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Epilepsy Research

Elsevier BV

Preprints posted in the last 7 days, ranked by how well they match Epilepsy Research's content profile, based on 14 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.

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Patient-Specific EEG Baseline Establishment Using the E-norms Method for Pediatric Seizure Detection Without Labeled Training Data

Jabre, J. F.

2026-07-16 neurology 10.64898/2026.07.13.26357876 medRxiv
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The aim of this work is to validate patient-specific EEG baseline establishment using the e-norms method as a screening and retrospective-review tool for seizure detection in pediatric epilepsy. The method was applied to 247 seizure-free EEG recordings (263.92 hours) from 10 patients in the CHB-MIT Scalp EEG Database (ages 3-18). A composite stability metric combining first-derivative dynamics, spectral entropy, variance, and line length was computed per 2-second epoch across 23 channels. Patient-specific detection thresholds were derived from each patient's seizure-free baseline using a weighted statistical procedure. Performance was validated against 72 expert-annotated seizures (2,705 epochs) across 62 seizure files, with durations spanning 6 to 264 seconds (44-fold range). The results show that detection achieved 94.4% event-level sensitivity (68 of 72 seizures; 95% CI 86.6-97.8%) and 81.5% epoch-level sensitivity (2,204 of 2,705 epochs; 95% CI 80.0-82.9%). Eight of ten patients achieved 100% event-level sensitivity with epoch-level sensitivity ranging from 58.7% to 100.0%. Two patients showed partial event-level failures (CHB-15: 17 of 20; CHB-18: 5 of 6), with the four missed events attributable to two characterizable failure modes. Patient-specific thresholds ranged from 4.06 to 4.81 (mean 4.51 +/- 0.25); threshold variation did not correlate reliably with age or sex, confirming that no universal threshold could achieve comparable performance. Detection margins ranged from 0.88 to 1.24 times. Patient-specific e-norms achieves 94.4% event-level sensitivity for pediatric EEG seizure detection without requiring labeled seizure training data, exceeding published human expert inter-rater agreement (50-76%) and recent automated approaches in adult cohorts using behind-the-ear EEG and wearable ECG. Two characterizable failure modes account for the four missed events and inform appropriate clinical use. As a high-sensitivity screening tool complementary to real-time alarm systems, the method is ready for adult validation, prospective deployment, and head-to-head benchmarking.

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Diagnosing Others, Hiding Self: Shame and Non-Disclosure Among Autistic Psychiatrists - An Interpretive Phenomenological Analysis

Doherty, M.; Chown, N.; Martin, N.; Grosjean, B.; Chaplin, E.; Dolezal, L.; Shaw, S. C.

2026-07-15 psychiatry and clinical psychology 10.64898/2026.07.13.26357917 medRxiv
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Autistic psychiatrists occupy a paradoxical position: trained to recognise and assess autism in others, yet navigating a professional culture in which their own autistic identity remains largely concealed. Despite growing visibility of autistic clinicians, the barriers autistic psychiatrists face to formal diagnosis and professional disclosure remain unexplored. This study used interpretive phenomenological analysis to examine the experiences of seven autistic psychiatrists in relation to diagnosis and disclosure. Data were generated through in-depth interviews and Retzinger's framework for identifying shame in discourse was applied as an analytical tool within the interpretive process. Shame emerged as the overarching theme across the dataset, operating through four group experiential themes. Its origins lay in childhood experiences of difference and perceived defectiveness, transmitted through family, peers, and the broader social environment. In professional life, shame was sustained and amplified by colleagues' misconceptions about autism, anticipated loss of credibility, and the deficit-based diagnostic criteria - which rendered self-recognition difficult and made formal diagnosis a perceived professional liability. Critically, shame did not only create barriers: it functioned as an override mechanism, rendering the known benefits of disclosure - to participants themselves, to colleagues, and to patients - insufficient to translate into action. This override function was not explained by fear of discrimination or rational career protection alone; it reflected shame's operation as an internal prohibition, dissociated from its original social source and persisting even where stigma had been intellectually processed and rejected. These findings reposition shame not as one barrier among many but as the organising force through which all barriers operate. Interventions aimed at increasing disclosure by raising awareness of its benefits misread the operative mechanism. Creating conditions in which autistic psychiatrists can make decisions about their identities freely requires naming and addressing shame - in research, in clinical training, and in the culture of psychiatry.

3
From Menarche to Menopause: Hormonal Influences on Functional Neurological Disorder

Palmer, D. D. G.; Warren, N.; Morton, A.; Lehn, A.

2026-07-18 neurology 10.64898/2026.07.16.26358260 medRxiv
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Background Functional neurological disorder (FND), one of the most common neurological conditions, affects women almost twice as frequently as men. The reasons for this are unknown, and there has been minimal research into how physiological and pathological features of women's health interact with symptoms of FND. Methods We conducted an online survey assessing the effect of several aspects of women's health with the severity of symptoms of FND. Results 484 people completed the survey. Among the 223 who had regular or fairly regular menstrual cycles, a strong difference across the menstrual cycle was seen, with symptoms at their best in the follicular phase, worsening in the luteal phase, and worst in the pre-menstrual period and the menses. This effect was not moderated by a proxy measure of pre-menstrual dysphoric disorder (PMDD). Participants who were taking the combined oral contraceptive (COC, n=43) and progesterone-based contraception (n=80) were more likely to report symptom improvement from starting the medication than worsening. When compared to menstruating participants who were not taking the COC, participants taking the COC reported less worsening in their symptoms of FND in the luteal, pre-menstrual, and menstrual phases. Of the 99 women who had passed menopause since developing FND, 76% reported worsening of their FND symptoms after menopause. Discussion This study demonstrates interactions between several aspects of women's health and symptoms of FND. The observed pattern of symptom fluctuation across hormonal states suggests a potential modulatory role of oestrogen, warranting further targeted investigation.

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Stereoelectroencephalography accuracy in a series of over 3000 trajectories

Thurairajah, A.; Gilmore, G.; Persad, A. R.; Youshani, A. S.; Taha, A.; Abbass, M.; Santyr, B.; Al-Orabi, K. M.; Burneo, J. G.; Pellegrino, G.; Suller-Marti, A.; Western Epilepsy Research Group, ; Parrent, A. G.; MacDougall, K. W.; Steven, D. A.; Lau, J. C.

2026-07-16 surgery 10.64898/2026.07.14.26358071 medRxiv
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Background and Objectives: Stereoelectroencephalography (SEEG) involves the implantation of intracerebral electrodes to investigate drug-resistant epilepsy. SEEG requires millimetric accuracy to ensure safety and optimal mapping. Although studies have evaluated SEEG accuracy, there is substantial variability in reporting. Here we report on implantation accuracy in a large series using the most common accuracy metrics described in the literature and perform a detailed analysis of contributing factors. Methods: SEEG implantations between 2013 and 2025 were included. Application accuracy was computed for each implanted electrode. Specifically, Euclidean, radial, depth, and angle error were calculated at both target and entry points. Correlative and multivariable analyses were conducted between each variable and error metric. Trajectories were also grouped by atlas-derived lobar target. Results: No metrics met assumptions of normality and thus we report accuracy using median with interquartile range (IQR). In a series of 3176 trajectories, median Euclidean target and entry errors were lower for robot-assisted electrodes (n=2858) at 2.19 (IQR: 1.54-2.98) mm and 1.38 (IQR: 0.89-2.01) mm respectively, compared to frame-based (n=318, p<.001) at 2.76 (IQR:1.79-3.76) mm and 2.21 (IQR: 1.42-3.32) mm. Correlation and multivariable regression analysis showed target error was positively correlated with implantation angle, scalp thickness, skull thickness, and trajectory length. Target error was also higher in obese patients. On lobar analysis, parietal lobe trajectories were the most accurate and frontal lobe trajectories were the least accurate. On temporal lobe trajectory analysis, posterior hippocampus trajectories were the most accurate and temporal pole trajectories were the least accurate. Presence of mesial temporal sclerosis also impacted accuracy. Conclusions: We present a detailed description of SEEG implantation accuracy, demonstrating the superior accuracy and speed of robot-assisted to frame-based methods. Furthermore, we analyzed how accuracy varies with specific factors from a global to trajectory level, which can be accounted for when planning SEEG implantations.

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Validity and Reliability of the Novel Indonesian Instrument for Aphasia Diagnosis (IDEA)

Prawiroharjo, P.; Fakhri, A.; Gabrielle, A.; Martalia, V.; Rahmayani, S. A.; Wijaya, V. G.

2026-07-19 neurology 10.64898/2026.07.17.26358303 medRxiv
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Aphasia diagnosis in Indonesia remains challenging due to limited culturally and linguistically appropriate instruments. Widely used tools such as the Boston Diagnostic Aphasia Examination (BDAE) and Western Aphasia Battery (WAB) are not adapted to the Indonesian context, while Tes Afasia untuk Diagnosis, Informasi, dan Rehabilitasi (TADIR) provides screening but lacks diagnostic accuracy. To address this gap, we developed the Instrumen Diagnosis dan Evaluasi Afasia (IDEA) for native Indonesian speakers and evaluated its validity, reliability, and normative cutoff values in cognitively healthy Indonesian adults. Eighty-three cognitively normal adults (screened using MoCA-Ina) with no history of neurological disease were assessed using IDEA, which evaluates six language domains. Items were adapted from existing tools and reviewed by experts. Content validity, internal consistency (Cronbachs alpha), and construct validity (Exploratory Factor Analysis) were analyzed using SPSS v25. A total of 83 participants were included (median age = 55.81 years, 54% secondary education). IDEA demonstrated good feasibility, with an average completion time of 45-60 minutes depending on participant engagement. Content validity was established by unanimous expert consensus. Construct validity showed meritorious sampling adequacy (KMO = .872) and significant sphericity (Bartletts test {chi}^2 (15) = 278.523, p<.001), supporting factor analysis. Internal consistency showed good reliability across six domains (Cronbachs = 0.896). IDEA is a valid and reliable tool for assessing aphasia in Indonesian natives. It is a culturally appropriate assessment tool which offers structured, domain-based evaluation and supports differential diagnosis of both classical and progressive aphasia syndromes. Keywords: Aphasia, Language Assessment, Indonesian, IDEA, Validity

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From CHESS to CHECKMATE: A Practical Score for Predicting Shunt Dependency Following Subarachnoid Hemorrhage

Salman, S.; Haidenberger, F.; Ahmad, M.; Rezai Jahromi, B.; Albaramony, N.; Patel, V.; Peel, J.; Ombada, M.; Gutierrez-Aguirre, S.; de Toledo, O.; Aguilar-Salinas, P.; Tawk, R.; Byrne, R.; Hanel, R.; Rabinstein, A.; Freeman, W. D.

2026-07-21 neurology 10.64898/2026.07.18.26358389 medRxiv
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Objective: Shunt-dependent hydrocephalus is a common and costly complication of aneurysmal subarachnoid hemorrhage (aSAH), affecting up to 28% of survivors. Existing prediction tools, including the Chronic Hydrocephalus Ensuing from SAH Score (CHESS), have limited discriminative accuracy. We developed the CHECKMATE score, a clinically practical tool to improve prediction of ventriculoperitoneal shunt dependency after aSAH. Methods: In this multicenter retrospective cohort of 486 patients with aSAH from Mayo Clinic (January 1, 2006-December 31, 2021), we used multivariable logistic regression and machine learning to identify independent predictors of ventriculoperitoneal shunt placement. The CHECKMATE score was derived from 5 weighted variables: symptomatic hydrocephalus (10 points), intraventricular hemorrhage (5 points), SAH volume greater than 10 mL (3 points), neutrophil-to-lymphocyte ratio greater than 12 (2 points), and 10-year incremental age thresholds starting at older than 60 years (1 point each). Results: Of 486 patients (mean age, 56.3 years; 64.6% female), 137 (28.2%) required ventriculoperitoneal shunt placement. The CHECKMATE score achieved an area under the curve of 0.808 (compared to 0.737 for CHESS), with a sensitivity of 0.85, specificity of 0.67, and negative predictive value of 0.92 at the optimal cutoff of 14 points. Conclusions: The CHECKMATE score outperforms CHESS for predicting ventriculoperitoneal shunt dependency after aSAH and is easily used at the bedside. Its high negative predictive value helps identify low-risk patients who may benefit from earlier external ventricular drain weaning and shorter hospital stays.

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Autism Research at a Crossroads: Global Progress, Persistent Gaps, and Future Pathways: A Bibliometric Analysis

zhong, Q.; Chen, L.; Ji, Y.; Zhu, F.; Zou, X.

2026-07-16 psychiatry and clinical psychology 10.64898/2026.07.14.26358066 medRxiv
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Background The global prevalence of autism spectrum disorder (ASD) has significantly increased over the past two decades. Despite substantial research advances, critical aspects, including etiology, diagnostic biomarkers, and pharmacological interventions, remain incompletely elucidated. This persistent knowledge gap warrants systematic mapping of the field's evolution to inform future research priorities. Methods A bibliometric analysis of ASD-related publications indexed in Web of Science was conducted from January 2020 to May 2025. Following a systematic deduplication process, original articles, reviews, case reports, and clinical trials were included in the analysis. The analytical framework comprised co-authorship networks, institutional collaboration patterns, national research contributions, and keyword co-occurrence structures, all of which were examined using CiteSpace (version 5.8.R3) and VOSviewer. Results After deduplication, 8,162 publications (January 2020-May 2025) were analyzed. The annual output grew steadily, confirming ASD as a sustained priority in neuroscience. Research remains academia-driven, led by the United States, with China as the second-largest contributor. Chinese institutions place greater emphasis on mechanistic and developmental phenotyping, which aligns with national priorities. These studies maintain strong methodological rigor, and their growing volume underscores the central role of ASD in translational neuroscience. Conclusion Future research on ASD should focus on strengthening case identification, refining clinical phenotyping, and expanding large-scale cohort studies to advance our understanding of its etiology and identify reliable diagnostic biomarkers. It is equally important to develop and evaluate targeted interventions for core symptoms and integrate telemedicine into service delivery models. A critical yet understudied priority is improving the quality of life for autistic individuals and their families, an area in which research globally, including in China, requires greater depth and consistency. With China's growing investment in autism research, it is well-positioned to contribute to these pressing international challenges.

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Quantitative Prognostic Modeling in Aneurysmal Subarachnoid Hemorrhage: Multicenter Validation of the eSAH Score

Salman, S.; Graf von Moy, C.; Haidenberger, F.; Ahmed, M.; Foettinger, F.; Sharma, R.; Gutierrez-Aguirre, S.; de Toledo, O.; Patel, V.; Yujia-Wei, D.; Rezai Jahromi, B.; Brandmeir, N.; Lakkaraju, K.; Ombada, M.; Aguilar-Salinas, P.; Miller, D.; Erickson, B.; Hanel, R.; Tawk, R.; Byrne, R.; Freeman, W. D.

2026-07-21 neurology 10.64898/2026.07.18.26358390 medRxiv
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Background: aneurysmal subarachnoid hemorrhage (aSAH) is neurological emergency associated with substantial mortality and disability. Current grading systems such as the modified Fisher Scale (mFS) and World Federation of Neurological Societies (WFNS) score, rely on semiquantitative and examination based assessments. Hence, they demonstrate limited predictive precision. The enhanced subarachnoid hemorrhage (eSAH) score is a simplified quantitative model integrating age, Glasgow Coma Scale (GCS), and cisternal subarachnoid hemorrhage volume (SAHV) to predict clinical outcomes after aSAH. Methods: We performed a retrospective multicenter cohort study that included 1088 patients across three tertiary-care centers the United States. Predictive performance for unfavorable functional outcome, in-hospital mortality and delayed cerebral ischemia (DCI) was evaluated using receiver operating characteristic (ROC) analysis and area under the curve (AUC). Comparative analyses were performed and compared to the WFNS and mFS grading systems. Results: the eSAH score demonstrated excellent discrimination for unfavorable functional outcome at discharge ( AUC 0.89 ) and in-hospital mortality (AUC 0.87). The DCI subscore demonstrated good discriminatory performance for predicting DCI (AUC 0.77). Compared with conventional grading systems, this was superior to both the WFNS (AUC 0.75) and the mFS ( AUC 0.70). increasing eSAH scores were additionally associated with progressively higher rates of mortality and unfavorable functional outcomes. Conclusion: the eSAH score demonstrates strong external validity, reproducibility and superior predictive performance compared with conventional grading systems in a large multicenter cohort. These findings support the clinical utility of quantitative hemorrhage burden integration for early risk stratification in patients with aSAH.

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Context-dependent facial-expression patterns during affective film viewing in patients with bipolar depression

Lee, E.; Sim, S. H.; Park, C.; Kim, H.; Ahn, W.-Y.; Park, C. H. K.

2026-07-21 psychiatry and clinical psychology 10.64898/2026.07.19.26358451 medRxiv
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Background: Emotion dysregulation is a core feature of bipolar disorder (BD), yet its behavioral expression during depressive episodes, and potential differences between its types, BD-I and BD-II, remain unclear. This study used automated facial-expression analysis during naturalistic affective film viewing to examine subtype-specific and context-dependent emotional responding in bipolar depression. Methods: The sample included 135 participants: 69 healthy controls and 66 patients with BD (BD-I, 23; BD-II, 43). Participants viewed nine emotionally evocative film clips spanning negative, positive, neutral, and socially threatening contexts, while their facial expressions were continuously recorded and quantified using computer vision-based facial-expression analysis. Results: Patients with BD-I showed a distinct, context-dependent facial-expression profile, characterized by greater negative responses across multiple contexts than other groups. Specifically, they showed increased sadness during sad, reward, and amusing clips, and elevated anger during sad and neutral clips. In socially threatening contexts, BD-I participants showed a multivalent pattern of elevated anger, fear, and joy, suggesting poorly coordinated or context-incongruent affective expression. In contrast, BD-II participants did not differ significantly from healthy controls on any emotion, despite depressive symptom severity comparable to BD-I participants. Conclusions: These findings suggest that facial-expression patterns in bipolar depression differ across subtypes. BD-I may be characterized by heightened negative reactivity and altered context-appropriate modulation of emotional expression, whereas BD-II may not show comparable alterations in overt facial output. Automated facial-expression analysis during naturalistic stimulation may provide a useful behavioral marker for characterizing subtype-specific affective disturbance in bipolar depression and related psychopathology.

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Electrophysiological features of signals recorded from white matter

Jafri, R.; Ortega, F. A.; Manivannan, P.; Jourahmad, Z.; Devara, D.; Mattar, L.; Krishna, S.; Liu, G.; Chamarthi, S.; Goldman, A. M.; Lin, L.; Krishnan, V.; Maheshwari, A.; Banks, G. P.; Hasen, M.; Paulo, D.; Watrous, A. J.; Hayden, B. Y.; Yau, J.; Sheth, S. A.; Provenza, N. R.; Murphy, N.; Heilbronner, S. R.; Bartoli, E.

2026-07-15 neuroscience 10.64898/2026.07.11.737939 medRxiv
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Intracranial neurophysiology studies have typically ignored signals from electrodes located in white matter (WM), assuming that their information content is artifactual or related to nearby gray matter (GM). Here, we tested the electrophysiological and functional features of signals recorded from different WM locations. Signals were recorded from 19 patients undergoing intracranial monitoring for drug-resistant epilepsy by means of stereo-electroencephalography (sEEG). Each sEEG electrode was classified into WM or GM based on the surrounding tissue. We obtained recordings from a total of 1,717 sEEG electrode contacts, 36% in WM, while the patients were in awake resting state (5 minutes). For each sEEG electrode, we employed a model-based spectral decomposition to separate periodic and aperiodic components, and we computed signal complexity metrics. For a subset of participants, we computed WM structural information from diffusion-weighted magnetic resonance imaging and we evaluated functional signals during a cognitive control task. Our results show that signals recorded from WM have different spectral features and higher complexity than GM. Complexity correlates positively with fractional anisotropy, and modulations related to behavior during the task were detected in WM. Overall, this indicates that WM signals carry information that may reflect signal propagation across WM fiber tracts.

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Intermittent theta burst stimulation modulates working memory-related theta-gamma coupling in adolescents with ADHD

Kavanaugh, B.; Vigne, M.; Legere, C.; Borden, Z.; Lynott, E.; Cheong, D.; Warren, A.; Acuff, W. L.; Tirrell, E.; Festa, E.; Jones, S.; Jones, R.; Spirito, A.; Carpenter, L.

2026-07-15 psychiatry and clinical psychology 10.64898/2026.07.13.26357958 medRxiv
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Objective: Working memory (WM) deficits are a co-occurring feature to numerous neuropsychiatric disorders, particularly attention-deficit/hyperactivity disorder (ADHD), and there remain no treatments that directly target WM. The coupling between the phase of theta band activity and amplitude of gamma band activity (i.e., TGC) is an established neural correlate of WM. However, no studies have examined WM-related TGC in ADHD or whether neuromodulation can modulate these oscillatory dynamics in youth. This set of studies examined the effects of intermittent theta burst stimulation (iTBS) to the left dorsolateral prefrontal cortex (DLPFC) and left posterior parietal cortex (PPC) on TGC in youth with ADHD. Methods: In two randomized, double-blind, sham-controlled crossover trials, adolescents with ADHD and clinically significant parent-reported WM symptoms first completed a single-session study comparing DLPFC versus PPC iTBS targeting (n = 47) and then a multi-session clinical trial comparing 10 sessions of active versus sham left DLPFC iTBS (n = 29). Participants completed a computerized visuospatial Sternberg WM task with concurrent electroencephalography (EEG) before and after the single sessions, as well as at baseline, midway through treatment, and approximately 24 hours after the final session within the multi-session trial. Phase-amplitude coupling between theta phase and gamma amplitude was quantified using the Kullback Leibler modulation index at frontoparietal electrodes. Linear mixed-effects models examined treatment effects and associations between change in TGC and WM status (including accuracy, reaction time, and clinical symptoms). Results: Across participants, lower TGC was associated with lower symptoms and better WM performance, including higher accuracy, faster and more consistent RT. Active iTBS increased frontoparietal TGC relative to sham stimulation, with effects observed both acutely after a single session and ~24 hours after multiple sessions. DLPFC-targeted iTBS increased TGC, whereas PPC-iTBS had no measurable effect. Change in TGC was associated with change in WM, such that a decrease in TGC was associated with faster RT and decreased RT variability. Higher baseline TGC was associated with greater improvement in WM. Active iTBS decoupled the TGC-WM association observed during sham iTBS, and greater electric field intensity of iTBS was associated with greater improvement in WM accuracy and greater decrease in TGC. Conclusions: Active iTBS to the left DLPFC modulated WM-related TGC in youth with ADHD. These findings provide preliminary evidence that neuromodulation may improve WW by modifying oscillatory dynamics within frontoparietal networks. Larger clinical trials with higher stimulation doses are needed to determine whether targeting oscillatory coupling represents a potential therapeutic strategy for WM deficits.

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Decoding and Characterizing the Intracranial Representation of Semantic Information

Smith, C.; Inchyna, S.; Barrentine, B.; Nelson, M. J.

2026-07-15 neuroscience 10.64898/2026.07.13.738249 medRxiv
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Brain-computer interfaces (BCIs) have achieved impressive performance by decoding motor and articulatory signals associated with speech production. However, considerably less is known about whether higher-level semantic representations can be decoded from human cortical activity. Demonstrating semantic decoding would advance both our understanding of language organization and the development of BCIs that rely on conceptual rather than purely articulatory information. We recorded intracranial neural activity from patients undergoing stereotactic electroencephalography (sEEG) for clinical epilepsy monitoring while they performed language tasks requiring semantic processing. High-gamma power was extracted from local field potentials and used to generate trial-level features for supervised machine-learning classification. Classification performance was evaluated using cross-validation. Semantic category information was decoded significantly above chance, with mean classification accuracy reaching 29.8% across 15 semantic categories (chance = 6.7%). These findings demonstrate that high-gamma activity contains information about conceptual category membership that can be extracted on individual trials. These results provide evidence that semantic information is accessible from intracranial population recordings and support the feasibility of semantic decoding as a complementary direction for future language BCIs. Beyond neuroprosthetic applications, this work contributes to understanding how conceptual knowledge is represented in the distributed human language network.

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Systematic Review and Meta-Analysis: Do Youth-Reported Psychosis Symptoms Predict Later Mental Health Diagnosis?

Shah, J. N.; Ameis, S. H.; Donato, C. A.; Wei, I.; Dabagh, Y. A.; Cleverley, K.; Courtney, D. B.; Foussias, G.; Kozloff, N.; Voineskos, A. N.; Wang, W.; Dickie, E. W.

2026-07-15 psychiatry and clinical psychology 10.64898/2026.07.13.26357957 medRxiv
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Objective Psychosis spectrum symptoms (PSS) are common among children and youth. These symptoms may be clinically significant as studies indicate a heightened risk of mental health disorders, in general, as well as psychotic disorders, specifically, in youth that endorse PSS. This systematic review and meta-analysis investigates the longitudinal association between PSS in children and youth and subsequent mental health diagnosis. Methods A comprehensive search of Ovid Medline, PsycINFO, and EMBASE databases was conducted to identify longitudinal studies that: (i) assess PSS at a baseline timepoint, (ii) in individuals under 25 years, and (iii) assess mental health disorder diagnosis using a structured assessment at a later time point in the same sample. We conducted a meta-analysis and calculated pooled odds ratios (ORs) for mental health and psychotic disorders using random-effects models. Post-hoc meta-regressions were performed to examine the influence of a number of moderators on the relationship between earlier recorded PSS and subsequent mental health disorders or psychotic disorders. Results The search yielded 41 eligible studies of which 25 were included in the meta-analysis. Most included studies assessed PSS using brief self-report measures and recruited their samples from clinical or community settings. Among children and youth without an identified mental health diagnosis at baseline assessment, baseline PSS were associated with a 2-fold (OR = 2.07, CI = 1.61 - 2.66, I2 = 86.92%, p < 0.0001) increased risk of meeting diagnostic criteria for subsequent mental health disorder diagnosis and a 3-fold increased risk (OR = 3.11, CI = 2.11 - 4.58, (I2 = 60.93%, p < 0.0090) of meeting diagnostic criteria for a subsequent psychotic disorder diagnosis with a minimum 1 year follow-up time from baseline assessment. Meta-regression analysis indicated that study quality and sample size explained a substantial proportion of between-study heterogeneity for psychotic disorder outcomes. Conclusions Our results suggest that administration of simple self-report measures of PSS in both clinical and community settings may be helpful to identify children and youth at higher risk of subsequently meeting criteria for a mental disorder generally, and for a severe mental illness (i.e., psychotic disorder), specifically. Future longitudinal studies should focus on improving study design characteristics to increase confidence in identified longitudinal associations. The results of our work suggests that integration of self-report measures of PSS may be useful in a variety of settings to identify youth at increased risk of subsequent mental illness.

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Revisiting the link between childhood adversity and stress-sensitive brain regions in psychosis and bipolar disorder: A systematic review and meta-analysis

Petrova, T.; Tennifjord, A.; Cavero, D.; Holohan, A.; Kizilkaya, M.; Ebrahimian-Roodbari, A.; Lepreux, I.; Reimer, M.; Sideli, L.; Gadelrab, R.; Trotta, G.; Rodriguez, V.; Andreassen, O.; Klauser, P.; Alameda, L.; Aas, M.

2026-07-19 psychiatry and clinical psychology 10.64898/2026.07.17.26358306 medRxiv
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Background Brain abnormalities related to childhood adversity (CA) have been reported across clinical presentations in psychotic disorder (PD) and bipolar disorder (BD). This systematic review and meta-analysis examined gray matter volume (GMV) alterations linked to CA in PD and BD. Methods A PRISMA-compliant systematic review was conducted (PROSPERO ID: CRD42022351133). The EMBASE, MEDLINE, and PsycINFO databases were searched from inception to June 2024 for studies investigating CA and structural brain imaging in PD and BD. Study quality was assessed with the Newcastle Ottawa Scale (NOS). Data were extracted and synthesized accounting for sex differences and CA subtypes with brain findings categorized by the presence and direction of associations. Meta-analyses were performed for hippocampal and amygdala volumes. Results In the systematic review (k = 29), 3,056 participants with PD and BD (mean age = 36.6; SD =16.1; 47% female), published between 2011 and 2023, were included. Study quality was fair, with high heterogeneity. Most studies reported significant negative associations between CA and GMV, especially in prefrontal regions, while findings for the hippocampus and amygdala were largely null or inconsistent. Meta-analyses of a study subset identified no significant association between CA and hemisphere-specific and combined volumes of the hippocampus (k = 5; p [&ge;] 8805; 0.66) or amygdala (k = 4; p [&ge;] 8805; 0.87). Conclusion CA was not consistently associated with hippocampal or amygdala volume alterations in PD and BD. More consistent evidence emerged for reduced GMV in prefrontal regions, suggesting that neurobiological impact of CA may be more robustly captured at the cortical level.

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Association between Glycemic Traits and Delayed Cerebral Infarction among Non-Diabetic Patients with Aneurysmal Subarachnoid Hemorrhage: A Nested Case-Control Study

Ji, P.; Zheng, K.; Tan, D.; Xu, J.; Chen, M.; Wu, Y.; He, Z.

2026-07-20 neurology 10.64898/2026.07.18.26358375 medRxiv
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ABSTRACT Objective Delayed cerebral infarction (DCIn) is a severe complication following aneurysmal subarachnoid hemorrhage (aSAH). Previous studies suggest that glycemic variability is associated with DCIn. However, whether diabetes status modifies the relationship between glycemic traits and DCIn remains unknown. Methods Clinical data were collected from aSAH patients admitted to the First Affiliated Hospital of Shantou University Medical College between January 2015 and April 2025. The collected data included demographic characteristics, clinical variables, and glycemic traits. Glycemic traits included mean blood glucose (GLU-M), standard deviation of blood glucose (GLU-SD), coefficient of variation of blood glucose (GLU-CV), variance of blood glucose (GLU-Var), range of blood glucose (GLU-R), average real variability of blood glucose (GLU-ARV), and variability independent of the mean (GLU-VIM). After 1:2 case-control matching, conditional logistic regression models were used to evaluate the associations between glycemic traits and DCIn risk, with stratified analyses performed according to diabetes status. Multiplicative interaction terms were additionally included to assess the potential modifying effect of diabetes status. Results A total of 306 patients with aSAH were included. Among them, 102 developed DCIn cases. For each of these 102 cases, two controls were matched by age ({+/-}5 years), sex and year of admission ({+/-}5 years). In the overall population, higher GLU-M and GLU-ARV were associated with increased DCIn risk, with odds ratios (ORs) per 1-SD increase of 1.62 (95% CI, 1.25-2.11) and 1.63 (95% CI, 1.25-2.11), respectively. Among patients without diabetes (n=266), the associations with DCIn per 1-SD were observed for GLU-M (OR, 2.23; 95% CI, 1.56-3.19), GLU-SD (OR, 1.53; 95% CI, 1.13-2.06), GLU-Var (OR, 1.48; 95% CI, 1.04-2.10), and GLU-ARV (OR, 1.88; 95% CI, 1.38-2.55). No significant associations were observed among patients with diabetes. Significant interactions were observed between diabetes status and GLU-SD and GLU-Var, with P for interaction values of 0.033 and 0.032, respectively. Conclusion Higher mean blood glucose and greater glycemic variability are associated with an increased risk of DCIn in aSAH patients, especially in those without diabetes.

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Trends and variations in Lithium usage across care settings in England between 2015-2024

Schiffer, H.; Fisher, L.; Curtis, H. J.; Wood, C.; Brown, A. D.; Bacon, S. C.; Croker, R.; Goldacre, B.; MacKenna, B.; Speed, V.; Macdonald, O.

2026-07-17 psychiatry and clinical psychology 10.64898/2026.07.15.26357641 medRxiv
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Lithium has been the gold standard for the treatment and prevention of relapse in bipolar disorder for over 60 years. Guidance from the National Institute for Health and Clinical Excellence states explicitly to 'offer lithium as a first-line, long-term pharmacological treatment for bipolar disorder'. Yet, in the last two decades its use has been in decline with clinicians favouring anticonvulsants or antipsychotics when treating this condition. In this study, we have used three openly available datasets containing prescribing data from primary and secondary care to explore trends in the use of lithium in England, showing both regional and temporal variance between 2015-2024. We have shown that lithium use declined in primary care by 20.9% in the last ten years (2015-2024) and 10.9% overall in the last five years (2019 to 2025). We have also shown how there is some regional variation in the source of lithium for patients, although the vast majority is prescribed in primary care. Further research into clinical behaviour is needed to understand what is driving the decrease in lithium usage, and what barriers and enablers may influence its use across the country.

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A Culturally Embedded Augmented Reality Task as a Neurocognitive Biomarker of Executive Function in Schizophrenia

Chatthong, W.; Rueankam, M.; Khemthong, S.

2026-07-16 psychiatry and clinical psychology 10.64898/2026.07.14.26358053 medRxiv
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Executive function (EF) deficits are central features of schizophrenia and strongly influence long-term functional outcomes. Conventional cognitive assessments often lack ecological validity and cultural relevance. This study introduces the Luk Chup Augmented Reality (LCAR) tool a video guided, clay modeling task delivered through wearable AR that integrates culturally familiar activity with realtime neurophysiological monitoring. Thirty individuals diagnosed with schizophrenia (mean age = 38.9, SD. = 7.15 years) completed a series of modeling and memory tasks using LCAR while undergoing quantitative EEG (QEEG). Task duration and theta/beta power were analyzed across procedural and color shape memory phases. Memory phases took significantly longer to complete and were associated with decreased lateral prefrontal theta and increased frontal midline theta activity (Fz, Cz), indicating higher EF demand. A repeated-measures ANOVA revealed significant condition, site, and interaction effects on theta power. The LCAR tool shows promise as a culturally grounded, dual-mode assessment of EF in schizophrenia. It offers a novel integration of performance-based and neurophysiological metrics that may inform future interventions in psychiatric rehabilitation.

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Trance practice and well-being measures: the case of Auto-Induced Cognitive Trance

Fernandez, A.; Foncelle, A.; Meunier, H.; Van-Der-Henst, J.-B.; Revillet, F.; Breton, A.

2026-07-17 psychiatry and clinical psychology 10.64898/2026.07.15.26358125 medRxiv
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Introduction Auto-Induced Cognitive Trance (AICT) is a non-ordinary state of consciousness (NOSC) that can be accessed by will alone once a standardised self-induction procedure has been learnt. The first research publication on AICT dates back only ten years, meaning that research on this phenomenon is still in its infancy. Previous reports concerning the phenomenology and neurophysiology of AICT revealed similarities with more extensively described NOSCs, as well as unusual features, raising questions about the potential benefits of AICT practice for well-being. Objective This study aimed to gather quantitative descriptive data on features associated with well-being in a large comparative sample of AICT practitioners and non-practitioners. Method This research followed a web-based survey study design which enquired AICT-trained and yet-to-be trained participants to self-report through validated standardised questionnaires on vitality, self-esteem, mental well-being, trait anxiety, life satisfaction, happiness, positive and negative affect, nature-relatedness and connectedness. Data on NOSCs practices, life history events that could have led to spontaneous NOSCs, and demographic data were collected for further inclusion as control variables in statistical models. Results The online questionnaire yielded 607 valid responses, (171 yet-to-be trained participants and 436 AICT-trained participants). AICT practice was found to be associated with increased self-esteem (RSE), overall connectedness (WCS) as well as all subdimensions of connectedness (WCS Self, WCS Others, WCS World). AICT practice Duration exhibited significant effects on global connectedness and all subdimensions of connectedness, self-esteem, trait anxiety (STAIT-5), and positive affect (PANAS+). Conclusions AICT seems to benefit to practitioners well-being shortly after training through increases in self-esteem and in the sense of connectedness. Prolonged AICT practice is associated with added decreased trait anxiety and increased positive affect. Further research is needed to confirm these findings with a sample including AICT-uninterested participants, and to clarify the underlying mechanisms of AICT.

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Beyond Binary Vasospasm: A Continuum Model Relating Severity and Distribution to Perfusion Deficits After Aneurysmal SAH

Thaler, C.; Meyer, L.; Tokareva, B.; Geest, V.; Kniep, H. C.; Heitkamp, C.; Dührsen, L.; Meyer, H. S.; Bester, M.; Fiehler, J.; Schlicht, F.

2026-07-18 neurology 10.64898/2026.07.16.26358285 medRxiv
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Background: Cerebral vasospasm is a frequent complication after aneurysmal subarachnoid hemorrhage (aSAH) and is associated with delayed cerebral ischemia (DCI) and unfavorable outcome. While CTA-based vasospasm grading is frequently used, its relationship with actual cerebral perfusion remains incompletely understood. This study investigates the association between vasospasm severity and distribution and territorial perfusion deficits. Methods: In this retrospective single-center study, 513 CT examinations (CTA and CT perfusion) from 194 patients with aSAH were analyzed. Vasospasm was graded per vessel segment using the CTA Vasospasm Score, and perfusion deficits were assigned to corresponding vascular territories (left/right anterior circulation, posterior circulation). Vasospasm distribution was further classified by severity and multifocality. Associations between vasospasm score and perfusion deficits were assessed using a generalized linear mixed model with binomial distribution, adjusting for Hunt & Hess grade, modified Fisher score, and days since hemorrhage. Results: Vasospasm was detected in 79.3% of examinations, and a perfusion deficit in at least one territory was present in 62.6%. The proportion of perfusion deficits increased progressively with both vasospasm severity and multifocality, ranging from 21.7-25.0% in the absence of vasospasm to 81.2-82.2% in severe multifocal vasospasm. The CTA Vasospasm Score was significantly associated with perfusion deficits in all territories (OR 1.36-1.50), with stronger associations in the anterior than posterior circulation. Conclusion: Vasospasm severity and distribution are strongly associated with perfusion deficits, supporting a continuum model of ischemic risk. However, the substantial proportion of perfusion deficits occurring independent of vasospasm suggests additional microcirculatory mechanisms not captured by CTA. CT perfusion should be considered complementary to CTA, particularly in clinically deteriorating or non-assessable patients.

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Profile of red blood cell disorders among healthy schoolchildren in the low malaria-endemic region in Indonesia

Pasaribu, A. P.; Nanine, I.; Ainur, F.; Jimanto, V.; Hutagalung, A. P.; Panggalo, L. V.; Devin, D.; Siregar, O. R.; Hasibuan, B. S.; Fahmi, F.; Trianty, L.; Coutrier, F. N.; Sasmono, R. T.; Satyagraha, A. W.

2026-07-21 epidemiology 10.64898/2026.07.20.26358521 medRxiv
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Red blood cell (RBC) disorders arose as an advantageous evolutionary response to malaria infections. In a heterozygous condition, such as in Southeast Asian Ovalocytosis (SAO), hosts are protected against severe malaria. In malaria-endemic regions, RBC disorders are presumed to be highly prevalent. Tanjung Leidong, a moderately endemic area in North Sumatra (API 1.13 in 2024), lacks comprehensive data on RBC disorder prevalence beyond G6PD deficiency. Therefore, this study aims to characterize the RBC disorders in this region as well as to characterize the anemia status in children living in Tanjung Leidong. Schoolers attending D. I. Panjaitan elementary to high school were recruited and screened for malaria by microscopy and G6PD deficiency using the STANDARD G6PD Assay. The DNA of the participants was also extracted to be genotyped for SAO, Hemoglobin E (HbE), and -thalassemia. Exclusively, G6PD-deficient DNA samples were genotyped further to determine variants. The proportion of G6PD deficiency, SAO, HbE, -thalassemia one-gene deletion, and two-gene deletion were 0.90%, 0.90%, 2.40%, 6.26%, and 0.30%, respectively. Anemia prevalence was approximately 14%, and RBC disorders were observed across children with normal to obese BMI. No malaria infections were detected by microscopy. The predominance of asymptomatic RBC disorders highlights that they are protective against malaria infection, although their protective role against malaria could not be directly assessed in this study. Both nutritional and genetic factors are found to contribute to anemia in this cohort. These findings underscore the importance of integrated screening strategies for RBC disorders and anemia in malaria-endemic settings.