medRxiv : the preprint server for health sciences最新文献

{"title":"Multivariate neural signatures of worry become more differentiated across adolescence and young adulthood: An ultra-high field (7T) fMRI study.","authors":"Cecilia A Westbrook, Helmet T Karim, Carmen Andreescu, Cecile D Ladouceur","doi":"10.64898/2026.09.26.26364082","DOIUrl":"10.64898/2026.09.26.26364082","url":null,"abstract":"<p><p>Worry is an important contributor to anxiety and depressive disorders, particularly in adolescence. Underlying changes in brain networks are thought to drive development of pathological worry, yet the degree to which neural correlates of worry vary by age is unknown. Here, we use multivariate pattern analysis (MVPA) to investigate individual variance in brain activity during worry in a cross-sectional sample of adolescents and adults varying in worry symptoms. Participants (n=69; ages 12-31) completed a personalized worry-induction fMRI task. Brain activity was averaged across k=268 brain regions from the Shen atlas. Participants also completed self-reports assessing trait worry (PSWQ), anxiety (SCARED), and depression (MFQ) severity. A random-forest model was trained on estimated parameters from worry vs. neutral blocks using leave-one-subject-out cross-validation. Age and symptomatology measures were correlated with model performance metrics. The overall cross-validated model had accuracy=66.71%, balanced accuracy=62.61%, sensitivity=80.43%, and specificity=44.78%. Trial-level accuracy increased with in-scanner worry ratings regardless of condition (<i>β</i>=0.62, <i>p</i><.001). Accuracy (<i>r</i>=0.30, <i>p</i>=.01) and balanced accuracy (<i>r</i>=0.31, <i>p</i>=.01) significantly correlated with age but did not relate to symptom severity. Brain patterns associated with worry become more differentiated across adolescence, suggesting that neural processes of worry consolidate across this period. Thus, early adolescence may be an opportune time for interventions to alter worry, but interventions adapted from adult populations may require tailoring for adolescent patients.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent <i>Borrelia burgdorferi</i> protein antigen in CD16 ⁺ monocytes is associated with monocyte-skewed immune dysregulation in post-treatment Lyme disease syndrome (PTLDS).","authors":"Bruce K Patterson, Edgar B Francisco, Nicolas Castaño, Kwat Medetgul-Ernar, Christopher Beaty, Kaeden Beaty, Patricia A Felder, Ram Yogendra","doi":"10.64898/2026.09.24.26363601","DOIUrl":"https://doi.org/10.64898/2026.09.24.26363601","url":null,"abstract":"<p><p>Post-treatment Lyme disease syndrome (PTLDS) is characterized by persistent symptoms after antibiotic therapy for <i>Borrelia burgdorferi</i> infection. The mechanisms underlying these symptoms remain incompletely understood and have been attributed to ongoing low-level infection, autoimmunity, or immune dysregulation driven by residual bacterial antigens. We investigated whether <i>Borrelia burgdorferi</i> protein antigen persists in long-lived monocyte subsets in PTLDS patients and is associated with broader immune dysregulation. CD14 ^⁺ CD16 ^⁺ monocytes from 10 patients with PTLDS were analyzed by mass spectrometry; plasma from all 10 was profiled on a 14-plex cytokine panel against 50 healthy donors; PBMCs from 6 patients (3 antigen-positive and 3 antigen-negative) underwent RT-qPCR and bulk RNA-seq with immune-compartment profiling. FlaB and OspC were detected in CD14 ^⁺ CD16 ^⁺ monocytes months to years after treatment, whereas <i>Borrelia burgdorferi</i> transcript was not detected. Plasma IFN-γ exceeded the healthy donor median in all 10 participants. Antigen-positive samples showed an antigen-associated inflammatory transcriptional profile, including increased TNFSF14/LIGHT, GSDMD, GBP5, and KCNJ2 expression, together with a compartment-level pattern of monocyte-skewed myeloid reconfiguration, higher neutrophil-related features, and selective T-cell-state changes. These findings link residual <i>Borrelia burgdorferi</i> protein in CD14 ^⁺ CD16 ^⁺ monocytes to monocyte-skewed immune remodeling in PTLDS, paralleling observations in long COVID and supporting a model in which post-infectious syndromes are sustained by antigen-fueled immune remodeling rather than ongoing infection.</p><p><strong>Importance: </strong>Many people treated for Lyme disease go on to experience fatigue, pain, and difficulty thinking for months or years, and the reason is unknown. Persistent infection has been a leading explanation, yet longer courses of antibiotics do not help. We found proteins from <i>Borrelia burgdorferi</i> , the bacterium that causes Lyme disease, inside long-lived blood monocytes of patients with lasting symptoms, years after treatment and with no sign that the bacterium was still active. Patients carrying these proteins showed a distinct inflammatory immune profile. These findings point to leftover bacterial material, rather than ongoing infection, as a possible driver of persistent symptoms, echo observations in long COVID, and argue that treatments directed at the immune response deserve study.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1Hz vs. cTBS Transcranial Magnetic Stimulation to Augment Behavior Therapy for Tics: A Randomized Clinical Trial.","authors":"Christine A Conelea, Sarah Kretsch, Deanna J Greene, Bryon A Mueller, Claire Breitenfeldt, Kerry Houlihan, Brianna Wellen, Timothy Hendrickson, Jennifer Alexander, Mark Fiecas, Erjia Cui, Kelly Duffy, David Schneck, Mo Chen, Charles P Lewis, Donovan Roediger, Alexander Opitz, Suma Jacob, Kelvin Lim","doi":"10.64898/2026.09.29.26364036","DOIUrl":"https://doi.org/10.64898/2026.09.29.26364036","url":null,"abstract":"<p><strong>Background: </strong>Response to Comprehensive Behavioral Intervention for Tics (CBIT), the first-line treatment for tic disorders, is suboptimal. We conducted Phase 1 of a two-phase, milestone-driven trial to determine if augmenting CBIT with repetitive transcranial magnetic stimulation (TMS) to supplementary motor area (SMA) could safely engage targeted sensorimotor circuitry and improve tic controllability.</p><p><strong>Methods: </strong>In a 3-arm, double-blind, sham-controlled randomized trial ( NCT04578912 ), 50 youth (ages 12-21) with moderate-to-severe tics received 10 sessions of either 1Hz rTMS, continuous theta burst stimulation (cTBS), or sham stimulation to the SMA, immediately followed by CBIT. Primary outcomes were safety, feasibility, and neural target engagement (fMRI SMA activation and resting-state functional connectivity [RSFC]). Secondary outcomes included change in tic controllability, tic frequency at rest, and urges.</p><p><strong>Results: </strong>The CBIT+TMS intervention was safe and feasible (96% completion). Treatment-related adverse events were mild-to-moderate and occurred more frequently in the 1Hz rTMS group (27% of sessions) vs. cTBS (14.7%) and sham (11.3%). While task-based SMA activation remained unchanged, cTBS demonstrated robust neural target engagement, reducing SMA-primary motor cortex (M1) RSFC and putamen-M1 RSFC. Conversely, 1Hz rTMS blunted the cortico-striatal connectivity reductions observed in the sham group. All groups exhibited significant reductions in tic frequency and improved controllability. Premonitory urges increased in the 1Hz rTMS group but decreased in sham and cTBS.</p><p><strong>Conclusions: </strong>SMA-directed cTBS is a safe, feasible augmentation that may amplify the neural effects of CBIT on sensorimotor circuitry. Findings identify cTBS as the preferred stimulation regimen for future efficacy testing.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov; Identifier: NCT04578912 .</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarker Convert: a novel approach to transform plasma pTau217 results across immunoassay and mass spectrometry analytical platforms.","authors":"Karen J Quadrini, Jiri Aubrecht, Frederique Vernhes, Xuemei Zeng, Ann D Johnson, Beth E Snitz, Ann D Cohen, Ryan E Tooker, Mary E Quiceno, Brian M Campbell, Thomas K Karikari, Chad J Swanson","doi":"10.64898/2026.09.28.26363900","DOIUrl":"https://doi.org/10.64898/2026.09.28.26363900","url":null,"abstract":"<p><strong>Introduction: </strong>We report the development and validation of a novel computational tool to cross-convert plasma pTau217 results from different assays to facilitate recruitment for therapeutic trials and observational studies.</p><p><strong>Methods: </strong>Participants underwent Aβ PET imaging and plasma pTau217 measurement on up to three assay platforms across three cohorts. We then developed conversion equations using Deming regression - collectively named <i>Biomarker Convert</i> - and evaluated robustness using independent research cohorts. Finally, we modeled the potential impact of pTau217 screening on trial enrollment.</p><p><strong>Results: </strong>While absolute plasma pTau217 concentrations differed, the assays had similar predictive characteristics for Aβ positivity (LC-MS/MS [C ₂ N], AUC=0.952; Janssen Simoa, AUC=0.946; Lumipulse, AUC=0.929). <i>Biomarker Convert</i> enabled transformation of plasma pTau217 data across assays independent of Aβ PET and clinical status. Plasma pTau217 reduced Aβ PET scans in the model screening paradigm by >60%.</p><p><strong>Discussion: </strong><i>Biomarker Convert</i> equations enable harmonization of plasma pTau217 values from immunoassay and mass spectrometry platforms, supporting direct data comparison.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Occupational endotoxin exposure, DNA methylation changes, and immune-cell remodeling: an epigenome-wide association study in two cohorts.","authors":"Hantao Wang, Mohammad L Rahman, Charles E Breeze, Gabriel Goodney, Jungeun Lim, Wei Hu, Batel Blechter, Jianxin Shi, Fengying Zhang, Qiuyin Cai, Gong Yang, Jirong Long, Li Su, Yu-Tang Gao, Xiao-Ou Shu, Nathaniel Rothman, Wei Zheng, Qing Lan, David C Christiani, Jason Y Y Wong","doi":"10.64898/2026.09.29.26364351","DOIUrl":"10.64898/2026.09.29.26364351","url":null,"abstract":"<p><strong>Background: </strong>Millions of textile and agricultural workers inhale organic dust containing endotoxin, an exposure associated with impaired respiratory function. However, the underlying biological pathways remain unclear. We conducted a two-cohort epigenome-wide association study (EWAS) to identify airborne endotoxin-associated DNA methylation (DNAm) alterations and pathways.</p><p><strong>Methods: </strong>In the discovery phase, we compared blood DNAm in 281 endotoxin-exposed cotton workers and 253 unexposed silk-workers from the Shanghai Textile Worker Study (STWS) measured using Illumina MethylationEPICv2 arrays. STWS endotoxin assessment combined detailed work histories and onsite measurements. For targeted parallel validation, we tested STWS signals in 686 incident lung cancer cases and 683 matched controls from the Shanghai Women's Health Study (SWHS), using occupation-derived low, medium, or high exposure-intensity ranks based on published evidence. To gain biological insight, we analyzed pathway enrichment, immune-cell composition, DNAm inflammation risk scores (IRSs), and respiratory phenotype associations in STWS.</p><p><strong>Results: </strong>In STWS, we identified 36 epigenome-wide significant DNAm sites (P<5×10⁻⁸), of which, 35 were hypomethylated. Among 30 sites testable in SWHS, 18 had concordant effect directions, and four were nominally significant: cg11869499 ( <i>POLG</i> ; P=0.041), cg16290931 ( <i>TSKS</i> ; P=0.044), cg05019530 ( <i>EPIC1</i> ; P=0.042), and cg26033526 ( <i>PSMB9/TAP1</i> ; P=0.013). Enrichment implicated immune and signal-transduction pathways, including IgSF cell-adhesion-molecule signaling (FDR=8.2×10⁻⁶). Neutrophils were higher in cotton workers than in silk workers (63.5% vs 58.9%, p=7.52×10⁻ ¹⁰ ). Cumulative endotoxin was associated with higher CRP-based IRSs, which showed the most consistent associations with lower lung function and airflow obstruction.</p><p><strong>Conclusions: </strong>Our EWAS findings suggest that occupational endotoxin may operate partly through immune-cell composition and inflammatory pathways.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-Stratified Patterns of Diagnostic Delay in Pertussis.","authors":"Emily A Serman, Iromi Jayawardena, Carolina Liskey, Robin Lacroix, Alain H Litwin, Jihad S Obeid, Scott R Curry, Lior Rennert","doi":"10.64898/2026.09.25.26364016","DOIUrl":"https://doi.org/10.64898/2026.09.25.26364016","url":null,"abstract":"<p><strong>Background: </strong>Pertussis has resurged in the post-COVID-19 era, yet diagnostic delay remains a barrier to timely treatment and transmission interruption, particularly among adults.</p><p><strong>Methods: </strong>Retrospective observational cohort study of 787 patients with confirmed pertussis from January 2016 through March 2026 across two South Carolina health systems. Electronic health record data from the 60 days preceding confirmation were used to characterize diagnostic timing (same-day vs. delayed), delay duration, and respiratory pathogen testing patterns including pertussis test modality.</p><p><strong>Results: </strong>Adults accounted for 48.4% of cases (median age 16 years [IQR 4-52]; 61.6% female). Same-day diagnosis was highest among children aged 1-4 years (75.4%) and lowest among adults aged 50 and older (approximately 50%). Among the 305 patients (38.8%) with delayed diagnosis, median delay ranged from 7-12 days in children to 22.5-26.5 days in adults aged 50 and older. Delay did not vary significantly by COVID-19 period, race, ethnicity, or insurance type. Testing breadth was greater in inpatient and emergency settings than outpatient. Pertussis testing was predominantly PCR-based in children but serologic in adults, potentially reflecting later clinical presentation relative to illness onset; however, the near-absence of PCR testing in older adults may contribute to missed diagnoses during the early illness window when PCR sensitivity is highest.</p><p><strong>Conclusions: </strong>Older adults experienced markedly delayed pertussis diagnoses compared with children. Earlier consideration of pertussis in adults with prolonged cough, including PCR testing early in illness before serologic conversion, may reduce diagnostic delay and facilitate timelier treatment and contact tracing.</p><p><strong>Summary: </strong>Among 787 confirmed pertussis patients across two health systems, adults aged 50 and older experienced diagnostic delays two to three times longer than children, likely driven by atypical symptom presentation and late-stage testing patterns that fall outside optimal diagnostic windows.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylation-associated Gene Expression (MaGE): a non-invasive, in vivo measure of cellular senescence.","authors":"Daniel J Simpson, Samuel J Crofts, Christos Mavrommatis, Thomas A White, Yossawat Suwanlikit, Kirstyn Loyva, Walter A Rocca, Kejal Kantarci, Michelle M Mielke, Anne Richmond, Riccardo E Marioni, Kristina Kirschner, Nathan K Lebrasseur, Tamir Chandra","doi":"10.64898/2026.09.29.26364335","DOIUrl":"10.64898/2026.09.29.26364335","url":null,"abstract":"<p><p>Cellular senescence is a central hallmark of aging, yet its measurement in humans remains invasive, low-throughput and tissue-specific, precluding population-scale study. We developed Methylation-associated Gene Expression (MaGE) predictors: whole-blood DNA methylation proxies of p14^ARF, p16^INK4A and p21^CIP1 expression, plus a composite score, providing the first scalable measure of senescence-marker expression. Deployed across Generation Scotland (n=18,859), MaGE yielded 45 Bonferroni-significant associations spanning 18 incident diseases and all-cause mortality. The two strongest associations recapitulated the established tissue specificity of p21^CIP1 and p16^INK4A activation, with MaGE-p21 associating with incident alcoholic liver disease and MaGE-p16 with pulmonary fibrosis. In a separate study, MaGE tracked disease severity and treatment response in Crohn's disease. MaGE is a scalable, interpretable biomarker of senescence that enables its study at population scale and offers a route to patient stratification in senolytic trials.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"I love my AI girlfriend\": a content analysis of youth social AI risk in online communities.","authors":"Anne Bischops, Thomas Berkane, David Martoma, Maimuna Majumder","doi":"10.64898/2026.09.25.26363809","DOIUrl":"https://doi.org/10.64898/2026.09.25.26363809","url":null,"abstract":"<p><p>Youth are increasingly engaging with generative AI beyond its use as a productivity tool, with a growing share turning to AI for social interaction and emotional support. This leads to unknown risks for their well-being and development. Online community discussions reveal that youth already perceive risks that caregivers have not recognized.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal Hematopoiesis Accelerates Frailty and Functional Decline.","authors":"Kun Zhao, Candice Quin, Yash Pershad, Liying Xue, Weizhi Cao, Grace I Bowman, Caitlyn Vlasschaert, Robert W Corty, J Brett Heimlich, Erica N DeJong, Caitlin Lee, Zil Patel, Marco M Buttigieg, Chris P Verschoor, Calum A Bane, Amy J M McNaughton, Dawn M E Bowdish, George A Kuchel, Eric A Whitsel, Aladdin H Shadyab, Charles Kooperberg, Andrea Z LaCroix, Alexander P Reiner, Michael J Rauh, Luke M Evans, Alexander G Bick","doi":"10.64898/2026.09.24.26363888","DOIUrl":"https://doi.org/10.64898/2026.09.24.26363888","url":null,"abstract":"<p><p>Frailty reflects declining physiological reserve across multiple organ systems with aging, yet the underlying biological mechanisms contributing to frailty remain poorly understood. We tested whether somatic mutations in the blood were associated with incident frailty and faster progression in 730,088 participants from UK Biobank, All of Us, BioVU and the Women's Health Initiative. We found that clonal hematopoiesis of indeterminate potential (CHIP) and autosomal mosaic chromosomal alterations showed strong associations with frailty, whereas mosaic loss of chromosome X or Y did not. Findings were consistent across survey-based, directly measured and clinically assessed frailty, as well as healthspan phenotypes. A <i>Tet2</i> mouse model demonstrated multisystem frailty-like functional decline and T-cell remodeling. In humans, T-cell activation-related proteins directly mediated the association between clonal hematopoiesis and frailty. Collectively, these findings support a model in which clonal hematopoiesis accelerates biological aging through immunosenescence.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined population and patient-specific brain networks predict electrical stimulation propagation.","authors":"Sarah B Lavelle, William K S Ojemann, Marc Jaskir, Zican Zou, Carlos A Aguila, Katherine Walsh, Odile Feys, Daniel J Zhou, Kathryn A Davis, Brian Litt, Erin C Conrad, Nishant Sinha","doi":"10.64898/2026.09.29.26364360","DOIUrl":"10.64898/2026.09.29.26364360","url":null,"abstract":"<p><strong>Objective: </strong>Cortico-cortical evoked potentials (CCEPs) are used during intracranial EEG (iEEG) monitoring to probe effective connectivity and guide epilepsy surgery. However, the factors governing spatial distribution and variability of stimulation-evoked responses across patients remain incompletely understood, making it difficult to distinguish physiological variation from pathological responses. We aimed to develop interpretable models of CCEP responses that integrate normative and patient-specific features, and to assess how these relationships are influenced by distance, brain-state, and epileptogenicity.</p><p><strong>Methods: </strong>We analyzed single-pulse stimulation data from 34 patients with drug-resistant epilepsy undergoing stereo-EEG monitoring. Significant CCEP responses were defined using N1 peak amplitude. For each stimulation-response pair, we derived multimodal features capturing Euclidean distance, effective connectivity priors from F-TRACT, a published population atlas of CCEP response probabilities, normative structural connectivity and communication metrics, and patient-specific functional connectivity estimated from iEEG during baseline and pre-stimulation periods. Lasso-regularized logistic regression models were trained to predict response using leave-one-patient-out cross-validation, and feature importance was examined across spatial scales and seizure onset zone (SOZ) involvement.</p><p><strong>Results: </strong>Performance to predict stimulation-evoked responses improved with the integration of multiple feature domains, with the full model achieving the highest accuracy (median AUC = 0.84). Feature relevance varied with spatial scale: short-range responses were dominated by distance and normative priors, whereas long-range responses depended strongly on patient-specific functional connectivity, especially when measured from pre-stimulation periods. Prediction errors were significantly higher for stimulation-response pairs within the SOZ, indicating deviations from normative connectivity-response relationships in epileptogenic networks.</p><p><strong>Significance: </strong>CCEP responses reflect an interaction between spatial constraints, network architecture, and patient-specific brain state. Multimodal modeling of CCEPs provides a principled framework to interpret stimulation responses and may offer complementary markers for identifying epileptogenic networks during presurgical evaluation.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}