Human Brain Mapping最新文献

{"title":"VarCoNet: A Variability-Aware Self-Supervised Framework for Functional Connectome Extraction From Resting-State fMRI","authors":"Charalampos Lamprou,&nbsp;Aamna Alshehhi,&nbsp;Leontios J. Hadjileontiadis,&nbsp;Mohamed L. Seghier","doi":"10.1002/hbm.70469","DOIUrl":"10.1002/hbm.70469","url":null,"abstract":"<p>Accounting for interindividual variability in brain function is key to precision medicine. Here, by considering functional interindividual variability as meaningful data rather than noise, we introduce VarCoNet, an enhanced self-supervised framework for robust functional connectome (FC) extraction from resting-state fMRI (rs-fMRI) data. VarCoNet employs self-supervised contrastive learning to exploit inherent functional interindividual variability, serving as a brain function encoder that generates FC embeddings readily applicable to downstream tasks even in the absence of labeled data. Contrastive learning is facilitated by a novel augmentation strategy based on segmenting rs-fMRI signals. At its core, VarCoNet integrates a 1D-convolutional neural network (CNN) with a Transformer encoder for advanced time-series processing, enhanced with robust Bayesian hyperparameter optimization. Our VarCoNet framework is evaluated on two downstream tasks: (i) subject fingerprinting, using rs-fMRI data from the Human Connectome Project (2117 recordings), and (ii) autism spectrum disorder (ASD) classification, using rs-fMRI data from the Autism Brain Imaging Data Exchange (ABIDE) I (995 recordings) and II (730 recordings) datasets. Using different brain parcellations, our extensive testing against state-of-the-art methods, including 13 deep learning methods, demonstrates VarCoNet's superiority, robustness, interpretability, and generalizability, achieving up to 98% subject fingerprinting accuracy and an area under the curve (AUC) of 72.6% for ASD classification. Overall, VarCoNet provides a versatile and robust framework for FC analysis in rs-fMRI.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12976809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trust Emerges From Shared Attention: Behavioural and Neural Evidence From Dual EEG Hyperscanning","authors":"Yuzhan Hang,&nbsp;Wei Wu,&nbsp;Runjin Li,&nbsp;Liangjiecheng Huang,&nbsp;Satoshi Shioiri,&nbsp;Xiaosong He","doi":"10.1002/hbm.70504","DOIUrl":"10.1002/hbm.70504","url":null,"abstract":"<p>Trust is central to human cooperation, yet the cognitive and neural mechanisms through which it emerges remain poorly understood. Here, we tested whether shared attention fosters trust behaviour and its neural underpinnings. Pairs of participants engaged in a joint flanker task to manipulate attentional alignment, followed by a multi-round trust game, whereas neural activity was recorded using dual EEG hyperscanning. Behaviourally, participants in the shared attention condition invested more and responded faster than those in the separated condition, with effects evident from the first round and persisting across repetitions. Neurally, shared attention was associated with increased prefrontal oscillatory power in the theta, alpha, and beta bands, stronger beta-band functional connectivity between prefrontal and posterior regions, and enhanced inter-brain theta synchronisation in right frontal areas. Together, these findings demonstrate that shared attention promotes trust through a multi-level mechanism spanning local oscillatory activity, intra-brain connectivity, and cross-brain coupling, establishing shared attention as a minimal yet robust pathway for trust formation beyond deliberative or experience-based accounts.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hbm.70504","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Regulation of Vasomotor and Cardiorespiratory Pulsations Is Disrupted in Primary Central Nervous System Lymphoma: A Case–Control fMRI Study","authors":"Valter Poltojainen,&nbsp;Matti Järvelä,&nbsp;Nina Keinänen,&nbsp;Michaela K. Bode,&nbsp;Juha-Matti Isokangas,&nbsp;Hanne Kuitunen,&nbsp;Juha Nikkinen,&nbsp;Vesa Korhonen,&nbsp;Niko Huotari,&nbsp;Lauri Raitamaa,&nbsp;Janne Kananen,&nbsp;Heta Helakari,&nbsp;Tommi Kalevi Korhonen,&nbsp;Sami Tetri,&nbsp;Outi Kuittinen,&nbsp;Vesa Kiviniemi","doi":"10.1002/hbm.70495","DOIUrl":"10.1002/hbm.70495","url":null,"abstract":"<p>Primary central nervous system lymphoma (PCNSL) alters (peri)vascular structures while increasing vasomotor and cardiorespiratory pulsations within the brain. Vasomotor pulsations may arise from amplitude modulations of respiratory (RPE) and cardiovascular (CHE) pulsations while cardiovascular fluctuations may be modulated by respiration through cardiorespiratory amplitude modulation (CREM). In this study, we examined glymphatic cerebrospinal fluid convection in brains of PCNSL patients by assessing these waves. Thirty PCNSL patients (median 66y; 9 females) and 40 healthy age-matched controls (median 62y; 29 females) were scanned using an fMRI-based MREG_BOLD sequence. Respective MREG_BOLD fluctuation amplitudes (AF_RPE; AF_CHE; AF_CREM) were compared between groups using nonparametric permutation. Regional amplitudes were compared using Mann–Whitney analysis and Cox survival analysis. Subject-specific pulsations were analyzed through Z-score mapping. AF_CREM and AF_RPE were significantly elevated across PCNSL brains, with lesser increases in AF_CHE. However, only significant increases in AF_RPE remained after correcting for sex and head displacement. AF_RPE showed a link to mortality as it was markedly elevated in deceased patients. While elevations in all pulsations were present within (peri)tumoral regions, AF_RPE elevations extended into extra-tumoral white matter and grey matter. Thus, altered cardiorespiratory fluctuations give rise to dysfunctional vasomotor and CSF pulsations in PCNSL, predicting impaired glymphatic function.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hbm.70495","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural Architecture of Familiar Person Perception: Contributions of Unimodal and Multimodal Brain Regions","authors":"Tianxing Zheng,&nbsp;Stefania Mattioni,&nbsp;Olivier Collignon,&nbsp;Xiaoqing Gao","doi":"10.1002/hbm.70488","DOIUrl":"10.1002/hbm.70488","url":null,"abstract":"<p>Faces and voices provide essential information for recognizing familiar people. The brain regions involved in processing person familiarity through these modalities have typically been studied independently, leaving unclear whether and where the auditory and visual networks overlap. In this study, we developed a novel frequency-tagging-based fMRI paradigm to examine the neural basis of familiarity processing from a multimodal perspective. Our findings indicate that the perception of person familiarity through faces and voices predominantly activates <i>sensory-specific</i> regions—the posterior superior temporal cortex (pSTC) for faces and the anterior superior temporal cortex (aSTC) for voices. Discrete regions in the temporal (posterior superior temporal sulcus, pSTS) and frontal (inferior frontal cortex, IFC) areas showed overlapping <i>multisensory</i> activity. pSTS sits as a spatial boundary between unimodal regions, whereas IFC shows connectivity-driven convergence without boundary constraints. These findings indicate shared neural processes for familiarity processing from faces and voices. All together, these results highlight the presence of distributed unisensory and multisensory networks engaging in recognizing familiar people.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12976657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Digital Anatomical Atlas of the Human Cerebellum at Subfolial Resolution","authors":"John G. Samuelsson,&nbsp;Jeremy D. Schmahmann,&nbsp;Martin I. Sereno,&nbsp;Bruce Rosen,&nbsp;Matti S. Hämäläinen","doi":"10.1002/hbm.70497","DOIUrl":"10.1002/hbm.70497","url":null,"abstract":"<p>Interest in the cerebellum has surged with the emerging consensus that it supports diverse functions that are topographically arranged across the cerebellar cortex. Further refinement of these in vivo structure–function relationships is limited by the resolution of existing atlases. Here we present a digital atlas derived from a recent reconstruction of the human cerebellar cortical surface with a mean inter-vertex spacing of 0.16 mm, sufficient to accurately trace the contours of the subfolia, while being consistent with the Schmahmann et al. atlas at the lobular level. We also present ARCUS, a diffeomorphic atlas-to-subject registration approach that yields an atlas-derived, lobule-labeled cerebellar cortical sheet with macroscale folding geometry in individual subjects from standard-resolution MRI. Publicly released, this atlas offers an anatomical ground-truth reference in both volumetric and surface representations at unprecedented granularity, enabling novel and more precise analyses and visualizations of cerebellar data.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12977127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delineating In Vivo T1-Weighted Intensity Profiles Within the Human Insula Cortex Using 7-Tesla MRI","authors":"C. Dalby,&nbsp;Austin Dibble,&nbsp;J. Carvalheiro,&nbsp;F. Queirazza,&nbsp;Michele Sevegnani,&nbsp;M. Harvey,&nbsp;Michele Svanera,&nbsp;Alessio Fracasso","doi":"10.1002/hbm.70486","DOIUrl":"10.1002/hbm.70486","url":null,"abstract":"<p>The integral role of the insula cortex in sensory and cognitive function has been well documented in humans, and fine anatomical details characterizing the insula have been extensively investigated ex vivo in both human and non-human primates. However, in vivo studies of insula anatomy in humans (in general) and within-insula parcellation (in particular) have been limited. The current study leverages 7 Tesla magnetic resonance imaging to delineate cortical depth intensity profiles within the human cortex. Our analysis revealed two separate clusters of relatively high and low signal intensity across the insula cortex located in three distinct compartments within the posterior, anterior-inferior, and middle insula. The posterior and anterior-inferior compartments are characterized by elevated T1-weighted signal intensities, contrasting with lower intensity observed in the middle insular compartment, compatible with ex vivo studies. Importantly, the detection of the high T1-weighted anterior cluster is determined by the choice of brain atlas employed to define the insular region of interest. We obtain reliable in vivo within-insula parcellation at the individual and group levels, across two separate cohorts acquired in two separate sites (<i>n</i>1 = 21, Glasgow, UK; <i>n</i>2 = 101, Amsterdam, NL). Results are further confirmed by deriving cortical depth dependent profiles from T1Map and R1Map images. These results reflect new insights into the insula anatomical structure, in vivo, while highlighting the use of 7 Tesla in neuroimaging with potential implications for individualized medicine approaches.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12976146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of an Age-Dependent and Harmonized 18F-FDG Brain PET Atlas Using a High-Sensitivity Short-Axial FOV PET/CT System","authors":"Yidan Wei,&nbsp;Shixiang Zhang,&nbsp;Qingxiang Wen,&nbsp;Lijie Yin,&nbsp;Sen Yang,&nbsp;Peng Liu,&nbsp;Zhi Zhou,&nbsp;Liping Fu","doi":"10.1002/hbm.70502","DOIUrl":"10.1002/hbm.70502","url":null,"abstract":"<p>¹⁸F-FDG brain PET atlas is widely used in clinical and neuroscience research. However, variation in PET scanner technology can lead to misinterpretation and quantification errors with mismatched atlases. This study aimed to develop high-resolution, age-stratified FDG brain atlases harmonized across different effective image resolutions (EIRs) to support diverse PET/CT scanners. A total of 140 adults (aged 20–90 years, 72 males) were retrospectively enrolled and divided into seven age groups (<i>n</i> = 20). All underwent ¹⁸F-FDG PET/CT at China-Japan Friendship Hospital (Jan 2022-May 2023) using the Siemens Biograph Vision 600 scanner. PET scans (4 min) were acquired 60 min after ¹⁸F-FDG injection (4.44 MBq/kg). System EIR was measured using a Hoffman phantom, and images were smoothed to emulate 5.0–6.0 mm and 8.0–10.0 mm resolutions. Images were normalized to MNI space (1.0 mm) via ANTs, and subjects with outlier FDG uptake values were excluded. SUVRs were calculated using the whole cerebellum as reference. Age-stratified and EIR-harmonized atlases were created. Gray/white contrast (GWC), age correlations, and SUVR differences were analyzed. After quality control, 97 participants were included for atlas construction. Atlases for both EIRs were generated. GWC was higher at 5.0–6.0 mm than at 8.0–10.0 mm (e.g., 2.73 vs. 1.76 in 20–30 years). SUVRs in cortical and subcortical regions negatively correlated with age; brainstem SUVRs correlated only at lower resolution. SUVRs were higher at high resolution across regions. A set of age-dependent, harmonized FDG-PET atlases was developed and the quantitative metrics across age were characterized.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12973123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visual Cortical Lateralization in Activations and Functional Connectivity to the Sight of Faces, Scenes, Body Parts, and Tools","authors":"Edmund T. Rolls,&nbsp;Jianfeng Feng,&nbsp;Ruohan Zhang","doi":"10.1002/hbm.70494","DOIUrl":"10.1002/hbm.70494","url":null,"abstract":"<p>The lateralization of cortical activations and functional connectivities was analyzed when 833 Human Connectome Project (HCP) right-handed participants were viewing faces, spatial scenes, body parts, and tools, using the HCP-Multimodal Parcellation atlas. Spatial scenes produce stronger activations (Bonferroni corrected) in the right hemisphere, especially in the ventromedial visual cortical stream from early visual cortical regions via ventromedial visual cortical regions (VMV1–3) and medial parahippocampal regions (PHA1–3) to the hippocampus, and in inferior parietal visual cortical regions (PGi, PGs, and PFm), and in posterior cingulate division regions. Faces, tools, and body parts produce stronger activations in the left hemisphere in some of the ventrolateral temporal lobe and superior temporal sulcus (STS) visual cortical regions. Some activations were independent of the stimulus type, such as language, and anterior temporal lobe STS semantic regions consistently have higher activations and/or functional connectivities on the left, consistent with the importance of the left hemisphere in language in right-handed people. Also, early visual cortical regions, V2–V4 and POS1, have higher activations in the right hemisphere independently of stimulus type. The lateralizations of the functional connectivities were largely consistent with the activations, but additionally showed that groups of functional connectivities lateralize together (e.g., inferior parietal PGi, PGs, and PFm on the right for scenes but not for any other stimuli), providing further evidence on computational units of the cerebral cortex.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12971613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Development of Hippocampal-Cortical Functional Connectivity in Infants and Toddlers","authors":"Sam Audrain,&nbsp;Shawn C. Milleville,&nbsp;Jenna M. Wilson,&nbsp;Jude Baffoe-Bonnie,&nbsp;Stephen J. Gotts,&nbsp;Alex Martin","doi":"10.1002/hbm.70475","DOIUrl":"10.1002/hbm.70475","url":null,"abstract":"<p>Infancy is a critical period for the development of the memory system, yet the functional neural changes that occur during this time remain poorly understood. In adults, long-term memory relies on hippocampal-neocortical coupling, which differs along the hippocampal long-axis. In this study, we investigated resting-state hippocampal-neocortical functional connectivity along the long-axis in 212 infants across the first two postnatal years. We found large increases in hippocampal connectivity with canonical adult memory regions across the first 6 months of age, accompanied by early functional differentiation along the hippocampal long-axis. However, anterior and posterior hippocampal connections continued to fine-tune with age with medial temporal and medial parietal memory-related cortical regions, but also with areas associated with social cognition, salience, and attention in adults. These systems are known to strongly modulate memory formation and retrieval in mature brains. These findings trace the early maturation of hippocampal-cortical coupling along the long-axis, which may play an important role in evolving long-term memory capacity with development.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-Varying Brain Functional Reconfiguration Patterns Associated With Fatigue in Multiple Sclerosis","authors":"Stefanie Hechenberger,&nbsp;Tommy A. A. Broeders,&nbsp;Marloes D. A. Bet,&nbsp;Birgit Helmlinger,&nbsp;Christian Tinauer,&nbsp;Stefan Ropele,&nbsp;Bettina Heschl,&nbsp;Sebastian Wurth,&nbsp;Anna Damulina,&nbsp;Michael Khalil,&nbsp;Menno M. Schoonheim,&nbsp;Christian Enzinger,&nbsp;Daniela Pinter","doi":"10.1002/hbm.70480","DOIUrl":"10.1002/hbm.70480","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;p&gt;Fatigue affects between 36.5% and 78% of people with multiple sclerosis (pwMS) and significantly impairs daily life. The neurobiological mechanisms underlying fatigue remain poorly understood and information about the time-varying communication between brain regions and the networks they form may offer new insights into the complex pathology of MS-related fatigue. Brain regions continuously reconfigure how they communicate within distinct networks (i.e., time-varying reconfigurations) and aberrant time-varying reconfigurations may contribute to the perception of fatigue in pwMS. This study aimed to explore if and how time-varying reconfigurations are associated with fatigue in pwMS. In this cross-sectional study, 155 pwMS (62% female; age = 39 ± 10 years; disease duration = 10 ± 8 years; median EDSS = 1.0 ± 2.0) and 48 healthy controls (HC) (71% female; age = 33 ± 10 years) underwent clinical, neuropsychological, and (resting-state functional) MRI assessments. Fatigue was evaluated with the “Fatigue Scale for Motor and Cognitive Function”, comprising total, motor, and cognitive fatigue scores. Time-varying connectivity was derived using a sliding-window approach, with data-driven assignment of brain regions to one of eight resting-state networks for each window. Promiscuity (dispersion of reconfigurations), flexibility (frequency of reconfigurations), cohesion (joint reconfigurations), and disjointedness (independent reconfigurations) described the time-varying reconfigurations of the whole brain and its networks. Among pwMS, 57% reported experiencing at least mild total fatigue (motor: 60%, cognitive: 57%). Higher total fatigue was correlated with greater global promiscuity (&lt;i&gt;r&lt;/i&gt; = 0.21, &lt;i&gt;p&lt;/i&gt; = 0.032) and disjointedness (&lt;i&gt;r&lt;/i&gt; = 0.24, &lt;i&gt;p&lt;/i&gt; = 0.008). Similarly, higher motor fatigue was associated with greater global promiscuity (&lt;i&gt;r&lt;/i&gt; = 0.25, &lt;i&gt;p&lt;/i&gt; = 0.008), flexibility (&lt;i&gt;r&lt;/i&gt; = 0.21, &lt;i&gt;p&lt;/i&gt; = 0.032), and disjointedness (&lt;i&gt;r&lt;/i&gt; = 0.28, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). The associations with disjointedness remained significant even after controlling for demographics, clinical measures, and structural brain damage, such as lesion load and atrophy (total fatigue: adj.&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.23, &lt;i&gt;β&lt;/i&gt; = 0.17, &lt;i&gt;p&lt;/i&gt; = 0.033; motor fatigue: adj.&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.38, &lt;i&gt;β&lt;/i&gt; = 0.16, &lt;i&gt;p&lt;/i&gt; = 0.026). Network-level analyses in pwMS revealed that higher total (&lt;i&gt;r&lt;/i&gt; = 0.25, &lt;i&gt;p&lt;/i&gt; = 0.016) and motor (&lt;i&gt;r&lt;/i&gt; = 0.25, &lt;i&gt;p&lt;/i&gt; = 0.016) fatigue were associated with greater limbic network promiscuity. No significant correlations were found for cognitive fatigue in pwMS, or for total, motor, and cognitive fatigue in HC (all &lt;i&gt;p&lt;/i&gt; &gt; 0.05). Elevated levels of fatigue, particularly motor fatigue, in pwMS were linked to more unstable network reconfigurations, particularly of regions in the limbic network, possibly reflecting dysfuncti","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}