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Brain Imaging and Behavior

Springer Science and Business Media LLC

Preprints posted in the last 90 days, ranked by how well they match Brain Imaging and Behavior's content profile, based on 16 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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Neuroanatomical subtypes of Long COVID reveal distinct cognitive profiles alongside longitudinal brain changes

Romero-Molina, A. O.; McCord, B.; Fernandez-Ruiz, J.; Owen, A. M.; Hernandez-Castillo, C.

2026-07-31 neuroscience 10.64898/2026.07.30.741878 medRxiv
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BackgroundLong COVID is characterized by persistent symptoms following SARS-CoV-2 infection, including cognitive deficits among its most disabling manifestations. However, their neurobiological basis is poorly understood. Previous neuroimaging studies reported structural brain alterations, but few have integrated cognitive assessment, network-based analyses, and longitudinal imaging to identify neurobiological subtypes. MethodsWe studied 42 individuals with persistent post-COVID cognitive symptoms and 14 matched healthy controls using cognitive assessment and structural MRI. Multilayer brain networks were constructed from regional morphometric measures, and hierarchical clustering identified patient subgroups. Cross-sectional and longitudinal comparisons of brain structure, cognition, and function were performed, with exploratory brain-behavior correlations over six months. ResultsClustering identified two subgroups with distinct structural patterns. Compared with controls, one subgroup showed reduced gray matter density in cerebellar lobules VIIIa/VIIIb and the putamen (p < 0.05, TFCE-corrected), whereas the other showed no significant alterations. Cognitive differences between clusters did not survive multiple-comparison correction; however, several measures showed medium-to-large effect sizes (d = 0.70-1.01), suggesting meaningful cognitive differences requiring confirmation in larger cohorts. Longitudinal analyses revealed increased medial frontal gray matter density (p < 0.05) associated with visuospatial/executive performance. ConclusionsThese exploratory findings suggest that post-COVID cognitive symptoms are associated with heterogeneous neurobiological profiles rather than a uniform pattern of impairment. Structural alterations involving cerebellar, striatal, and frontal regions may reflect distinct neuroanatomical phenotypes. Longitudinal findings suggest medial frontal structural reorganization with functional relevance. These findings support data-driven stratification for characterizing neurobiological heterogeneity in Long COVID and provide a foundation for future hypothesis-driven studies.

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The Illusion of Understanding: A Randomized Controlled Trial of LLM-Generated Lay Summaries of Brain MRI Reports

Le Guellec, B.; Bentegeac, R.; Tran, V.-T.; El Homsi, M.; Amouyel, P.; Kuchcinski, G.; Hamroun, A.

2026-08-07 radiology and imaging 10.64898/2026.08.05.26359773 medRxiv
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Background: Large language models have been proposed to improve patient comprehension of radiology reports. However, whether they improve objective understanding remains unproven. Purpose: To evaluate the effect of appending an LLM-generated lay summary to brain MRI reports on objective and subjective patient comprehension in a randomized controlled trial. Materials and Methods: In this randomized controlled trial, 2,727 adult participants from the ComPaRe e-cohort were randomly assigned to interpret six standardized brain MRI reports for headache, presented either in their native format (control; n = 1,401) or appended with a lay summary generated by an open-weights LLM (Mistral Small 3.2) (intervention; n = 1,326). The primary outcome was objective comprehension, defined as the rate of correct classification of whether the report provided a probable explanation for the headache, with ground truth established by four-radiologist consensus. Secondary outcomes included satisfaction, subjective comprehension, anxiety, and willingness to contact a healthcare professional. Generalized estimating equations accounted for repeated within-participant observations. Results: A total of 2,727 participants (mean age, 52 years +/- 15; 75.2% women) were evaluated. Objective comprehension did not differ between arms (58.3% vs 59.4%; odds ratio (OR) 0.97; 95% CI: 0.90-1.06; P = .54). The intervention significantly improved overall satisfaction (64.9% vs 36.7%; OR 3.26; 95% CI: 2.93-3.64; P < .001) and subjective comprehension (50.3% vs 24.0%; OR 3.17; 95% CI: 2.82-3.56; P < .001). High anxiety was modestly reduced (25.1% vs 26.6%; OR 0.92; P = .037). The effect on objective comprehension varied by report type (P for interaction < .001): summaries improved comprehension of symptom-explaining reports (42.4% vs 37.4%; P < .001) but reduced it for normal reports (72.5% vs 76.6%; P = .001). Conclusion: LLM-generated lay summaries appended to brain MRI reports improved patient satisfaction and subjective comprehension but did not improve objective comprehension, indicating a gap between perceived and actual understanding that should be addressed before clinical integration.

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White Matter Microstructural Alterations and Symptom Correlates in Functional Motor Disorder

Westlin, C.; Bleier, C.; Guthrie, A. J.; Finkelstein, S. A.; Maggio, J.; Godena, E.; Millstein, D.; Freeburn, J.; Adams, C.; Stephen, C. D.; Kubicki, M.; Diez, I.; Perez, D. L.

2026-08-28 neurology 10.64898/2026.08.25.26361322 medRxiv
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Background: Neuroimaging studies implicate network alterations in functional motor disorder (FND-motor), yet white matter remains poorly characterized. Objectives: To characterize white matter microstructure in FND-motor relative to healthy (HCs) and psychiatric (PCs) controls and examine symptom associations. Methods: Fifty individuals with FND-motor, 50 age- and sex-matched HCs, and 50 PCs matched on age, sex, depression, anxiety, and post-traumatic stress disorder severity underwent multi-shell diffusion MRI. Voxel-based analyses examined whole-brain white matter using diffusion tensor imaging (fractional anisotropy [FA], mean diffusivity [MD]) and neurite orientation dispersion and density imaging (NODDI) (neurite density index [NDI], orientation dispersion index, and free water fraction [FWF]) metrics. Cross-metric convergence was characterized using atlas-based tract overlap analyses and probabilistic tractography. Associations with FND symptoms and transdiagnostic physical symptoms were also evaluated. Results: Compared with HCs, FND-motor showed higher FA/NDI and lower MD/FWF, predominantly in the middle cerebellar peduncle. Compared with PCs, differences were limited to lower MD/FWF, involving the corpus callosum, middle cerebellar peduncle, and left inferior longitudinal fasciculus. Greater FND symptom severity was associated with a lower FA/NDI and higher MD/FWF in the corpus callosum and right-lateralized association and projection pathways, whereas greater transdiagnostic physical symptom burden across FND-motor and PCs was associated with higher FA and lower MD/FWF in the middle cerebellar peduncle. Conclusions: This study provides a comprehensive multi-metric diffusion-weighted characterization of white matter microstructure in FND-motor relative to both HCs and PCs - highlighting cortico-cerebellar connections via the middle cerebellar peduncle as distinct in FND-motor and associated transdiagnostically with physical symptom burden.

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Cognitive Control in Pediatric Cancer Survivors: A task-fMRI study

Nayak, S.; Nandi, S.; McKenna, F.; Henry, S.; Duong, T.

2026-06-29 neuroscience 10.64898/2026.06.23.734009 medRxiv
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Background Chemotherapy-related cognitive impairment is a well-documented concern among cancer survivors, yet the neural mechanisms underlying deficits in cognitive control remain poorly understood. This study examined group differences in brain activation during a flanker task using functional MRI (fMRI) between chemotherapy-exposed participants and healthy controls. Methods Participants (21 survivors (24.9 years old; 71.4 % female; 15 years from diagnosis) and 21 healthy controls (26.7 years old; 61.9 % female) completed a flanker task during fMRI, with congruent and incongruent conditions. Reaction time, accuracy, and Flanker scores were collected. Whole-brain group comparisons were performed for congruent, incongruent, and incongruent > congruent contrasts. Associations between the incongruent > congruent contrast and cognitive performance were examined. Results Compared to controls, the Chemo group had longer reaction times in both congruent and incongruent conditions (p < .001) and lower NIH Flanker scores (p = .01), with no differences in accuracy. They showed reduced activation in the bilateral inferior frontal gyri, supplementary motor area, and bilateral caudate, but greater activation in the right inferior temporal and cerebellar regions. The incongruent > congruent contrast correlated with increased activation in the orbitofrontal cortex, inferior temporal gyri, and fusiform gyrus with cognitive performance. Conclusions Chemotherapy-exposed participants showed cognitive control deficits and altered neural activation during a flanker task, indicating disrupted recruitment of frontoparietal and subcortical regions key for conflict processing. These findings improve understanding of neural causes of chemotherapy-related cognitive impairment and may help identify at-risk survivors and guide personalized rehabilitation.

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Reduced Functional Coordination within the Default Mode Network in Schizophrenia During Naturalistic Neuroimaging

Lyu, Y.; Shen, Y. L.; Esparza, L. C.; Reavis, E. A.; Parkinson, C.

2026-08-20 neuroscience 10.64898/2026.08.11.744321 medRxiv
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BackgroundSocial dysfunction is a major source of disability in schizophrenia, yet the neural mechanisms that contribute to impaired social understanding remain poorly understood. Converging evidence points to the role of the default mode network (DMN) in integrating social information over time to construct interpretations of social behaviors. Here, we tested the hypothesis that individuals with schizophrenia show reduced stimulus-driven coordination between brain regions within the DMN during free viewing of naturalistic social stimuli. MethodsA sample of 124 adults (schizophrenia: n=63; healthy controls: n=61) viewed naturalistic video clips during fMRI. Inter-subject functional connectivity (ISFC) was computed within the two groups. Group differences were identified via permutation testing. We also explored group differences in other brain networks to examine whether effects were specific to the DMN. ResultsIndividuals with schizophrenia showed weaker stimulus-driven coupling within the DMN compared to healthy controls, specifically between areas such as the parahippocampal gyrus, precuneus, and medial prefrontal cortex. Group differences in ISFC were specific to the DMN. Furthermore, no between-group differences emerged for within-participant functional connectivity in the DMN, suggesting that the observed effects reflect reduced stimulus-driven coordination among DMN regions when processing social stimuli rather than a more general decline in DMN connectivity. ConclusionsSchizophrenia is characterized by impaired coordination within the DMN as it dynamically integrates social information over time, which could contribute to difficulties in constructing coherent interpretations of real-world social situations. These findings suggest that disrupted stimulus-driven network coordination might underlie social cognitive impairments in schizophrenia, highlighting the value of naturalistic paradigms for revealing network-level dysfunction under conditions that closely approximate real-world experience.

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Altered Dorsolateral Prefrontal Glutamate Dynamics During Working Memory in Trauma-Exposed Individuals With and Without PTSD: A 7T Functional Magnetic Resonance Spectroscopy Study

Beaver, A. S.; Whiteman Sitts, S. E.; Camden, A. A.; Jeffirs, S. M.; Weathers, F. W.; Denney, T. S.; Reid, M. A.

2026-08-19 neuroscience 10.64898/2026.08.10.744040 medRxiv
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Post-traumatic stress disorder (PTSD) has been associated with impairments in cognitive function, including working memory, and may involve altered glutamatergic regulation in the prefrontal cortex. In this study, we used 7T functional magnetic resonance spectroscopy (fMRS) to examine dorsolateral prefrontal cortex (DLPFC) glutamate during working memory in individuals with PTSD, trauma exposure without PTSD (TE), and no trauma exposure (NT). Eighty participants (27 PTSD, 27 TE, 26 NT) underwent baseline MRS followed by fMRS during a letter n-back task. A linear mixed-effects model was used to evaluate glutamate concentrations across baseline, 0-back, 1-back, 2-back, and post-task fixation conditions. Behavioral performance was assessed using repeated-measures ANOVA for percentage correct, reaction time, and the discrimination index (d) across the 0-back, 1-back, and 2-back conditions. Glutamate differed significantly by group, condition, and the group x condition interaction. Individuals with PTSD exhibited lower glutamate than NT at baseline and during the 0-back, 1-back, and 2-back conditions. TE participants also showed lower glutamate than NT during the 1-back and 2-back conditions. Within-group analyses showed higher glutamate during the 0-back, 1-back, and 2-back conditions than at baseline in the NT group, whereas these baseline-to-task differences were limited in the PTSD and TE groups. Accuracy decreased and reaction time increased with increasing working memory load, and discrimination (d) was lower in PTSD than NT. These findings demonstrate altered DLPFC glutamate dynamics during working memory in PTSD and trauma-exposed individuals. Functional MRS provides complementary information beyond resting-state MRS by characterizing glutamatergic responses during cognitive engagement and may improve our understanding of neurochemical alterations associated with trauma and PTSD.

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Edge controllability is associated with treatment response to repetitive transcranial magnetic stimulation in depression.

Dey, S.

2026-07-17 neuroscience 10.64898/2026.07.11.737986 medRxiv
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Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD), yet variability in treatment response remains a significant challenge. Network control theory provides a framework to quantify how brain networks facilitate state transitions, but prior work has focused primarily on node level metrics. Here, I investigate whether edge based controllability of the structural connectome is associated with rTMS outcomes. Twenty five patients with treatment-resistant depression underwent diffusion MRI prior to a five week course of high frequency rTMS targeting the dorsolateral prefrontal cortex. Structural connectomes were constructed using MRtrix3 and the Destrieux atlas, and edge based controllability metrics were computed at baseline. Controllability of specific middle frontal gyrus centered edges showed significant associations with changes in HAMD-24 scores, including connections to the superior frontal gyrus, hippocampus, angular gyrus, and orbital gyrus (r = 0.470-0.597, p < 0.05). These findings suggest that edge based controllability captures circuit level properties relevant to treatment response and may inform personalized neuromodulation strategies.

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Distinct associations between thalamo-amygdala pathways and state anxiety

Cinca-Tomas, M. T.; Kosteletou-Kassotaki, E.; Dominguez-Borras, J.

2026-06-08 neuroscience 10.64898/2026.06.08.730327 medRxiv
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Neurobiological models of emotion have proposed the existence of multiple direct subcortical pathways in humans, often referred to as "low roads", linking the thalamus to the amygdala and implicated in affective function. Among these, pulvinar-amygdala structural connectivity has been associated with individual differences in anxiety and anxiety-related conditions. However, whether distinct thalamo-amygdala pathways across thalamic subnuclei differentially relate to anxiety remains unknown. Using diffusion MRI in 34 healthy participants, we reconstructed four candidate subcortical "low roads" bilaterally from the medial geniculate body (MGB), as well as the medial, inferior and lateral pulvinar to the basolateral amygdala (BLA). We then tested whether their structural connectivity strength was associated with individual differences in state and trait anxiety. Linear regression analyses revealed that fiber density in three left thalamo-amygdala pathways predicted state, but not trait, anxiety. Importantly, our results showed a functional dissociation across pathways. While fiber density in MGB-BLA and medial pulvinar-BLA pathways was negatively related to state anxiety, the inferior pulvinar-BLA tract showed the opposite association. These findings support differentiated contributions across thalamo-amygdala pathways in humans to state anxiety. The results highlight these subcortical pathways as potentially relevant neurobiological substrates for understanding anxiety and affective function. Key pointsO_LIFiber density of three left thalamo-amygdala pathways explained 24.1% of the variance in state anxiety across 34 healthy individuals C_LIO_LIFiber density in the left medial geniculate body and left medial pulvinar-amygdala pathways was negatively associated with state anxiety C_LIO_LIFiber density in the left inferior pulvinar-amygdala pathway was positively associated with state anxiety C_LI

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Longitudinal gray matter trajectories and cognitive performance during rehabilitation after moderate to severe traumatic brain injury: a longitudinal VBM pilot study

Jalal, R.; Yoon, J.; Ashley, J.; Ashley, M.; Griesbach, G.; Bartnik Olson, B.

2026-07-09 radiology and imaging 10.64898/2026.07.06.26357170 medRxiv
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Moderate-to-severe traumatic brain injury (msTBI) is recognized as a chronic and evolving neurological condition characterized by progressive structural brain changes and persistent cognitive impairment. While prior studies have demonstrated widespread atrophy following msTBI, less is known regarding the longitudinal trajectory of gray matter (GM) changes during recovery and post-rehabilitation. The current study used longitudinal voxel-based morphometry (VBM) to characterize GM volume changes over a period of 9 months, in individuals with msTBI relative to healthy controls (HC). Associations between regional GM volume and neuropsychological functioning were examined. Twenty-eight participants (14 msTBI, 14 HC) completed MRI and neuropsychological assessments across three timepoints spanning outpatient rehabilitation and follow-up. Longitudinal VBM analyses revealed significant group and time interactions within subcortical and limbic regions. Relative to HC, individuals with msTBI showed lower GM volume in these regions at baseline, with trajectories that converged toward HC values (right hippocampus) or increased relative to HC over the rehabilitation period (bilateral pulvinar), whereas the right amygdala and inferior cerebellar vermis remained persistently reduced. Significant longitudinal improvements in memory and psychomotor speed during the rehabilitation period were demonstrated in msTBI. Greater (preserved) GM volume within the right hippocampus, thalamus, and bilateral pulvinar was associated with better performance across measures of verbal memory, processing speed, executive functioning, and cognitive flexibility. These findings suggest that msTBI is associated with dynamic structural brain changes involving subcortical, limbic, and cerebellar networks, and that the rehabilitation period was accompanied by relative volumetric stabilization in these regions and by meaningful cognitive improvement.

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The Mammillary Body-Fornix Gate in Long COVID An exploratory structural and diffusion MRI study of tremor-like symptoms, internal vibrations, and neuromuscular fatigue

Ziaja, C. P.; Young, S. Y.; Stark, M. S.-C.; Zurek, G.; Sedlacik, J.; Wright, F. M.

2026-08-03 radiology and imaging 10.64898/2026.07.31.26359395 medRxiv
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Abstract Background: Long COVID frequently includes post-exertional malaise, neuromuscular fatigue, internal vibrations, tremor-like symptoms, orthostatic intolerance, sleep disturbance, cognitive dysfunction, and autonomic instability. Neuroimaging studies in Long COVID and post-infectious ME/CFS have identified abnormalities across limbic, thalamic, mesiotemporal, brainstem, cerebellar, and white-matter systems, but no single established circuit accounts for this clinical phenotype. We examined whether abnormalities cluster at the mammillary body-fornix-superior tuberal hypothalamic interface and within connected brainstem-cerebellar pathways. Methods: Structural MRI and diffusion tensor imaging were analysed in 88 participants with clinician-diagnosed Long COVID and 34 healthy controls (total N = 122). Thirty-three patients were classified as bedridden. Volumetric and diffusion analyses focused on the mammillary bodies, superior tuberal hypothalamic region, fornix, dorsal and median raphe, midbrain reticular formation, and cerebellar peduncles. Fractional anisotropy was used as an index of white-matter microstructural organisation. Exploratory clinical associations included motor impairment, proprioceptive dysfunction, autonomic symptoms, fatigue, internal vibrations, and tremor-like symptoms. Results: Three mammillary-body volume phenotypes were identified: reduced, enlarged, and control-range. Left and right mammillary-body volumes differed across groups, with large effect estimates. Segmentation showed narrowing or loss of a visible internal passage at the superior tuberal-mammillary interface, while the fornix showed altered diffusion measures and reduced tract coherence in the hypothesised gate region. Additional findings included lower superior cerebellar peduncle volume, lower middle cerebellar peduncle fractional anisotropy, and lower dorsal raphe and midbrain reticular formation volumes in Long COVID. Conclusions: The findings support an exploratory mammillary body-fornix gate model in which a vulnerable periventricular hypothalamic-limbic interface may contribute to network dysfunction in a subgroup of patients with severe Long COVID. The data do not establish direct viral invasion, a coronavirus entry route, axonal destruction, or a single causal pathway. Prospective replication with standardised acquisition, preregistered regions of interest, correction for multiple comparisons, objective movement and autonomic measures, and longitudinal follow-up is required. Keywords: Long COVID; post-COVID condition; ME/CFS; mammillary body; fornix; hypothalamus; diffusion tensor imaging; internal vibrations; tremor-like symptoms; neuromuscular fatigue; dysautonomia; brainstem

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Neural mechanisms of impaired self-compassion in depressed adolescents during social exclusion

Sun, H.; Zou, W.; Wang, D.; Zhang, Y.; Bai, C.; Li, W.; Xiao, Y.; Niu, X.; Shao, X.; Wang, X.; Hommel, B.; Yang, Y.; Wang, K.

2026-08-11 neuroscience 10.64898/2026.08.04.741714 medRxiv
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BackgroundSelf-compassion has shown to be an effective emotion regulation strategy, but its neural mechanisms remain understudied in adolescents with depression who suffer from social exclusion. This study employed event-related potentials to investigate the psychophysiological mechanisms underlying impaired self-compassion in adolescents with depression during social exclusion. MethodsThirty-seven adolescents with major depressive disorder (age = 16.46 {+/-} 2.02) and thirty-two demographically matched healthy controls (age = 16.54 {+/-} 2.29) completed a social exclusion scenario imagination task. This task presented participants with social exclusion scenarios, asking them to imagine themselves as the excluded individual and subsequently rate their negative emotions. The regulation session required participants to use self-compassionate statements to regulate their emotional responses while imagining and rate how much self-compassion they have engaged in; the non-regulation required them not to use those statements and rate their negative emotions immediately following imagination. EEG signals were recorded during the task, and the late positive potential (LPP) was analyzed to examine the neural responses associated with self-compassion regulation following social exclusion. ResultsCompared with the non-regulation condition, both groups showed less negative emotion during the self-compassion regulation condition. Adolescents with depression exhibited significantly lower self-compassion ratings than healthy controls, and showed a significantly smaller decrease in negative emotions. Higher self-compassion ratings were correlated with greater emotion regulation effect, particularly in adolescents with depression. Furthermore, LPP amplitudes were significantly higher in adolescents with depression than in healthy controls during both regulation and non-regulation conditions. ConclusionsAdolescents with depression were characterized by impairment in using self-compassion to downregulate negative emotions when confronted with social exclusion. LPP amplitudes were consistently elevated in adolescents with depression, underscoring their potential as a critical focus for psychophysiologically-informed therapies.

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The role of the Angular Gyrus in the Elaboration of Specific and Categoric Memories

Bush, A.; Lancelotte, F.; Johnen, A.-K.; Melega, G.; Guo, D.; Lopez Saquisili, C. E.; Jefferies, E.; Brooks, J.; Renoult, L.

2026-07-17 neuroscience 10.64898/2026.07.17.739117 medRxiv
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This study investigated the role of the angular gyrus (AG) and its subregions in the elaboration of specific and categoric autobiographical memories (AMs). Using a cue-word fMRI paradigm, thirty-nine participants retrieved and elaborated on episodic (specific) and semantic (categoric) memories, rating the amount of detail of each recollection. Parametric analyses revealed that AG activity, particularly in posterior AG, was positively associated with the amount of detail retrieved, regardless of memory type. Specific memories elicited greater activation in right AG subregions compared to categoric memories. These findings support the AGs involvement in both episodic and semantic memory retrieval and suggest functional differentiation between its subregions.

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Brain State Dynamics and Developmental Differences in Reading Comprehension

Zhang, J.; Liu, L.; Chen, J.; Zhao, N.; Li, H.; Yang, X.; Meng, X.; Ding, G.

2026-08-20 neuroscience 10.64898/2026.08.12.744344 medRxiv
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Reading comprehension is a complex cognitive task that involves dynamic interactions between the brain and external information. Previous studies on reading development primarily focused on localized or static brain activities. However, it remains an enigma how brain state dynamics evolve with development underlying reading comprehension. This study aims to address this issue by combining functional magnetic resonance imaging (fMRI) with Hidden Markov Model (HMM) to explore brain state dynamics. A total of 35 typically developing children and 31 adults were scanned while reading a story. Our results demonstrated a tripartite brain state organization, characterized respectively by high activities in the visual (State #1), language (State #2), and default mode network (DMN, State #3) regions. Children exhibited significantly longer dwell time in the DMN state (State #3) compared to adults, along with a higher probability of transitioning from the language state (State #2) to the DMN state (State #3). In addition, adults exhibited greater flexibility in state transitions during reading comprehension. Finally, the alignment between the dynamic states of children and the average states of adults was a significant positive predictor of their reading comprehension performance. This study provides a novel, intuitive perspective on how brain state dynamics evolve during the development of reading comprehension.

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Individualized surface parcellation enhances characterization of resting-state brain dynamics and their alterations in schizophrenia

Watters, H. N.; Furstova, P.; Tintera, J.; Spaniel, F.; Hlinka, J. N.

2026-07-27 neuroscience 10.64898/2026.07.24.740570 medRxiv
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Resting-state functional MRI (rs-fMRI) studies in schizophrenia commonly rely on normalization to volumetric templates and fixed atlas parcellations derived from neurotypical populations. While these approaches enable group-level comparisons, they may obscure individual variation in cortical organization and intrinsic brain dynamics. In this study, we compared four preprocessing and parcellation strategies across two independent schizophrenia cohorts (MRI site 1, n=159; MRI site 2, n=255) to evaluate how analytic choices affect static functional connectivity and dynamic quasi-periodic pattern (QPP) measures, including default mode-dorsal attention network opposition, QPP component rank, explained variance, event rate, and associations with PANSS symptom severity. Across datasets, individualized surface-based parcellation (IndiPar) consistently detected more pronounced QPP dynamics, stronger default mode / dorsal attention network opposition, and greater explained variance of QPPs relative to atlas-based pipelines. IndiPar also produced larger and more reproducible patient-control differences in functional connectivity and QPP event-rate measures, suggesting improved sensitivity through preservation of subject-specific organization. IndiPar additionally detected a significantly increased QPP event rate and more symptom associations in patients in the larger dataset. However, associations between fMRI measures and symptom severity showed limited stability across cohorts. These findings extend previous reports of altered resting-state activity in schizophrenia, and demonstrate that preprocessing and parcellation choices substantially influence both static and dynamic rs-fMRI results. Individualized surface-based parcellation appears to better preserve subject-specific variability and improves detection of intrinsic brain dynamics. At the same time, the limited cross-dataset replication of symptom associations highlights the challenges of deriving stable brain-symptom relationships from heterogeneous psychiatric cohorts.

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Nondual mindfulness meditation alters self representation and brain connectome in expert meditators

Czajko, S.; Zorn, J.; Abdoun, O.; Margulies, D. S.; Blanke, O.; Lutz, A.

2026-07-03 neuroscience 10.64898/2026.07.01.735757 medRxiv
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Nonduality is a foundational but conceptually elusive notion across several contemplative traditions. Nondual traditions challenge the assumption that a subject-object structure characteristic of ordinary experience is an intrinsic feature of conscious awareness. However, little remains known about the neurocognitive mechanisms associated with such experiential state. Here, we investigated how Open Presence (OP) meditation, a form of non-dual mindfulness practice, modulates bodily self-representation and large-scale brain functional organization. We combined the Full-Body Illusion Experience (FBIE), a virtual reality paradigm manipulating bodily self-processing, with resting-state functional connectivity gradient analyses in expert meditators (>10,000 hours of practice) and meditation novices. We hypothesized that OP would attenuate bodily self susceptibility as measured by FBIE and increase large-scale integration of functional brain networks, consistent with prior findings linking reduced self-boundaries and ego-dissolution to increased connectome integration. Seventy-five participants (28 experts, 47 novices) underwent fMRI scanning during OP meditation. Brain network organization was assessed using connectivity gradients and network dispersion/ eccentricity metrics. Group differences were evaluated using bootstrap statistics and support vector classification. Compared with novices, expert practitioners showed reduced global network eccentricity during OP, particularly within dorsal attention, ventral attention, and frontoparietal networks, suggesting greater large-scale integration of functional networks. These neural patterns were positively correlated with FBIE self-report measures and negatively with cognitive defusion scores, a construct thought to reflect reduced self-grasping toward thoughts and mental contents. Together, these findings suggest that nondual meditation is associated with alterations in self-representation and increased large-scale functional integration, providing candidate neural markers of nondual awareness.

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Sex-Specific Regional Brain Morphometric Correlates of Neighborhood Socioeconomic Disadvantage in Clinical Neuroimaging

Willbrand, E. H.; Vazquez, L. A.; Fromandi, M. B.; Frautschi, P. C.; Powell, T. B.; Yu, J.-P. J.

2026-08-19 neuroscience 10.64898/2026.08.10.743987 medRxiv
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BACKGROUND AND PURPOSENeighborhood-level socioeconomic disadvantage is associated with adverse brain morphometry, yet whether these associations differ by biological sex remain opaque. Here, we investigated sex-specific associations between the area deprivation index and brain morphometry derived from routine clinical MRI in a real-world clinical population. MATERIALS AND METHODSIntracranial volume-normalized regional brain volumes were extracted from T1-weighted MRI examinations performed in 2,863 consecutive clinical patients (median age 54 years [IQR 38-68]; 61.2% female) at a single academic medical center and associated community partners using an automated atlas-based segmentation pipeline. Exploratory factor analysis was applied to 131 regional brain volumes to identify latent neuroanatomical morphometric networks. Sex-stratified linear regression models examined associations between area deprivation index national percentile rank and each factor score, adjusting for age, with correction for multiple comparisons. RESULTSFactor analysis identified five neuroanatomical morphometric networks: cerebellar (ML1), frontal/executive (ML2), subcortical-ventricular (ML3), medial temporal/limbic (ML4), and posterior cortical/visual (ML5). In male patients (n = 1,112), linear regressions revealed that greater neighborhood-level socioeconomic disadvantage was significantly associated with lower factor scores on the cerebellar ({beta} = -0.006, 95% CI [-0.009, -0.003], P < .001), medial temporal/limbic ({beta} = -0.004, 95% CI [-0.007, -0.001], P = .01), and frontal/executive ({beta} = -0.004, 95% CI [-0.007, -0.0004], P = .04) networks. No significant associations were observed in female patients (all Ps [&ge;] .61). CONCLUSIONSIn a real-world clinical population, neighborhood-level socioeconomic disadvantage was associated with lower regional brain volumes across cerebellar, frontal/executive, and medial temporal/limbic neuroanatomical morphometric networks in male but not female patients. These findings suggest that the neuroanatomical correlates of neighborhood disadvantage may be sex-specific, and that sex-stratified analyses may be necessary to fully characterize the relationship between the social exposome and brain morphometry in clinical neuroimaging research.

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Stronger brain responses to acute stress reflect greater everyday stress variability

Kördel, M.; Kühnel, A.; Kimmig, A.-C. S.; Beinbauer, S.; Kogler, L.; Sundström-Poromaa, I.; Henes, M.; Kroemer, N. B.

2026-09-01 neuroscience 10.64898/2026.08.26.747278 medRxiv
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Laboratory stress tasks are widely used to assess individual differences in acute stress reactivity, yet it remains unclear how these responses correspond to stress experienced in everyday life. Here, we combined the Montreal imaging stress task (MIST) with ecological momentary assessment (EMA) over three months to assess acute and everyday stress in 67 healthy women. Greater within-person variability in everyday stress, but not average stress levels, were associated with stronger overall stress-related brain responses (b = 0.73, p = .039), with a whole-brain association particularly evident in the bilateral caudate (rROI = .32, pcluster.FWE < .001). Greater everyday stress variability was also associated with stronger stress-related functional connectivity between the ventromedial prefrontal cortex (vmPFC) and parietal and posterior medial regions (pcluster.FWE < .001). We conclude that acute neural stress responses relate more closely to fluctuations in perceived stress than to how stressed an individual feels on average. This suggests that laboratory stress tasks capture acute stress responsivity that is distinct from average stress exposure, highlighting the importance of considering what these tasks measure when interpreting individual differences in acute stress responses.

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Functional projection of cognitive functions through the human corpus callosum

Bonandrini, R.; Tettamanti, M.; Luzzatti, C.

2026-06-17 neuroscience 10.64898/2026.06.16.732587 medRxiv
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Reconciling the anatomical observation that the human brain comprises two asymmetrical halves with the phenomenal unity of the mind is a puzzle that has challenged neuroscientists since the dawn of research in the field. White-matter commissural fibres of the corpus callosum constitute a critical anatomical substrate for the functional resolution of this anatomical duality. However, the extent of the functional involvement of the callosum in different domains of cognition represents, to this day, a mostly uncharted territory. Here we present a probabilistic characterization of callosal involvement in a set of cognitive functions. In particular, we estimated structural callosal connections by means of the Disconnectome approach applied to a reference sample of healthy participants while using the macro-anatomical cortical areas contained in the Harvard-Oxford template as seeds. By multiplying structural connectivity by the involvement of each cortical area in a set of cognitive functions (as derived from Neurosynth meta-analyses), we produced a voxel-wise characterization of the corpus callosum in different functional domains. We were able to highlight greater involvement of posterior callosal regions in vision and episodic memory, greater involvement of more anterior callosal regions in decision making and working memory, with somatosensory and motor functions more related to the central dorsal portion of the callosum.

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Combined Metabolic and Microstructural Tractometry of the Superior Longitudinal Fasciculus in Healthy Brains: A Proof-of-Concept Study

Rajan, A.; Bhaduri, S.; Bera, S.; de Godoy, L. L.; Hanaoka, M.; Sheriff, S.; Ingalhalikar, M.; Loevner, L. A.; Mohan, S.; Chawla, S.

2026-08-28 radiology and imaging 10.64898/2026.08.25.26361054 medRxiv
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Introduction The superior longitudinal fasciculus (SLF) is a major association fiber bundle implicated in cognition, visuospatial attention, language, and motor control, and its impairment is linked to several neurological and neuropsychiatric disorders. This proof-of-concept study was performed with three main objectives in healthy adults. First, to fuse whole brain spectroscopic (WBSI) and diffusion MRI (dMRI) derived parametric maps along the SLF I and II segments to quantify their spatial concordance, second, to evaluate regional metabolite concentrations and microstructural properties along these trajectories and finally, to determine the relationships between the WBSI and dMRI parameters within these segments. Methods Ten healthy adults (4F, 6M; mean age 31.4 {+/-} 7.53 years) underwent 3T MRI including multi-shell high angular resolution diffusion imaging and WBSI. After preprocessing and non-linear co-registration, WBSI-derived white matter metabolite maps and neurite orientation dispersion and density imaging (NODDI) / diffusion tensor imaging (DTI) derived parametric maps were spatially aligned and projected along the centroid of reconstructed SLF I and II segments divided into 20 discrete, anatomically contiguous sections. Results A strong spatial alignment between WBSI and dMRI imaging modalities was confirmed by mutual information and Pearson's correlation analyses. Intra-subject repeatability, as assessed from a single participant scanned three times, demonstrated high tract reconstruction reliability (mean Dice similarity coefficients >0.79; track density-weighted Dice >0.97) and acceptable intra-subject coefficients of variation. Inter-subject coefficients of variation were within acceptable ranges ({approx}3-17%) for most parameters, with free water fraction (fiso) exhibiting relatively higher variability. Single and multivariate regression analyses revealed significant associations between WBSI and dMRI tract profiles: choline/creatine (Cho/Cr) and choline/ N-acetyl aspartate (Cho/NAA) ratios showed positive linear associations with intra-cellular volume fraction (ficvf) and fractional anisotropy (FA), and negative associations with mean diffusivity (MD) along bilateral SLF I, with ficvf and MD identified as the strongest combined predictors of metabolite ratios. Conclusion Co-localization/fusion of WBSI and NODDI/DTI data into one framework offers a reliable, user-independent way for mapping regional metabolite and microstructural alterations along the path of SLF. Moving forward, this image processing pipeline has the potential to enhance diagnosis and clinical assessment of neurological disorders linked to SLF damage.

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Region-Specific Delta and Alpha2 Relative Power Alterations in Male Adolescent Schizophrenia: Occipital Predominance in Resting-State EEG

Hazra, S.; Chakrabarti, N.

2026-07-20 neuroscience 10.64898/2026.07.14.738386 medRxiv
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Resting-state electroencephalography (EEG) studies consistently report increased slow-wave activity and reduced alpha power in schizophrenia. However, the regional distribution of EEG relative power (RP) across finer frequency bands, particularly in adolescent schizophrenia, remains poorly characterized. We analyzed a publicly available resting-state EEG dataset comprising 45 male adolescents with schizophrenia (SCZ; mean age: 12.3 {+/-} 1.2 years) and 39 age- and sex-matched healthy controls (CON; mean age: 12.3 {+/-} 1.3years), recorded using 16 scalp electrodes (10-20 system). Following band-pass filtering, artefact subspace reconstruction, spline interpolation, average re-referencing and independent component analysis, RP was computed for nine frequency bands across five cortical regions (frontal, central, parietal, temporal, and occipital). Group differences were assessed using three-way repeated-measures analysis of variance (ANOVA), followed by Bonferroni false discovery rate (FDR)-corrected post-hoc pairwise comparisons using estimated marginal means (emmeans). Compared to controls, the SCZ group showed significantly higher delta RP in the frontal, parietal, and occipital regions and significantly lower alpha2 RP, dissociable from alpha1, in the central, parietal, temporal, and occipital regions (all FDR < 0.001). The occipital cortex showed the greatest increase in delta RP (|Cohens d|=0.82) and the greatest reduction in alpha2 RP (|d|=0.73), with moderate-to-large effect sizes. Topographic maps demonstrated widespread delta enhancement and attenuated occipito-parietal alpha2 activity in the SCZ group. These findings demonstrate region-specific alterations in resting-state EEG relative power in adolescent schizophrenia, particularly within the occipital cortex, and suggest that regional RP may serve as a promising neurophysiological feature for early-onset schizophrenia. HighlightsO_LIResting-state EEG relative power was analyzed in adolescent schizophrenia. C_LIO_LIDelta relative power increased (occipital > parietal > frontal). C_LIO_LIAlpha2, but not alpha1, relative power decreased (occipital > parietal > temporal > central). C_LIO_LIOccipital cortex showed the largest EEG spectral abnormalities. C_LIO_LINine-band analysis improved regional spectral characterization. C_LI