></div><div><h3>Results</h3><div>Forty-eight records were reviewed (20 published studies, 28 ongoing trials). Of published studies, 16 single-session and 4 multi-session studies assessed safety, mechanistic outcomes, or therapeutic effects of tTIS in 820 participants. Stimulation was most commonly delivered at beta (20 Hz) or gamma (30–130 Hz) envelope frequencies. Neuroimaging studies support target engagement of the motor cortex, basal ganglia, and hippocampus in humans, particularly when stimulation is paired with behavioural tasks. Preliminary clinical findings in small samples demonstrated acute symptom improvements in bradykinesia and tremor within 60 min following a single tTIS session in Parkinson's disease and essential tremor. Reported adverse events across studies were mild (e.g., tingling, itching). Emerging trials increasingly utilize multi-session protocols (2–40 sessions) and are extending tTIS to patients with neurological and psychiatric disorders, particularly epilepsy and depression.</div></div><div><h3>Conclusions</h3><div>Phase 1 studies demonstrate that tTIS is safe, well-tolerated, and capable of engaging deep brain targets in humans. Well-controlled Phase 2 trials are needed to assess its therapeutic potential in patient populations.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 6","pages":"Pages 2054-2066"},"PeriodicalIF":8.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.brs.2025.10.025
Yixuan Song , Yuchen Huang , Qihong Zheng , Xiaoqin Yang , Yang Guo , Yanan Geng , Huixing Gou , Junjie Bu , Tianye Jia , Guangdong Zhou , Lin Lu , Jie Shi , Yan Sun
Background and objectives
Internet Gaming Disorder (IGD) is prevalent with limited treatment efficacy. Targeting reducing craving triggered by gaming cues is a critical therapeutic objective. This study aimed to establish optimized electroencephalography (EEG) biomarkers for IGD and develop a novel targeted neuromodulation protocol.
Methods
In the exploratory study, the optimized EEG indicators of IGD diagnose were identified through machine learning models based on event-related potential (ERP) and band power during game cue exposure across two independent datasets (Dataset 1: twenty-five IGD, twenty-two Recreational Game Users, twenty-eight non-gaming Healthy Controls (HC); Dataset 2: twenty-three IGD and twenty-three HC). Subsequently, in the intervention study, a double-blind randomized trial was conducted on forty-six IGD participants to compare active and sham transcranial direct current stimulation (tDCS) targeting the region where the optimized EEG marker was located—central parietal lobe (Pz). Active stimulation (1.5 mA, 20 min, 2 days) was applied during cue exposure (cathode: Pz; anode: right trapezius).
Results
Parieto-occipital P300 (peaked at Pz, IGD > HC) during game reactivity emerged as novel optimized EEG indicators for IGD discrimination (accuracy>80 %), linked to craving. Then, Pz targeted cathodal tDCS synchronized with game cue exposure could significantly reduce craving (p < 0.001), gaming time (p < 0.001), and P300 alpha (p = 0.048) after intervention and at 1–4 weeks follow-ups, with concomitant improvement of decision-making in the active group. Importantly, these effects generalized to unpresented gaming cues. Besides, we identified baseline delta power at Pz during gaming cues as a significant predictor for treatment effects.
Conclusion
Our findings establish cue-synchronized tDCS as an effective intervention approach and position the Pz as a novel therapeutic target for IGD neuromodulation.
{"title":"Effects of cue-synchronized parietal cathodal tDCS on internet gaming disorder: A randomized double-blind sham-controlled trial","authors":"Yixuan Song , Yuchen Huang , Qihong Zheng , Xiaoqin Yang , Yang Guo , Yanan Geng , Huixing Gou , Junjie Bu , Tianye Jia , Guangdong Zhou , Lin Lu , Jie Shi , Yan Sun","doi":"10.1016/j.brs.2025.10.025","DOIUrl":"10.1016/j.brs.2025.10.025","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Internet Gaming Disorder (IGD) is prevalent with limited treatment efficacy. Targeting reducing craving triggered by gaming cues is a critical therapeutic objective. This study aimed to establish optimized electroencephalography (EEG) biomarkers for IGD and develop a novel targeted neuromodulation protocol.</div></div><div><h3>Methods</h3><div>In the exploratory study, the optimized EEG indicators of IGD diagnose were identified through machine learning models based on event-related potential (ERP) and band power during game cue exposure across two independent datasets (Dataset 1: twenty-five IGD, twenty-two Recreational Game Users, twenty-eight non-gaming Healthy Controls (HC); Dataset 2: twenty-three IGD and twenty-three HC). Subsequently, in the intervention study, a double-blind randomized trial was conducted on forty-six IGD participants to compare active and sham transcranial direct current stimulation (tDCS) targeting the region where the optimized EEG marker was located—central parietal lobe (Pz). Active stimulation (1.5 mA, 20 min, 2 days) was applied during cue exposure (cathode: Pz; anode: right trapezius).</div></div><div><h3>Results</h3><div>Parieto-occipital P300 (peaked at Pz, IGD > HC) during game reactivity emerged as novel optimized EEG indicators for IGD discrimination (accuracy>80 %), linked to craving. Then, Pz targeted cathodal tDCS synchronized with game cue exposure could significantly reduce craving (<em>p</em> < 0.001), gaming time (<em>p</em> < 0.001), and P300 alpha (<em>p</em> = 0.048) after intervention and at 1–4 weeks follow-ups, with concomitant improvement of decision-making in the active group. Importantly, these effects generalized to unpresented gaming cues. Besides, we identified baseline delta power at Pz during gaming cues as a significant predictor for treatment effects.</div></div><div><h3>Conclusion</h3><div>Our findings establish cue-synchronized tDCS as an effective intervention approach and position the Pz as a novel therapeutic target for IGD neuromodulation.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 6","pages":"Pages 2016-2027"},"PeriodicalIF":8.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.brs.2025.10.022
Seyyed Bahram Borgheai , Bryan Howell , Faical Isbaine , Angela M. Noecker , Enrico Opri , Benjamin B. Risk , Cameron C. McIntyre , Svjetlana Miocinovic
Background
Optimizing deep brain stimulation (DBS) parameter settings requires postoperative adjustments through a time-consuming trial-and-error process. As such, researchers have been developing computational models to guide DBS programming. Despite growing interest in image-guided DBS technology, and recent adoption into clinical practice, the direct validation of the prediction accuracy remains limited.
Objective
The objective of this study was to establish a comparative framework for validating the accuracy of various DBS computational modeling methodologies in predicting the activation of clinically relevant pathways using in vivo measurements from PD patients undergoing subthalamic (STN) DBS surgery.
Methods
In this study, we compared the accuracy of six computational modeling variations for predicting the activation of the corticospinal/bulbar tract (CSBT) and cortico-subthalamic hyperdirect pathway (HDP) using very short- (<2 ms) and short-latency (2–4 ms) cortical evoked potentials (cEPs). We constructed the variations using three key factors: modeling method (Driving Force [DF] vs. Volume of Tissue Activated [VTA]), imaging space (native vs. normative), and anatomical representation (pathway vs. structure). The model performances were quantified using the coefficient of determination (R2) between the cEP amplitudes and percent pathway or structure activation.
Results
We compared model accuracy for 11 PD patients. The DF-Native-Pathway model was the most accurate method for quantitatively predicting experimental subcortical pathway activations. Additionally, our analysis showed that using normative brain space significantly diminished the accuracy of model predictions.
Conclusion
The choice of methodology should depend on the specific application and the required level of precision for the intended analysis. However, model parameters should be optimized to accurately predict known experimental activation measures.
{"title":"Evaluation of DBS computational modeling methodologies using in-vivo electrophysiology in Parkinson's disease","authors":"Seyyed Bahram Borgheai , Bryan Howell , Faical Isbaine , Angela M. Noecker , Enrico Opri , Benjamin B. Risk , Cameron C. McIntyre , Svjetlana Miocinovic","doi":"10.1016/j.brs.2025.10.022","DOIUrl":"10.1016/j.brs.2025.10.022","url":null,"abstract":"<div><h3>Background</h3><div>Optimizing deep brain stimulation (DBS) parameter settings requires postoperative adjustments through a time-consuming trial-and-error process. As such, researchers have been developing computational models to guide DBS programming. Despite growing interest in image-guided DBS technology, and recent adoption into clinical practice, the direct validation of the prediction accuracy remains limited.</div></div><div><h3>Objective</h3><div>The objective of this study was to establish a comparative framework for validating the accuracy of various DBS computational modeling methodologies in predicting the activation of clinically relevant pathways using in vivo measurements from PD patients undergoing subthalamic (STN) DBS surgery.</div></div><div><h3>Methods</h3><div>In this study, we compared the accuracy of six computational modeling variations for predicting the activation of the corticospinal/bulbar tract (CSBT) and cortico-subthalamic hyperdirect pathway (HDP) using very short- (<2 ms) and short-latency (2–4 ms) cortical evoked potentials (cEPs). We constructed the variations using three key factors: modeling method (Driving Force [DF] vs. Volume of Tissue Activated [VTA]), imaging space (native vs. normative), and anatomical representation (pathway vs. structure). The model performances were quantified using the coefficient of determination (R<sup>2</sup>) between the cEP amplitudes and percent pathway or structure activation.</div></div><div><h3>Results</h3><div>We compared model accuracy for 11 PD patients. The DF-Native-Pathway model was the most accurate method for quantitatively predicting experimental subcortical pathway activations. Additionally, our analysis showed that using normative brain space significantly diminished the accuracy of model predictions.</div></div><div><h3>Conclusion</h3><div>The choice of methodology should depend on the specific application and the required level of precision for the intended analysis. However, model parameters should be optimized to accurately predict known experimental activation measures.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 6","pages":"Pages 1996-2007"},"PeriodicalIF":8.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.brs.2025.11.004
Kim Butts Pauly
{"title":"Letter to the Editor in response to “Brain injury during focused ultrasound neuromodulation for substance use disorder”","authors":"Kim Butts Pauly","doi":"10.1016/j.brs.2025.11.004","DOIUrl":"10.1016/j.brs.2025.11.004","url":null,"abstract":"","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 6","pages":"Pages 2075-2076"},"PeriodicalIF":8.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.brs.2025.10.013
Hengda He , Xiaoxiao Sun , Jayce Doose , Josef Faller , James R. McIntosh , Golbarg T. Saber , Sarah Huffman , Linbi Hong , Spiro P. Pantazatos , Han Yuan , Lisa M. McTeague , Robin I. Goldman , Truman R. Brown , Mark S. George , Paul Sajda
Introduction
Transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (L-DLPFC) is an established intervention for treatment-resistant depression (TRD), yet the underlying therapeutic mechanisms remain not fully understood.
Methods
This study employs an integrative approach that combines TMS with concurrent functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), aimed at assessing the acute/immediate effects of TMS on brain network dynamics and their correlation with clinical outcomes. Furthermore, this study explored the brain-state dependent effects of TMS, as the brain-state indexed by the phase of EEG prefrontal alpha oscillation.
Results
Our study demonstrates that TMS acutely modulates connectivity within vital brain circuits, particularly the cognitive control and default mode networks. We found that the baseline TMS-evoked responses in the cognitive control and limbic networks significantly predicted clinical improvement in patients receiving a novel EEG-synchronized repetitive TMS treatment. Clinical outcomes in this novel treatment were linked to state-specific TMS-modulated functional connectivity within a pivotal brain circuit of the L-DLPFC and the posterior subgenual anterior cingulate cortex within the limbic system.
Conclusions
These findings contribute to our understanding of the therapeutic effects underlying TMS treatment in depression and support the potential of assessing state-dependent TMS effects. This study emphasizes the importance of personalized timing of TMS for optimizing target engagement of specific clinically relevant brain circuits. Our results are crucial for future research into the development of personalized neuromodulation therapies for TRD patients.
{"title":"TMS-induced modulation of brain networks and its associations to rTMS treatment for depression: a concurrent fMRI-EEG-TMS study","authors":"Hengda He , Xiaoxiao Sun , Jayce Doose , Josef Faller , James R. McIntosh , Golbarg T. Saber , Sarah Huffman , Linbi Hong , Spiro P. Pantazatos , Han Yuan , Lisa M. McTeague , Robin I. Goldman , Truman R. Brown , Mark S. George , Paul Sajda","doi":"10.1016/j.brs.2025.10.013","DOIUrl":"10.1016/j.brs.2025.10.013","url":null,"abstract":"<div><h3>Introduction</h3><div>Transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (L-DLPFC) is an established intervention for treatment-resistant depression (TRD), yet the underlying therapeutic mechanisms remain not fully understood.</div></div><div><h3>Methods</h3><div>This study employs an integrative approach that combines TMS with concurrent functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), aimed at assessing the acute/immediate effects of TMS on brain network dynamics and their correlation with clinical outcomes. Furthermore, this study explored the brain-state dependent effects of TMS, as the brain-state indexed by the phase of EEG prefrontal alpha oscillation.</div></div><div><h3>Results</h3><div>Our study demonstrates that TMS acutely modulates connectivity within vital brain circuits, particularly the cognitive control and default mode networks. We found that the baseline TMS-evoked responses in the cognitive control and limbic networks significantly predicted clinical improvement in patients receiving a novel EEG-synchronized repetitive TMS treatment. Clinical outcomes in this novel treatment were linked to state-specific TMS-modulated functional connectivity within a pivotal brain circuit of the L-DLPFC and the posterior subgenual anterior cingulate cortex within the limbic system.</div></div><div><h3>Conclusions</h3><div>These findings contribute to our understanding of the therapeutic effects underlying TMS treatment in depression and support the potential of assessing state-dependent TMS effects. This study emphasizes the importance of personalized timing of TMS for optimizing target engagement of specific clinically relevant brain circuits. Our results are crucial for future research into the development of personalized neuromodulation therapies for TRD patients.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 6","pages":"Pages 1955-1965"},"PeriodicalIF":8.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.brs.2025.10.018
Carlos Andrés Sánchez-León , Pablo Alejandro Reyes-Velasquez , Christoph van Thriel , Michael A. Nitsche
Background
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique mainly used in humans, in which weak direct currents are applied over the scalp to alter cortical excitability and induce neuroplasticity. Previous studies have demonstrated the value of tDCS for modulating sensory, motor, and cognitive functions, nevertheless, knowledge about how externally applied electric fields affect different components of neuronal networks is still incomplete, and in vivo animal models, which are required for a deeper understanding, are not fully developed. To evaluate the impact of tDCS on cortical excitability, many human experiments assess motor evoked potentials elicited by motor cortex (M1) stimulation.
Methods
To develop a related in vivo animal model, we recorded electrical activity in M1 of alert mice during and after administration of tDCS over M1. M1 excitability was chronically recorded from layers 2–3, layer 5 and layer 6, evoked by stimulation of the ventral lateral nucleus of the thalamus (VAL). M1-tDCS was applied at 100 and 200 μA for 5 s to test the acute effects on neuronal excitability, and for 15 min to induce after-effects.
Results
Acute M1-tDCS increased and decreased the amplitude of VAL-evoked potentials in a polarity-, layer- and intensity-dependent manner. For 15 min of anodal or cathodal tDCS, a similar polarity- and intensity-dependent modulation of VAL-evoked potential amplitudes during the 15 min of stimulation was observed. After tDCS was switched off, the highest intensity of anodal stimulation induced a significant excitability enhancement during at least 2 h after stimulation, whereas the after-effects of cathodal tDCS were less pronounced.
Conclusions
The current study demonstrates the feasibility of a mouse model of M1-tDCS to accomplish similar modulatory effects of tDCS on cortical excitability as observed in human experiments. A proper adjustment of tDCS parameters, as compared to application in humans, is however required to obtain these translational effects since a higher density current was necessary in this study to obtain effects comparable to those achieved in humans.
{"title":"An in vivo model for transcranial direct current stimulation of the motor cortex in awake mice","authors":"Carlos Andrés Sánchez-León , Pablo Alejandro Reyes-Velasquez , Christoph van Thriel , Michael A. Nitsche","doi":"10.1016/j.brs.2025.10.018","DOIUrl":"10.1016/j.brs.2025.10.018","url":null,"abstract":"<div><h3>Background</h3><div>Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique mainly used in humans, in which weak direct currents are applied over the scalp to alter cortical excitability and induce neuroplasticity. Previous studies have demonstrated the value of tDCS for modulating sensory, motor, and cognitive functions, nevertheless, knowledge about how externally applied electric fields affect different components of neuronal networks is still incomplete, and <em>in vivo</em> animal models, which are required for a deeper understanding, are not fully developed. To evaluate the impact of tDCS on cortical excitability, many human experiments assess motor evoked potentials elicited by motor cortex (M1) stimulation.</div></div><div><h3>Methods</h3><div>To develop a related <em>in vivo</em> animal model, we recorded electrical activity in M1 of alert mice during and after administration of tDCS over M1. M1 excitability was chronically recorded from layers 2–3, layer 5 and layer 6, evoked by stimulation of the ventral lateral nucleus of the thalamus (VAL). M1-tDCS was applied at 100 and 200 μA for 5 s to test the acute effects on neuronal excitability, and for 15 min to induce after-effects.</div></div><div><h3>Results</h3><div>Acute M1-tDCS increased and decreased the amplitude of VAL-evoked potentials in a polarity-, layer- and intensity-dependent manner. For 15 min of anodal or cathodal tDCS, a similar polarity- and intensity-dependent modulation of VAL-evoked potential amplitudes during the 15 min of stimulation was observed. After tDCS was switched off, the highest intensity of anodal stimulation induced a significant excitability enhancement during at least 2 h after stimulation, whereas the after-effects of cathodal tDCS were less pronounced.</div></div><div><h3>Conclusions</h3><div>The current study demonstrates the feasibility of a mouse model of M1-tDCS to accomplish similar modulatory effects of tDCS on cortical excitability as observed in human experiments. A proper adjustment of tDCS parameters, as compared to application in humans, is however required to obtain these translational effects since a higher density current was necessary in this study to obtain effects comparable to those achieved in humans.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 6","pages":"Pages 1978-1989"},"PeriodicalIF":8.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.brs.2025.10.017
Denise Oswalt, Michael S. Beauchamp, Han-Chiao Isaac Chen, Daniel Yoshor
{"title":"Reducing artifacts during human intracranial electrical stimulation by separating current return from recording ground","authors":"Denise Oswalt, Michael S. Beauchamp, Han-Chiao Isaac Chen, Daniel Yoshor","doi":"10.1016/j.brs.2025.10.017","DOIUrl":"10.1016/j.brs.2025.10.017","url":null,"abstract":"","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 6","pages":"Pages 2040-2042"},"PeriodicalIF":8.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145421121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 10.1016/j.brs.2025.10.011
Jackson R. Richards , Benjamin D. Pace , Alison C. Lynch , Andrea N. Weber , Joel E. Bruss , Jatin G. Vaidya , Rana Jawish , Keith G. Jones , Brian J. Mickey , Ryan M. Carnahan , Nicholas T. Trapp
{"title":"Dual-target theta burst rTMS for the treatment of methamphetamine use disorder: An open-label pilot clinical trial","authors":"Jackson R. Richards , Benjamin D. Pace , Alison C. Lynch , Andrea N. Weber , Joel E. Bruss , Jatin G. Vaidya , Rana Jawish , Keith G. Jones , Brian J. Mickey , Ryan M. Carnahan , Nicholas T. Trapp","doi":"10.1016/j.brs.2025.10.011","DOIUrl":"10.1016/j.brs.2025.10.011","url":null,"abstract":"","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 6","pages":"Pages 1952-1954"},"PeriodicalIF":8.4,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145359185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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