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Frontiers in Neuroimaging

Frontiers Media SA

Preprints posted in the last 30 days, ranked by how well they match Frontiers in Neuroimaging's content profile, based on 11 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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Network- and Measure-Specific Mid-Term Reliability of Multi-Echo Resting-State Functional Magnetic Resonance Imaging on a Compact 3 Tesla Scanner

Kang, D.; Welker, K. M.; Hermes, D.; Bernstein, M. A.; Huston, J.; Shu, Y.

2026-08-13 neuroscience 10.64898/2026.08.07.743542 medRxiv
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1.IntroductionUnderstanding mid-term test-retest reliability and within-subject variability is important for interpreting changes observed in longitudinal and intervention studies. The reliability of resting-state functional magnetic resonance imaging (rs-fMRI) is known to vary across measures and brain regions. However, how reliability differs across functional networks and connectivity-and amplitude-based measures, and whether multi-echo acquisition and processing modify these patterns, remain incompletely characterized. MethodsTwenty-two healthy volunteers underwent two rs-fMRI sessions 15.7 {+/-} 4.0 days apart on a Compact 3T scanner. Multi-echo, middle-echo, and independently acquired single-echo datasets were compared, with multi-echo independent component analysis additionally evaluated as a denoising approach. Functional connectivity (FC) and three amplitude-based measures were evaluated using the Schaefer 400 parcellation. Reliability was systematically assessed using intraclass correlation coefficient (ICC), within-subject standard deviation (wSD), and systematic bias at edge or regional, and network levels. ResultsAcquisition-dependent differences in reliability were generally modest. Multi-echo acquisition and processing increased functional connectivity strength and the magnitude of amplitude-based measures and improved inferior cortical coverage, but these enhancements did not consistently translate into substantially higher ICC or lower wSD. In contrast, reliability showed clear network-dependent differences. FC reliability varied markedly across network pairs and was not explained by connectivity strength alone; pairs involving the default mode and control networks generally showed more favorable profiles than several somatomotor and visual network pairs. Fractional amplitude of low-frequency fluctuations (fALFF) also showed network-dependent reliability, with the most favorable regional reproducibility observed in the default mode and control networks and lower reproducibility in the somatomotor and visual networks. ConclusionThese findings provide practical mid-term reliability benchmarks for rs-fMRI on a Compact 3T scanner and show that measurement stability varies more clearly across measures and functional networks than across acquisition approaches. Key pointsO_LIMid-term test-retest reliability varied more clearly across resting-state measures and functional networks than across acquisition and processing approaches. C_LIO_LIMulti-echo acquisition and processing enhanced functional connectivity strength, amplitude-based signal magnitude, and inferior cortical coverage but did not consistently improve reliability. C_LIO_LIFunctional connectivity strength and fractional amplitude of low-frequency fluctuations showed distinct network-specific reliability profiles, with more favorable reproducibility in default mode and control networks than in several somatomotor and visual networks. C_LI

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From Channel-Pair Connectivity to Brain Networks: An Open Graph Theoretical Pipeline for fNIRS Hyperscanning

Moshe, Y. H.; Sharma, M.; Dahan, A.; Gvirts, H.

2026-08-28 neuroscience 10.64898/2026.08.25.746918 medRxiv
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Despite the growing use of functional near-infrared spectroscopy (fNIRS) hyperscanning to record brain activity simultaneously from interacting individuals in naturalistic settings, most analyses quantify functional connectivity separately for each channel pair. The resulting collection of pairwise estimates is difficult to integrate into a network-level characterization of intra- and inter-brain organization. Here, we present an open, configuration-driven Python toolkit that transforms preprocessed fNIRS hyperscanning time series into functional connectivity graphs. The toolkit constructs a bipartite inter-brain network for each dyad and separate intra-brain networks for each participant, computes node- and graph-level measures, and exports adjacency matrices, edge lists, analysis-ready summary tables, reproducibility metadata, and standardized visualizations. Dataset-specific parameters, including directory structure, participant naming, channel selection, epoch extraction, and edge-retention criteria, are defined in a human-readable YAML configuration file, enabling the same workflow to accommodate differently organized datasets without changes to the source code. We illustrate the pipeline using a representative recording from a mother-infant fNIRS hyperscanning dataset and present the resulting network outputs. The toolkit provides a reproducible framework for moving from pairwise functional connectivity estimates to network-level analyses of dyadic and individual brain organization.

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Testing the reliability of novel Voxel Placement approaches for Magnetic Resonance Spectroscopy

Chhabra, H.; Hehl, M.; Cuypers, K.; Dydak, U.; Nitsche, M. A.; Genc, E.; Burke, M.

2026-08-21 neuroscience 10.64898/2026.08.11.744164 medRxiv
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BackgroundSingle-voxel magnetic resonance spectroscopy (MRS) is a non-invasive method for measuring clinically and cognitively relevant metabolites. Reliable measurements require precise voxel placement across sessions and participants. We developed a scanner-console-based approach to improve voxel placement precision. MethodsIn a crossover design (n=7; six sessions each), we compared test-retest reliability of three voxel placement methods in a reference benchmark (left parietal cortex) and a technically challenging region (left ventromedial prefrontal cortex). Methods included (1) conventional anatomy-based placement, (2) mask-guided real-time positioning (MGRP), and (3) semiautomated session-locked voxel repositioning (SSVR). Resting-state MRS data were acquired using PRESS and MEGA-PRESS. Within-subject reliability of voxel placement and metabolite concentrations, namely, total N-acetylaspartate (tNAA), total Creatine (tCr), GABA (gamma-aminobutyric acid), and Glx (glutamate + glutamine) are reported using the coefficient of variation (CV), the intraclass correlation coefficient (ICC), minimal detectable change (MDC), and the spatial overlap. ResultsSSVR markedly improved voxel placement reliability, increasing spatial overlap (up to 88%) and achieving near-perfect geometric reproducibility (ICC = 0.99) compared to conventional anatomy-based placement and MGRP. SSVR improved tissue composition consistency and reduced metabolite variability in the technically challenging region (variability reduction of [~]70% tCr, [~]59% tNAA, and [~]51% Glx) while further refining already stable measurements in the benchmark region (tNAA from [~]15% to [~]10%). ConclusionBoth MGRP and SSVR improved voxel placement and metabolite measurement reproducibility compared with conventional anatomy-based placement. SSVR further enhanced within-subject reproducibility across repeated sessions, particularly in the technically challenging region, providing a robust approach for longitudinal single-voxel MRS studies.

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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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Predicting Worry Mental States using Long Short-Term Memory (LSTM) Recurrent Deep Neural Networks

Campion, J.-Y.; Desmidt, T.; Gross, J. J.; Tudorascu, D. L.; Andreescu, C.; Karim, H. T.

2026-08-17 psychiatry and clinical psychology 10.64898/2026.08.14.26360462 medRxiv
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Severe worry is a transdiagnostic syndrome associated with significant morbidity in older adults. In this study, we aim to infer worry-related mental states though brain activity timeseries. We acquired fMRI on two cohorts (N=116 and N=88), using an in-scanner worry induction and reappraisal task. We trained a recurrent long short-term memory (LSTM) neural network, using the first cohort as the train/validation and the second cohort as an independent test set. We predicted worry induction, reappraisal, and neutral states (area under the curve 0.89, 0.77, 0.91 for the test set and 0.78, 0.63, 0.81 for the independent set). The model was most accurate when participants reported high worry during the induction state. Dorsal attention network, and networks seeded on the anterior hippocampus, and supplementary motor area were most important for predicting worry states. The LSTM approach may have critical translational implications for identifying and treating severe worry in older adults.

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Biomarker Fidelity Score - A Quantitative Framework for Individual-Level Validation of Explainability Methods in 3D Alzheimer's Disease MRI Classification

Lepcha, D. C.; Ali, A.; Martin, S. A.; Syed-Abdul, S.

2026-08-20 neuroscience 10.64898/2026.08.15.744687 medRxiv
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Explainability methods applied to deep learning models for Alzheimer's disease neuroimaging produce attribution maps that vary substantially across methods and architectures, yet no validated quantitative framework exists for determining which method most faithfully localises attribution signal within established AD biomarker anatomy at the individual subject level. Existing validation approaches rely on group-level comparisons or qualitative visual inspection, leaving individual-level biomarker alignment uncharacterised. We introduce the Biomarker Fidelity Score (BFS), a quantitative tool measuring spatial overlap between individual-level 3D explainability attention maps and atlas-registered AD-relevant neuroimaging ROIs across thirteen anatomically defined structures including hippocampus, entorhinal cortex, amygdala, and parahippocampal gyrus. Five explainability methods (GradCAM++, Integrated Gradients, DeepSHAP, LRP, ScoreCAM) were benchmarked across three volumetric architectures (3D ResNet-18, DenseNet-121, Swin-UNETR) on 327 balanced ADNI-3 subjects. Integrated Gradients achieved the highest BFS across all architectures while GradCAM++ consistently showed the lowest biomarker alignment (all p<0.001, Friedman test). The complete BFS pipeline replicated these rankings without retraining on 207 independent OASIS-3 subjects, with maximum absolute difference of 0.0005 across all fifteen method-architecture combinations and Spearman rank correlation of 0.964 between cohort rankings. By offering an externally validated, individual-level, biomarker-grounded quantitative standard, BFS equips clinicians and AI developers with practical guidance for selecting trustworthy explainability methods in AD neuroimaging.

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Precision Confidence Mapping: An approach to determining individualized network topography with limited data

Ramirez, J. S. B.; Hermosillo, R. J. M.; Moser, J.; Grimsrud, G. J.; Tarakci, E.; Pham, H. H. N.; Godfrey, K. J.; Sjoberg, H.; Morgan, V.; Madison, T. J.; Laumann, T. O.; Gordon, E. M.; Dosenbach, N. U. F.; Weldon, K. B.; Miranda-Dominguez, O.; Tervo-Clemmens, B.; Nelson, S. M.; Fair, D. A.

2026-08-21 neuroscience 10.64898/2026.08.17.744952 medRxiv
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Individualized resting-state functional magnetic resonance imaging (rs-fMRI) is increasingly used to guide neuromodulation target selection. However, clinical scans are often short and noisy, and standard pipelines for functional network identification do not provide information about confidence of network assignment. With limited data, unstable network assignments can misdirect stimulation toward off-target regions, making it critical to know which assignments can be trusted. We developed Precision Confidence Mapping (PCM), a bootstrap-based framework that makes this uncertainty explicit and actionable. PCM repeatedly resamples the time series and reruns network detection to estimate how consistently each vertex is assigned to a given network. The resulting confidence maps can be thresholded to exclude less stable regions. We evaluated PCM across scan durations from 5 to 70 minutes using positive predictive value (PPV) as the primary measure of network-assignment precision. PPV quantified the proportion of vertices assigned to a network that received the same label in an independent within-subject 70 minute reference map. Confidence thresholding markedly improved PPV across functional networks, with the largest gains for short scan durations. Compared with standard network assignment, PCM significantly increased agreement with this independent reference. Within-subject agreement remained greater than between-subject agreement, indicating that thresholding preserved individual-specific network topography. These precision gains came with modest reductions in reference-network coverage, particularly at shorter scan durations. This tradeoff may be acceptable for neuromodulation applications that prioritize minimizing off-network assignments. By adding a reliability layer to individualized mapping, PCM supports more cautious and precise neuromodulation targeting under real-world clinical scan constraints.

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A multi-b-value test-retest diffusion MRI brain dataset for model validation and reproducibility assessment

Pieciak, T.; Guadilla, I.; Ciupek, D.; Navarro-Gonzalez, R.; Merino-Caviedes, S.; Villacorta-Aylagas, P.; Magdaleno Humayor, L.; Villa Aparicio, M.; Rueda-Ramos, J.; Santiesteban Mendo, R.; Moro Boyero, R.; Tristan Vega, A.

2026-08-27 neuroscience 10.64898/2026.08.23.746449 medRxiv
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Transparent assessment of diffusion magnetic resonance imaging (dMRI) techniques with empirical verification of confounding factors requires adequately designed protocols and collected datasets. Publicly available diffusion-weighted MR datasets often provide limited sampling across b-values, making it difficult to study optimal acquisition protocols or the relationships between different processes occurring in brain tissue. In this work, we introduce a new densely sampled longitudinal test-retest diffusion-weighted MR dataset of the brain. Our dataset was collected from eleven healthy volunteers, each scanned four times: two sessions on consecutive days, which form the test data, followed by two additional sessions completed one week later (retest data). The data were acquired using twenty-two b-values ranging from 10 to 3000 s/mm2, along with structural T1-weighted scans. Potential applications of the dataset include, but are not limited to, assessing longitudinal reproducibility and reliability of quantitative metrics, evaluating robust and outlier-resistant estimation techniques, investigating experimental factors affecting estimation procedures, and verifying optimal acquisition protocols for different signal models. The dataset is publicly available in raw and fully preprocessed variants.

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Multimodal Transformer Modeling of Rapamycin Treatment in Alzheimer's Disease via Random Forest Feature Filtering

Wang, C.; Woods, C.; Nguyen, T.; Liu, J.; Lin, A.-L.; Cheng, J.

2026-08-26 health informatics 10.64898/2026.08.22.26361114 medRxiv
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Alzheimer's Disease (AD) remains a leading cause of cognitive decline with no known cure, motivating the development of therapies that slow neurodegeneration. Rapamycin, an FDA-approved inhibitor of the mammalian target of rapamycin (mTOR) pathway, has demonstrated promising anti-aging and neuroprotective effects. However, characterizing its treatment effects and identifying the biological factors that contribute to treatment response remain challenging because of complex interactions across multiple biological systems and the limited availability of patient data. In this work, we propose a three-stage multimodal deep learning framework called TreatmentFormer for predicting rapamycin treatment status from heterogeneous biomedical data including both brain imaging data and tabular data (e.g., microbiome profiles, blood-based biomarkers, cerebral blood flow measurements, and clinical variables (e.g., gender, age, and body mass index)). First, a Random Forest-based feature selection module reduces noise in high-dimensional tabular data while preserving representation across modalities. Second, modality-specific encoders map imaging and tabular inputs into a shared latent space via self-supervised contrastive learning, enabling alignment across modalities. Finally, a transformer-based architecture integrates these representations to capture cross-modal interactions and perform treatment classification. Evaluated on a cohort of 23 participants with baseline and post-treatment timepoints, TreatmentFormer achieves an average prediction accuracy of 71.25\% across 10 independent test runs. Despite the challenges of small sample size and heterogeneous data, the model demonstrates stable and consistent performance. Post hoc SHAP-based feature analysis further identifies key biomarkers associated with treatment response, particularly within blood-based and inflammatory modalities. These findings demonstrate that combining feature selection with multimodal representation learning provides a promising and robust approach for modeling treatment effects in small-sample biomedical studies. Importantly, this framework may have significant implications for clinical research and medical applications by identifying the biological features and quantitative measurements that drive individual responses to rapamycin. Such insights could facilitate the development of predictive biomarkers, improve patient stratification, and ultimately inform future approaches to AD diagnosis and therapeutic development.

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Anomalous Emotion Regulation & Reward Network Connectivity Underlying Suicidal & Non-Suicidal Self-Injury in Early Psychosis

An, C. L.; Dhaher, S.; Kilicoglu, M.; Turner, J. A.; Westlund Schreiner, M.; Moe, A.

2026-08-07 neuroscience 10.64898/2026.08.05.743099 medRxiv
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BackgroundIndividuals with early psychosis (EP) have elevated risk for suicide, the leading cause of death in the first five years following diagnosis. Non-suicidal self-injury (NSSI) significantly predicts suicidal behavior, yet studies of self-injury often exclude participants with psychosis. We investigated effective connectivity in emotion regulation and reward network regions among participants with lifetime history of NSSI or suicide attempt (SA) with and without EP. MethodsResting-state fMRI data were acquired for 23 individuals with EP and 34 non-clinical controls (NCC). We estimated effective connectivity models for regions implicated in the self-injury literature: middle cingulate cortex (MCC), posterior cingulate cortex (PCC), caudate, putamen, posterior superior temporal gyrus (STG), orbitofrontal cortex (OFC), and insula. There were 3 models characterizing different groupings: diagnosis (NCC vs. EP); NSSI (present[+], n=21 vs. absent[-], n=36); and SA (present[+], n=21 vs. absent[-], n=36). ResultsEP was associated with increased STG to PCC and insula to putamen connectivity. NSSI+ (n=7 NCC, 14 EP) had increased PCC to insula lagged connectivity and increased contemporaneous bilateral putamen activity, relative to NSSI- (n=27 NCC, 9 EP). NSSI was positively correlated with lagged insula to putamen activity (p=0.016). SA and NSSI were associated with reduced PCC to caudate connectivity. ConclusionNSSI is associated with increased connectivity within emotion regulation regions and disrupted connectivity between emotion regulation and reward networks modulated by the STG and striatum. Findings are consistent with broader self-injury literature, supporting the utility of using similar interventions from other disorders to address self-injury within EP.

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Benchmarking Open-Source Vision-Language Models for Brain Metastasis Assessment on Single-Slice Contrast-Enhanced MRI

Kim, J.; Kim, B.-s.; Ko, J. S.; Dong, J.; Youn, S. Y.; Jang, J.; Ahn, K.-J.

2026-08-26 radiology and imaging 10.64898/2026.08.24.26361169 medRxiv
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Purpose Open-source vision-language models (VLMs) can be locally deployed without external internet access, potentially enhancing data security. This study compared the diagnostic performance of general-purpose and medical-purpose open-source VLMs and evaluated their ability to characterize brain metastases on contrast-enhanced (CE) MRI. Materials and Methods Sixty lesion-positive axial CE T1-weighted images and sixty matched lesion-negative images from 60 patients were analyzed using three general-purpose VLMs-InternVL3-8B, Qwen2.5-VL-7B-Instruct, and MiniCPM-V-4.5-and three medical-purpose VLMs-MedGemma-4B-it, LLaVA-Med v1.5, and HuatuoGPT-Vision-7B. Lesion detection performance was assessed using sensitivity, specificity, and balanced accuracy. On lesion-positive images, accuracy was evaluated for lesion count, laterality, anatomic location, enhancement pattern, necrosis, vasogenic edema, and mass effect. Model differences were assessed using Cochran's Q tests followed by pairwise McNemar tests with Benjamini-Hochberg correction. Results The median age of the study patients was 67 years (IQR, 61.0-70.5 years), and 35 patients were male (58.3%). MiniCPM-V-4.5 showed the most balanced diagnostic performance, with a sensitivity of 78.3% (95% CI, 66.4-86.9%) and a specificity of 85.0% (95% CI, 73.9-91.9%), and significantly higher balanced accuracy than all other models. Significant overall differences were observed for lesion count, laterality, location, enhancement pattern, necrosis, and mass effect, but not for vasogenic edema (FDR-adjusted P = 0.056). HuatuoGPT-Vision-7B and MedGemma-4B-it showed relatively consistent accuracy across multiple image assessment tasks, although their performance remained modest. Conclusion Our study demonstrated substantial heterogeneity in the performance of open-source VLMs in brain metastasis evaluation, and medical-purpose VLMs did not outperform general-purpose VLMs.

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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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10.5 Tesla High-Resolution Macaque Brain MRI for In vivo and Ex vivo Connectivity Studies

Warrington, S.; Selim, M. K.; Tendler, B. C.; Moeller, S.; Farooq, H.; Wu, W.; Pisharady, P. K.; Adriany, G.; Auerbach, E. J.; Folloni, D.; Bratch, A.; Manea, A. M.; Grafft, T.; Jungst, S.; Harel, N.; Waks, M.; Pestilli, F.; Yacoub, E.; Lenglet, C.; Ugurbil, K.; Heilbronner, S. R.; Miller, K. L.; Jbabdi, S.; Zimmermann, J.; Sotiropoulos, S. N.

2026-08-26 neuroscience 10.64898/2025.12.22.695917 medRxiv
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Mapping brain connectivity in primates remains a major challenge due to difficulties in resolving microscopic white matter architecture, while maintaining whole-brain coverage. Increasing imaging spatial resolution is key for disambiguating fibre configurations within smaller anatomical volumes. Here, we present novel developments that allow high-resolution diffusion MRI of the macaque brain using one of the world's highest-field human MRI scanners operating at 10.5 Tesla, allowing both in vivo and ex vivo macaque brain imaging. Our approach achieves very high spatial resolution across both tissue states, (up to 580 m)3 in vivo and (300 m)3 ex vivo, with diffusion weighting up to b = 6000 s/mm2. We detail methodological advances in data acquisition, image reconstruction, processing and whole-brain tractography that overcome critical challenges associated with ultra-high-field imaging. This work establishes a new framework for high-resolution in vivo and ex vivo neuroimaging of the NHP brain at 10.5 T using a human bore scanner, paving the way for subsequent analyses of brain connectivity across species and tissue states at unprecedented detail. The dataset, along with all processing pipelines, containerised workflows, and reusable web services, is openly shared to support reproducibility and future integration with microscopy for studying white matter microstructure and connections at the mesoscale.

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Single-shot simultaneous BOLD and velocity-encoding MRI for functional and slow-flow imaging

Widmaier, M. S.; Chao, T.-H.; Emir, U.; Chang, W.-T.

2026-08-11 neuroscience 10.64898/2026.08.05.743034 medRxiv
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Cerebrospinal fluid (CSF) motion is coupled with global blood oxygenation level-dependent (BOLD) fluctuations, but the spatial relationship between regional brain activity and CSF dynamics remains poorly understood. Here, we developed a single-shot BOLD-VENC sequence that combines gradient-echo BOLD imaging with spin-echo velocity encoding following the same RF excitation, enabling simultaneous measurement of brain-wide BOLD activity and spatially resolved slow CSF velocity at 3T. The velocity measurement was validated in a slow-flow phantom and in five healthy participants using paced-breathing, breath-holding, and visual-stimulation experiments. Phantom measurements showed strong agreement with prescribed velocities over 0.1-1.0 mm/s (R2 = 0.93-0.98). In vivo measurements demonstrated respiratory- and cardiac-dependent changes in CSF velocity magnitude and direction across the ventricles and cortical subarachnoid spaces (SAS). The established coupling between the negative derivative of the global BOLD signal and fourth-ventricle CSF inflow was reproduced, with a peak lag of 0.9 s. Global BOLD fluctuations were also coupled with spatially distributed CSF velocity changes across ventricular and cortical CSF spaces, with a similar peak lag of 1.2 s. During visual checkerboard stimulation, BOLD-CSF velocity coupling was localized primarily to the SAS surrounding the activated visual cortex, demonstrating a regional relationship between local BOLD activity and nearby CSF motion. These findings establish the feasibility of simultaneous BOLD and slow CSF velocity imaging and extend BOLD-CSF coupling from a global measure toward spatially resolved assessment of hemodynamic-CSF interactions.

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Experimental hypoxia to probe neuro-metabolic and vascular dysregulation in ME/CFS: a multimodal proof-of-concept MRI study

Bader, V.; Estermann, K.; Niess, E.; Zrzavy, T.; Fischmeister, F.; Haider, T.; Ludwig, B.; Barkhof, F.; Mutsaerts, H.; Kasprian, G.; Niess, F.; Bogner, W.; Kollndorfer, K.; Haider, L.

2026-08-12 radiology and imaging 10.64898/2026.08.10.26359935 medRxiv
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Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a poorly understood, debilitating multisystem condition. Converging evidence implicates impaired cellular bioenergetics, neuroinflammation and defective neurovascular coupling that may manifest as "virtual hypoxia" only under physiological stress. Methods We performed a single-session multimodal 3T MRI study combining brain volumetry, arterial spin labelling (ASL) and multivoxel proton magnetic resonance spectroscopy under normoxia and two controlled hypoxic challenges (oxygen saturation 87 {+/-} 3%) in 26 ME/CFS patients and 27 age- and sex-matched healthy controls. Results After intracranial-volume normalization, patients showed a reduced brainstem volume (1.46 0.14 vs. 1.55 {+/-} 0.18 % of eTIV; p = 0.013, FDR-p = 0.039), whereas deep grey matter and whole-brain parenchymal fraction did not differ between groups. Whole-brain cerebral blood flow (CBF) rose under hypoxia in both groups (controls +4.8 {+/-} 13.0%, patients +3.7 {+/-} 11.7%), with greater initial inter-individual variability in patients (patient-to-control variance ratio up to 6.94; FDR-p = 0.001). Thalamic lactate-to-creatine (Lac/tCr) ratios increased with hypoxia in controls (FDR-p = 0.028) but were already elevated at normoxia in patients (0.171 vs. 0.135; FDR-p = 0.021) and did not rise further (FDR-p = 0.38). In exploratory analyses, patients showed exaggerated inverse coupling between thalamic total N-acetylaspartate (tNAA/tCr) and white-matter CBF. Conclusions These findings provide in vivo evidence of impaired neuro-metabolic and vascular adaptive capacity in ME/CFS, supporting the virtual hypoxia hypothesis and highlighting candidate imaging markers for stratification that warrant validation.

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Schizophrenia-like neurodevelopmental pathology reshapes experience-dependent brain network remodeling following adolescent alcohol exposure

Houdant, C.; Khalilian, M.; Fortineau, Z.; Rouanet, C.; Leuillier, E.; Madeline, M.; Fall, S.; Aarabi, A.; Jeanblanc, J.; Naassila, M.

2026-09-01 neuroscience 10.64898/2026.08.26.747060 medRxiv
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Background Alcohol use disorder (AUD) is highly prevalent in schizophrenia, yet the neurobiological basis of this vulnerability remains poorly understood. Neurodevelopmental models suggest that pre-existing brain dysconnectivity may increase vulnerability to AUD. We therefore tested whether schizophrenia-like neurodevelopmental pathology alters how alcohol-related experience is incorporated into large-scale brain networks. Methods Resting-state functional connectivity was assessed in male Sprague-Dawley rats (n = 18-21/group) with neonatal ventral hippocampal lesions (NVHL), a neurodevelopmental model of schizophrenia, and sham-operated controls, with or without voluntary adolescent alcohol exposure. Functional connectivity was assessed using seed-to-voxel and seed-to-seed analyses within a cortico-striato-limbic network. We additionally examined whether individual alcohol intake during adolescence predicted adult functional connectivity according to neurodevelopmental status. Results NVHL and adolescent alcohol exposure independently produced predominantly hypoconnected cortico-striato-limbic networks. However, alcohol exposure did not exacerbate NVHL-associated dysconnectivity but instead induced a distinct network reorganization characterized by functional hyperconnectivity. Although alcohol intake was comparable between groups, dose-dependent relationships between adolescent alcohol consumption and adult functional connectivity were observed in sham animals but were absent or markedly attenuated in NVHL rats. These effects were primarily centered on prelimbic cortex connectivity with the amygdala, hippocampus, and dorsal striatum, highlighting this circuitry as a major locus of altered experience-dependent remodeling. Conclusions These findings suggest that vulnerability to AUD associated with schizophrenia-like neurodevelopment may arise less from additive network dysfunction than from an altered capacity of large-scale brain networks for experience-dependent functional remodeling. Schizophrenia-like neurodevelopmental pathology may therefore change how alcohol-related experience is translated into persistent brain network organization.

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Longitudinal Brain Correlates of Cognitive Performance in Early Psychosis

Mignondje, K. A.; Connolly, J. G.; Beermann, A.; Crabtree, E.; Vandekar, S.; Roeske, M. J.; Biernacki, K.; Coleman, M. J.; Shenton, M. E.; Brady, R. O.; Lewandowski, K. E.; Ward, H. B.

2026-08-31 psychiatry and clinical psychology 10.64898/2026.08.28.26361680 medRxiv
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Background: Cognitive impairment is the leading cause of disability in schizophrenia with limited treatments. A major barrier to treatment development is the absence of reproducible, mechanistically grounded neural targets. Cross-sectional studies have identified dorsomedial prefrontal cortex (DMPFC)-somatomotor connectivity as a neural marker of cognitive performance on the Auditory Continuous performance task (ACPT), a measure of attention. To test the stability of this marker, we tested the relationship between DMPFC-somatomotor connectivity and ACPT performance in a longitudinal psychosis sample. Methods: Individuals with early psychosis (n=251) and matched controls (n=90) were enrolled and underwent resting-state neuroimaging and neurocognitive assessment. A subset completed longitudinal assessments over 2-4 years. We calculated DMPFC-somatomotor resting-state functional connectivity using a previously identified DMPFC region and a seed in the somatomotor cortex. We performed linear mixed effects models to predict ACPT performance based on connectivity, time, psychosis type, and their interaction. Results: In the psychosis sample, time (p=.0037) and affective psychosis diagnosis (p<.0001) predicted better ACPT performance. In a model predicting ACPT performance, we observed a significant interaction effect of DMPFC-somatomotor connectivity*psychosis subtype (p=.0079) such that DMPFC-somatomotor connectivity predicted ACPT performance only in individuals with non-affective psychosis (p=.0051). We then tested the specificity of this connectivity-cognitive performance relationship. In a model predicting DMPFC-somatomotor connectivity, only ACPT performance (p=.017), but not fluid cognition, was a significant predictor. Conclusions: DMPFC-somatomotor connectivity is longitudinally associated with cognitive performance in early psychosis. This relationship is strongest in nonaffective psychosis, suggesting a novel, reliable target for intervention for cognitive deficits in early psychosis.

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Blood flow rather than oxygen extraction accounts for a size-dependent capillary-function DSC-MRI oxygen-metabolism contrast in glioblastoma

Oechsner, M.; Neubauer, A.; Stahl, R.; Liebig, T.; Forbrig, R.; Reis, J.

2026-08-17 radiology and imaging 10.64898/2026.08.14.26360305 medRxiv
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Background. Dynamic susceptibility contrast MRI with capillary-function post-processing exports a relative maximum cerebral metabolic rate of oxygen, formed from blood flow and a transit-time-derived extraction term. The share each contributes to an observed contrast is unquantified. Methods. In a retrospective single-centre cohort with untreated glioblastoma, six perfusion maps normalised to normal-appearing white matter were sampled in automatically segmented enhancing tumour and peritumoral brain. The paired compartment contrast in the oxygen-metabolism index was partitioned into flow, extraction and residual terms and examined against tumour-core volume. Results. Of 131 patients, 122 were analysable. Flow-linked maps were about twice as high in enhancing tumour, the transit and extraction maps only modestly (all q < 0.05). Flow accounted for 92.6% (95% CI 85.9-98.8) of the contrast and extraction for 6.6% (0.7-12.9). Across volume tertiles the flow share rose from 67.8% to 104.0%, a gradient arising peritumorally: every map changed with volume there, none in enhancing tumour. Conclusion. The compartment contrast in the oxygen-metabolism index is largely accounted for by blood flow and varies with lesion size, that dependence originating peritumorally. It should be read within the complete perfusion panel, not as independent metabolic evidence.

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An Explainable and Comparative Transfer Learning Framework for Brain Tumor Classification from MRI Images

Bethala, S.; Vanshika,

2026-08-10 radiology and imaging 10.64898/2026.08.06.26359900 medRxiv
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Automated detection of brain tumors from Magnetic Resonance Imaging (MRI) can accelerate diagnosis and reduce inter-reader variability, yet many existing studies report only top-line accuracy on small datasets, omit efficiency analysis, and provide no interpretability, limiting their clinical credibility. We present a reproducible, comparative, and explainable transfer- learning framework for binary brain-tumor classification. Our framework (i) standardizes a configurable preprocessing pipeline combining CLAHE contrast enhancement and unsharp-mask sharpening, (ii) evaluates a custom CNN baseline and pretrained backbones under an identical training budget, (iii) reports a full metric suite (accuracy, precision, recall, F1, ROC-AUC, PR-AUC, parameter count, and inference latency), and (iv) applies Grad- CAM for spatial interpretability. On a public 253-image MRI dataset (38-image held-out test set), MobileNetV2 achieves the best overall performance (94.74% accuracy, 0.994 ROC-AUC, 0.996 PR-AUC) with only 2.59M parameters and 5.9 ms per- image inference, making it the most deployment-friendly model. Larger backbones (Xception, EfficientNetB0) and the custom CNN converge to degenerate all-positive predictions under the same limited budget, illustrating the small-data overfitting risk that accuracy-only reporting conceals. Grad-CAM confirms that the best model attends to the tumor region. All source code, con- figuration files, and trained evaluation scripts are publicly avail- able at https://github.com/blck-iris/explainable-brain-tumor-mr

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Small but systematic bias introduced by EEG electrodes in PET imaging

Stöhrmann, P.; Ponce de Leon, M.; Dörl, G.; Milz, C.; Graf, S.; Eggerstorfer, B.; Murgas, M.; Reed, M. B.; Falb, P. C.; Al Barede, K.; Nics, L.; Rasul, S.; Hacker, M.; Lanzenberger, R.; Hahn, A.

2026-08-13 radiology and imaging 10.64898/2026.08.12.26360268 medRxiv
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Purpose: Attenuation correction (AC) of PET images is essential for accurate quantification. Brain PET studies comprising simultaneous EEG (PETEEG) may suffer from metal artifacts in CT images (CTEEG), or improper correction when electrodes are not present in the CT (CT0). As these influences are not well-characterized, we aim to compare metal artifact reduction (MAR) techniques for CTEEG images, and evaluate differences between attenuated-corrected PETEEG using CT0 and CTEEG with MAR, synthetically placed electrodes (CTEEG-synth) and extended Hounsfield unit (HU) range. Methods: 19 healthy participants underwent two total-body PET/CT scans with [18F]FDG, with and without 32 EEG scalp electrodes, respectively. We evaluated five MARs to reduce streaks caused by the EEG electrodes in the CTEEG. Finally, CT0, CTEEG with (CTEEG-iMAR-Ext) and without extended HU range (CTEEG-iMAR) and CTEEG-synth were used to perform attenuation correction of PETEEG. We compared our results to PET0/CT0 scan using relative differences. Results: CTEEG and CTEEG-iMAR showed the smallest differences to CT0. PETEEG/CTEEG-iMAR-Ext exhibited the lowest differences to PET0/CT0 (average bias across all regions of -0.46%), followed by similar performance of PETEEG/CTEEG-iMAR (-0.73%) and PETEEG/CTEEG (-0.76%). Conversely, PETEEG/CT0 demonstrated the largest average differences (-1.81%), with values reaching -2.71% in the parietal lobe. These differences were consistent across subjects, yielding significant effects in most of the brain (pFWE < 0.05). CTEEG-synth performed not as good as CTEEG (-1.21%). Conclusions: CTEEG with extended HU range is most suitable for attenuation correction of PETEEG images, with MAR correction offering little additional improvement.