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Frontiers in Integrative Neuroscience

Frontiers Media SA

Preprints posted in the last 90 days, ranked by how well they match Frontiers in Integrative Neuroscience's content profile, based on 15 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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Serotype-dependent differences in AAV cellular transduction rates in the hypothalamus of Arctic ground squirrels

Laughlin, B. W.; Sugiura, M. H.; Tupone, D.; Fenno, L. E.; Weltzin, M. M.

2026-05-15 neuroscience 10.64898/2026.05.13.724954 medRxiv
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Adeno-associated viral (AAV) vectors are foundational tools for dissecting brain structure-function relationships, but AAV serotype tropism varies across brain regions and species, requiring empirical validation to inform experimental design. This need is especially important in non-model organisms, where molecular neuroscience tools remain underdeveloped and access to research subjects is often limited. The Arctic ground squirrel (AGS, Urocitellus parryii) is a valuable model for studying extreme physiology, including metabolic suppression during hibernation and resistance to cerebral ischemia/reperfusion, yet no studies have evaluated AAV performance in the AGS brain. Here, we investigated the ability of AAV serotypes 1, 8, 9, and DJ to transduce the AGS hypothalamus using the human synapsin (hSyn) promoter and directly compared cellular transduction rates in a region implicated in thermoregulation and hibernation. To maximize data collection from a limited experimental population, we used a within-animal, contralateral stereotaxic injection design. Recombinant AAV vectors expressing enhanced green fluorescent protein or mCherry were delivered bilaterally, and reporter expression was analyzed four weeks later. All tested serotypes produced clear and reproducible reporter expression, establishing AAV as a viable molecular tool in the AGS hypothalamus. AAV1 produced significantly greater cellular transduction rates than AAV-DJ (17.2% {+/-} 3.5% vs 8.4% {+/-} 2.9%, paired t-test, p = 0.032). AAV8 and AAV9 showed transduction rates of 22.8% {+/-} 0.6% and 20.1% {+/-} 1.5%, respectively; however, with only two biological replicates per serotype, formal statistical comparison was not performed. These findings provide the first direct characterization of AAV-mediated gene delivery in the AGS brain and establish a foundation for future molecular interrogation of hypothalamic circuits in this extreme mammalian hibernator.

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Baseline neurological exposome characteristics in a nationwide community-based screening cohort for movement disorders in marginalized and integrated Roma populations

Fricova, D.; Belak, A.; Necpal, J.; Ferenc, M.; Giertlova, M.; Krauz, M.; Balko, R.; Baranova, A.; Buransky, M.; Drencakova, P.; Grofik, M.; Gurcik, L.; Han, V.; Haring, J.; Jaselska, S.; Jelenova, B.; Kalafusova, G.; Koren, M.; Kulcsarova, K.; Kusnirova, A.; Mosejova, A.; Mankos, J.; Matiskova, Z.; Mazerikova, Z.; Mistrik, M.; Okalova, K.; Orkuty, S.; Ostrozovicova, M.; Papikova, J.; Shabatiuk, O.; Trckova, L.; Skorvanek, M.; PURE-MD study group,

2026-07-02 neurology 10.64898/2026.06.30.26356866 medRxiv
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Background: Roma, the largest ethnic minority in Europe,, are almost absent from movement-disorder research despite living in environments with biomass combustion, poor sanitation, and unprotected water, creating a high-risk neurological exposome. Objective: To describe baseline exposome profiles in a nationwide Roma screening cohort and compare exposures between marginalized and integrated communities, and between screen-positive and screen-negative participants. Methods: A nationwide community-based program combined door-to-door recruitment of marginalized Roma with recruitment of integrated Roma through neurological services. Participants completed standardized exposome questionnaires and a brief, non-diagnostic motor symptom screen. Results: Among 541 Roma (350 marginalized; 191 integrated), marginalized participants showed greater environmental and socioeconomic disadvantage, and screen-positive individuals tended to cluster at the more adverse end of this exposome spectrum. Conclusion: This nationwide Roma movement-disorder screening cohort with exposome assessment reveals substantial disparities relevant for future clinical and genetic research.

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From Cause to Recovery: The Influence of Traumatic Brain Injury Mechanisms on Long-Term Functional Independence

Beth, M. J.; Marwitz, J.; Valadi, N.; Baweja, N.; Baweja, H. S.

2026-07-13 neurology 10.64898/2026.07.10.26357252 medRxiv
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Background/Objectives: This systematic review examines how different mechanisms of Traumatic Brain Injury (TBI) influence post-injury functional independence and aims to clarify whether recovery patterns vary by injury type. A total of 105 studies (n = 59,621) involving adults with TBI were synthesized. These findings can guide clinicians and researchers in predicting outcomes and effectively customizing rehabilitation plans. Methods: A review following PRISMA standards analyzed English-language studies published from 1975 to 2025, assessed functional outcomes using the Functional Independence Measure (FIM) or the Glasgow Outcome Scale-Extended (GOSE), converted them to z-scores, and aggregated them via a random-effects model with inverse-variance weighting to demonstrate their relevance. Results: Recreational TBIs show the highest functional independence (z = +1.77), followed by MVAs (z = +1.56), with falls (z = +0.70) and assault-related TBIs (z = -0.12) showing moderate outcomes, and TBIs with penetrating trauma (z = -1.15) indicating the most adverse results. Conclusions: TBI mechanisms appear to meaningfully influence long-term post-injury functional independence. Highlighting this can inspire clinicians and researchers to trust these insights to improve prognosis and rehabilitation strategies, underscoring their crucial role in advancing patient care.

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From Injury to Independence: Longitudinal Locomotor Recovery Patterns Following Traumatic Brain Injury - a TBI Model Systems Study

Beth, M. J.; Marwitz, J.; Murrah, W.; Valadi, N.; Baweja, N.; Baweja, H. S.

2026-07-09 neurology 10.64898/2026.07.07.26357255 medRxiv
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Background/Objectives: Traumatic Brain Injuries (TBIs) affect more than 50 million individuals worldwide each year. Approximately 90% of individuals survive and experience persistent motor, cognitive, and emotional deficits, substantially contributing to a reduced quality of life and a global economic burden. TBI mechanisms are a foundational determinant of long-term recovery. The objective of this study was to examine long-term trends in functional locomotion ability over extended follow-up durations (>10 years) across distinct TBI mechanisms. The researchers hypothesized that TBIs caused by falls or violent mechanisms would be associated with poorer functional locomotor abilities and, subsequently, lower item scores than those sustained through automotive or recreational activities. Methods: Data were obtained from the Traumatic Brain Injury Model Systems (TBIMS) database at Craig Hospital in Englewood, Colorado, the largest longitudinal TBI data repository in the world. Functional locomotion was assessed using the Functional Independence Measure (FIM) Locomotion item as the primary outcome measure. To enhance measurement precision and ensure interval-level scaling, raw FIM scores were converted into logit-based estimates of latent functional ability using Rasch modeling. Longitudinal changes of these Rasch-transformed scores were analyzed using linear mixed-effects regression, accounting for individual-level variability and unbalanced follow-up data. Results: The findings demonstrated a clinically meaningful decline in functional ability among individuals with TBIs from violent mechanisms, particularly assault-related injuries and gunshot wounds, which were associated with chronic medical complications and limited functional independence. Conversely, TBIs from bicycling, unclassified vehicular incidents, and winter sports showed significant positive estimates, possibly reflecting higher premorbid physical fitness. Motor vehicle, motorcycle, pedestrian, and fall-related TBIs demonstrated steep early gains, followed by a period of recovery stabilization and plateau. In contrast, violence-related mechanisms were characterized by consistently low median scores, with minimal long-term improvement. Falls, gymnastics, track & field, and water sports did not exhibit meaningful changes in the context of the primary hypothesis. Conclusions: TBI mechanisms play a vital role in shaping long-term functional locomotion outcomes, with violence-related TBIs associated with poorer long-term functional independence. The results have clinically important implications, supporting earlier identification of high-risk populations and the development of targeted rehabilitation strategies during periods of heightened neuroplasticity. Rasch analysis integrated with linear mixed-effects modeling yields a robust analytic framework that uncovers subtle but meaningful differences in recovery trajectories across TBI mechanisms.

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A Stronger Association Between Screen Time and Externalizing Problems in Typically Developing Children than in Children with Autism Spectrum Disorder

Miyashita, S.; Hirosawa, T.; Yoshimura, Y.; Hasegawa, C.; Tanaka, S.; Miyagishi, Y.; Naito, N.; Kikuchi, M.

2026-05-28 scientific communication and education 10.64898/2026.05.24.727542 medRxiv
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Excessive screen use is associated with childhood behavioral problems, but whether associations differ between typically developing (TD) children and those with autism spectrum disorder (ASD) is unclear. Our cross-sectional study included 108 children aged 5-9 years (61 TD, 47 ASD). ASD was diagnosed using standardized clinical instruments. Measures included parent-reported screen time (excluding TV/DVD), cognitive ability (K-ABC), and behavioral problems (Vineland-II). Screen time and externalizing problems were associated in the TD group (Spearmans {rho} = 0.361, p < 0.01), but not in the ASD group. In the regression model, screen time ({beta} = 0.40, t = 2.60, p < 0.05), ASD status ({beta} = 0.70, t = 8.30, p < 0.001), and their interaction ({beta} = -0.34, t = -2.06, p < 0.05) significantly predicted externalizing problems. Considering the diversity within the autism spectrum, future studies with larger sample sizes should consider individual heterogeneity when examining the association between behavioral outcomes and screen time.

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EEG responses to auditory stimuli are less context-dependent in preschoolers with autism spectrum disorder compared to typical development

Shao, M.; McNair, K. A.; Parra, G.; Tam, C.; Sullivan, N.; Senturk, D.; Gavornik, J. P.; Levin, A. R.

2026-04-25 neurology 10.64898/2026.04.17.26350631 medRxiv
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Individuals with autism spectrum disorder (ASD) often exhibit atypical auditory processing, yet it remains unclear whether and how the integration of simple acoustic features and contextual information is impacted in ASD. One real-world example of this integration is the auditory looming bias, the prioritized processing and perception of approaching auditory stimuli. We designed a paradigm that presents intensity-rising (looming) and intensity-falling (receding) auditory stimuli to 3-4-year-old children with ASD (n = 21), children with sensory processing concerns who do not have ASD (SPC; n = 16) and children with typical development (TD; n = 30). We recorded neural responses using electroencephalography (EEG) and found evidence of looming bias in the SPC and TD groups, as indexed by greater P1 peak amplitude during the looming than receding stimuli (TD: t(64) = 6.87, p < .001; SPC: t(64) = 4.07, p < .001). But this finding was not present in the ASD group (p = .194). Additionally, the ASD group showed reduced differentiation between looming and receding stimuli, as indicated by significantly lower Rise-Fall Difference Score (RFDS) in comparison to the TD group (Z = -3.00, padj = .008). These findings suggested altered context-dependent modulation of sensory input in ASD. Lay SummaryMany children with autism show differences in how they process sounds. Using sound patterns in which loudness gradually increased and decreased over time, like many real-world sounds, we found that children with autism showed less neural differentiation between increasing and decreasing sounds. This finding suggested that the brain may process changes in sound differently in autism, particularly in how it adjusts to sounds as they change over time, which could contribute to the sensory challenges many children with autism experience in daily life.

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Stereotaxic targeting of the Dorsal Vagal Complex

Robar, B.; Smith, H. E.; Heisler, L. K.; Filippi, B. M.; Martinez de Morentin, P. B.

2026-06-04 neuroscience 10.64898/2026.06.01.729222 medRxiv
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The Dorsal Vagal Complex (DVC) is a critical brainstem relay for visceral sensory information, sympathetic regulation, and gut-brain communication. Current weight-reducing pharmacotherapies are reported to target this brainstem region to elicit their main satiety actions. Despite its importance, no published step-by-step protocol exists for stereotaxic targeting of this region in rodents. Here, we present a detailed protocol for bilateral administration of substances into the DVC of mice using the atlanto-occipital membrane approach. We describe the surgical access, obex-referenced coordinate system, injection parameters, and we provide a histological validation. This protocol is useful for the study of DVC cells and efferent and afferent neuronal DVC circuits using common neuroscience tools such as tracings, optogenetics or chemogenetics. For complete details on the use and execution of this protocol, please refer to Martinez de Morentin et al.(Martinez De Morentin et al., 2024)

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Effectiveness of RMSSD-Based Adaptive Music Therapy (Skitii) in Reducing Treatment-Related Anxiety in Head and Neck Cancer Patients: Protocol for a Randomized Controlled Trial

Adhikari, P.; M, D.; Subramanium, V.; Krishna, T.; B, A.; Jain, C. B.

2026-05-15 oncology 10.64898/2026.05.13.26353099 medRxiv
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Background: Head and neck cancer (HNC) patients experience clinically significant anxiety and depression in 65-85% of cases during active treatment. Current supportive care lacks personalized, real-time non-pharmacological interventions. Skitii is a novel HRV-adaptive music therapy system that uses continuous RMSSD (root mean square of successive differences) monitoring via a Polar H10 chest sensor to select music in real-time, targeting parasympathetic recovery (RMSSD >=30ms). Methods: This is a prospective, open-label, randomized controlled trial (1:1 allocation) at Yenepoya Medical College Hospital, Mangalore, India. Adults aged 18-75 years with confirmed head and neck cancer (any subsite, Stage I-IV) undergoing radiotherapy and/or chemotherapy with baseline distress (HADS >=8 or NCCN Distress Thermometer >=4) will be enrolled. Participants are randomized to Skitii adaptive music therapy (20-minute sessions, 3 times daily, 3 weeks) or static music therapy control. Skitii uses a two-phase algorithm: Phase 1 (0-2.5 minutes) uses heart rate as a stress proxy for immediate music selection; Phase 2 (2.5-20 minutes) uses RMSSD to adapt music every 2.5 minutes when physiological state changes by >=20%. Primary endpoints are HADS-Anxiety score and resting RMSSD at Week 3. Sample size is 70 (35 per arm), powered at 80% to detect a 2.5-point HADS difference (SD=3.8, alpha=0.05, 15% dropout). Analysis is ANCOVA, intent-to-treat. Discussion: This is the first randomized controlled trial evaluating RMSSD-based adaptive music therapy in cancer patients. The active control design isolates the effect of the adaptive algorithm from music exposure alone. If positive, results will support a scalable, cost-effective supportive care intervention with objective physiological monitoring, and provide the clinical evidence base for CDSCO Class B medical device approval for Skitii in India, with future CE Mark and FDA applications planned. Trial Registration: Clinical Trials Registry - India CTRI CTRI/2025/11/116732

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Shortened Cortical Silent Period in Children with Attention Deficit Hyperactivity Disorder

Feier, D. S.; Gilbert, D. L.; Crocetti, D.; Migneault, K. Y.; Huddleston, D. A.; Horn, P. S.; Mostofsky, S. H.; Wu, S. W.

2026-05-28 neurology 10.64898/2026.05.26.26354157 medRxiv
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Background and Objectives In ADHD, a heterogeneous neurodevelopmental condition, behavioral and motor manifestations may reflect multiple inefficient or perturbed inhibitory systems. To evaluate Transcranial Magnetic Stimulation (TMS) evoked cortical silent period (CSP) duration, an indicator of GABA(B) receptor-mediated inhibition in motor cortex, as a potential biomarker of Attention-Deficit/Hyperactivity Disorder (ADHD) in children. Method We retrospectively analyzed TMS data, obtained using both round and figure-of-8 coils, from three cross-sectional studies conducted in 8- to 12-year-old children with ADHD (n=79; 10.7 +/- 1.5 years old) and age-and-sex-matched typically developing controls (n=96; 10.5 +/- 1.4 years old). Results Median CSP was 32% shorter in ADHD (p=0.02). Regression analysis demonstrated a relationship between shorter CSP and both lower active motor thresholds (p < 0.0001) and more severe hyperactivity symptom rating (p = 0.026). Test-retest CSP measures in 83 children showed moderate reliability (intraclass correlation 0.77 [ADHD], 0.75 [controls]). Conclusion TMS-evoked CSP may be a useful biomarker in future investigations of ADHD subtypes, domains of impaired function, or treatment outcomes.

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Population Dynamics and Short-Horizon Forecastability of the Burst-Suppression Ratio After Cardiac Arrest: Implications for Closed-Loop Brain-State Monitoring

Gorenshtein, A.; Adiniaev, Y.; Liba, T.; Klang, E.; Daniel, O.

2026-07-06 neurology 10.64898/2026.07.02.26357133 medRxiv
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Objective. Closed-loop brain-state control uses the burst-suppression ratio as its manipulated variable, assuming the signal is estimable, non-saturated, and predictable over the control horizon. Whether the injured brain's burst-suppression ratio meets these conditions under routine care is unknown. Approach. We analysed continuous electroencephalography from 607 comatose cardiac-arrest survivors across 5 hospitals in the International Cardiac Arrest Research Consortium database. For each patient we streamed one 24-minute window near 24 hours after return of spontaneous circulation, computed the algorithmic burst-suppression ratio on a 5-second grid, and derived non-saturated occupancy, within-window stability, and short-horizon forecastability. Forecastability was benchmarked against temporal-shuffle surrogates. Main results. The burst-suppression ratio occupied a non-saturated band (0.10 to 0.90) for a median of 0.250 of monitored time (95% CI 0.200 to 0.306) and sat toward suppression (median operating level 0.824). The operating level was stable within the window yet not forecastable beyond its mean: absolute out-of-sample R-squared was near zero at 1 to 5 minute horizons, matched temporal-shuffle surrogates, remained near zero in higher-occupancy windows, and was not improved by a sequence model. An autoregressive forecast showed an apparent skill of 0.46 against a persistence baseline, an artifact exposed by the surrogate analysis. Greater occupancy and a lower operating level were associated with good discharge outcome after adjustment (adjusted odds ratio 2.34 and 0.38; both p <= 0.002). Significance. Passive burst-suppression-ratio history provided little multi-minute predictive information beyond the current operating level, although that level was itself estimable and stable within the window. A closed-loop system with a reliable actuator could still regulate the signal by feedback, but model-predictive control from passive dynamics alone would add little.

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Modulation of social behavior in adult zebrafish (Danio rerio): a systematic review and meta-analysis

Muller, D. V.; Gallas-Lopes, M.; Abreu, M. B.; Arbo, B. D.; Bastos, L. M.; Frohlich, N. T.; Marcon, M.; Moraes, I. B.; da Silva, L. C. C. P.; Zurchimitten, G. R.; Herrmann, A. P.

2026-05-29 neuroscience 10.64898/2026.05.28.728488 medRxiv
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Social behavior is a fundamental phenotype across vertebrates. Zebrafish (Danio rerio) have emerged as a valuable translational model for investigating the neurobiological mechanisms underlying sociability, particularly due to their robust shoaling behavior and experimental tractability. However, the literature presents issues of reproducibility and inconsistent findings regarding the modulation of social preference and shoal cohesion in adult zebrafish. We conducted a systematic review and meta-analysis to synthesize studies evaluating the effects of pharmacological interventions that modulate the central nervous system and stress-related interventions on social behavior in adult zebrafish and, when available, anxiety-like behavior. The literature search was performed in three databases (Embase, PubMed, and Web of Science), followed by a two-step screening process based on inclusion/exclusion criteria. The included studies underwent extraction of qualitative and quantitative data, as well as risk of bias assessment. Interventions from the included studies (n = 108) were categorized according to their nature, mechanism of action, and/or therapeutic purpose, resulting in seven, four, and five meta-analyses for social preference, shoal cohesion, and anxiety-related tests, respectively. Ethanol, NMDA antagonists, pro-dopaminergic agents, and stress-related interventions decreased social preference, while stress-related interventions increased shoal cohesion. The fact that stress produced opposite effects suggests that these paradigms measure distinct sociability constructs, or perhaps are differentially modulated by confounding factors, like anxiety for example. The studies presented high heterogeneity, with prediction intervals compatible with effects in both directions, as well as methodological limitations and deficiencies in data reporting, as evidenced by the risk of bias assessment. These findings emphasize the need for well-designed new studies to validate the findings and expand the evidence on interventions that currently lack sufficient studies for quantitative synthesis.

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A clinically integrated, frameless human Neuropixels workflow

Layard Horsfall, H.; Toma, A. K.; Watkins, L.; Akram, H.; Marcus, H. J.; Stewart, A.; Chatburn, J.; Vanhoestenberghe, A.; Coughlin, B. F.; Paulk, A. C.; Cash, S. S.; Welkenhuysen, M.; Dutta, B.; Schaefer, A. T.; Kollo, M.; Muirhead, W.

2026-05-18 neurology 10.64898/2026.05.07.26351853 medRxiv
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High-density electrophysiological recording using Neuropixels probes enables single-unit resolution of human neural activity. However, integrating these systems into clinical environments remains challenging. Reported human recordings have been limited to a few centres in the United States utilising variable regulatory, sterilisation and operative techniques. Here, we present human Neuropixels recordings under a nationally managed ethical and regulatory framework in the United Kingdom. We provide a reproducible roadmap to overcome regulatory and equipment constraints. Guided by the IDEAL Stage 2a (Development) framework, we established a frameless intraoperative workflow utilising manufacturer-sterilised probes and a commercially available, clinical-grade setup for Neuropixels insertion including micromanipulator and endoscope holder. We prospectively evaluated this workflow across six participants (mean age 62.5 years) undergoing elective ventriculoperitoneal shunt surgery. Iterative failure-mitigation cycles successfully resolved key technical barriers, including neuronavigation interference and hardware instability. Assessed across three predefined endpoints (clinical safety, procedural timing, and neural data yield), the workflow achieved zero research-related adverse events and maintained a strict 30-minute procedural extension. Progressive technical refinements increased single-unit yield from 25 units during early development to 146 manually curated units. This approach provides a scalable, clinically integrated workflow to safely perform high-density electrophysiology in routine neurosurgical environments.

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Somatic yoga therapy for functional neurological disorder: An experimental pilot study examining cognitive and affective mechanisms

Millman, L. S. M.; Kennedy-Barnes, E.; Duarte, A.; Pacelli, J.; Basamh, Y.; Hodsoll, J.; Pick, S.

2026-06-29 psychiatry and clinical psychology 10.64898/2026.06.26.26356668 medRxiv
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Accumulating evidence suggests alterations in neurocognitive, affective, interoceptive and autonomic processing in functional neurological disorder (FND), yet interventions targeting these processes remain underexplored. This study investigated the possible immediate and longer-term effects of a somatic yoga intervention on cognitive control, emotion regulation, state dissociation and affect, autonomic arousal, and interoceptive processing in FND. Twenty-three adults with FND completed six weeks of somatic yoga (N=12) or six weeks of a music-based relaxation control (N=11). At baseline, post-single session, and post-six weeks, participants completed laboratory measures of sustained attention, response inhibition, interoception, emotion regulation, and state dissociation and affect. Electrocardiography and galvanic skin conductance were recorded throughout. Linear mixed effects models assessed potential change on day one, immediately pre/post a single session, and from day 1 to the end of the six-week programme. After one session, stop signal reaction time, negative affect, and heartrate decreased in both groups ({Delta}=.69-.75). After one session and at six weeks, improved sustained attention, elevated positive affect, and reduced dissociation were seen in both groups, with a larger magnitude of change in yoga ({Delta}=.50-1.10). The yoga group exhibited fewer direction errors on the response inhibition task and shorter response times on the sustained attention task, with the opposite seen in the music group ({Delta}=.50-1.17). Both in the short- and longer-term, somatic yoga might lead to adaptive changes in attention and executive functioning, arousal, state affect and dissociation.

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Persistent sensory processing and behavioral atypicalities in a mouse model of neonatal encephalopathy

Narwekar, S.; Khalifa, M.; Mulhern, H.; Simonds, N. K.; Burnsed, J. C.; Ribic, A.

2026-06-26 neuroscience 10.64898/2026.06.22.733663 medRxiv
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Neonatal hypoxia-ischemia (HI) injury is a major risk factor for lifelong cognitive impairments. Given its systemic impact, the neural mechanisms of impairments associated with HI injury remain unclear. In this study, we used a mouse model of neonatal HI injury to study its impact on goal-directed behavior and neural activity in adulthood using a head-fixed visual discrimination task. While neonatal HI injury did not impair discriminability or learning, it was associated with increased motor output in form of licking, faster reaction times and liberal decision bias, indicating an impulsive-like phenotype. These behavioral changes were accompanied by suppressed neuronal activity in the primary visual cortex (V1) and elevated cue-driven fluctuations in trial-to-trial firing variability in the prefrontal cortex (PFC), the latter of which was predictive of decision bias in HI mice. Our findings identify the long term impact of neonatal HI injury on goal-directed behavior, describe in detail the task-related patterns of neural activity in HI mice, and implicate abnormal neural variability in the PFC as a driver of impulsive-like behavior in adults that suffered neonatal HI injury.

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Clinical Characteristics and Predictors of Delayed Cerebral Ischemia in High-Altitude Aneurysmal Subarachnoid Hemorrhage

Song, Z.; Hu, C.; Wujin, D.; Duoji, Y.; Chang, X.; Cao, X.; Ren, Z.; Wu, G.

2026-06-23 neurology 10.64898/2026.06.19.26356110 medRxiv
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Background and Purpose-Aneurysmal subarachnoid hemorrhage (aSAH) remains a devastating cerebrovascular event, with delayed cerebral ischemia (DCI) representing its most feared complication. High-altitude environments induce profound cerebrovascular adaptations, yet no study has systematically examined aSAH outcomes in chronically hypoxic populations. We characterized clinical features and identified DCI predictors among aSAH patients on the Tibetan Plateau. Methods-This single-center retrospective cohort included 256 consecutive aSAH patients admitted at a tertiary neurosurgical center in Tibet (altitude 2,330-4,920 m) between 2013 and 2015. The primary outcome was DCI per consensus criteria. Multivariable logistic regression identified independent predictors; receiver operating characteristic analysis evaluated model performance. Altitude and hemoglobin were specifically evaluated as altitude-related risk factors. Results-DCI occurred in 26 patients (10.2%). In-hospital mortality was 1.6%. Most patients presented with good-grade aSAH (Hunt-Hess I-II, 73.0%; Fisher I-II, 73.1%). On multivariable analysis, only Fisher grade independently predicted DCI (odds ratio, 3.63 [95% CI, 1.14-11.52]; P=0.029). Neither altitude (P=0.697) nor hemoglobin concentration (P=0.858) was associated with DCI risk. The predictive model achieved an area under the curve of 0.812. At 1-year follow-up, 77.8% achieved favorable functional outcomes (modified Rankin Scale 0-2). Conclusions-Fisher grade is the sole independent predictor of DCI in high-altitude aSAH patients, while chronic hypoxia and compensatory hemoglobin elevation do not significantly modify DCI risk. Established sea-level prognostic frameworks remain valid in high-altitude settings, supporting their continued use for clinical risk stratification. Keywords: aneurysmal subarachnoid hemorrhage; high altitude; delayed cerebral ischemia; Fisher grade; Tibetan Plateau; prognosis

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Alterations in Early Alpha-band Connectivity emerge in Infancy among children later diagnosed with Autism

Chung, H.; An, W. W.; Wilkinson, C. L.; Davila Mejia, G.; Tager-Flusberg, H.; Nelson, C. A.

2026-07-08 neurology 10.64898/2026.06.25.26353501 medRxiv
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Autism is a heterogeneous neurodevelopmental condition, often accompanied by challenges in language and cognitive development. Although atypical functional connectivity (FC) has been reported in autism, the timing of when it first emerges and its relevance for later behavior remain poorly understood. In this study, we examined developmental trajectories of alpha-band FC and network organization across the first three years of life. We computed global alpha-band measures, including peak alpha connectivity frequency (PACF), mean FC, clustering coefficient, and modularity, to characterize nonlinear developmental trajectories from longitudinal EEGs collected from 238 children (3-to-36-month-olds) with (Autism; n=58) and without (LL-noAutism; n=180) autism. Network-based statistics (NBS-Predict) identified subnetworks contributing to group differences at each age. Exploratory graph analyses (EGA) examined associations among FC, network measures, and language outcomes. We observed that PACF increased linearly with age in both groups. Global alpha-band connectivity measures showed a similar developmental pattern, with mean global FC, clustering coefficient, and modularity all increasing rapidly during the first year in both groups. Thereafter, these measures declined in the Autism group but continued to gradually increase in the LL-noAutism group. Compared to LL-noAutism, NBS-Predict identified both hyper- and hypo-connectivity subnetworks in Autism at 3 months, followed by a hypo-connectivity subnetwork at 24 and 36 months. EGA indicated that early hyperconnectivity predicted later hypoconnectivity and was associated with subsequent network organization and language outcomes. These findings indicate that altered alpha-band connectivity trajectories are detectable in infancy in children later diagnosed with autism and may contribute to later differences in developmental outcomes.

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High school science fair: Characterizing student communication and presentation practices and their association with SEF outcomes

Grinnell, F.; Dalley, S.; Reisch, J.

2026-06-12 scientific communication and education 10.64898/2026.06.10.731420 medRxiv
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Obtaining, Evaluating, and Communicating Information is one of the eight Science and Engineering Practices in the National Research Council framework that underlies Next Generation Science Standards (NGSS). Scientific inquiry requires evaluation and communication of research findings. These skills are part of scientific inquiry itself. The goal of this study was to characterize the communication practices students used during Science and Engineering Fairs (SEFs). To examine these practices, we included the following question in our online anonymous and voluntary national high school SEF surveys carried out during 2021-22 and 2022-23, "What types of communication and presentation skills did you use in your science fair project?" The possible answers were literature review; research notebook; software to prepare tables, graphs, or images; written report; poster board preparation; PowerPoint presentation; and interview with the judges. Literature review and research notebook are part of developing research questions and data collection. Software to prepare tables, graphs, or images, and PowerPoint presentation contribute to analyzing research and developing a presentation. Written reports, poster board preparation, and interviews with the judges provide the opportunity to present the findings. Overall, 1789 students answered the question. The percentage of students utilizing these skills ranged from 17.3% doing a literature review to 67.6% preparing a poster board. On average, students indicated the use of three skills. Poster board preparation and interview with the judges were selected by students more than twice as frequently as literature review and research notebook. More positive SEF outcomes were associated with a greater number of skills used by students. Among the different skills, use of a research notebook showed the strongest association. In this paper, we present the findings and discuss implications regarding use of notebooks and other communication and presentation skills in students SEF experiences and engagement with scientific inquiry.

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Validation of video engagement assessments using electrodermal activity

Flo, E. E.

2026-05-18 scientific communication and education 10.64898/2026.05.13.723692 medRxiv
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Engagement is widely recognised as central to learning and academic achievement. Electrodermal activity (EDA) has emerged as an objective physiological indicator of engagement, as it measures sympathetic nervous system activation. However, the high cost of wearable EDA sensors has limited its widespread application. This study answers the call for affordable, high-temporal-resolution engagement measures by validating a video-based quantitative assessment method. Researchers collected 75 minutes of synchronised EDA and video data from 12 upper secondary students (aged 17-18) during regular instruction. Novel software was developed to analyse student movement and sound level for academically relevant content. The OpenPose AI model for pose estimation was also applied. This approach produced six distinct movement variables: two AI-based and four non-AI-based. Six linear models using varying movement variables and sound level were tested to predict tonic EDA levels. All models effectively predicted EDA levels, with non-AI-based movement metrics outperforming AI-based alternatives. The four non-AI-based movement models showed similar performance, indicating that compressed versions reduced computational time without sacrificing predictive power. These findings validate a novel, objective method for comparing engagement across learning activities on short timescales. This method is particularly useful for collaborative learning environments and enables controlling for movement and sound in quantitative classroom analyses.

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Surviving Severe Acute Brain injury: Care trajectories and missed opportunities

Bunker, A. L.; Engelberg, R. A.; Holloway, R. G.; Creutzfeldt, C. J.

2026-06-09 neurology 10.64898/2026.06.01.26354480 medRxiv
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INTRODUCTION Severe acute brain injury (stroke, traumatic brain injury or hypoxic-ischemic encephalopathy; SABI) is increasingly recognized as a chronic condition with care and communication needs beyond the initial hospitalization. This study aimed to characterize post-acute care patterns among SABI survivors, focusing on healthcare utilization and outpatient communication. METHODS Data were collected from a prospective cohort of hospitalized SABI patients using surveys, chart reviews, and the ED Information Exchange database. Socioeconomic disadvantage was assessed using the Area Deprivation Index (ADI), and qualitative analysis of outpatient notes examined conversations around palliative care needs and goals-of-care. RESULTS Two-thirds of patients (140/222) survived until discharge, primarily to nursing facilities (39%) or inpatient rehabilitation (38%). Among 109 with one-year follow-up, there were 89 hospitalizations, 104 ED visits, and 28 deaths. Patients from the most disadvantaged neighborhoods had significantly higher odds of rehospitalization or ED use within 30 days (OR 3.37, p=0.036). ADI was not linked to one-year utilization. seen outpatient by primary care (40%), neurology/neurosurgery (57%), and palliative care (1%), but conversations rarely revisited prognosis or goals-of-care. CONCLUSIONS Our findings highlight the need for improved long-term care planning and communication, particularly for socioeconomically disadvantaged survivors of SABI.

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Divergent Recovery Trajectories: The Influence of Injury Mechanism on Stair-Climbing Outcomes After Traumatic Brain Injury - a TBI Model Systems Study

Beth, M. J.; Marwitz, J.; Valadi, N.; Baweja, N.; Baweja, H. S.

2026-07-10 neurology 10.64898/2026.07.04.26357287 medRxiv
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Background/Objectives: Traumatic Brain Injuries (TBIs) often cause profound functional impairments, yet the influence of TBI mechanisms on stair-climbing functional independence over extended timelines remains poorly understood. This study assesses whether Rasch-transformed FIM Stairs scores varied by TBI mechanism over follow-ups spanning 10 years or more. Methods: Data from the TBI Model Systems database were analyzed. The original 30,768 data entries were reduced to 6,226, corresponding to individuals with at least 10 years of data. Functional Independence Measure Stairs data were transformed to logit units via Rasch analysis before being evaluated with a linear mixed-effects regression, incorporating TBI mechanisms, age, follow-up time, and their interactions, with random effects accounting for the participant ID and pre-injury residence location. Results: TBI mechanisms meaningfully shape very long-term stair-climbing. Gunshot wounds and pedestrian-related accidents are associated with poorer performances, whereas motorcycles, bicycles, unclassified vehicular accidents, winter sports, other sports, and fall-related TBIs demonstrated relatively better function. Age, follow-up time, and their interaction also reached significance. Conclusions: Stair-climbing recovery trajectories over extended time significantly vary by TBI mechanism, with individuals with TBIs from gunshots and pedestrian-related accidents showing the most unfavorable recoveries. These findings support the development of mechanism-specific prognostic guidance and individualized rehabilitation strategies, thereby encouraging tailored approaches to improve outcomes.