Hum Brain Mapp [JOURNAL]
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200 papers
Trust Emerges From Shared Attention: Behavioural and Neural Evidence From Dual EEG Hyperscanning.
Hang Y, Wu W, Li R … +3 more , Huang L, Shioiri S, He X
Hum Brain Mapp · 2026 Mar · PMID 41814624 · Full text
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 underpinni...
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.
Delineating In Vivo T1-Weighted Intensity Profiles Within the Human Insula Cortex Using 7-Tesla MRI.
Dalby C, Dibble A, Carvalheiro J … +5 more , Queirazza F, Sevegnani M, Harvey M, Svanera M, Fracasso A
Hum Brain Mapp · 2026 Mar · PMID 41813562 · Full text
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...
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 (n1 = 21, Glasgow, UK; n2 = 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.
A Digital Anatomical Atlas of the Human Cerebellum at Subfolial Resolution.
Samuelsson JG, Schmahmann JD, Sereno MI … +2 more , Rosen B, Hämäläinen MS
Hum Brain Mapp · 2026 Mar · PMID 41810813 · Full text
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...
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.
VarCoNet: A Variability-Aware Self-Supervised Framework for Functional Connectome Extraction From Resting-State fMRI.
Lamprou C, Alshehhi A, Hadjileontiadis LJ … +1 more , Seghier ML
Hum Brain Mapp · 2026 Mar · PMID 41810518 · Full text
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 enhan...
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.
Neural Architecture of Familiar Person Perception: Contributions of Unimodal and Multimodal Brain Regions.
Zheng T, Mattioni S, Collignon O … +1 more , Gao X
Hum Brain Mapp · 2026 Mar · PMID 41808569 · Full text
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 uncl...
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 sensory-specific 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 multisensory 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.
Generation of an Age-Dependent and Harmonized F-FDG Brain PET Atlas Using a High-Sensitivity Short-Axial FOV PET/CT System.
Wei Y, Zhang S, Wen Q … +5 more , Yin L, Yang S, Liu P, Zhou Z, Fu L
Hum Brain Mapp · 2026 Mar · PMID 41804807 · Full text
F-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 t...
F-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 (n = 20). All underwent F-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 F-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.
Visual Cortical Lateralization in Activations and Functional Connectivity to the Sight of Faces, Scenes, Body Parts, and Tools.
Rolls ET, Feng J, Zhang R
Hum Brain Mapp · 2026 Mar · PMID 41804040 · Full text
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...
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.
Brain Bases for Navigating Acoustic Features.
Billig AJ, Sedley W, Gander PE … +6 more , Kumar S, Lad M, Chait M, Mohammadi Y, Berger JI, Griffiths TD
Hum Brain Mapp · 2026 Mar · PMID 41797407 · Full text
Whether physical navigation shares neural substrates with mental travel in other behaviourally relevant domains is debated. With respect to sound, pure-tone working memory in humans elicits hippocampal as well as auditor...
Whether physical navigation shares neural substrates with mental travel in other behaviourally relevant domains is debated. With respect to sound, pure-tone working memory in humans elicits hippocampal as well as auditory cortical and inferior frontal activity, and rodent work suggests that hippocampal cells that usually track an animal's physical location can also map to tone frequency when task-relevant. We generated a sound dimension based on the density of random-frequency tones in a stack, resulting in a percept ranging from low- ('beepy') to high-density ('noisy'). We established that unlike tone frequency, which listeners automatically associate with vertical position, this density dimension elicited no consistent spatial mapping. During functional magnetic resonance imaging, human participants held in mind the density of a series of tone stacks and, after a short maintenance period, adjusted further stacks to match the target ('navigation'). Density of the currently heard sound was represented most strongly in bilateral non-primary auditory cortex, specifically bilateral planum polare, whereas density of the maintained target was represented in right anterior hippocampus and left inferior temporal gyrus. Encoding and maintenance activity in bilateral hippocampus, inferior frontal gyrus, planum polare and posterior cingulate was positively associated with subsequent navigation success. Bilateral inferior frontal gyrus and hippocampus were among regions with elevated activity during adjustment, compared to a parity-judgement condition with closely matched acoustics and motor demands. Bilateral orbitofrontal cortex was more active when navigation was toward a target density than when participants adjusted density in a control condition with no particular target. We find that self-initiated travel along a non-spatial auditory dimension engages a brain system overlapping with that supporting physical navigation.
Time-Varying Brain Functional Reconfiguration Patterns Associated With Fatigue in Multiple Sclerosis.
Hechenberger S, Broeders TAA, Bet MDA … +10 more , Helmlinger B, Tinauer C, Ropele S, Heschl B, Wurth S, Damulina A, Khalil M, Schoonheim MM, Enzinger C, Pinter D
Hum Brain Mapp · 2026 Mar · PMID 41797387 · Full text
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 ti...
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 (r = 0.21, p = 0.032) and disjointedness (r = 0.24, p = 0.008). Similarly, higher motor fatigue was associated with greater global promiscuity (r = 0.25, p = 0.008), flexibility (r = 0.21, p = 0.032), and disjointedness (r = 0.28, p < 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.R = 0.23, β = 0.17, p = 0.033; motor fatigue: adj.R = 0.38, β = 0.16, p = 0.026). Network-level analyses in pwMS revealed that higher total (r = 0.25, p = 0.016) and motor (r = 0.25, p = 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 p > 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 dysfunctional reward processing. More frequent dispersion requires more energy and may therefore contribute to increased fatigue. TRIAL REGISTRATION: This project was pre-registered at ClinicalTrials.gov (registration number: NCT04892134).
Brain Folding Trajectories in Amyotrophic Lateral Sclerosis.
Shafie M, Tamba C, Bhinder H … +3 more , Canadian ALS Neuroimaging Consortium (CALSNIC), Kalra S, Pizzagalli F
Hum Brain Mapp · 2026 Mar · PMID 41795629 · Full text
Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous neurodegenerative disease, and neuroimaging markers offer a promising avenue to capture this variability. Cortical folding alterations in ALS remain large...
Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous neurodegenerative disease, and neuroimaging markers offer a promising avenue to capture this variability. Cortical folding alterations in ALS remain largely unexplored despite growing interest in neuroimaging markers of the disease. This study is the first whole-brain investigation of sulcal morphometry in ALS. A total of 222 individuals diagnosed with ALS and 194 healthy controls (HC) were recruited through the Canadian ALS Neuroimaging Consortium (CALSNIC) for a longitudinal investigation. Using T1-weighted MRI processed with FreeSurfer and BrainVISA, we extracted cortical thickness and four sulcal features: width, mean depth, surface area, and length, across 123 sulci. We identified widespread alterations in ALS, with 19 sulci showing increased width and length alongside reduced depth and surface area, primarily in frontal and parietal regions surrounding the motor strip. The central sulcus (CS) emerged as the most consistently affected region, displaying bilateral widening and reduced depth, changes that closely tracked motor decline. Longitudinal analyses revealed progressive widening and reduced depth and surface area of the CS. These alterations closely tracked the progression of motor symptoms over the course of the disease and aligned with regional cortical thickness alterations. Our findings demonstrate that brain folding patterns, and in particular CS, are altered in ALS and correlate with clinical progression, resembling the neurodegenerative pattern of the disease. By revealing complementary and sensitive changes, sulcal-based metrics may offer promising neuroimaging biomarkers for early detection, prognosis, and patient stratification in ALS.
The Development of Hippocampal-Cortical Functional Connectivity in Infants and Toddlers.
Audrain S, Milleville SC, Wilson JM … +3 more , Baffoe-Bonnie J, Gotts SJ, Martin A
Hum Brain Mapp · 2026 Mar · PMID 41795623 · Full text
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...
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.
Untamed: Unconstrained Tensor Decomposition and Graph Node Embedding for Cortical Parcellation.
Liu Y, Li J, Wisnowski JL … +1 more , Leahy RM
Hum Brain Mapp · 2026 Mar · PMID 41787960 · Full text
Cortical parcellation is fundamental to neuroscience, enabling the division of cerebral cortex into distinct, non-overlapping regions to support interpretation and comparison of complex neuroimaging data. Although extens...
Cortical parcellation is fundamental to neuroscience, enabling the division of cerebral cortex into distinct, non-overlapping regions to support interpretation and comparison of complex neuroimaging data. Although extensive literature has investigated cortical parcellation and its connection to functional brain networks, the optimal spatial features for deriving parcellations from resting-state fMRI (rsfMRI) remain unclear. Traditional methods such as Independent Component Analysis (ICA) have been widely used to identify large-scale functional networks, while other approaches define disjoint cortical parcellations. However, bridging these perspectives through effective feature extraction remains an open challenge. To address this, we introduce Untamed, a novel framework that integrates unconstrained tensor decomposition using NASCAR to identify functional networks, with state-of-the-art graph node embedding to generate cortical parcellations. Our method produces near-homogeneous, spatially coherent regions aligned with large-scale functional networks, while avoiding strong assumptions like statistical independence required in ICA. Across multiple datasets, Untamed consistently demonstrates improved or comparable performance in functional connectivity homogeneity and task contrast alignment compared to existing atlases. The pipeline is fully automated, allowing for rapid adaptation to new datasets and the generation of custom parcellations. The atlases derived from the Genomics Superstruct Project (GSP) dataset, along with the code for generating customizable parcel numbers, are publicly available at https://untamed-atlas.github.io.
Neural Representations of Death-Related Concepts Identify Conceptual Alteration of Self in Suicidal Youth.
Just MA, Mason R, Pan L … +4 more , McMakin D, Cha C, Nock MK, Brent D
Hum Brain Mapp · 2026 Mar · PMID 41787939 · Full text
The understanding of suicidal ideation would be significantly enhanced by a biologically based measure that can meaningfully inform about the nature of the underlying neurocognitive alteration, as well as objectively ide...
The understanding of suicidal ideation would be significantly enhanced by a biologically based measure that can meaningfully inform about the nature of the underlying neurocognitive alteration, as well as objectively identify individuals experiencing suicidal thoughts. Here we report on such an approach that assesses alterations in the neural representations of concepts related to death in people who engage in suicidal ideation. Young healthy control participants and participants with Suicidal Ideation thought about the meaning of 28 stimulus concepts, among them concepts referring to death or suicide, while their brain activity was assessed using fMRI. Their brain activity was analyzed using a machine-learning algorithm (Gaussian Naïve Bayes) to distinguish the two groups, based on their brain activity in brain regions previously found to be related to thinking about oneself. The classifier distinguished the two groups with moderate but reliable accuracy, based on alterations in the fMRI signatures of the self-representation when they thought about death-related concepts. The study establishes a biological, neurocognitive basis that identifies meaningful alterations in psychological representations in participants with suicidal ideation.
Frequency-Resolved Cortical Functional Connectivity Across the Adult Lifespan.
Ruuskanen S, Avendano-Diaz JC, Liljeström M … +1 more , Parkkonen L
Hum Brain Mapp · 2026 Mar · PMID 41755554 · Full text
The operation of the human brain relies on functional networks enabled by inter-areal oscillatory synchronization between neuronal populations. Although disruptions in this functional connectivity are associated with bra...
The operation of the human brain relies on functional networks enabled by inter-areal oscillatory synchronization between neuronal populations. Although disruptions in this functional connectivity are associated with brain disorders, evidence on its healthy age-dependent variation and behavioral relevance remains limited. Utilizing magnetoencephalography (MEG) recordings from 576 adults aged 18-87 years, we investigated the evolution of resting-state functional connectivity (rs-FC) across the healthy adult lifespan. We observed age-related, frequency-specific changes in widespread cortical networks. Alpha-band (8-13 Hz) rs-FC decreased, while delta (1-4 Hz), theta (4-8 Hz), and gamma-band (40-90 Hz) rs-FC increased with age. Beta-band (13-30 Hz) rs-FC followed a non-linear trajectory, peaking in middle age. The global delta, theta, alpha, and beta-band patterns differed from concurrent changes in oscillatory power, underscoring their dissociable contributions. Notably, reduced beta-band rs-FC was associated with increased sensorimotor attenuation, indicating that changes in rs-FC are behaviorally relevant for sensorimotor function. These findings advance our understanding of healthy brain aging and highlight a link between resting-state brain activity and sensorimotor integration.
Exploring the Role of the Rich Club in Network Control of Neurocognitive States.
Podschun AN, Betzel RF, Braun U … +1 more , Markett S
Hum Brain Mapp · 2026 Mar · PMID 41749476 · Full text
The brain's rich club is a network of particularly densely interconnected regions, metabolically costly to maintain but central to the balance between functional segregation and integration. We assessed whether the rich...
The brain's rich club is a network of particularly densely interconnected regions, metabolically costly to maintain but central to the balance between functional segregation and integration. We assessed whether the rich club can accordingly be described as a control center of the brain, and present a systematic analysis of its involvement in maintenance of and traversal between various cognitively relevant functional states. Brain states were defined based on fMRI task-evoked and resting-state patterns of activity as provided by the Human Connectome Project (HCP). Using tools from network control theory (NCT), we computed the necessary effort needed for control of dynamics when the rich club, versus a size-matched set of low-degree peripheral regions, was prohibited from exerting control over dynamics. Control energy needed to traverse functional states was significantly higher, and stability of states significantly lower, when the set of peripheral regions was prohibited from control. Findings were stable across various rich-club and null model definitions and across different parameter settings. A region's contribution to optimal control processes was instead associated with its affiliation with certain intrinsic connectivity networks and its position on the visual-sensorimotor, but not sensory-transmodal cortical gradient. We accordingly report that the rich club was systematically less involved in control of dynamics than the size-matched set of peripheral regions. These results do not negate an integratory role of the rich club, but question its proposed role as a driver of control. Indeed, if it would inhabit such a role, we would have expected opposite results. Our findings fit with a position describing the rich club as a passive "data-highway" which, by means of its high connectivity, can be easily controlled by peripheral regions and thus facilitate relevant communication channels between them. We call for methodological expansions of the control theoretical toolbox allowing for elaborations on the temporal dynamics of control processes.
Dynamic Functional Connectivity, Major Depression, and Suicidal Ideation in Children.
Wanger TJ, Fiecas MB, Başgöze Z … +9 more , Roediger DJ, Island E, Wiglesworth A, Fu Z, Calhoun V, Mueller BA, Klimes-Dougan B, Luciana M, Cullen KR
Hum Brain Mapp · 2026 Feb · PMID 41733392 · Full text
There is an urgent need to advance understanding of the neural underpinnings of depression, especially early in the life span. Examination of neural dynamics using resting-state functional magnetic resonance imaging (fMR...
There is an urgent need to advance understanding of the neural underpinnings of depression, especially early in the life span. Examination of neural dynamics using resting-state functional magnetic resonance imaging (fMRI) data can provide indices of neural flexibility, which may provide important new insights for the neurobiology of pediatric depression. Here we applied Hidden Markov Modeling (HMM) to resting-state fMRI data to investigate neural flexibility in relation to depression and suicidal thinking in children. We utilized data from the Adolescent Brain Cognitive Development℠ Study (ABCD Study), and included data from 10,763 children (9-10 years) who completed two 5-min resting state fMRI scans at the baseline visit. After applying the NeuroMark framework to the data, HMM was applied with a varying number of states; a six-state model was selected from candidate models based on between-scan reliability. We applied linear mixed-effect modeling to test the relationship between two clinical predictors: current major depressive disorder (MDD) diagnosis and presence of suicidal ideation (SI) with our primary outcome for neural flexibility: the frequency of transitions between HMM-derived states ("state-switching"), while including sex, age, and other socio-demographic variables as covariates. Analyses were conducted both with and without correction for head motion. We also explored relationships with total time and dwell time in each state of the six states. Lower state-switching during rest was associated with both MDD and SI, although these findings were no longer significant after correcting for head motion. Notably, state-switching was inversely related to head motion and was higher in females than males. Exploratory analysis showed that MDD was associated with shorter dwell time in one state and longer dwell time in another, suggesting altered temporal persistence of specific neural configurations. Tentative evidence supported our hypothesis that lower state-switching in children with MDD and SI may reflect a reduction in brain flexibility, potentially contributing to a tendency to become "stuck" in negative patterns of thinking and feeling. However, the relatively low frequency of these problems in late childhood reduced statistical power after correcting for motion. Future research is needed to assess these relationships at later adolescent time points, when higher prevalence of depression and SI and lower prevalence of head motion will allow more powerful tests of these associations.
Longitudinal Neuroimaging Reveals Divergent Clinical Associations of Glymphatic Dysfunction and Dopaminergic Degeneration in Parkinson's Disease.
Liu T, Shen Y, Bai Y … +5 more , Gao S, Meng N, Wei W, Roberts N, Wang M
Hum Brain Mapp · 2026 Feb · PMID 41731626 · Full text
To investigate the association between glymphatic function and dopaminergic degeneration in PD assessed via diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) and dopamine transporter imaging stria...
To investigate the association between glymphatic function and dopaminergic degeneration in PD assessed via diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) and dopamine transporter imaging striatal binding ratio (DAT-SBR), aiming to clarify their controversial relationship and distinct roles in disease progression. A total of 70 early-stage, drug-naïve patients with PD and 70 age- and sex-matched healthy controls (HCs) were selected from the Parkinson's Progression Markers Initiative database for cross-sectional analysis. Longitudinal data at 4-year follow-up were available for the PD group. Glymphatic function was evaluated using DTI-ALPS, and dopaminergic function using DAT-SBR derived from DAT-SPECT imaging. Clinical motor and non-motor assessments were performed at baseline and follow-up. Correlations between imaging index and clinical variables were analyzed using Spearman correlation and multivariate regression. At baseline, both DTI-ALPS and DAT-SBR index were significantly lower in PD patients compared to HCs. Notably, no significant correlation was observed between ALPS and SBR index. Clinically, the DTI-ALPS index showed negative correlations with body mass index, disease duration, Hoehn and Yahr stage, and UPDRS III scores, and its longitudinal decline correlated with white matter microstructural degeneration. The DAT-SBR index was negatively correlated with Epworth Sleepiness Scale, REM sleep behavior disorder score, and serum urate. Our findings suggest that glymphatic dysfunction and nigrostriatal denervation represent independent, parallel pathological trajectories in early PD. While the ALPS index may serve as a potential imaging marker of structural network integrity linked to motor execution. These indices offer distinct, complementary mechanistic insights into PD pathology.
Correction to "An Imaging-Guided Neural Model Explains Lexical Stress Alteration in Acquired Apraxia of Speech".
Hum Brain Mapp · 2026 Feb · PMID 41731348 · Full text
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Bias in Structural MRI Correlates of Delay Discounting due to Head Motion.
Read-Tannock J, Reid A, Farcot E … +2 more , Schürmann M, Madan CR
Hum Brain Mapp · 2026 Feb · PMID 41725039 · Full text
A growing number of studies report that delay discounting, a measure used to evaluate impulsive behaviour, is associated with the regional volume or thickness of cortical grey matter. Using 1096 participants' MRI data fr...
A growing number of studies report that delay discounting, a measure used to evaluate impulsive behaviour, is associated with the regional volume or thickness of cortical grey matter. Using 1096 participants' MRI data from the open Human Connectome Project Young Adults dataset, we show that delay discounting correlates significantly with in-scanner head motion, a prevalent cause of artifacts in magnetic resonance imaging. Furthermore, head motion was found to bias estimates of grey matter thickness downwards across much of the neocortex, including many of the regions where delay discounting has been associated with reduced grey matter, suggesting these effects may be confounded by motion artifacts. The effects associated with delay discounting were also significantly correlated with the cortical thinning effects associated with motion under a spin permutation null model. In conclusion, we suggest that any future studies investigating structural correlates of delay discounting should correct for motion effects-either during data acquisition or by including a movement covariate when fitting models.
Deep Learning-Based Structural Brain Age Estimation in Bipolar Disorder and Schizophrenia: A Single-Site Pilot Study.
Weerasekera A, Zhou S, Wang C … +11 more , Qiu Z, Stein A, Ameer M, Chouinard VA, Shinn A, Lewandowski KE, Murphy M, Halko M, Türközer HB, Öngür D, Du F
Hum Brain Mapp · 2026 Feb · PMID 41714875 · Full text
Accelerated brain aging has been implicated in severe mental illnesses, particularly schizophrenia (SZ) and bipolar disorder (BD). Brain-PAD, derived from structural MRI, offers a promising biomarker of neurobiological a...
Accelerated brain aging has been implicated in severe mental illnesses, particularly schizophrenia (SZ) and bipolar disorder (BD). Brain-PAD, derived from structural MRI, offers a promising biomarker of neurobiological aging, but its developmental course, within-group variability, and regional drivers remain incompletely understood. A three-dimensional convolutional neural network (3D-CNN) was trained exclusively on healthy controls (HC; n = 155) and then applied to independent BD (n = 122) and SZ (n = 161) groups. Brain-PAD was computed as predicted brain age minus chronological age. Age-by-group interactions, within-group dispersion, and sensitivity analyses (e.g., piecewise regression, inverse probability weighting) were conducted. Gradient-weighted Class Activation Mapping (Grad-CAM) was used to identify regional contributions to brain age predictions. The 3D-CNN achieved high accuracy in HC (MAE = 3.05 years, r = 0.96), with reduced accuracy in BD (MAE = 8.86, r = 0.51) and SZ (MAE = 9.01, r = 0.48). Mean Brain-PAD was significantly elevated in BD (+4.2 ± 10.2 years) and SZ (+6.7 ± 8.7 years) relative to HC (+0.7 ± 3.5 years). Age-by-group analyses revealed that BD and SZ exhibited elevated Brain-PAD at younger ages, converging toward HC trajectories by midlife, followed by renewed divergence beyond age 40. This pattern was supported by piecewise and spline models showing steeper negative slopes in BD and SZ compared with HC. Variance and quantile regression indicated greater heterogeneity in BD and SZ across the Brain-PAD distribution. Grad-CAM highlighted temporal and frontal regions as central contributors across all groups; in SZ, Brain-PAD correlated positively with whole-brain (r = 0.23, p = 0.004), frontal (r = 0.21, p = 0.009), and temporal (r = 0.20, p = 0.012) activations, whereas BD showed weaker and more diffuse associations. SZ and BD exhibit elevated Brain-PAD early in adulthood with greater heterogeneity than healthy controls. Frontotemporal regions contribute prominently to brain-age predictions, reflecting model sensitivity to age-informative structure. These findings support Brain-PAD as a group-level marker of apparent brain aging and motivate longitudinal study of midlife divergence.
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