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Journal of Neurophysiology

American Physiological Society

Preprints posted in the last 7 days, ranked by how well they match Journal of Neurophysiology's content profile, based on 302 papers previously published here. The average preprint has a 0.18% match score for this journal, so anything above that is already an above-average fit.

1
Flexible predictive control in human interception under visual occlusion and altered gravity

Russo, M.; Chaigneau, A.; Pezzulo, G.

2026-07-15 neuroscience 10.64898/2026.07.09.737249 medRxiv
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Interception of moving objects requires the nervous system to compensate for sensory delays and uncertainty, yet how behavior is controlled remains debated. Key questions concern whether predictive processes play any role at all and, if so, whether they rely on simple motion extrapolation or incorporate internalized physical priors, such as gravity. Another open question is whether observers adopt a single control strategy or flexibly switch between predictive and reactive control - or between different predictive strategies - depending on task demands. To address these questions, we developed a virtual interception task in which participants intercepted moving targets under systematically varied conditions. We manipulated gravity (1g vs. 0g), visual availability (occluded vs. non-occluded), target velocity, and the initial spatial configuration of the ball and paddle (same vs. opposite side). Results indicate that interception is supported by predictive mechanisms across conditions. Behavioral patterns during occluded 0g trials suggest that participants extrapolate target motion using expectations consistent with gravity. Target velocity, visual occlusion, and task geometry modulated movement strategies, indicating that predictive control is flexibly adapted to task demands. These findings support the view that interception relies on predictive internal models incorporating structured physical priors while revealing flexible, context-dependent adaptations to sensory and task constraints.

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Articulatory timing and form support distinct neural benefits during audiovisual speech

Nidiffer, A.; O'Sullivan, A.; Lalor, E. C.

2026-07-15 neuroscience 10.64898/2026.07.14.738583 medRxiv
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In noisy environments, visible speech articulations improve listening comprehension. The benefit derives from several sources, including articulatory timing and shape. Recent research has shown that visual cortex encodes a categorical representation of articulatory features and that visual speech can benefit both acoustic and phonetic feature processing separately. The present study advances the hypothesis that the shape of the articulators specifically influences the categorization of auditory speech in terms of its phonetic features. We tested this by linearly modeling electroencephalographic responses to natural, continuous speech (in noise) in terms of the acoustic and articulatory features of the speech. We compared the performance of these models in conditions where the speech was accompanied by a natural video of the speaker with their mouth visible, and a video where their mouth was covered by a dynamic ellipse obscuring articulatory shape but preserving dynamics. The dynamic mask reduced comprehension, neural processing of phonetic features, the associated multisensory benefits, and indices of visual-only linguistic processing over occipital scalp. Our findings support substantial visual involvement in speech comprehension, derived largely from the shape of the articulators. They also corroborate several proposals involving audiovisual speech processing hierarchy and the nature of the information contained in visible speech. HighlightsO_LIVisual speech provides at least two forms of information to enhance acoustic speech processing: redundant temporal dynamics and complementary articulatory information C_LIO_LICovering the mouth with a dynamic mask preserves horizontal and vertical lip movement information, but largely removes articulatory detail C_LIO_LIVisual speech with a mask preserves some general multisensory benefits but removes visual linguistic information and its ability to enhance auditory processing at the level of phonetic features. C_LI

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Brain Structural and Resting-state Functional Network Changes Following Expiratory Musculature Targeted Resistance Training in Healthy Young Adults: A Pilot Study

Krishnamurthy, R.; Schultz, D.; Wang, Y.; Barlow, S. M.; Dietsch, A. M.

2026-07-15 neuroscience 10.64898/2026.07.09.737407 medRxiv
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Multimodal imaging approaches that combine structural and functional neuroimaging provide a robust framework for examining neuroplastic adaptations that may not be captured by any single modality. The present study investigated the effects of a four-week expiratory muscle strength training (EMST) program on structural and resting-state functional connectivity in healthy young adults. Five healthy young adult males (aged 19-35 years) completed a standard four-week EMST protocol and underwent pre- and post-training imaging assessments. Structural neuroimaging included T1-weighted and diffusion-weighted MRI, which were analyzed using voxel-based morphometry, surface-based morphometry, and white-matter structural connectivity. Functional neuroimaging consisted of resting-state fMRI to assess training-related changes in functional architecture, network connectivity, and global network measures. Structural MRI analyses revealed no significant changes in gray or white matter volume, cortical morphology, or white-matter structural connectivity following EMST (all FWE- or FDR-corrected p > .05). In contrast, resting-state fMRI demonstrated a significant increase in whole-brain functional connectivity (FDR-corrected p = .036), accompanied by greater network integration, reflected in increased local efficiency and transitivity and reduced modularity. Network-level analyses showed enhanced within- and between-network connectivity in sensorimotor and cognitive circuits. Our findings demonstrate robust functional reorganization following EMST, despite the absence of detectable macrostructural or large-scale white-matter connectivity changes, at least within the timescale and sample characteristics of the current study. These results reflect early-stage neuroplasticity, both globally and within the networks underlying speech and swallowing control and suggest that functional reorganization occurs early in training and likely precedes longer-term structural modifications in these networks.

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Learned landmark associations support online visual control under degraded visibility

Roessling, G.; Fajen, B.

2026-07-15 animal behavior and cognition 10.64898/2026.07.13.738310 medRxiv
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Humans and other animals often act in environments that are at least partly familiar, where aspects of the spatial layout are known. Although such knowledge is known to support navigation and spatial cognition, its role in the online control of action remains unclear. We investigated whether drivers use knowledge of road layout to guide steering in high and low visibility and, if so, the form of such knowledge. In two simulated driving experiments (total N = 90), participants repeatedly drove winding roads containing segments with and without fog. Drivers who repeatedly experienced the same road exhibited more stable steering and lane positioning than drivers encountering novel roads, but only when visibility was reduced. These advantages were accompanied by superior performance on post-tests assessing knowledge of road geometry. We next examined the form of such knowledge by dissociating global knowledge of road layout from local associations between landmarks and road segments. Disrupting landmark-road segment associations produced the largest impairment in steering performance. The benefits of prior experience were largely preserved when road-segment order was scrambled but landmark associations remained intact. These findings show that spatial knowledge can support moment-to-moment steering control when visibility is reduced. Rather than relying on a globally coherent representation of the environment, drivers use local associations between landmarks and upcoming road geometry to anticipate future demands. More broadly, the results elucidate how familiarity with environmental structure contributes to the control of action when visual information is degraded, revealing a close interplay between spatial knowledge and visual control. Significance StatementPeople routinely act within surroundings they have encountered before, from commuting on the same streets to walking familiar hallways. Whether the spatial knowledge acquired from such experience actually shapes online visual control remains an open question. Using a simulated driving task, we show that familiarity with a road improves steering stability specifically when visibility is reduced, and that this benefit depends on learned associations between landmarks and upcoming road geometry rather than a global cognitive map. The results indicate that spatial knowledge plays a key role in moment-to-moment control, letting drivers anticipate road segments they cannot yet see. Unfamiliar roads and impaired spatial learning may compound the risks of poor visibility, suggesting a role for driver-assistance systems that leverage landmarks.

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Temperature modulation of microvascular, inflammatory and perceptual responses to mechanical loading of the skin in young and older adults and in spinal cord injury patients

Stevens, C. E.; Gordon, R. J. F. H.; Bergstrand, S.; Feldt, A.; Ghafouri, B.; Marginean, D.; Worsley, P. R.; Filingeri, D.

2026-07-15 dermatology 10.64898/2026.07.14.26358023 medRxiv
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Cooling the skin may increase its tolerance to mechanical loading and decrease the risk of developing pressure ulcers. Yet, the mechanisms of action (e.g. cooling-modulation of cytotoxic, post-occlusive hyperaemia), and their individual variability, remain unclear. We investigated the effects of different cooling levels (24{degrees}C and 16{degrees}C) on microvascular, inflammatory and perceptual responses to mechanical loading of the sacrum in healthy young (N=23) and older adults (N=19), and in spinal cord injury patients (SCI; N=10). Healthy participants underwent 45-min loading (~60 mmHg) and 20-min unloading of the sacrum, using an instrumented indenter probe set at either 38{degrees}C (control condition), 24{degrees}C or 16{degrees}C. SCI participants completed a more conservative protocol (i.e. 25min, ~45mmHg loading, 38{degrees}C and 16{degrees}C conditions). Pre-insult skin structure was characterised with optical coherence tomography; skin blood flow (SkBF) at the loading site was continuously measured, alongside thermal acceptability; and post-insult inflammatory responses were determined via skin-sebum cytokines analyses. Compared to control, 24{degrees}C- and 16{degrees}C-cooling induced a similar ~8-fold decrease in peak post-occlusive reactive hyperaemia in healthy participants, with similar temperature-related differences observed in SCI. Pro-inflammatory cytokines decreased post-insult; yet this occurred similarly across all temperatures and groups. The majority of participants ([≥]70%) rated both 24{degrees}C- and 16{degrees}C-cooling as thermally acceptable. We conclude that cooling is a potent modulator of the skin microvascular response to mechanical loading in younger, older, and vulnerable skin (SCI). These findings can inform design parameters for thermal technology aimed at preventing the loss of skin integrity (e.g. integrating 24{degrees}C-cooling in support surfaces and skin wearables).

6
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.

7
Structural Composition Enables Very Fast Learning

Riveland, R.; Pouget, A.; Latham, P.

2026-07-15 neuroscience 10.64898/2026.07.14.738142 medRxiv
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AO_SCPLOWBSTRACTC_SCPLOWThere is a gap between neuroscientific theories of learning and the speed of learning observed in many experiments. Since the Cognitive Revolution of the 1950s, compositionality has played a central role in efforts to bridge this gap. Roughly, a compositional system is one where distinct modules are combined according to a set of rules in order to accomplish complex tasks. Recently, significant progress has been made in understanding the emergence of modules in both biological and artificial neural systems. How, and under what conditions, the rules of module recombination are represented in these systems remains an open question. Here we present a neural model that can leverage these rules to dramatically speed up learning. We first show that when faced with multiple tasks which share subcomponents, models learn a low-dimensional representation that captures how subcomponents are reused across the task set. These low-dimensional spaces encode the structure that governs how modules should be recombined. Restricting learning to these subspaces greatly reduces the amount of experience needed to acquire a novel task, even when learning from reinforcement on single trials. In some cases, we can leverage the geometric regularities of these representations to reduce learning to a form of hypothesis testing over a small set of discrete points. Finally, we use this theory to model both behavioral and neural data from non-human primates performing a compositional task, and show that key features in this data are consistent with a model in which exploration during learning is restricted to these low-dimensional spaces. Overall, this work shows that the advantages of modularity in neural systems can be greatly improved upon when models represent the structure of module reuse. Both these features working in tandem lead to learning on timescales similar to biological intelligences, and hence provide a model for how such fast, adaptable behavior can emerge from systems of neurons.

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Evidence of predictive information compression in latent space in humans during speech listening

Corsini, A.; Schneider, S.; Tomassini, A.; Pedani, L.; Fadiga, L.; D'Ausilio, A.

2026-07-15 neuroscience 10.64898/2026.07.14.738305 medRxiv
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Speech perception requires transforming acoustic input into neural representations that support linguistic understanding, yet its underlying computational principles remain unclear. Classical efficient coding theories posit optimal compression of sensory input, whereas alternative accounts propose that neural systems preferentially encode information that supports prediction. A key open question is whether such predictive encoding operates on fixed inputs or on flexible internal representations. We instantiated three hypothesis models of speech processing: (i) optimal compression with deep autoencoders, (ii) predictive reconstruction with predictive autoencoders, and (iii) predictive information representation via latent-space prediction using contrastive learning. We compared resulting speech latent representations to electroencephalographic (EEG) activity during speech listening. Representations learned under the predictive information objective best explained neural latents. Crucially, only representations that selectively compressed predictive information predicted behavioral performance, suggesting that neural speech representations are structured to encode predictive information in latent space rather than to maximize compression or input prediction.

9
A geometric and dynamical theory of latent computations in biological neural networks

Dinc, F.; Blanco-Pozo, M.; Klindt, D.; Acosta, F.; Sylber, C.; Jiang, Y.; Ebrahimi, S.; Shai, A.; Tanaka, H.; Yuan, P.; Miolane, N.; Schnitzer, M. J.

2026-07-15 neuroscience 10.64898/2026.07.10.737763 medRxiv
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Many neural recordings have revealed low-dimensional sets of behaviorally relevant variables encoded within large-scale neural activity patterns. However, dimensionality reduction analyses alone cannot yield causal explanations for how networks stably implement computations that are resilient to the substantial variability of single neuron dynamics. Further, existing methods for dimensionality reduction often rely on simplifying assumptions about network structure that limit their applicability and explanatory power. To provide a theoretical framework describing the dynamics of low-dimensional computation in high-dimensional neural networks, here we introduce the concept of latent processing units (LPUs), which are architecture-agnostic computational elements operating within biological neural circuitry. Six theorems governing coding and computation by LPUs collectively provide explanations for a range of common biological findings: low-dimensional sets of coding variables can generate high-dimensional neural dynamics; many neurons have activity patterns that represent behaviorally relevant variables but exert little influence on downstream circuits; linear readouts of neural population activity commonly permit near-optimal decoding; the drift of neural representations is often substantial even while network computations remain intact. Overall, our treatment of LPUs, as enacted in network dynamics, unifies the geometric and dynamical views of neural computation under a joint framework and provides systems neuroscience with a causal account of how the brain executes reliable computations.

10
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.

11
Trait Resilience Modulates the Association Between Cortisol and Aperiodic Neural Dynamics

Lee, K. F. A.; Asharaf, S. T.; Liang, L.; Lee, T. M. C.

2026-07-15 neuroscience 10.64898/2026.07.09.737399 medRxiv
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Cortisol, our stress hormone, exerts widespread influence on neural activity. However, its influence on the aperiodic component of the electroencephalography power spectrum remains to be investigated. Given individual differences in the capacity to cope with stress and adversity, it also remains unclear whether trait resilience moderates this relationship. Hence, the present study examined whether individual differences in trait resilience moderates the association between resting cortisol and aperiodic activity. Participants (N=145) completed various self-report questionnaires (e.g., trait resilience). Electroencephalography was recorded over a 20-minute baseline period, followed by salivary cortisol collection. The results revealed a significant moderating effect of trait resilience in the occipital scalp region. Specifically, higher cortisol concentration was associated with flatter 1/f slopes amongst individuals with low trait resilience, whereas this association was reversed amongst those with high trait resilience. Overall, our findings highlight the role of individual differences in trait resilience in shaping hypothalamic-pituitary-adrenal axis-related neural dynamics.

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Laterality of subcortical structures predicts spontaneous brain dynamics

Ghafari, T.; Quinn, A. J.; Jensen, O.

2026-07-15 neuroscience 10.64898/2026.07.13.738145 medRxiv
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Subcortical structures play a key role in shaping cortical computation through distributed cortico-subcortical networks, yet it remains unclear whether individual differences in subcortical anatomy are reflected in resting-state cortical oscillations. We analysed resting-state magnetoencephalography (MEG) and structural MRI from 533 healthy adults in the Cambridge Centre for Ageing and Neuroscience (CamCAN) cohort to test whether hemispheric asymmetries in subcortical volume predict asymmetries in cortical oscillatory power. Lateralisation indices were calculated for subcortical volumes and for oscillatory power across homologous MEG sensor pairs. Cluster-based permutation testing revealed frequency-specific associations between subcortical anatomy and cortical activity. Globus pallidus asymmetry was positively associated with posterior alpha-band power lateralisation, putamen and caudate asymmetries were associated with beta-band lateralisation, and hippocampal asymmetry was negatively associated with delta-band lateralisation. These findings extend previous task-based observations linking pallidal anatomy with alpha oscillations to the resting state and demonstrate that distinct subcortical structures are associated with specific cortical frequency bands. Our results suggest that resting-state MEG captures functional signatures of cortico-subcortical organisation and provides a non-invasive framework for studying healthy ageing and disorders involving subcortical degeneration.

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Effects of acute intranasal allergen exposure on resident immune cells and sensory neurons in the mouse olfactory epithelium

Owens, R. E.; Matthews, B. E.; Mastrangelo, M. A.; Meeks, J. P.; Rowe, R. K.

2026-07-15 neuroscience 10.64898/2026.07.09.737488 medRxiv
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The main olfactory epithelium (MOE) is the primary site of olfaction and consists of multiple cell types including olfactory sensory neurons (OSNs), sustentacular cells, and immune cells. Neuroimmune interactions in epithelial tissues are critical in maintaining tissue function, but how OSNs and immune cells interact in the MOE in healthy and diseased states is largely unknown. Cellular responses in the MOE determine how and whether OSNs maintain olfactory function and are repaired or replenished following inflammatory environmental exposures. We hypothesized that acute nasal aeroallergen exposure alters immune cell function in the MOE to elicit a neuroprotective response, thereby preserving OSN function. We developed an environmental aeroallergen exposure consisting of one week of daily intranasal house dust mite extract (HDM) instillations. Spectral flow cytometry indicated only subtle changes in resident immune cells proportions and phenotypes in the MOE. Immunohistochemical evaluation did not reveal extensive changes in immune cell distribution in the sensory epithelium or lamina propria, but instead we observed increases in axonal olfactory marker protein (OMP) expression in the lamina propria, where resident immune cells are most abundant. To evaluate the effects of HDM exposure on OSN function, we performed live ex vivo Ca2+ imaging of MOEs from HDM- and sham-exposed transgenic mice using objective-coupled planar illumination (OCPI) microscopy. OSN responses to multiple odorants revealed increased chemosensory sensitivity and decreased across-trial adaptation in HDM-treated epithelia. These results indicate that short-term nasal aeroallergen exposure minimally alters immune cell phenotypes, and instead induces functional changes in OSN physiology that preserve olfactory function.

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Detecting Sleep Deprivation from Running Biomechanics Using Machine Learning Classification: A Comparison Between Wearable and Laboratory Motion Capture

Seynaeve, M.; Hendrickx, K.; Vanwanseele, B.; de Beukelaar, T.

2026-07-15 bioengineering 10.64898/2026.07.14.738397 medRxiv
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Sleep deprivation is associated with impaired endurance performance and an increased risk of running-related injury. Previous research has identified alterations in running biomechanics following a single night of sleep deprivation under laboratory conditions. However, whether these biomechanical changes can be detected using wearable technology remains unknown. Twenty-one recreationally active runners completed submaximal treadmill running under both normal sleep and total sleep deprivation conditions in a randomized crossover design. Biomechanical features were extracted simultaneously using a full-body motion capture system and a trunk-mounted wearable sensor. Five machine learning classifiers were evaluated in two classification tasks: a within-subject task using paired recordings from the same individual, and a between-subject task performed without individual baseline data. Within-subject classification consistently exceeded chance level for both measurement systems, with best accuracies of 85% for the wearable sensor (Logistic Regression) and 83% for the motion capture system (Random Forest). These findings indicate that sleep deprivation produces a systematic and individually consistent biomechanical signature during running. In contrast, between-subject classification failed across nearly all models and systems, with accuracies remaining close to chance level ([~]50%), demonstrating that inter-individual variability obscures the sleep-deprivation signal in the absence of personalized baseline data. Both systems converged on temporal organization, loading-related variables, and stride-to-stride variability as the most discriminative feature domains. Contrary to expectations, the laboratory motion capture system did not outperform the wearable sensor. Together, these findings demonstrate that individualized, baseline-referenced monitoring is essential for detecting sleep-deprivation-related changes in running gait, and suggest that a single trunk-mounted wearable sensor may provide a practical solution for real-world monitoring when paired recordings are available.

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Pediatric traumatic brain injury elicits acute neuroinflammation and long-term changes in social, cognitive, and decision-making behaviors in male and female rats

Smail, M. A.; McDonald, M. Y.; Boland, R.; Breach, M. R.; Dye, C. N.; McCloskey, J. E.; Martens, K. M.; Walters, A. E.; Zaleta Lastra, A.; Roush, J.; Yeung, E.; Weinstein, A.; Gorman-Sandler, E.; Vonder Haar, C.; Kokiko-Cochran, O. N.; Lenz, K. M.

2026-07-15 neuroscience 10.64898/2026.07.09.737495 medRxiv
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Traumatic brain injury (TBI) is one of the leading causes of emergency room visits in children under 10. Children are potentially more vulnerable to the adverse effects of TBI, given that their brains are still developing at the time of injury. Indeed, early life TBI has been linked to cognitive, social, and mood-related impairments later in life. The neuroimmune system has been implicated in adult TBI mechanisms and plays numerous key roles in brain development, making it an interesting candidate for linking pediatric TBI and prolonged behavioral alterations. Here we establish a rat model of mild pediatric TBI to investigate the relationship between early life TBI, acute responses of neuroimmune cells, and chronic behavioral dysregulation. At postnatal day 15, which is roughly equivalent to toddler age, male and female rat pups received a TBI via lateral fluid percussion injury. At 3 days post injury, TBI increased microglia and astrocyte coverage locally in the Perilesional Cortex but not in more distant corticolimbic regions. However, the hippocampus and prefrontal cortex did exhibit increased expression of the phagocytic marker CD68 in microglia, suggesting widespread glial activation even in the absence of gross coverage change. TBI also impacted mast cells, early-response innate immune cells, increasing their number and degranulation in multiple regions. In the juvenile and early adult periods, TBI impaired cognitive function, reduced sociability, and increased avoidance, with no change in anxiety-like behavior. Later in adulthood, TBI continued to impact cognitive behavior, increasing risky decision-making and impairing optimization months after injury. Together, these results suggest that pediatric TBI causes lasting cognitive and social dysregulation, possibly via acute neuroimmune alterations following injury at a critical period of brain development.

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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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Evaluating Goodness of Pronunciation and Phonological Posteriors as Objective Markers of Speech Severity in Motor Speech Disorders

Wang, F.; Utianski, R. L.; Duffy, J. R.; Barnard, L. R.; Botha, H.

2026-07-16 neurology 10.64898/2026.07.14.26358076 medRxiv
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This study examined the extent to which goodness of pronunciation (GoP) scores and phonological posterior probabilities capture perceptual ratings of speech severity in individuals with motor speech disorders (MSD). Speech recordings of the word catastrophe were obtained from 489 participants, including 333 neurologically typical controls and 156 individuals with MSD. GoP scores were derived using traditional acoustic features and self-supervised speech representations, including WavLM and XLS-R, across multiple modeling approaches, while phonological posterior probabilities were extracted using Phonet. Model performance was evaluated using Kendall's rank correlations, regression, and receiver operating characteristic analyses against speech-language pathologists' perceptual ratings of sound distortion and intelligibility. Both GoP and phonological posterior probabilities were significantly associated with perceptual ratings. Self-supervised speech representations substantially outperformed traditional acoustic features, with WavLM-based GoP using k-nearest neighbors achieving the strongest performance. Across correlation, regression, and classification analyses, GoP consistently outperformed phonological posterior probabilities for both sound distortion and intelligibility. Age and gender had minimal influence on model-derived measures or their relationships with perceptual ratings. These findings demonstrate the value of self-supervised GoP as an objective measure of speech impairment while highlighting the complementary role of phonological posterior probabilities in characterizing articulatory aspects of motor speech disorders.

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Hyperbolic Brain Modelling and Neurocognitive Decline Analysis for Disease Detection

Mukhopadhyay, A.; Halder, K.; Neogy, R.

2026-07-15 neuroscience 10.64898/2026.07.09.737540 medRxiv
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Mapping hierarchical brain networks within traditional Euclidean space causes significant structural distortion, undermining neuroimaging diagnostic frameworks. While hyperbolic models like the Poincare ball preserve these nested topologies, they demand heavy computational overhead due to intricate Mobius operations and curved geodesics. This paper introduces a highly efficient non-Euclidean framework for analyzing neurocognitive decline utilizing the Beltrami-Klein ball model. By projecting hyperbolic geodesics as Euclidean straight lines, this approach converts complex distance calculations into simple dot products, radically reducing processing demands. We validated our methodology against state-of-the-art Poincare and Lorentz baselines using datasets for Schizophrenia, Parkinsons Disease, and Alzheimers Disease. The Klein-based framework demonstrates superior performance, delivering both higher diagnostic precision and accelerated processing velocities across all three neurocognitive disorders.

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Diffusion MRI Profiles Map onto Distinct Inflammatory States After Adolescent Concussion: A CARE4Kids Study

Lim, A.; Gill, J. M.; Bickart, K. C.; Onicas, A. I.; Bazarian, J. K.; Alice, J.; Mac Donald, C. L.; Brown, A.; Cook, L.; Rivara, F. P.; Gioia, G. A.; Giza, C. C.; Dennis, E. L.; Concussion Assessment, Research, and Education for Kids (CARE4Kids) Consortium,

2026-07-20 neurology 10.64898/2026.07.17.26358354 medRxiv
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Importance: Neuroinflammation is a key component of the response to injury after concussion, but direct links between diffusion MRI metrics and specific plasma inflammatory pathways in human concussion have not been established. Objective: To examine associations between diffusion MRI metrics and pathway-level inflammatory proteomic signatures in adolescents during the subacute period after concussion. Design, Setting, and Participants: Cross-sectional analysis of data from the CARE4Kids Consortium, a six-site prospective study. Participants were English-speaking adolescents ages 11-17.99 with concussion and symptoms at 7-35 days post-injury. Data were collected between 2022-2024. Of 370 enrolled participants, 122 had both diffusion MRI and plasma proteomics available for analysis. Exposure: Advanced diffusion MRI metrics were converted to z-scores and participants were grouped by the spatial extent of outlier values (potholes and peaks) across 15 white matter regions of interest. Nine non-redundant groupings were selected for primary analysis. Main Outcomes and Measures: Pathway-level inflammatory profiles derived from gene set enrichment analysis (GSEA) of ~5,400 plasma proteins measured by Olink proximity extension assay, targeting nine hallmark inflammatory pathways spanning initiation through resolution. Persistent symptoms were assessed 64-115 days post-injury. Results: Diffusion metrics reflecting tissue disorganization were associated with upregulation of the coagulation pathway, consistent with hemostatic-inflammatory signaling. Metrics reflecting reduced tissue complexity and neurite density were associated with upregulation of interferon- and interferon-{gamma} response pathways, consistent with microstructural remodeling driven by cellular immune activation. Elevated free water content was associated with downregulation of most inflammatory pathways and trend-level transforming growth factor - {beta} upregulation, reflecting inflammatory resolution. Time since injury did not differ between groups based on free water (Kolmogorov-Smirnov p = 0.97), suggesting these differences reflect individual variability in recovery pace. Exploratory analyses showed a trend toward lower odds of persistent symptoms in the group with elevated free water content (odds ratio = 0.51, p = 0.18). Conclusions and Relevance: Multiple diffusion MRI metrics are differentially sensitive to distinct neuroinflammatory states in the subacute period after adolescent concussion. These findings suggest that diffusion imaging could serve as a non-invasive tool for inflammatory phenotyping, with potential implications for identifying patients who may benefit from targeted immunomodulatory intervention.

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Machine learning and data-driven models for predicting post-stroke dysphagia: a systematic review and meta-analysis

Mohammadi Yazdi, S.; Motevaselian, M.; Khatami, S.; Radfar, N.; jourahmad, z.; Perez, H. A.

2026-07-17 neurology 10.64898/2026.07.15.26358113 medRxiv
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Background: Post-stroke dysphagia (PSD) contributes to aspiration, pneumonia, malnutrition, prolonged hospitalization and mortality. We evaluated the discrimination, validity and readiness of machine learning and data-driven prediction models for PSD-related outcomes. Methods: Following a prospectively registered protocol (PROSPERO CRD420261419259), we searched PubMed/MEDLINE, Embase, Web of Science Core Collection, CINAHL and CENTRAL from inception through June 7, 2026. Eligible studies developed or validated multivariable prediction models for PSD-related outcomes in adults with stroke. We used PROBAST and PROBAST+AI to assess risk of bias and applicability and TRIPOD+AI to evaluate reporting. Area under the curve (AUC) estimates were pooled on the logit scale with random-effects models. Results: Twenty-four studies were included and ten contributed to meta-analysis. Four studies predicting early or incident PSD yielded a pooled AUC of 0.94 (95% CI 0.60-0.99; I2 = 95.6%). Pooled AUCs were 0.84 (95% CI 0.71-0.92) for aspiration or penetration-aspiration and 0.89 (95% CI 0.24-1.00) for severe dysphagia. The exploratory analysis of all ten risk-prediction models produced an AUC of 0.90 (95% CI 0.80-0.95), but heterogeneity was substantial (I2 = 90.3%) and the prediction interval was 0.51-0.99. Every study had high risk of bias because of analysis-domain concerns; calibration and external validation were uncommon. Conclusions: Reported discrimination was often high, but the evidence does not establish reliable performance in care. Independent validation, calibration, complete model reporting and clinical-impact studies are needed before these models guide post-stroke swallowing care. Keywords: Post-stroke dysphagia; Stroke; Deglutition disorders; Machine learning; Clinical prediction model; Area under the curve; Meta-analysis