Brain StimulationPub Date : 2025-04-10DOI: 10.1016/j.brs.2025.03.021
Luke E. Osborn , Breanne Christie , David P. McMullen , Victoria Arriola , Tessy M. Thomas , Ambarish S. Pawar , Robert W. Nickl , Manuel A. Anaya , Brock A. Wester , Charles M. Greenspon , Gabriela L. Cantarero , Pablo A. Celnik , Sliman J. Bensmaia , Jeffrey M. Yau , Matthew S. Fifer , Francesco V. Tenore
{"title":"Subthreshold intracortical microstimulation of human somatosensory cortex enhances tactile sensitivity","authors":"Luke E. Osborn , Breanne Christie , David P. McMullen , Victoria Arriola , Tessy M. Thomas , Ambarish S. Pawar , Robert W. Nickl , Manuel A. Anaya , Brock A. Wester , Charles M. Greenspon , Gabriela L. Cantarero , Pablo A. Celnik , Sliman J. Bensmaia , Jeffrey M. Yau , Matthew S. Fifer , Francesco V. Tenore","doi":"10.1016/j.brs.2025.03.021","DOIUrl":"10.1016/j.brs.2025.03.021","url":null,"abstract":"<div><h3>Background</h3><div>Intracortical microstimulation (ICMS) of the somatosensory cortex activates neurons around the stimulating electrodes and can elicit tactile sensations.</div></div><div><h3>Objective</h3><div>It is not clear how the direct activation of cortical neurons influences their ability to process additional tactile inputs originating from the skin.</div></div><div><h3>Methods</h3><div>In a human implanted with chronic microelectrode arrays in both left and right somatosensory cortices, we presented mechanical vibration to the skin while simultaneously delivering ICMS and quantified the effects of combined mechanical and electrical stimulation on tactile perception.</div></div><div><h3>Results</h3><div>We found that subthreshold ICMS enhanced sensitivity to touch on the skin, as evidenced by a reduction in vibrotactile detection thresholds (median: 1.5 dB), but subthreshold vibration did not systematically impact the detectability of ICMS. Suprathreshold vibration led to an increase in ICMS thresholds (median: 2.4 dB) but suprathreshold ICMS had little impact on vibrotactile thresholds. The ICMS-induced enhancement of vibrotactile sensitivity was location dependent with the effect size decreasing as the projected field of the stimulating electrode and the locus of vibratory stimulation became farther apart.</div></div><div><h3>Conclusion</h3><div>These results demonstrate that targeted microstimulation of cortex alone can focally enhance tactile sensitivity, potentially enabling restoration or strengthening of retained tactile sensations after injury.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 3","pages":"Pages 900-908"},"PeriodicalIF":7.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860623","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}
Brain StimulationPub Date : 2025-04-09DOI: 10.1016/j.brs.2025.04.001
Mascha van ’t Wout-Frank , David O. Sorensen , Lucas C. Parra , Yu Huang , Alexis Harle , Benjamin D. Greenberg , Amanda R. Arulpragasam , Noah S. Philip
{"title":"Pathway to response: Associations between individual electrical fields and psychophysiological habituation to predict clinical outcomes to transcranial direct current stimulation combined with virtual reality for PTSD","authors":"Mascha van ’t Wout-Frank , David O. Sorensen , Lucas C. Parra , Yu Huang , Alexis Harle , Benjamin D. Greenberg , Amanda R. Arulpragasam , Noah S. Philip","doi":"10.1016/j.brs.2025.04.001","DOIUrl":"10.1016/j.brs.2025.04.001","url":null,"abstract":"","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 3","pages":"Pages 797-799"},"PeriodicalIF":7.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835164","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}
Brain StimulationPub Date : 2025-04-09DOI: 10.1016/j.brs.2025.04.002
Jasmina Paneva , Teresa Schuhmann , Stefanie De Smet , Terence De Meza , Felix Duecker , Alexander T. Sack
{"title":"Affective state-dependent effects of prefrontal rTMS on the cognitive control of negative stimuli in healthy and depressed individuals","authors":"Jasmina Paneva , Teresa Schuhmann , Stefanie De Smet , Terence De Meza , Felix Duecker , Alexander T. Sack","doi":"10.1016/j.brs.2025.04.002","DOIUrl":"10.1016/j.brs.2025.04.002","url":null,"abstract":"<div><h3>Introduction</h3><div>High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) targeting the left dorsolateral prefrontal cortex (lDLPFC) is an established, clinically effective treatment for major depressive disorder (MDD). However, evidence of the cognitive effects of lDLPFC HF-rTMS, especially those cognitive functions affected by MDD, is mixed.</div></div><div><h3>Methods</h3><div>We here assessed the cognitive effects of a single, offline, 10Hz rTMS session on task performance in an emotional faces N-back (EFNBACK) task, in both healthy and depressed individuals. We measured response times, accuracy, and sensitivity, in a sham-controlled, pre-post design. Importantly, using the Beck Depression Inventory (BDI-II), we assessed whether the cognitive effects of the stimulation are state-dependent on trait-state depression.</div></div><div><h3>Results</h3><div>We found lDLPFC HF-rTMS enhanced cognitive control over angry distractors. More importantly, these cognitive control effects were state-dependent on trait-state depression. HF-rTMS produced distinct performance changes dependent on baseline BDI-II scores. As a function of BDI-II scores, we observed either increased or decreased response times on the task. Further, we observed improved accuracy and sensitivity only on angry distractor trials as BDI-II scores increased, as a consequence of lDLPFC stimulation.</div></div><div><h3>Conclusion</h3><div>These results underscore the role of HF-rTMS in enhancing executive control over negative emotional information by modulating lDLPFC, with effects varying according to depression state at the moment of the treatment session. HF-rTMS thus not only enhances inhibitory control over emotional stimuli but also exhibits such cognitive effects contingent on depressive state, contributing to our understanding of the state-dependence of therapeutic rTMS.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 3","pages":"Pages 745-752"},"PeriodicalIF":7.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825736","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}
Brain StimulationPub Date : 2025-04-08DOI: 10.1016/j.brs.2025.03.023
Tulika Nandi , Benjamin R. Kop , Kim Butts Pauly , Charlotte J. Stagg , Lennart Verhagen
{"title":"Response to ‘Safety considerations for transcranial ultrasound stimulation: A comment on Nandi et al.’","authors":"Tulika Nandi , Benjamin R. Kop , Kim Butts Pauly , Charlotte J. Stagg , Lennart Verhagen","doi":"10.1016/j.brs.2025.03.023","DOIUrl":"10.1016/j.brs.2025.03.023","url":null,"abstract":"","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 3","pages":"Page 755"},"PeriodicalIF":7.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825737","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}
Brain StimulationPub Date : 2025-04-08DOI: 10.1016/j.brs.2025.04.006
Andrew D. Geoly, Katy H. Stimpson, Flint M. Espil, Brandon S. Bentzley, Nolan R. Williams
{"title":"Durability of clinical benefit with Stanford Neuromodulation Therapy (SNT) in treatment-resistant depression","authors":"Andrew D. Geoly, Katy H. Stimpson, Flint M. Espil, Brandon S. Bentzley, Nolan R. Williams","doi":"10.1016/j.brs.2025.04.006","DOIUrl":"10.1016/j.brs.2025.04.006","url":null,"abstract":"<div><h3>Background</h3><div>Depression, the leading cause of disability worldwide, is a chronic disease characterized by a relapsing-remitting course. Acute treatments such as electroconvulsive therapy, ketamine, and repetitive transcranial magnetic stimulation are often effective at initiating remission, but relapse to a major depressive episode is common without ongoing interventions. Stanford Neuromodulation Therapy (SNT) produces high rates of remission after five days of acute treatment; however, the duration of this remission following a single course of SNT in people suffering from treatment-resistant depression is unknown, which poses a significant limit on clinical decision-making.</div></div><div><h3>Methods</h3><div>Forty-six participants with treatment-resistant depression (TRD), received five days of SNT. Functional connectivity derived from resting-state functional MRI (fMRI) was used to individually target the region of the left dorsolateral prefrontal cortex most functionally anticorrelated with the subgenual anterior cingulate cortex. The 6-item Hamilton Depression Rating Scale (HDRS-6) was collected fortnightly for up to 24 weeks. Relapse was defined as two consecutive HDRS-6 scores of 5 or above.</div></div><div><h3>Results</h3><div>Seventy percent (32 of 46) of participants entered remission the week following treatment. After 12 weeks of treatment, 15 of 46 (33 %) participants remained in remission. Of the participants who entered remission, 15 of 32 (47 %) remained in remission.</div></div><div><h3>Conclusions</h3><div>At 12 weeks, a subset of participants remained in remission, suggesting that the durability of SNT warrants further study. Comparisons with conventional rTMS should be interpreted cautiously given differences in study design, populations, and outcome measures.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 3","pages":"Pages 875-881"},"PeriodicalIF":7.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843232","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}
Brain StimulationPub Date : 2025-04-05DOI: 10.1016/j.brs.2025.04.004
Amirreza Dastan , Paulina Skrzypkowska , Tomasz Szmuda , Piotr Zieliński
{"title":"Letter to the editor on “Cost-effectiveness analysis of deep brain stimulation for the treatment of alcohol use disorder and alcoholic liver disease”","authors":"Amirreza Dastan , Paulina Skrzypkowska , Tomasz Szmuda , Piotr Zieliński","doi":"10.1016/j.brs.2025.04.004","DOIUrl":"10.1016/j.brs.2025.04.004","url":null,"abstract":"","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 3","pages":"Pages 736-737"},"PeriodicalIF":7.6,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802510","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}
Brain StimulationPub Date : 2025-04-05DOI: 10.1016/j.brs.2025.04.003
Divya Rajasekharan , Michelle R. Madore , Paul Holtzheimer , Kelvin O. Lim , Leanne M. Williams , Noah S. Philip
{"title":"Personalized models of Beam/F3 targeting in transcranial magnetic stimulation for depression: Implications for precision clinical translation","authors":"Divya Rajasekharan , Michelle R. Madore , Paul Holtzheimer , Kelvin O. Lim , Leanne M. Williams , Noah S. Philip","doi":"10.1016/j.brs.2025.04.003","DOIUrl":"10.1016/j.brs.2025.04.003","url":null,"abstract":"<div><h3>Background</h3><div>Clinical transcranial magnetic stimulation (TMS) for depression routinely relies on the scalp-based Beam/F3 targeting method to identify stimulation targets in the dorsolateral prefrontal cortex (dLPFC). Scalp-based targeting offers a low-cost and easily implemented method for TMS coil placement, enhancing treatment availability. However, limited anatomical and functional specificity of the Beam/F3 method may affect treatment outcomes, motivating assessment of the clinical standard.</div></div><div><h3>Methods</h3><div>In a naturalistic clinical trial of TMS conduced at four Veterans Affairs hospitals, the authors evaluate the Beam/F3 method using neuroimaging incorporated before TMS, after five treatment sessions, and after all thirty sessions. Personalized anatomical and electric field (E-field) models were developed to assess target location and network engagement, as well as subsequent effects on clinical outcomes.</div></div><div><h3>Results</h3><div>Anatomical models demonstrate that the Beam/F3 method produced reliable targets in the dLPFC across individuals and repeated treatment sessions. E-field models revealed that baseline anticorrelation between the stimulation center and the sgACC was associated with antidepressant symptom response after five TMS sessions (<span><math><mrow><mi>p</mi><mo>=</mo><mn>0.032</mn><mo>,</mo><msup><mi>r</mi><mn>2</mn></msup><mo>=</mo><mn>0.100</mn><mo>,</mo><mi>N</mi><mo>=</mo><mn>46</mn></mrow></math></span>) and at the end of treatment (<span><math><mrow><mi>p</mi><mo>=</mo><mn>0.042</mn><mo>,</mo><msup><mi>r</mi><mn>2</mn></msup><mo>=</mo><mn>0.107</mn><mo>,</mo><mi>N</mi><mo>=</mo><mn>39</mn></mrow></math></span>). Relatedly, E-field magnitude at the sgACC-anticorrelated peak in the prefrontal cortex correlated with symptom response throughout treatment (early treatment: <span><math><mrow><mi>p</mi><mo>=</mo><mn>0.001</mn><mo>,</mo><msup><mi>r</mi><mn>2</mn></msup><mo>=</mo><mn>0.220</mn><mo>,</mo><mi>N</mi><mo>=</mo><mn>46</mn></mrow></math></span>; end of treatment: <span><math><mrow><mi>p</mi><mo>=</mo><mn>0.026</mn><mo>,</mo><msup><mi>r</mi><mn>2</mn></msup><mo>=</mo><mn>0.127</mn><mo>,</mo><mi>N</mi><mo>=</mo><mn>39</mn></mrow></math></span>).</div></div><div><h3>Conclusions</h3><div>This work establishes that scalp-based targeting can produce reliable targets in the dLPFC and be successfully evaluated using a combination of neuroimaging and E-field modeling in pragmatic, multisite applications. Importantly, this investigation also found that significant network effects occur early in treatment and that Beam/F3 targets can engage functional mechanisms in TMS.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 3","pages":"Pages 829-837"},"PeriodicalIF":7.6,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802511","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}
Brain StimulationPub Date : 2025-04-01DOI: 10.1016/j.brs.2025.03.022
David Satzer , Lesley C. Kaye , Steven G. Ojemann , Daniel R. Kramer , John A. Thompson
{"title":"Aperiodic activity as a biomarker of seizures and neuromodulation","authors":"David Satzer , Lesley C. Kaye , Steven G. Ojemann , Daniel R. Kramer , John A. Thompson","doi":"10.1016/j.brs.2025.03.022","DOIUrl":"10.1016/j.brs.2025.03.022","url":null,"abstract":"<div><h3>Introduction</h3><div>Mounting evidence suggests the efficacy of neuromodulation for epilepsy is mediated by network remodeling and neural state. Epilepsy network related pathophysiology has been associated with variation in the aperiodic exponent, which describes the inverse relationship between frequency and power and has been linked to synaptic-level processes. This study sought to assess relationships between periodic and aperiodic activity, disease state, and responsive stimulation.</div></div><div><h3>Methods</h3><div>Chronic intracranial EEG was recorded from 13 patients undergoing responsive neurostimulation for epilepsy. Recordings containing clinician-annotated seizures, stimulation triggered by device-detected interictal epileptiform activity (IEA), and stimulation-free interictal periods were analyzed. Multidien IEA cycles were identified, and recordings were classified by cycle phase. Power spectra were parameterized into periodic and aperiodic components using an established algorithm.</div></div><div><h3>Results</h3><div>The aperiodic exponent was larger during seizures and pre-stimulation intervals than stimulation-free interictal recordings, and decreased following stimulation. A rise in aperiodic exponent was observed in the 12 h preceding seizures. Larger aperiodic exponent was observed during the rising phase of multidien IEA cycles. Periodic alpha and beta power were larger during seizures, pre-stimulation intervals, and high-risk (rising and/or peak) IEA cycle phases, whereas periodic theta and gamma power exhibited variable relationships. Periodic power did not change after stimulation or in the hours before seizures for any studied frequency band.</div></div><div><h3>Conclusions</h3><div>The aperiodic exponent was positively related to instantaneous and multidien disease state severity and negatively related to therapeutic stimulation. Aperiodic activity may emerge as a practical biomarker of disease state and treatment response to guide neuromodulation for epilepsy.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 3","pages":"Pages 738-744"},"PeriodicalIF":7.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779164","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}
Brain StimulationPub Date : 2025-04-01DOI: 10.1016/j.brs.2025.03.024
Yang Gao , Anna Helin Koyun , Veit Roessner , Ann-Kathrin Stock , Moritz Mückschel , Lorenza Colzato , Bernhard Hommel , Christian Beste
{"title":"Transcranial direct current stimulation and methylphenidate interact to increase cognitive persistence as a core component of metacontrol: Evidence from aperiodic activity analyses","authors":"Yang Gao , Anna Helin Koyun , Veit Roessner , Ann-Kathrin Stock , Moritz Mückschel , Lorenza Colzato , Bernhard Hommel , Christian Beste","doi":"10.1016/j.brs.2025.03.024","DOIUrl":"10.1016/j.brs.2025.03.024","url":null,"abstract":"<div><h3>Background</h3><div>Metacontrol is the ability to optimize the balance between cognitive persistence and flexibility. Recent research points to aperiodic EEG activity as a neurophysiological marker for metacontrol and its modulations. However, the causal link between metacontrol and aperiodic activity is still unclear.</div></div><div><h3>Objective</h3><div>We provide mechanistic insights into the neurobiological foundations of metacontrol and the means to enhance it. We evaluated the interplay of anodal transcranial direct current stimulation (atDCS) and Methylphenidate (MPH), both of which are known to alter cortical noise, a factor that can be measured by aperiodic exponents derived from EEG data.</div></div><div><h3>Methods</h3><div>We examined the impact of right inferior frontal (midpoint between electrodes FC4 and F8) 20 min offline atDCS at 2-mA and MPH administration, both separately and combined, on aperiodic EEG activity while healthy adult participants (N = 98) performed a Go/NoGo task. We used the FOOOF (fitting oscillations & one over f) algorithm to examine aperiodic activity.</div></div><div><h3>Results</h3><div>We obtained an interaction between atDCS stimulation and MPH administration, indicating that atDCS is effective in reducing aperiodic neural activity (i.e., increased aperiodic exponents) when being combined with MPH administration.</div></div><div><h3>Conclusion</h3><div>Aperiodic neural activity can be modulated through pharmacology-tuned atDCS. atDCS and MPH rely on overlapping neurobiological mechanisms. Metacontrol depending on aperiodic neural activity can be modulated through combined atDCS-MPH stimulation. Hence, atDCS and MPH are suitable tools to achieve an exogenous modulation of metacontrol bias and aperiodic exponents are indices to demonstrate the effectiveness of such tools.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 3","pages":"Pages 720-729"},"PeriodicalIF":7.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779165","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}