Most recent paper

J Neurol. 2025 Nov 27;272(12):787. doi: 10.1007/s00415-025-13515-0.

ABSTRACT

BACKGROUND: Resting-state functional connectivity (FC) alterations in people with multiple sclerosis (PwMS) have been hypothesized to reflect either adaptive or maladaptive plasticity. Investigating FC longitudinal evolution and its relationship with disability progression can help clarify this issue. This study examined 5-year FC changes in pwMS and their clinical relevance.

METHODS: From the Italian Neuroimaging Network Initiative database, we included 156 pwMS with two clinical visits and 3T-MRI scans acquired on the same scanner 4-6 years apart. Clinical/neuropsychological visits included the Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test (9HPT), Timed 25-Foot Walk Test (T25FWT), Paced Auditory Serial Addition Test (PASAT3), and Symbol Digit Modalities Test (SDMT). One hundred fifty-six age- and sex-matched healthy subjects (HS) with baseline MRI and the same tests were also included. Based on the EDSS, pwMS were divided into three groups: low disability (0-1.5; N = 78), mild disability (2-3.5; N = 50), and high disability (≥ 4; N = 28). Resting-state networks (RSNs) were identified using independent component analysis. Baseline and longitudinal FC changes were correlated with baseline and follow-up clinical/neuropsychological measures.

RESULTS: At baseline, the low-disability group showed significantly higher FC in all RSNs (FDR-corrected p < 0.05) compared to HS, which correlated with better baseline scores (SDMT, T25FWT) and less worsening at follow-up (PASAT3, 9HPT). The mild- and high-disability groups exhibited mixed FC abnormalities, with both higher and lower FC than HS in several RSNs. In the mild-disability group, higher FC was associated with worse baseline scores (SDMT, T25FWT) and greater clinical worsening (PASAT3, 9HPT, T25FWT). In the high-disability group, higher sensorimotor baseline FC correlated only with worse baseline 9HPT. Longitudinally, all RSNs showed FC increase in the low-disability group, but a FC decrease in the other groups. FC increases in the low-disability group generally correlated with better clinical outcome (T25FWT), while FC decreases in the mild-disability group correlated with clinical worsening (9HPT, T25FWT).

CONCLUSIONS: FC increases appear to reflect compensatory mechanisms in low-disability pwMS, while in more disabled patients, FC alterations likely represent maladaptive responses. These findings support resting-state FC as a biomarker for monitoring disease progression and treatment response in MS.

PMID:41307737 | DOI:10.1007/s00415-025-13515-0

Neuroinformatics. 2025 Nov 27;23(4):55. doi: 10.1007/s12021-025-09757-y.

ABSTRACT

The fasciola cinerea (FC) is a slender archicortical band at the posterior hippocampal tail, and its human morphology and network role are poorly defined. To generate a reproducible in vivo three-dimensional (3D) model of the FC, quantify its geometry, characterize structural and functional connectivity within posterior-medial memory networks, and test a tractography-constrained computational model in which the FC acts as a multiplicative gate. Open 7 T datasets, structural, diffusion, and resting-state functional magnetic resonance imaging (fMRI) were anchored to BigBrain and Julich-Brain priors. A semi-automated, atlas-guided pipeline was used to segment the FC and derive morphometrics (volume, thickness, width, curvature, and Laplace-Beltrami spectral shape). Reliability was assessed using the Dice, 95% Hausdorff distance, and test-retest intraclass correlation coefficient (ICC). Diffusion tractography was used to estimate the FC structural pathways toward retrosplenial (RSC), parahippocampal (PHC), posterior cingulate (PCC), and thalamic targets. Resting-state coupling was summarized using Fisher-z correlations and narrowband coherence. A Wilson-Cowan neural mass model, constrained by tractography, simulated FC-dependent FC-RSC coherence with morphometric scaling of gating gain. Segmentation was reliable (Dice = 0.78 ± 0.05; 95% Hausdorff = 1.62 ± 0.41 mm; ICC_volume = 0.88; ICC_thickness = 0.82). Group morphometrics: volume 84.3 ± 17.9 mm³, mean thickness 0.92 ± 0.15 mm, width 1.86 ± 0.31 mm, centerline length 14.2 ± 2.1 mm. FC showed preferential connectivity: FC→RSC 0.21 ± 0.09; FC→PHC 0.18 ± 0.08; FC→PCC 0.11 ± 0.06; FC→Thalamus 0.06 ± 0.04. Resting-state coupling was strongest for FC-RSC (z = 0.24 ± 0.12) with a slow-band coherence enhancement. Thickness predicted the FC→RSC strength (β = 0.17 per 0.1 mm) and FC-RSC z (β = 0.08 per 0.1 mm), and higher curvature was negatively related. The gating model reproduced empirical FC-RSC coherence (r = 0.52 ± 0.11), and morphometric scaling improved the fit (Δr = + 0.06). We provide an anatomically grounded and mathematically validated 3D FC model that links microstructures to mesoscale connectivity. Preferential posterior-medial coupling and morphometry-dependent gating support the FC as a modulatory interface in human memory networks and yield testable markers for individualized mapping and clinical translation.

PMID:41307597 | DOI:10.1007/s12021-025-09757-y

Pain. 2025 Nov 13. doi: 10.1097/j.pain.0000000000003841. Online ahead of print.

ABSTRACT

Impairments in lumbar sensory perception, including reduced tactile acuity, occur in patients with nonspecific low back pain (LBP). Tactile acuity is linked to primary somatosensory cortex (S1) activity and structure, but neural markers of lumbar-specific tactile acuity tests remain unvalidated. This cross-sectional study investigated associations between lumbar two-point discrimination (TPD) and estimation (TPE) with functional and structural properties of S1, as well as S1-thalamic connectivity. Resting-state functional MRI and diffusion-weighted MRI assessed S1-thalamic functional connectivity (FC) and structural connectivity, as well as regional homogeneity (ReHo) and mean diffusivity (MD) of S1 grey matter in 78 LBP patients and 39 pain-free controls. Participants with LBP were subdivided into 2 groups: 1 with pain (LBP+, n = 39) and 1 without pain (LBP-, n = 39) on the day of assessment. Higher TPD (ie, worse tactile acuity) was associated with higher contralateral S1-thalamic FC (β = 19.97 mm, 95% CI = 8.47-31.46 mm) and lower contralateral S1-MD (β = -76.98 mm, 95% CI = -142.83 to -11.13 mm). Higher TPE was associated with higher S1-ReHo (β = 19.67 mm, 95% CI = 0.35-39 mm). Two-point discrimination and two-point estimation were positively correlated (r = 0.25, P < 0.001). No between-group differences were found for the MRI variables or TPE, but the LBP+ group showed higher TPD thresholds than pain-free controls (MDiff. = 6.05 mm, Padj. = 0.023). Our findings question the validity of TPE as a measure of tactile acuity. Both neural markers of TPD may not explain tactile acuity impairments in LBP but instead reflect a baseline indicator of tactile performance capability, suggesting poor validity as an LBP-specific marker of neuroplasticity.

PMID:41307249 | DOI:10.1097/j.pain.0000000000003841

Eur J Neurosci. 2025 Nov;62(10):e70338. doi: 10.1111/ejn.70338.

ABSTRACT

Despite a renewed scientific interest in lysergic acid diethylamide (LSD), its local neural effects remain underexplored. This functional magnetic resonance imaging (fMRI) study explored and compared LSD-induced changes in local activity (amplitude of low-frequency fluctuations: ALFF) and local connectivity (regional homogeneity: ReHo), assessing their relationship to regional receptor density. Imaging data of 15 healthy adults from an open dataset were analyzed. For each participant, two pairs of resting-state runs were available (rest1 and rest2), one performed under placebo and one following the intravenous administration of 75-μg LSD. Voxel-wise paired t-tests compared ALFF and ReHo in the LSD versus placebo conditions. Rest1*rest2 test-retest reliability and ALFF*ReHo cross-modal associations were assessed with conjunction maps and vertex-wise correlations. Finally, neurochemical enrichment analyses related LSD-induced ALFF and ReHo changes to cortical density maps of LSD-related neurotransmitter receptors and transporters. Both ALFF and ReHo decreased in somatosensory/visual cortices under LSD compared to placebo. Specific decreases were observed for ALFF in associative regions belonging to the default mode and frontoparietal networks, and for ReHo in subcortical regions (cluster-based corrected p < 0.05). Test-retest reliability was high for ALFF (rho = 0.80, p = 0.001) and moderate for ReHo (rho = 0.46, p = 0.001). ALFF*ReHo LSD-induced changes were moderately associated (rest1: rho = 0.36, p = 0.001; rest2: rho = 0.56, p = 0.001). Neurochemical enrichment analysis showed that LSD-induced ALFF/ReHo alterations were reliably and negatively correlated with the density of D2 and 5-HT1A receptors (FDR-corrected p < 0.05). These preliminary findings suggest that LSD may engage complex and dynamic neurochemical processes beyond its known 5-HT2A receptor target, warranting further investigation.

PMID:41305961 | DOI:10.1111/ejn.70338

Brain Sci. 2025 Nov 20;15(11):1245. doi: 10.3390/brainsci15111245.

ABSTRACT

Background/Objectives: Deep brain stimulation (DBS) of the globus pallidus interna (GPi) is a safe and established therapy for management of refractory motor fluctuations and dyskinesia in Parkinson's disease (PD). However, the relationship between stimulation site connectivity and improvement of axial gait symptoms remains poorly understood, particularly when stimulating in the GPi. This study investigated functional and structural connectivity patterns specifically associated with axial symptom outcomes following bilateral GPi-DBS, and, as a secondary exploratory analysis, examined whether Volumes of tissue activated (VTAs)-based connectivity related to overall UPDRS-III change. Methods: We retrospectively analyzed 19 PD patients who underwent bilateral GPi-DBS at the University of Florida (2002-2017). Unified Parkinson's Disease Rating Scale (UPDRS-III) axial gait subscores were assessed at baseline and 36-month follow-up. VTAs were reconstructed using Lead-DBS and coregistered to Montreal Neurological Institute (MNI) space. Structural connectivity was evaluated with diffusion tractography, and functional connectivity was estimated using normative resting-state fMRI datasets. Correlations between VTA connectivity and clinical improvement were examined using Spearman correlation and voxelwise analyses. Results: Patients with axial improvement in motor scales demonstrated specific VTA connectivity to sensorimotor and supplementary motor networks, particularly lobule V and lobules I-IV of the cerebellum. These associations were specific to axial gait subscores. In contrast, worsening axial gait symptoms correlated with connectivity to cerebellar Crus II, cerebellum VIII, calcarine cortex, and thalamus (p < 0.05). Total UPDRS-III scores did not show a significant positive correlation with supplementary motor area or primary motor cortex connectivity; a non-significant trend was observed for VTA-M1 connectivity (R = 0.41, p = 0.078). Worsening total motor scores were associated with cerebellar Crus II and frontal-parietal networks. These findings suggest that distinct connectivity patterns underlie differential trajectories in axial and global motor outcomes following GPi-DBS. Conclusions: Distinct connectivity profiles might underlie axial gait symptom outcomes following GPi-DBS. Connectivity to motor and sensorimotor pathways supports improvement, whereas involvement of Crus II and occipital networks predicts worsening. Additional studies to confirm and expand on these findings are needed, but our results highlight the value of connectomic mapping for refining patient-specific targeting and developing future programming strategies.

PMID:41300251 | DOI:10.3390/brainsci15111245

Brain Sci. 2025 Oct 24;15(11):1139. doi: 10.3390/brainsci15111139.

ABSTRACT

Background/Objectives: Accumulating evidence suggests that cognitive training can induce functional reorganization of intrinsic connectivity networks involved in higher-order cognitive processes. However, few interventions have specifically targeted language, an essential domain tightly interwoven with memory, attention, and executive functions. Given their foundational role in communication, reasoning, and knowledge acquisition, enhancing language-related abilities may yield widespread cognitive benefits. This study investigated the neural impact of a new structured, language-based cognitive training program on neurotypical older adults. Methods: Twenty Brazilian Portuguese-speaking women (aged 63-77 years; schooling 9-20 years; low-to-medium socioeconomic status) participated in linguistic activities designed to engage language and general cognitive processing. Behavioral testing and resting-state functional Magnetic Resonance Imaging (fMRI) were conducted before and after the intervention. Results: Functional connectivity analyses revealed significant post-intervention increases in connectivity within the frontoparietal network, critical for language processing, and the ventral attentional network, associated with attentional control. Conclusions: The observed neural enhancements indicate substantial plasticity in cognitive networks among older adults, highlighting the effectiveness of linguistic interventions in modulating critical cognitive functions. These findings provide a foundation for future research on targeted cognitive interventions to promote healthy aging and sustain cognitive vitality.

PMID:41300147 | DOI:10.3390/brainsci15111139

Brain Sci. 2025 Oct 23;15(11):1136. doi: 10.3390/brainsci15111136.

ABSTRACT

BACKGROUND: Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental condition for which accurate and automated diagnosis is crucial to enable timely intervention. Resting-state functional magnetic resonance imaging (rs-fMRI) serves as one of the key modalities for diagnosing ASD and elucidating its underlying mechanisms. Numerous existing studies using rs-fMRI data have achieved accurate diagnostic performance. However, these methods often rely on a single brain atlas for constructing brain networks and overlook the data heterogeneity caused by variations in imaging devices, acquisition parameters, and processing pipelines across multiple centers.

METHODS: To address these limitations, this paper proposes a multi-view, low-rank subspace graph structure learning method to integrate multi-atlas and multi-center data for automated ASD diagnosis, termed M3ASD. The proposed framework first constructs functional connectivity matrices from multi-center neuroimaging data using multiple brain atlases. Edge weight filtering is then applied to build multiple brain networks with diverse topological properties, forming several complementary views. Samples from different classes are separately projected into low-rank subspaces within each view to mitigate data heterogeneity. Multi-view consistency regularization is further incorporated to extract more consistent and discriminative features from the low-rank subspaces across views.

RESULTS: Experimental results on the ABIDE-I dataset demonstrate that our model achieves an accuracy of 83.21%, outperforming most existing methods and confirming its effectiveness.

CONCLUSIONS: The proposed method was validated using the publicly available Autism Brain Imaging Data Exchange (ABIDE) dataset. Experimental results demonstrate that the M3ASD method not only improves ASD diagnostic accuracy but also identifies common functional brain connections across atlases, thereby enhancing the interpretability of the method.

PMID:41300144 | DOI:10.3390/brainsci15111136

Brain Sci. 2025 Oct 22;15(11):1133. doi: 10.3390/brainsci15111133.

ABSTRACT

Background: Resting-state functional connectivity (RSFC) is widely used to identify abnormal brain function associated with depression. Resting-state functional magnetic resonance imaging (fMRI) scans have many potential confounds, and task-based FC might provide complementary information leading to better insight on brain function. Methods: We used MATLAB's (version 2024b) CONN toolbox (version 22a) to evaluate FC in 40 adults with and without major depressive disorder (MDD) (nMDD = 23, nHC = 17). fMRI acquisition was performed while participants were at rest and while performing the Selves Task, an individualized goal priming task. Seed-based analyses were performed using two seeds: medial prefrontal cortex (mPFC) and left hippocampus. Results: Both groups showed strong positive RSFC between the mPFC and other DMN regions, including the anterior cingulate cortex and precuneus, which had more focal positive FC to the mPFC during the task in both groups. Additionally, the MDD group had significantly lower RSFC between the mPFC and several regions, including the right inferior temporal gyrus. The left hippocampus seed-based analysis revealed a pattern of hypoconnectivity to multiple brain regions in MDD, including the cerebellum, which was present at rest and during the task. Conclusions: Our results indicated multiple FC differences between adults with and without MDD, as well as distinct FC patterns and contrast results in resting state and task-based analyses, including differential FC between mPFC-cerebellum and hippocampus-cerebellum. These results emphasize that resting-state and task-based fMRI capture distinct patterns of brain connectivity. Further investigation into combining resting-state and task-based FC could inform future neuroimaging research.

PMID:41300141 | DOI:10.3390/brainsci15111133

Sci Rep. 2025 Nov 27. doi: 10.1038/s41598-025-28507-3. Online ahead of print.

ABSTRACT

This study aims to explore the neural correlates of postoperative pain and its relationship with preoperative psychological issues in patients with rotator cuff tear (RCT). Functional MRI data were collected from 78 RCT patients and 48 healthy controls (HC). Voxel-wise comparisons assessed regional homogeneity (ReHo) differences between groups. Pearson correlation and mediation analyses investigated the links between clinical data and brain changes. Additionally, machine learning using support vector machines (SVM) classified RCT patients based on postoperative pain intensity. RCT patients showed functional alterations in brain areas such as the dorsal anterior cingulate cortex (dACC), primary somatosensory cortex (SI), precuneus, and cerebellum. Increased depression levels correlated positively (r² = 0.249, P < 0.001) with ReHo in the dACC. The relationship between depression and postoperative pain intensity was mediated by dACC ReHo (indirect effect: 0.22, CI: 0.01-0.26). The combined analysis of ReHo patterns and clinical data achieved a classification accuracy of 90.4% for distinguishing RCT patients with postoperative pain. Our findings indicate a notable link between depression and postoperative pain in RCT patients, potentially linked to functional abnormalities in the dACC. Neuroimaging markers may help identify individuals at higher risk for postoperative pain.

PMID:41298760 | DOI:10.1038/s41598-025-28507-3

J Affect Disord. 2025 Nov 24:120725. doi: 10.1016/j.jad.2025.120725. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic stress impacts brain function and emotion regulation, increasing depression risk. How chronic stress shapes neural dynamics in response to acute stress remains unclear. This study investigates how chronic stress influences neural responses after acute stress, focusing on ventromedial prefrontal cortex (vmPFC)-amygdala and vmPFC-hippocampus functional connectivity (FC) and their relationship to depression symptoms.

METHODS: Eighty-seven adults underwent resting-state fMRI at baseline, during acute stress, and during recovery. Participants were divided into High and Low chronic stress groups based on perceived stress over the past 4 weeks. Depression symptoms were measured with the Symptom Checklist-90. Linear mixed-effect model and repeated-measures ANOVA were used to analyse neural dynamics and interaction effects. Recovery-related changes in FC were calculated as differences between acute stress and recovery.

RESULTS: Distinct neural dynamics patterns across stress phases emerged between groups. The Low group showed significant decreases in vmPFC-amygdala and vmPFC-hippocampus connectivity from acute stress to recovery, while the High group exhibited no changes. Chronic stress moderated the association between the recovery-related changes in vmPFC-amygdala connectivity and depression symptoms. In the High chronic stress group, greater decreases in FC from stress to recovery were associated with higher depression symptoms.

CONCLUSIONS: Chronic stress modulates neural dynamics during acute stress response and recovery, and their association with depression symptoms. Individuals with higher chronic stress exhibit blunted cortical-limbic circuit dynamics, potentially increasing depression vulnerability. Rapid disengagement of emotion regulation circuits may represent a maladaptive response supporting the allostatic load model. These findings clarify stress, brain, and depression relationships.

PMID:41297681 | DOI:10.1016/j.jad.2025.120725

Behav Brain Res. 2025 Nov 24:115962. doi: 10.1016/j.bbr.2025.115962. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to investigate the neural correlates of cognitive fusion (CF) in drug-naïve patients with obsessive-compulsive disorder (OCD) and to explore the potential involvement of neurotransmitter systems in these abnormalities.

METHODS: Following quality control, 54 first-episode, drug-naïve OCD patients and 56 matched healthy controls underwent resting-state functional magnetic resonance imaging (fMRI) scanning. The amplitude of low-frequency fluctuations (ALFF) and functional connectivity analyses were performed to examine differences in brain activity between the groups. Clinical assessments, including the Yale-Brown Obsessive Compulsive Scale, Beck Anxiety Inventory, Beck Depression Inventory, and CF questionnaire, were administered to measure the severity of obsessive-compulsive, anxiety, and depressive symptoms, as well as CF levels. Mediation and correlation analyses were conducted to explore the relationships between brain activity, CF, and OCD symptoms. Additionally, spatial correlation analyses were conducted to investigate the relationship between neural abnormalities and neurotransmitter systems.

RESULTS: OCD patients exhibited elevated ALFF in prefrontal regions. Crucially, the activity of the left dorsolateral superior frontal gyrus (SFGdl) mediated 45.11% of CF's effect on obsessive-compulsive symptoms (indirect effect = 0.060, 95%CI = [0.005,0.133]). Moreover, neurochemical analysis revealed significant negative correlations between regional ALFF in the left SFGdl and neurotransmitter systems, including dopamine, acetylcholine, and glutamate.

CONCLUSION: Our findings suggest that CF is associated with altered brain activity in prefrontal regions, which may contribute to the cognitive and emotional dysfunction observed in OCD. The negative correlations between these neural abnormalities and neurotransmitter systems provide further insight into the neurochemical mechanisms underlying OCD. These results offer novel perspectives on the pathophysiology of OCD and highlight potential targets for future therapeutic interventions.

PMID:41297562 | DOI:10.1016/j.bbr.2025.115962

Neuroimage Clin. 2025 Nov 22;48:103913. doi: 10.1016/j.nicl.2025.103913. Online ahead of print.

ABSTRACT

OBJECTIVE: Disruptions in resting-state functional brain networks are consistently observed in dementia, yet their underlying relationships remain incompletely understood. This study aimed to investigate potential associations between resting-state functional MRI (rs-fMRI) phenotypes and various dementia subtypes.

METHODS: We performed bidirectional two-sample Mendelian randomization (MR) analyses using summary statistics from 191 rs-fMRI phenotypes (n = 34,691) and five types of dementia (n = 6,618 to 373,159). Forward MR assessed the effects of rs-fMRI phenotypes on dementia risk, while reverse MR evaluated the impact of dementia on rs-fMRI phenotypes.

RESULTS: Forward MR analysis identified seven rs-fMRI phenotypes significantly associated with dementia risk. Enhanced dorsolateral superior frontal gyrus connectivity, part of the default mode network, was linked to reduced Alzheimer's disease risk (odds ratio (OR) = 0.52, 95 % confidence interval (CI): 0.41-0.66, P = 1.10 × 10-7). Increased connectivity within the default mode and central executive networks correlated with lower vascular dementia risk (OR = 0.60, 95 % CI: 0.48-0.75, P = 9.44 × 10-6). Reverse MR revealed significant associations between dementia subtypes and rs-fMRI phenotypes, including Alzheimer's disease-related increases in limbic connectivity and decreases in default mode and central executive networks. For Lewy body dementia, heightened connectivity in salience and sensorimotor networks and reduced default mode connectivity were observed.

INTERPRETATION: Our findings identify functional networks whose connectivity patterns may be associated with dementia risk and could provide potential insights for biomarker discovery or preventive research. However, these results are based on statistical inference and require further validation in longitudinal and experimental studies to confirm their clinical relevance and potential translational implications.

PMID:41297292 | DOI:10.1016/j.nicl.2025.103913

Sci Rep. 2025 Nov 26;15(1):42022. doi: 10.1038/s41598-025-29976-2.

ABSTRACT

Memory decline is a central cognitive symptom in Parkinson's Disease (PD). While task-fMRI studies link hippocampal activity (AHA) to poorer memory and olfactory performance, this relationship during rest remains understudied. The objectives of this study are to examine differences in resting-state hippocampal networks, explore the occurrence of reduced AHA within these networks, and investigate its impact on memory and olfaction in PD. Thirty-nine PD patients awaiting evaluation for device-aided Parkinson therapy and 46 healthy controls (HC) underwent resting-state fMRI (rs-fMRI). PD patients also completed a memory and olfactory assessment. Co-activation pattern (CAP) analysis was performed on the rs-fMRI data. Our results demonstrated reduced activity in two hippocampal networks in PD: Network 1, incorporating the visual cortex, cerebellum, superior parietal lobule, and precuneus, and Network 5, incorporating parts of the central executive network. PD subgroups with reduced AHA in Network 1 and 5 performed significantly worse on tests of auditory-verbal short-term, long-term and recognition memory, as well as odor identification. In conclusion, within specific resting-state hippocampal networks, reduced AHA in PD is linked to poorer auditory-verbal memory and odor identification.

PMID:41298806 | DOI:10.1038/s41598-025-29976-2

Biol Psychiatry Cogn Neurosci Neuroimaging. 2025 Nov 24:S2451-9022(25)00362-3. doi: 10.1016/j.bpsc.2025.11.005. Online ahead of print.

ABSTRACT

BACKGROUND: Between-subjects studies suggest that psychostimulants can shift whole-brain functional connectivity toward patterns linked to heightened sustained attention. In this study, we examined how a single dose of methamphetamine (MA, 20 mg) changes sustained attention and associated network-level functional organization in healthy adults.

METHODS: We conducted a within-subject study in which 76 healthy participants completed two fMRI scanning sessions after taking MA or placebo. We tested whether MA selectively affects behavioral and fMRI connectivity signatures of sustained attention and arousal.

RESULTS: Under MA, participants showed improved sustained attention task performance as well as functional connectivity signatures of higher sustained attention and arousal. These network changes emerged consistently across resting-state and task-based fMRI, indicating that MA influences attention- and arousal-related networks regardless of cognitive context. Furthermore, a support vector classifier distinguished functional connectivity patterns observed during the MA and placebo conditions, identifying connections overlapping with networks related to arousal.

CONCLUSIONS: Together, these findings align with prior work on other psychostimulants like methylphenidate, showing that MA modulates sustained attention and related large-scale brain networks. By revealing how MA modulates attention-relevant brain connectivity patterns, our results highlight the utility of psychostimulants as causal tools for probing the robustness, generalizability, and interpretability of brain-based biomarkers of behavior.

PMID:41297882 | DOI:10.1016/j.bpsc.2025.11.005

Brain Res Bull. 2025 Nov 24:111653. doi: 10.1016/j.brainresbull.2025.111653. Online ahead of print.

ABSTRACT

BACKGROUND: Migraine without aura (MWoA) is linked to abnormal subcortical/cortical network activity and neurotransmitter dysregulation. However, the alteration of functional integration and the information flow between brain networks participated in pain sensory pathway and the patterns of neurotransmitter dysregulation during the interictal period remain unclear.

METHODS: This cross-sectional study compared 53 interictal MWoA patients and 51 healthy controls using resting-state fMRI. Whole-brain functional integration (degree centrality, DC) and effective connectivity (EC) were analyzed. JuSpace toolbox mapped spatial correlation between functional alterations and neurotransmitter systems.

RESULTS: MWoA patients showed decreased DC in the left putamen and increased DC in the left angular gyrus. Altered EC from subcortical to cortical regions included pathways from the left putamen to right medial superior frontal gyrus, supramarginal gyrus, dorsolateral superior frontal gyrus, and postcentral gyrus, as well as bilateral caudate to left angular gyrus. Cortical-to-subcortical EC changes involved right dorsolateral superior frontal gyrus to left putamen and left angular gyrus to left caudate. EC from left putamen to right postcentral gyrus inversely correlated with headache frequency, while right caudate to left angular gyrus EC positively correlated with disease duration. Altered DC patterns spatially overlapped with serotonergic, dopaminergic, and glutamate pathways and correlated with quality-of-life impairments (MSQ scores).

CONCLUSION: MWoA involves disrupted functional integration and bidirectional subcortical-cortical connectivity during interictal periods, associated with headache severity and neurotransmitter system imbalances. These findings highlight network-level pathophysiology and neurochemical dysregulation underlying migraine.

PMID:41297797 | DOI:10.1016/j.brainresbull.2025.111653

IEEE J Biomed Health Inform. 2025 Nov 26;PP. doi: 10.1109/JBHI.2025.3637772. Online ahead of print.

ABSTRACT

Dynamic functional connectivity (dFC) analysis investigates how the functional interactions between brain regions change over time by identifying recurring connectivity patterns, known as dFC states, and tracking transitions between them. Non-negative matrix factorization (NMF) has been used in dFC analysis because it produces non-negative dFC states and coefficients, interpreting dFC states and their transitions straightforwardly. However, existing NMF-based methods are limited to processing dFC data with exclusively positive values, failing to align with the functional correlations and anti-correlations between brain regions. This paper proposes an orthogonal semi-nonnegative matrix factorization (OSemiNMF) method, extending NMF to directly handle mixed-sign dFC data. Furthermore, an orthogonality constraint on the bases (i.e., dFC states) is incorporated to enhance the uniqueness of dFC states. For 10 simulated datasets with varying properties, our method outperforms comparison methods, supporting its superior ability to capture dFC states and state transitions. Using four resting-state fMRI datasets consisting of 708 healthy controls (HCs) and 537 schizophrenia patients (SZs), our method identifies reproducible dFC states and state transitions across datasets. Further, our findings reveal that SZs spend less time in high-connectivity states compared to HCs. Our study identifies meaningful and reproducible biomarkers of schizophrenia, mainly involving the connectivity associated with the sub-cortical domain. In summary, the OSemiNMF method facilitates the dFC analysis for understanding brain dynamics.

PMID:41296953 | DOI:10.1109/JBHI.2025.3637772

Hum Brain Mapp. 2025 Dec 1;46(17):e70409. doi: 10.1002/hbm.70409.

ABSTRACT

Recent studies suggest that it is possible to predict an individual brain's spatial activation pattern in response to a paradigm from their functional connectivity at rest (rsFC). However, it is unclear whether this prediction works across the brain. We here aim to understand whether individual task activation can be best predicted in local regions that are highly specialised to the task at hand or whether there are domain-independent regions in the brain that carry most information about the individual. To answer this question, we used fMRI data from participants at rest and during an auditory oddball paradigm. We then predicted individual differences in brain responses to melodic deviants from their rsFC both across the whole brain and within the auditory cortices. Predictability was consistently higher in sensory association cortices: In the local (auditory cortex) parcellation, the best predicted area was the right superior temporal gyrus (STG), an auditory association area, while in the global parcellation, the best predicted network was the bilateral visual association cortex. Our results indicate that individual differences can be predicted in paradigm-relevant areas or general areas with high inter-individual variability. Predicting individual task activation from rsFC may be of clinical relevance in cases where patients are unable to carry out a certain task, such as, to inform surgical targets.

PMID:41293889 | DOI:10.1002/hbm.70409

Front Hum Neurosci. 2025 Nov 10;19:1669164. doi: 10.3389/fnhum.2025.1669164. eCollection 2025.

ABSTRACT

INTRODUCTION: Emotional well-being (EWB) is a multifaceted construct essential for human health, conceptualized as an umbrella term for related psychometric concepts such as psychological well-being (PWB), positive mental health, health-related quality of life, thriving, and subjective well-being (SWB). However, varying definitions have prompted calls for a consensus definition. Understanding the neural mechanisms of EWB is crucial for health and intervention efforts, yet findings remain inconsistent in both empirical studies and systematic reviews. The inconsistencies in prior systematic reviews may arise from diverse definitions, an emphasis on task-independent over task-dependent modalities, and biases introduced when statistical analyses are lacking.

METHODS: To address these gaps, this study presents the first preliminary systematic review and meta-analysis of the neural correlates of EWB using a consensus definition developed in 2023 by NIH EWB Research Network, which includes five domains: goal pursuit, life satisfaction, positive affect, quality of life, and sense of meaning. Importantly, we used a hypothesis-driven approach to separately examine task-dependent (task-based fMRI; n = 14) and task-independent modalities (resting-state fMRI and structural MRI; n = 7 each), clarifying their distinct and overlapping neural contributions of EWB.

RESULTS: The left pallidum as a key region associated with task-dependent modality, likely reflecting incentive and rewards processing, while task-independent findings implicate the right superior temporal gyrus (STG) and insula, suggesting roles in social cognition and interoceptive awareness. Across both modalities, frontoparietal regions emerge as shared substrates likely contributing to cognitive control processes central to EWB.

CONCLUSION: Despite limited sample sizes, this review provides a preliminary neural framework of EWB, highlighting distinct and shared contributions across modalities and lay an empirical foundation for future large-scale investigations.

SYSTEMATIC REVIEW REGISTRATION: https://osf.io/ymtb8/overview.

PMID:41293483 | PMC:PMC12640920 | DOI:10.3389/fnhum.2025.1669164

bioRxiv [Preprint]. 2025 Nov 12:2025.11.10.687633. doi: 10.1101/2025.11.10.687633.

ABSTRACT

Executive function (EF) develops rapidly during adolescence. However, deficits in EF also emerge in adolescence, representing a transdiagnostic symptom associated with many forms of psychopathology. To promote transdiagnostic research on EF during development, we introduce a new data resource - the Penn Longitudinal Executive functioning in Adolescent Development study (Penn LEAD) - that combines longitudinal multi-modal imaging data with rich clinical and cognitive phenotyping. These data include 225 imaging sessions from 132 individuals (8-16 years old at the time of enrollment) who are typically developing (27.3%), or meet criteria for attention-deficit hyperactivity disorder (20.5%) or the psychosis-spectrum (52.3%). In addition to phenotypic data from multiple cognitive tasks focused on EF, the study includes data from structural MRI, diffusion MRI, n -back task fMRI, resting-state fMRI, and arterial spin-labeled MRI. Notably, all raw data, fully-processed derived data, and detailed quality control recommendations are publicly shared on OpenNeuro. We anticipate that such analysis-ready data will accelerate research on EF development in psychiatry.

PMID:41292855 | PMC:PMC12642398 | DOI:10.1101/2025.11.10.687633

Sci Rep. 2025 Nov 25;15(1):41998. doi: 10.1038/s41598-025-26083-0.

ABSTRACT

Delayed encephalopathy after carbon monoxide poisoning (DEACMP) is the most severe and prevalent neurological sequela associated with carbon monoxide exposure. This study aims to investigate the time-varying characteristics of dynamic brain networks and their topological properties in DEACMP patients using resting-state functional magnetic resonance imaging (rs-fMRI). We conducted Functional MRI scans and clinical assessments for 25 DEACMP patients and 25 healthy controls (HCs). To capture the variability patterns of dynamic functional connectivity (dFC) between the two groups, we employed a sliding time window analysis method. Additionally, theoretical graph analysis was utilized to examine the variations in the topological properties of whole-brain functional networks. We found that DEACMP patients have two dFC states characterized by different connection patterns, State 1 and State2, and there were multiple inter-network and intra-network dynamic interactions in State2.Next, Abnormal dFC indicators were related to the MoCA scores. Finally, the dynamic brain network topological properties were variable. These findings may provide valuable insights into the disruptions in local information transmission and processing functions within the brain's functional networks in individuals with DEACMP.

PMID:41290957 | DOI:10.1038/s41598-025-26083-0