Brain Stimulation最新文献

{"title":"Low- vs. high-frequency deep brain stimulation in Parkinson's disease: A two-center double-blind crossover trial","authors":"Carmelo Luca Smeralda , David De Monte , Alice Cinesi , Alessandro Giannotta , Enrico Belgrado , Andrea Bernardini , Mariarosaria Valente , Christian Lettieri , Simone Rossi","doi":"10.1016/j.brs.2025.09.006","DOIUrl":"10.1016/j.brs.2025.09.006","url":null,"abstract":"","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 6","pages":"Pages 1741-1743"},"PeriodicalIF":8.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058303","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}

{"title":"Photoswitching endogenous glutamate receptors in neural ensembles and single synapses in vivo","authors":"Aida Garrido-Charles ,&nbsp;Miquel Bosch ,&nbsp;Hyojung Lee ,&nbsp;Xavier Rovira ,&nbsp;Silvia Pittolo ,&nbsp;Artur Llobet ,&nbsp;Hovy Ho-Wai Wong ,&nbsp;Ana Trapero ,&nbsp;Carlo Matera ,&nbsp;Claudio Papotto ,&nbsp;Carme Serra ,&nbsp;Amadeu Llebaria ,&nbsp;Eduardo Soriano ,&nbsp;Maria V. Sanchez-Vives ,&nbsp;Christine E. Holt ,&nbsp;Pau Gorostiza","doi":"10.1016/j.brs.2025.09.005","DOIUrl":"10.1016/j.brs.2025.09.005","url":null,"abstract":"<div><h3>Purpose</h3><div>To interrogate animal physiology <em>in vivo</em>, there is a lack of non-genetic methods to control the activity of endogenous proteins with pharmacological and spatiotemporal precision. To address this need, we recently developed targeted covalent photoswitchable (TCP) compounds that enable the remote control of endogenous glutamate receptors (GluRs) using light.</div></div><div><h3>Methods</h3><div>We combine the photopharmacological effector TCP9 with neuronal activity sensors to demonstrate all-optical reversible control of endogenous GluRs across multiple spatiotemporal scales in rat brain tissue <em>ex vivo</em> and in <em>Xenopus</em> tadpole brains <em>in vivo</em>.</div></div><div><h3>Findings</h3><div>TCP9 allows photoactivation of neuronal ensembles, individual neurons, and single synapses in <em>ex vivo</em> tissue and in intact brain <em>in vivo</em>, which is challenging using optogenetics and neurotransmitter uncaging. TCP9 covalently targets AMPA and kainate receptors, maintaining their functionality and photoswitchability for extended periods (&gt;8 h) after a single compound application. This allows tracking endogenous receptor physiology during synaptic plasticity events such as the reduction of functional AMPA receptors during long-term depression in hippocampal neurons.</div></div><div><h3>Conclusion</h3><div>TCP9 is a unique non-invasive tool for durable labeling, reversible photoswitching, and functional tracking of native receptors in brain tissue without genetic manipulation.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 6","pages":"Pages 1779-1793"},"PeriodicalIF":8.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058375","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}

{"title":"Optimizing subthalamic deep brain stimulation for treatment-refractory obsessive compulsive disorder: A practical guide to advanced parameter tuning","authors":"Mickael Amagat ,&nbsp;Federica Porpiglia ,&nbsp;Moussa A. Chalah ,&nbsp;Yannick Longuet ,&nbsp;Fabien Vinckier ,&nbsp;Raphael Gaillard ,&nbsp;Lucie Berkovitch ,&nbsp;Johan Pallud ,&nbsp;Gonzague Defrance ,&nbsp;Marc Zanello ,&nbsp;Philippe Domenech","doi":"10.1016/j.brs.2025.09.007","DOIUrl":"10.1016/j.brs.2025.09.007","url":null,"abstract":"","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 6","pages":"Pages 1719-1722"},"PeriodicalIF":8.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058372","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}

{"title":"Multidimensional Motor Evoked Potentials (MultiMEP): Digging up buried information from single trials","authors":"Francesca Genovese ,&nbsp;Elena Mussini ,&nbsp;Agnese Zazio ,&nbsp;Fabio Beltrami ,&nbsp;Marta Bortoletto ,&nbsp;Luigi Cattaneo ,&nbsp;Paolo Rota ,&nbsp;Francesco Negro ,&nbsp;Martina Fanghella ,&nbsp;Corrado Sinigaglia ,&nbsp;Guido Barchiesi","doi":"10.1016/j.brs.2025.09.001","DOIUrl":"10.1016/j.brs.2025.09.001","url":null,"abstract":"<div><h3>Background</h3><div>To investigate covert motor processes, transcranial magnetic stimulation (TMS) studies often use motor-evoked potentials (MEPs) as a proxy for inferring the state of motor representations. Typically, these studies test motor representations of actions that can be produced by the isolated contraction of one muscle, limiting both the number of recorded muscles and the complexity of tested actions. Furthermore, univariate analyses treat MEPs from different muscles as independent, overlooking potentially meaningful intermuscular relationships encoded in MEPs amplitude patterns at the single-trial level.</div></div><div><h3>Objective</h3><div>We addressed these limitations by adopting a decoding approach to MEPs analogous to multivoxel pattern analysis in neuroimaging.</div></div><div><h3>Methods</h3><div>Using our novel <em>Multidimensional Motor Evoked Potentials (MultiMEP)</em> approach, we tested 22 participants by applying a decoding analysis to MEPs recorded from 24 electrodes during motor imagery of three complex hand actions.</div><div>Additionally, to test whether imagery and action production shared common representations, we conducted an exploratory cross-classification analysis by training a classifier on one domain (MultiMEP evoked during motor imagery or action execution electromyographic patterns) and testing it on the other.</div></div><div><h3>Results</h3><div>Imagined actions were classified, based on MultiMEP patterns, with an accuracy of 74 %.</div><div>The cross-classification analysis yielded above-chance accuracies of 54 % (execution-to-imagery) and 71 % (imagery-to-execution).</div></div><div><h3>Conclusions</h3><div>This proof-of-principle study demonstrates that MEPs encode richer information than previously assumed both at single-subject and at single-trial levels.</div><div>Our results suggest that MultiMEP decoding represents a first step toward a paradigm shift in studying motor processes with TMS, much like multivoxel pattern analysis revolutionized the way the brain-cognition relationship has been studied through neuroimaging.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 6","pages":"Pages 1750-1763"},"PeriodicalIF":8.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008158","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}

{"title":"Trigeminal nerve stimulation as an active control condition in TMS clinical trials: Evidence from heart-brain coupling and clinical outcomes.","authors":"Martijn Arns, Nolan R Williams, Jonathan Downar, Aleksandra Dojnov, John Coetzee, Roberto Goya-Maldonado","doi":"10.1016/j.brs.2025.07.004","DOIUrl":"10.1016/j.brs.2025.07.004","url":null,"abstract":"<p><p>The inertness of sham controls in transcranial magnetic stimulation (TMS) studies, particularly those involving Transcutaneous Electrical Nerve Stimulation (TENS), remains controversial. Using heart-brain coupling (HBC) as a frontal-vagal engagement measure, we analyzed pilot data and data from two placebo-controlled accelerated intermittent theta burst stimulation (aiTBS) trials (combined N = 100). Active-TMS induced significantly stronger HBC compared to sham in both studies, with the effect size for TENS-sham considerably attenuated, and significantly stronger HBC for TENS-sham relative to SAINT-sham (d = 0.9). HBC in the TENS-sham group was associated with clinical improvement (d = 1.12), reflecting antidepressant effects of trigeminal nerve stimulation. These findings suggest TENS-sham should be seen as an active control condition, also controlling for trigeminal nerve stimulation, resulting in downstream vagal and cortical engagement and thus controlling for this non-specific effect of TMS. Future studies should be aware of this active effect and conduct power-analyses accordingly, modifying the expected effect size. Furthermore, HBC could be used to titrate the intensity of TENS-stimulation to minimize active effects.</p>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":" ","pages":"1403-1406"},"PeriodicalIF":8.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616276","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}

{"title":"A novel home-based, combined occipital and trigeminal afferent stimulation therapy for major depressive disorder: Efficacy and safety results from a double-blind multicenter randomized sham-controlled study","authors":"Linda L. Carpenter ,&nbsp;Mark S. George ,&nbsp;Nancy Navarro ,&nbsp;Lisa Deutsch ,&nbsp;Andrew F. Leuchter","doi":"10.1016/j.brs.2025.08.022","DOIUrl":"10.1016/j.brs.2025.08.022","url":null,"abstract":"<div><h3>Objective</h3><div>Patients with Major Depressive Disorder (MDD) who fail to achieve satisfactory benefits with existing antidepressants have limited treatment options. This study assessed the safety and efficacy of a novel non-invasive brain neuromodulation therapy which delivers external Combined Occipital and Trigeminal Afferent Stimulation (eCOT-AS) as a therapeutic option for MDD.</div></div><div><h3>Methods</h3><div>124 adults with MDD who failed to respond to antidepressants and with a baseline Hamilton Depression Rating Scale (HDRS21) score ≥20 were enrolled in a randomized, double-blind, sham-controlled, multicenter study of self-administered daily active or sham eCOT-AS (n = 62 per arm) for eight weeks. The double-blind phase was followed by an 8-week active open label phase. HDRS17 was used to assess outcomes.</div></div><div><h3>Results</h3><div>Baseline depression scores were similar for both groups and reflected moderate to very severe depression. After 8 weeks of treatment, the adjusted mean HDRS17 improvement in the active treatment group was 8.62 points versus 6.01 for sham (<em>p</em> = 0.0196). Compared to sham treatment, participants receiving active treatment had significantly higher remission rates (21.3 % vs 6.0 %, <em>p</em> = 0.027) and achieved significantly more shifts to lower HDRS17 depression severity categories. Participants further improved during the subsequent eight weeks of open-label active stimulation with a mean reduction of almost 10 points from baseline and achieved a remission rate of 32 %. The treatment was well-tolerated with generally mild and transient adverse events.</div></div><div><h3>Conclusion</h3><div>This home-based brain neuromodulation system is safe and effective in treating depression. These findings support eCOT-AS as a promising new adjunct therapy for MDD patients with nonresponse to antidepressants.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 5","pages":"Pages 1695-1704"},"PeriodicalIF":8.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943386","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}

{"title":"Removal of stimulation artifacts in high-density Neuropixels recordings using sample clock-synchronized stimulation pulses.","authors":"Kantapon Pum Wiboonsaksakul, Dale C Roberts, Kathleen E Cullen","doi":"10.1016/j.brs.2025.07.009","DOIUrl":"10.1016/j.brs.2025.07.009","url":null,"abstract":"","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":" ","pages":"1423-1425"},"PeriodicalIF":8.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625384","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}

{"title":"Single pointwise samples of electric field on a neuron model cannot predict activation threshold by brain stimulation","authors":"Boshuo Wang ,&nbsp;Minhaj A. Hussain ,&nbsp;Torge Worbs ,&nbsp;Axel Thielscher ,&nbsp;Warren M. Grill ,&nbsp;Angel V. Peterchev","doi":"10.1016/j.brs.2025.08.025","DOIUrl":"10.1016/j.brs.2025.08.025","url":null,"abstract":"","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 5","pages":"Pages 1667-1670"},"PeriodicalIF":8.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991112","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}

{"title":"Tumor treating fields combined with ionizing radiation inhibit the malignant phenotype of lung cancer brain metastasis cells by suppressing DNA damage repair pathways.","authors":"Guilong Tanzhu, Haiqin Peng, Liu Chen, Gang Xiao, Jiaoyang Ning, Ling Chen, Rongrong Zhou","doi":"10.1016/j.brs.2025.07.014","DOIUrl":"10.1016/j.brs.2025.07.014","url":null,"abstract":"<p><strong>Background: </strong>Brain metastasis (BrM) is a common complication of advanced tumors with poor prognosis. Although radiotherapy remains a key treatment for BrM, it is plagued by issues such as radiation-induced brain necrosis, neurocognitive impairment, and progress post-treatment. Tumor Treating Fields (TTFields) therapy employs medium frequency (100∼300 kHz) and low intensity (1∼3 v/cm) alternating electric fields to inhibit tumors. We explored the effects and mechanisms of TTFields combined with ionizing radiation (IR) on the malignant phenotype of lung cancer brain metastasis (LCBM) cells, with the aim of advancing the clinical adoption of TTFields.</p><p><strong>Methods: </strong>LCBM cells H1915, PC9-Brm and primary cells were used. The experiments included four groups: Control, 6 Gy, TTFields, and 6 Gy + TTFields group. Cell viability and the number of EDU or Ki67-positive cells, ability of migration and colony formation were assessed; Cell morphology was observed by H&E staining; Bulk transcriptome revealed the potential mechanisms, with the protein levels of differentially expressed genes (DEGs) verified through immunofluorescence assay. DNA damage repair pathways were validated by Western Blot. Additionally, ROS levels, and HO-1 expression were evaluated.</p><p><strong>Results: </strong>The combination of 150 kHz, 2∼2.5 v/cm TTFields and 6 Gy IR effectively suppressed the viability and the number of EDU-positive and Ki67-positive LCBM cells. Following TTFields and IR, the tumor cells exhibited altered morphology and reduced clonogenic and migratory capacities. RNA-seq revealed associations between TTFields combined with IR and various biological processes and mechanisms, including redox reactions (primarily related to mitochondria), DNA replication, transition metal ion transmembrane transport, and heme metabolism. Furthermore, TTFields combined with IR enhanced γH2AX and 53BP1 levels. Increased ROS and HO-1 expression were observed post-treatment. Similarly, LCBM primary cells exhibited decreased Ki67-positive cells along with increased γH2AX and 53BP1 foci following TTFields and IR. TTFields combined with IR exhibited significant suppression on homologous recombination (HR) markers (p-ATM, RAD51), non-homologous end joining (NHEJ) components (DNA-PKcs, KU70, KU80), and microhomology-mediated end joining (MMEJ) effectors (PARP1, p95-NBS1) versus RT alone.</p><p><strong>Conclusions: </strong>TTFields combined with IR effectively inhibits LCBM cells. Mechanistically, this combined treatment enhanced DNA damage, suppressed DNA damage repair, and elevates ROS levels.</p>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":" ","pages":"1426-1440"},"PeriodicalIF":8.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741239","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}

{"title":"Invasive and non-invasive tumor-treating electric field (TTF) therapy: An exciting advance in oncologic neuromodulation.","authors":"Thomas Eckert, Rishishankar Suresh, M S Zobaer, Nathan C Rowland","doi":"10.1016/j.brs.2025.07.018","DOIUrl":"10.1016/j.brs.2025.07.018","url":null,"abstract":"<p><strong>Background: </strong>Tumor-treating fields (TTF) have been shown to slow glioblastoma (GBM) cell growth through mitotic arrest, increased membrane and blood-brain barrier permeability, and other cellular mechanisms. TTF as currently used prolongs GBM survival by 5 months, but there are areas of possible improvement. One of the interesting problems is optimization of TTF delivery to tumor cells, which is attenuated by intervening anatomy and shunting. Current research involving invasive approaches including cranial remodeling, intracortical TTF and intratumoral modulation therapy (IMT) may improve outcomes.</p><p><strong>Objective: </strong>Present the history of TTF and discuss current areas of research with a focus on invasive TTF.</p><p><strong>Methods: </strong>We obtained and analyzed studies referencing TTF, invasive TTF, and any of transcranial electrical stimulation (tES), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), vagus nerve stimulation (VNS), peripheral nervous system (PNS), focused ultrasound (FUS), and transcranial magnetic stimulation (TMS) with respect to mechanism of action or anti-cancer-related effects.</p><p><strong>Results: </strong>Invasive strategies including cranial remodeling and IMT, through stereotaxis like DBS, would help alleviate the current limitations of TTF. In addition, FUS and VNS induce similar blood brain barrier effects and immune modulation as TTF that may enhance and promote an insurmountable host immune response against the immunosuppressive tumor microenvironment.</p><p><strong>Conclusions: </strong>TTF as currently practiced is a remarkable advance in cancer treatment. Improvements which exploit the effects of TTF in combination with other neuromodulatory modalities or in immunotherapy promise to improve this even further.</p>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":" ","pages":"1357-1366"},"PeriodicalIF":8.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752443","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}