Most recent paper

Brain Topogr. 2026 Sep 10;39(6):95. doi: 10.1007/s10548-026-01244-0.

ABSTRACT

Bilingual experiences have been shown to induce functional and structural neuroplasticity, yet how the age of second language acquisition (AoA-L2) shapes the functional network dynamics remains unclear. In this study, we investigated the effect of AoA-L2 on the temporal properties of dynamic functional connectivity (dFC) states and the variability of dFC and functional network topological organization in bilinguals by using resting-state fMRI data. Compared with late bilinguals, early bilinguals spent a greater proportion of time in sparsely connected states within the subcortical and ventral attention networks and exhibited greater variability of dFC involving multiple systems, including auditory, frontoparietal, subcortical, and attentional networks. In addition, the L2 proficiency was positively associated with the variability of dFC between the cingulo-opercular and default mode networks but negatively associated with the variability of dFC between the frontoparietal and visual networks. These findings suggest that AoA-L2 modulates the temporal flexibility of functional network organization, providing novel perspectives on the functional neuroplasticity induced by bilingualism.

PMID:42722775 | DOI:10.1007/s10548-026-01244-0

Neurotoxicology. 2026 Sep 10:103560. doi: 10.1016/j.neuro.2026.103560. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to investigate abnormal spontaneous brain activity in patients with occupational chronic benzene poisoning (OCBP) using resting-state functional magnetic resonance imaging (rs-fMRI) and to explore the within-sample discriminative value of rs-fMRI features.

METHODS: 20 patients with OCBP and 20 age- and sex-matched healthy controls (HCs) underwent rs-fMRI scanning and neuropsychological assessments. Amplitude of low- frequency fluctuations (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo) were used to assess local spontaneous brain activity. Group comparisons and correlation analyses were performed. Imaging features from significantly altered regions were selected using Least Absolute Shrinkage and Selection Operator (LASSO) and used to construct Support Vector Machine (SVM) classification models. Model performance was evaluated by leave- one-out cross-validation.

RESULTS: Compared with HCs, OCBP patients showed widespread abnormalities in brain regions associated with the default mode network, salience network, and executive control network. The right precuneus exhibited alterations across all three indices. Six fALFF-symptom associations had unadjusted P values below 0.05, but none remained significant after correction across 70 tests (minimum q = 0.196). The combined model yielded an accuracy of 77.5% and an AUC of 0.873 (95% CI, 0.742-0.966), numerically exceeding the single-measure models; right-precuneus ALFF and fALFF features had the largest weights.

CONCLUSION: OCBP patients display extensive spontaneous brain activity abnormalities involving multiple networks and the limbic system, with the right precuneus as a key region. Multi-indicator rs-fMRI-based machine learning models show good classification performance, but the symptom associations and classifier require independent validation in larger, exposure-characterized cohorts.

PMID:42722076 | DOI:10.1016/j.neuro.2026.103560

Front Psychiatry. 2026 Aug 26;17:1900163. doi: 10.3389/fpsyt.2026.1900163. eCollection 2026.

ABSTRACT

BACKGROUND: Early-life parental separation due to rural labor migration represents a prevalent form of early-life social adversity; however, its neural correlates in adulthood remain insufficiently understood, particularly from the perspective of dynamic brain network organization.

METHODS: In this study, resting-state fMRI data were analyzed in adults with left-behind experience (LBE, n = 152) and participants in the non-left-behind comparison group (NLB, n = 145). Group independent component analysis was first used to extract major resting-state networks. Dynamic functional network connectivity was then estimated with a sliding-window approach, and recurrent connectivity configurations were identified using clustering analysis. Group differences in static connectivity, dynamic connectivity states, and temporal properties were examined while accounting for demographic and motion-related covariates. Associations of State 6 temporal properties with LBE duration, psychological resilience, and depressive symptom severity were further explored.

RESULTS: No significant group differences were observed in static functional connectivity or in state-wise connectivity strength. In contrast, significant group differences were identified only in the temporal properties of State 6. Specifically, individuals with LBE exhibited reduced fraction of time (FT) and mean dwell time (MDT) in State 6 after FDR correction, reflecting less frequent and shorter engagement with this connectivity pattern. Among LBE participants who exhibited State 6, longer LBE duration was associated with lower FT in this state after controlling for covariates. Furthermore, MDT in this state was positively associated with optimism scores after controlling for covariates.

CONCLUSIONS: These findings suggested that rural left-behind experience was associated with differences in the temporal engagement of a specific dynamic connectivity state in adulthood, despite the absence of detectable group differences in static connectivity or state-wise connectivity strength. The associations of State 6 temporal properties with LBE duration and optimism provided preliminary correlational evidence that dynamic brain-state measures may be related to both characteristics of early-life experience and adaptive capacity.

PMID:42718789 | PMC:PMC13553950 | DOI:10.3389/fpsyt.2026.1900163

Front Cell Neurosci. 2026 Aug 26;20:1908231. doi: 10.3389/fncel.2026.1908231. eCollection 2026.

ABSTRACT

BACKGROUND: Functional magnetic resonance imaging (fMRI) has revealed abnormal brain activity patterns in stroke patients, yet the genetic correlates underlying functional homotopy - defined as synchronized spontaneous activity between bilateral homologous brain regions - remain poorly characterized. This study investigates the genetic basis of voxel-mirrored homotopic connectivity (VMHC) abnormalities in stroke patients.

METHODS: We analyzed resting-state fMRI data from 50 stroke patients and 50 healthy controls (HC) to quantify VMHC. Spatial transcriptome-neuroimaging correlations were established using the Allen Human Brain Atlas (AHBA) to identify VMHC-associated genes. Transcriptomic analyses combined pathway-centric functional annotation (DAVID) with protein-protein interaction (PPI) network modeling (STRING v12.0).

RESULTS: Stroke patients exhibited significantly reduced VMHC in the rectus gyrus, superior temporal gyrus, middle occipital gyrus, cuneus, and right calcarine/left posterior cingulate gyrus (p < 0.05, GRF-corrected). VMHC alterations correlated positively and negatively with 1,198 genes each. Transcriptomic profiling revealed significant enrichment in synaptic vesicle trafficking, mitochondrial energy metabolism, and neuroinflammation-related pathways. PPI mapping uncovered multi-tiered networks with hub genes including BRCA1, CDK9, ACTB, and ATP6V1A/F involved in transcriptional regulation, cytoskeletal dynamics, and vesicular acidification.

CONCLUSION: This multimodal integration study elucidates polygenic correlates of post-stroke VMHC abnormalities, demonstrating that interhemispheric coordination may depend on synergistic interactions among functionally diverse gene clusters. Our findings provide a molecular framework for understanding post-stroke neural network reorganization and offer a link between functional neuroimaging phenotypes and gene expression, though all associations remain correlational and require mechanistic validation.

PMID:42718694 | PMC:PMC13553374 | DOI:10.3389/fncel.2026.1908231

Brain Spine. 2026 Aug 29;6:106661. doi: 10.1016/j.bas.2026.106661. eCollection 2026.

ABSTRACT

INTRODUCTION: Neuropathic pain (NP) may persist after decompression surgery for degenerative cervical myelopathy (DCM). Although clinical factors associated with postoperative NP have been reported, neuroimaging correlates based on functional connectivity (FC) remain poorly understood.

RESEARCH QUESTION: Are specific preoperative resting-state FC patterns associated with postoperative NP status in patients with DCM?

MATERIAL AND METHODS: In this retrospective observational study using prospectively collected data, we analyzed 34 patients who underwent cervical decompression surgery for DCM between 2020 and 2024. NP was assessed using the Spine painDETECT Questionnaire (SPDQ) preoperatively and 6 months postoperatively. Patients were classified into NP improvement group (n = 7) and non-improvement group (n = 27). Preoperative resting-state functional MRI data underwent whole-brain ROI-to-ROI FC analysis using the CONN toolbox. Between-group FC differences, correlations with patient-reported outcomes, and factors associated with postoperative SPDQ scores were evaluated.

RESULTS: Two preoperative FC networks showed significant between-group differences. FC1, between the right middle frontal gyrus and right thalamus, was higher in the NP improvement group (p-FDR = 0.034), whereas FC2, between the left temporal fusiform cortex and left occipital fusiform gyrus, was higher in the NP non-improvement group (p-FDR = 0.024). FC2 showed moderate correlations with changes in pain intensity, quality of life, and upper-limb function. Multivariable analysis identified FC1 as independently associated with postoperative SPDQ scores (β = -24.05, p = 0.001).

DISCUSSION AND CONCLUSION: Distinct preoperative FC patterns were associated with postoperative NP status. Preoperative FC may provide exploratory neuroimaging correlates of postoperative NP, although further validation is warranted.

PMID:42718643 | PMC:PMC13553560 | DOI:10.1016/j.bas.2026.106661

Front Med (Lausanne). 2026 Aug 26;13:1918075. doi: 10.3389/fmed.2026.1918075. eCollection 2026.

ABSTRACT

OBJECTIVES: To investigate local and global neurovascular coupling (NVC) alterations in H-type hypertension (HHT) and their relationships with homocysteine (Hcy) levels and cognitive deficits and whether they reflect cognitive and disease severity.

METHODS: Fifty-eight HHT patients and fifty normotensive healthy controls, matched for demographics and comorbidities and meeting MRI quality control standards, were included. Data collected included demographic, clinical, biochemical, cognitive, and multimodal MRI measures.

NVC ANALYSIS: After preprocessing and spatial normalization to MNI space, rs-fMRI and ASL data were used to calculate indices of neural activity-ALFF, fALFF, ReHo, FCD-and cerebral blood flow (CBF). Using the AAL atlas and partial correlation, global and regional NVC values were calculated.

RESULTS: HHT patients exhibited elevated Hcy and cognitive impairment (lower MoCA/MMSE). Imaging revealed DMN alterations, increased basal ganglia ALFF, and hypertension-related CBF redistribution (decreased parietal/posterior flow; increased frontal/hippocampal flow). Global and local NVC were generally reduced, particularly in occipital and temporal regions. Crucially, global NVC correlated negatively with systolic BP and Hcy, and positively with cognitive scores.

CONCLUSIONS: HHT patients exhibit reduced global and altered regional NVC-especially in somatosensory and default mode networks. Because the design is cross-sectional, these findings provide multimodal MRI evidence of how altered neurovascular coupling is associated with HHT-highlighting the neural mechanisms underlying cognitive impairment in HHT.

PMID:42718425 | PMC:PMC13553259 | DOI:10.3389/fmed.2026.1918075

Addict Biol. 2026 Sep;31(9):e70184. doi: 10.1111/adb.70184.

ABSTRACT

Internet gaming disorder (IGD) is a behavioural addiction characterized by substantial clinical heterogeneity. The present study aimed to investigate this heterogeneity by analysing the deviation patterns of interindividual brain functional connectivity. Resting-state functional magnetic resonance imaging (fMRI) data from 87 patients with IGD and 56 healthy controls (HCs) were included. First, functional connectivity matrices were constructed, and the interindividual deviation of functional connectivity (IDFC) of each patient with IGD relative to the HC group was quantified at the network level. K-means clustering was then applied to identify IGD subtypes. Edge-wise functional connectivity analysis with network contingency analysis (NCA) was used to characterize subtype-specific patterns of altered connections. Finally, support vector regression (SVR) based on network-level IDFC features was used to predict Internet Addiction Test (IAT) scores in the overall IGD cohort. Two distinct IGD subtypes were identified based on IDFC patterns. Compared with HCs, Subgroup 1 showed a widespread hypoconnectivity pattern, whereas Subgroup 2 showed a relative hyperconnectivity pattern. Network-level IDFC features also predicted IAT scores in the overall IGD cohort using SVR (r = 0.391, one-tailed permutation p = 0.038). Patients with IGD exhibit substantial interindividual variability in brain functional connectivity. Subtyping IGD based on these connectivity deviation patterns may improve the understanding of its neurobiological heterogeneity and facilitate the development of more precise individualized interventions.

PMID:42717747 | DOI:10.1111/adb.70184

EBioMedicine. 2026 Sep 9:106468. doi: 10.1016/j.ebiom.2026.106468. Online ahead of print.

ABSTRACT

BACKGROUND: Brain age deviation is a promising neuroimaging biomarker of brain health, but its relevance in young and mid-life adults and its biological underpinnings remain insufficiently characterised. We aimed to test whether a functional-connectivity-derived brain ageing index (BAI) captures reproducible variability in early brain ageing and whether it is associated with cognitive-affective function and gut-derived biological signatures.

METHODS: We analysed resting-state fMRI from a discovery cohort (n = 674) with validation in a replication cohort (n = 444) and an independent cohort (n = 344). Whole-brain functional connectivity was computed using a 100-region Schaefer parcellation, and Bayesian ridge regression was used to predict chronological age; BAI was defined as the age-bias-corrected residual (predicted brain age minus chronological age). We tested associations between BAI and cognitive and affective measures across cohorts. In the independent cohort, we applied multi-view sparse partial least squares to integrate stool metagenomic and metabolomic profiles with BAI, and performed KEGG pathway enrichment analyses on features with non-zero weights.

FINDINGS: Predicted brain age correlated with chronological age across cohorts (r = 0.50-0.59). Higher BAI was consistently associated with connectivity patterns involving posterior cingulate/praecuneus and medial frontal regions, poorer cognitive performance, particularly working memory and executive function, and greater depressive symptoms. Multi-omics integration identified microbial taxa and stool metabolites, including ceramides, 24-hydroxycholesterol, dicarboxylic acids, and inverse associations with estetrol, linked to BAI. Enrichment analyses suggested involvement of neuroimmune, vascular, synaptic, and mitochondrial pathways.

INTERPRETATION: A connectivity-derived BAI captures reproducible variability in early brain ageing and links large-scale brain network organisation to gut-derived biological signatures. These findings suggest that BAI captures individual variability associated with brain health-related phenotypes and support the potential association of peripheral brain-gut biological pathways in early brain ageing.

FUNDING: National Institutes of Health, National Institute on Ageing.

PMID:42716835 | DOI:10.1016/j.ebiom.2026.106468

Ageing Res Rev. 2026 Sep 9:103365. doi: 10.1016/j.arr.2026.103365. Online ahead of print.

ABSTRACT

Randomized controlled trials (RCTs) targeting cognitive health in older adults increasingly incorporate resting-state functional MRI (rs-fMRI) to evaluate intervention-related neural change and its association with cognitive outcomes. However, these trials are typically small, and rs-fMRI data are high-dimensional and sensitive to measurement variability, making neural representations developed and evaluated within the same trial vulnerable to instability and overfitting. Neural representations learned from large observational datasets can reduce dependence on within-trial model development, but strong predictive performance after transfer does not establish prospective validity in an intervention setting. Here, we propose an operational framework for using externally developed neural representations in RCTs, separating representation development, optional adaptation, and trial use. The framework distinguishes target validation, in which the target and evaluation procedure are specified before outcomes are examined, from target discovery, in which outcomes may inform downstream fitting, selection, or interpretation, with the resulting patterns treated as candidate targets requiring independent confirmation. Using two RCTs as worked examples, we illustrate validation-oriented evaluation of an externally developed connectivity representation and discovery-oriented use of an adapted rs-fMRI foundation-model representation. This framework provides a practical basis for accumulating evidence across trials and distinguishing neural features that are consistently intervention-responsive from those that are context dependent.

PMID:42716443 | DOI:10.1016/j.arr.2026.103365

Neuroimage. 2026 Sep 9:122211. doi: 10.1016/j.neuroimage.2026.122211. Online ahead of print.

ABSTRACT

Most studies of brain networks use resting-state fMRI to characterize the brain's intrinsic functional organization. However, recent work has questioned whether we should rely exclusively on resting-state data to define this organization. Using a connectivity fingerprint modeling framework, we test whether functional connectivity estimated from task fMRI data can predict task selectivity in visual, language, and spatial working memory tasks, at the individual subject level. We find that connectivity derived from these task contexts predicts responses comparably to connectivity derived from resting-state data. This pattern held across the three controlled cognitive localizers acquired within the same preprocessing framework. These findings suggest that task fMRI can capture fine-grained individual differences in brain network architecture that are comparable to those captured at rest, broadening the potential utility of task data for investigating functional organization of brain networks.

PMID:42716360 | DOI:10.1016/j.neuroimage.2026.122211

Biol Psychiatry Cogn Neurosci Neuroimaging. 2026 Sep 9:S2451-9022(26)00258-2. doi: 10.1016/j.bpsc.2026.09.002. Online ahead of print.

ABSTRACT

BACKGROUND: Few human imaging studies investigate psychotogenic models during late adolescence. The "triple network" model posits that hallucinations are related to abnormal connectivity among the frontoparietal (FPN), default mode (DMN) and salience/cingulo-opercular (CON) networks but has not been tested during this age range, and is not well integrated with the hyper-dopaminergic model of psychosis.

METHODS: We performed a cross-sectional analysis of 171 14-17 year-old community adolescents. Hallucinatory experience severity was measured using the Specific Psychotic Experiences Questionnaire. Resting-state functional connectivity was calculated among a priori DMN, FPN, and CON cortical regions. Long-term dopaminergic function was assessed using neuromelanin-sensitive MRI (NM-MRI) in the ventral tegmental area (VTA). We examined associations between hallucinatory experience severity, network-based connectivity, and VTA NM-MRI.

RESULTS: Greater hallucinatory experience severity was associated with higher connectivity in a subnetwork composed of CON-DMN and CON-FPN edges, as well as with lower global system segregation. While VTA NM-MRI was not associated with hallucinatory experience severity, it negatively correlated with connectivity in the hallucination-related subnetwork and positively correlated with DMN connectivity among midline regions.

CONCLUSIONS: Among 14-17-year-old community dwelling youth, abnormal triple network connectivity was associated with hallucination severity, replicating similar studies in psychotic adults. Long-term dopamine function and hallucination severity were associated with some similar aspects of the triple network. Pediatric studies of prodromal psychosis may benefit from tracking developmental trajectories of triple network connectivity, dopaminergic function, and hallucination-like phenomena.

PMID:42716338 | DOI:10.1016/j.bpsc.2026.09.002

Brain Res Bull. 2026 Sep 9:112115. doi: 10.1016/j.brainresbull.2026.112115. Online ahead of print.

ABSTRACT

OBJECTIVE: This study combined static and dynamic amplitude of low-frequency fluctuation (sALFF and dALFF) to investigate the abnormalities of local spontaneous brain activity in patients with chronic tinnitus and their relationships with the spatial distributions of multiple neurotransmitters, thereby providing a theoretical basis for understanding the neural mechanisms underlying chronic tinnitus.

METHODS: This study included 80 patients with chronic tinnitus and 68 healthy controls. Resting-state functional magnetic resonance imaging (rs-fMRI) data were used to calculate sALFF and dALFF metrics in both groups, and between-group differences were subsequently compared. Furthermore, the relationships between ALFF alterations and neurotransmitter distributions in patients with chronic tinnitus were analyzed.

RESULTS: Compared with the healthy control group, the sALFF value in the left superior temporal gyrus of patients with chronic tinnitus was significantly increased, and the dALFF value in the right precuneus was significantly decreased (GRF correction, voxel level P<0.001, cluster level P<0.05). Moreover, the alterations of sALFF correlated with the spatial distribution of serotonin transporter, dopamine, glutamate systems, and GABAergic, and the alterations of dALFF correlated with the spatial distribution of serotonin transporter, dopaminergic, and the vesicular acetylcholine transporter (VAChT).

CONCLUSIONS: Chronic tinnitus exhibits not only abnormalities in sALFF, but also aberrant dynamic temporal fluctuations, which spatially correlate with the distribution patterns of different neurotransmitter systems, thereby deepening the understanding of the neural mechanisms underlying chronic tinnitus.

PMID:42716315 | DOI:10.1016/j.brainresbull.2026.112115

PNAS Nexus. 2026 Aug 24;5(9):pgag285. doi: 10.1093/pnasnexus/pgag285. eCollection 2026 Sep.

ABSTRACT

Understanding how intrinsic brain dynamics are organized is critical for explaining cognition and sensory processing. Theoretical frameworks propose a hierarchical architecture in which some neural systems behave as orchestrators, broadcasting information across the brain, whereas others serve as net receivers (integrators), transforming incoming signals. Here, we test whether this orchestration-integration framework is embedded in intrinsic brain activity, that is, in the absence of cognitive/sensorial tasks. We adopt a multivariate fractional modeling framework originally developed in financial mathematics to characterize how volatility propagates across interacting markets, thereby identifying systems that act as orchestrators or integrators. We then test whether this integrator-orchestrator axis is related to human intelligence. To this end, using 7T resting-state functional magnetic resonance imaging data from 173 healthy young adults, we model spontaneous brain fluctuations with a multivariate fractional Ornstein-Uhlenbeck process to derive directional influence indices. Consistent with our predictions, we identified a bipartite organization, stable across modeling choices. At the subcortical level, the anterior thalamus, putamen, and caudate emerged as orchestrating transmitters, whereas the posterior thalamus, globus pallidus, hippocampus, amygdala, and nucleus accumbens acted as integrating receivers. At the cortical level, attentional and sensory networks functioned as orchestrating transmitters, while higher-order cognitive networks served as integrating receivers. These findings provide support for a theoretically grounded integration-orchestration framework, showing that directional asymmetries in brain spontaneous fluctuations are organized along this axis, with a moderate association with intelligence scores. The proposed fractional framework offers a principled tool to investigate how disruptions of this balance may contribute to brain disorders.

PMID:42713480 | PMC:PMC13552504 | DOI:10.1093/pnasnexus/pgag285

Front Hum Neurosci. 2026 Aug 25;20:1873697. doi: 10.3389/fnhum.2026.1873697. eCollection 2026.

ABSTRACT

INTRODUCTION: This study used ATC students with a comparable civil aviation educational background and aviation-related cognitive demands, but no actual flight experience, as the control group. This study aimed to systematically compare the performance of static and dynamic functional connectivity in distinguishing flight cadets and to explore time-varying brain network characteristics associated with flight training.

METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 39 flight cadets and 37 ATC students, from which static functional connectivity (sFC) and dynamic functional connectivity (dFC) features were extracted. Following feature selection, five classifiers, including Support Vector Machine (SVM), eXtreme Gradient Boosting (XGBoost), Random Forest (RF), Gaussian Naive Bayes (GNB), and K-Nearest Neighbors (KNN), were systematically evaluated.

RESULTS: The primary analysis showed that dFC generally achieved better classification performance than sFC. The optimal dFC-SVM model reached an Area Under the ROC Curve (AUC) of 0.949, with an accuracy of 0.895, a sensitivity of 0.945, and a specificity of 0.848, whereas the best sFC model achieved an AUC of only 0.828. Under a more stringent supplementary validation procedure, the dFC-SVM and sFC-SVM models achieved AUCs of 0.65 and 0.59, respectively. The window-length sensitivity analysis showed that model performance remained within a similar range across the tested window lengths. High-contribution connections identified in the primary analysis involved brain regions such as the left insula and parahippocampal gyrus and were distributed across the Default Mode Network (DMN), Central Executive Network (CEN), and Sensorimotor Network (SMN).

DISCUSSION: Taken together, dFC may contain additional time-varying discriminative information beyond static connectivity. However, the magnitude of this advantage was limited in the supplementary validation, and the related findings should be regarded as preliminary evidence requiring further validation. By adopting a comparable control design within the aviation domain, this study further characterized neurofunctional representations associated with flight training experience and provided neuroimaging clues for subsequent longitudinal validation incorporating training stage, behavioral performance, and flight performance, as well as for exploring adaptive monitoring of flight training and multidimensional auxiliary assessments.

PMID:42713245 | PMC:PMC13551478 | DOI:10.3389/fnhum.2026.1873697

Front Psychiatry. 2026 Aug 25;17:1825054. doi: 10.3389/fpsyt.2026.1825054. eCollection 2026.

ABSTRACT

OBJECTIVE: This study aimed to investigate alterations in functional connectivity (FC) of the nucleus accumbens (NAc) in patients with persistent postural-perceptual dizziness (PPPD) using resting-state functional magnetic resonance imaging (rs-fMRI), and to examine the relationship between aberrant FC and clinical characteristics.

METHODS: Twenty-four patients with PPPD and 25 age and gender matched healthy controls (HCs) were enrolled. Rs-fMRI data was preprocessed using DPABI. The bilateral NAc were selected as seed regions, and seed-to-voxel FC analysis was performed. FC differences between groups were assessed using two-sample t-tests with age, sex, HAMA, and HAMD scores as covariates (voxel-level FDR-corrected q < 0.05). Correlation analysis was conducted between abnormal FC values and clinical variables.

RESULTS: Compared with HCs, patients with PPPD exhibited significantly enhanced FC between the right NAc and the left superior occipital gyrus (Occipital_Sup_L; peak MNI: -24, -96, 24; T value = 4.35; voxel-level FDR-corrected q < 0.001), as well as between the right NAc and the right Inferior Frontal Gyrus, Orbital part (Frontal_Inf_Orb_R; peak MNI: 39, 45, -3; T value = 4.90; voxel-level FDR-corrected q < 0.001). No significant FC abnormalities were detected for the left NAc seed. Correlation analysis revealed a significant negative correlation between the FC value of right NAc to left superior occipital gyrus and disease duration in PPPD patients (r = -0.61, FDR-corrected q = 0.03).

CONCLUSION: Patients with PPPD exhibit enhanced FC between the right NAc and visual- and emotion-related cortical regions, including the superior occipital gyrus and orbitofrontal cortex. The negative correlation with disease duration suggests that these FC alterations may be most pronounced in the early stages of the disorder. These findings provide new insights into the neural mechanisms of visual dependence and emotional dysregulation in PPPD.

PMID:42712887 | PMC:PMC13550862 | DOI:10.3389/fpsyt.2026.1825054

Front Neurosci. 2026 Aug 25;20:1879109. doi: 10.3389/fnins.2026.1879109. eCollection 2026.

ABSTRACT

INTRODUCTION: Pediatric mild traumatic brain injury (pmTBI) constitutes 70-90% of childhood traumatic brain injury cases. While magnetic resonance imaging (MRI) reveals subtle brain alterations, fragmented evidence across modalities limits understanding of long-term neurobiological consequences.

METHODS: This systematic review synthesized 42 studies from MEDLINE/PubMed, Web of Science, Cochrane Library, and Scopus (inception to December 2025) employing structural MRI and functional MRI (fMRI). Methodological quality was assessed using a modified GRADE framework.

RESULTS: White matter investigations (n = 18) suggested widespread microstructural alterations in limbic and commissural pathways-alongside reduced global network efficiency and disrupted hub connectivity in executive and salience networks. Gray matter studies (n = 9) identified regional cortical thinning in prefrontal and parietal regions, hippocampal atrophy persisting up to 1 year. Resting-state fMRI studies (n = 5) revealed diminished default mode network (DMN) integrity and elevated striatal spontaneous activity. Task-based fMRI studies (n = 10) demonstrated compensatory hyperactivation during working memory and inhibitory tasks-manifesting as enhanced preparatory activation but resource depletion during execution-alongside lower DMN deactivation and persistent cerebrovascular reactivity abnormalities extending to chronic phases.

DISCUSSION: In sum, multimodal MRI provides evidence suggesting systematic structural and functional alterations in pmTBI encompassing white matter disruption, gray matter vulnerability, and network reorganization.

PMID:42712630 | PMC:PMC13550148 | DOI:10.3389/fnins.2026.1879109

Front Hum Neurosci. 2026 Aug 25;20:1900612. doi: 10.3389/fnhum.2026.1900612. eCollection 2026.

ABSTRACT

BACKGROUND: Traumatic brain injury is frequently followed by persistent executive dysfunction linked to disruption of frontal and frontoparietal networks. High-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) has been proposed as a potential adjunctive intervention to support frontal-network recovery. Still, evidence remains heterogeneous and biomarker-guided interpretation is limited.

METHODS: This retrospective multicenter observational cohort study evaluated adults with traumatic brain injury and persistent executive dysfunction who received standard neurorehabilitation with or without adjunctive high-frequency rTMS. Patients were classified into an rTMS-exposed cohort and a non-rTMS comparison cohort according to documented treatment exposure. Primary outcomes were changes in Frontal Assessment Battery (FAB) and MoCA executive-domain scores. Secondary outcomes included Glasgow Outcome Scale-Extended and Trail-Making Test A/B performance. Multimodal biomarkers included TMS-EEG N100/P200 amplitudes, fNIRS task-evoked left DLPFC oxyhemoglobin (HbO2) response, and resting-state fMRI DLPFC-frontoparietal connectivity. Adjusted regression analyses were performed to estimate associations between documented rTMS exposure and study outcomes.

RESULTS: Forty-eight patients were included, with 24 in the rTMS-exposed cohort and 24 in the non-rTMS comparison cohort. Documented rTMS exposure was associated with greater improvement in FAB score at post-treatment assessment (+3.1 points; 95% CI, 1.6 to 4.6; p < 0.001) and MoCA executive-domain score (+2.8 points; 95% CI, 1.3 to 4.3; p = 0.001). Functional recovery and Trail-Making Test performance also favored the rTMS-exposed cohort. Biomarker analyses showed greater N100/P200 modulation, increased left DLPFC HbO response, and stronger DLPFC-frontoparietal connectivity. Observed biomarker changes were correlated with executive-function improvement; however, these associations should be interpreted as exploratory and hypothesis-generating given the observational design and limited sample size. Adverse events were mild, with no documented seizures or serious adverse events.

CONCLUSION: High-frequency left-DLPFC rTMS exposure was associated with improved executive recovery and measurable frontal-network modulation after traumatic brain injury. These findings suggest that multimodal neurophysiological and imaging biomarkers may provide useful measures of target engagement for future prospective studies. Given the retrospective observational design, modest sample size, and short-term follow-up, causal inferences regarding treatment effects or biomarker-guided neurorehabilitation cannot be established.

PMID:42712626 | PMC:PMC13549988 | DOI:10.3389/fnhum.2026.1900612

Front Neurol. 2026 Aug 25;17:1824731. doi: 10.3389/fneur.2026.1824731. eCollection 2026.

ABSTRACT

AIM: Episodic Migraine (EM) is a highly prevalent and disabling neurological disorder. Recent therapeutic advances have targeted the calcitonin gene-related peptide (CGRP), a neuropeptide implicated in the pathophysiology of migraine. Promising outcomes have been obtained with monoclonal antibodies and, more recently, with a new class of drugs consisting of small-molecule CGRP receptor antagonists, known as gepants. Atogepant, an oral agent of the gepant class, has demonstrated efficacy in migraine prevention, yet its effects on central brain activity and neurotransmitter circuits remain largely unclear. This exploratory study investigates changes in brain functional connectivity and changes related to key neurotransmitter systems, following 12 weeks of treatment with atogepant in a group of EM patients.

METHODS: This is an exploratory single-arm longitudinal study assessing clinical and neuroimaging changes before and after 12 weeks of atogepant treatment. We enrolled patients diagnosed with EM according to ICHD-3 criteria, without prior exposure to anti-CGRP therapies. Participants underwent clinical assessments (monthly migraine days MMD, acute drugs intake MAM) and resting-state functional MRI (rs-fMRI) before and after 12 weeks of treatment with atogepant 60 mg once daily. Longitudinal functional connectivity analyses were performed at the whole-brain level with a region-of-interest analysis. Additionally, longitudinal neurotransmitter-related functional connectivity was investigated within the serotoninergic and the dopaminergic systems.

RESULTS: A total of 15 patients completed the evaluation. A significant group-level reduction in MMD (T = -7.09, p < 0.001) and MAM (T = -6.35, p < 0.001) following 12 weeks of atogepant treatment was observed, accompanied by a reduction of allodynia symptoms, albeit not statistically significant. Patients exhibited significant longitudinally increased functional connectivity, involving the right superior frontal gyrus, bilateral putamen, left pallidum, left anterior and bilateral posterior cingulate cortex. The greater the longitudinal increase in anterior-posterior cingulate cortices connectivity, the larger the improvement in MMD, MAM, and allodynia symptoms after treatment. Additionally, longitudinal connectivity changes were observed within the orbitofrontal cortex in the mesocorticolimbic dopaminergic system.

DISCUSSION: In this exploratory cohort, significant clinical improvement after atogepant treatment was accompanied by longitudinal functional connectivity changes in EM patients. These preliminary findings may reflect either direct or indirect central modulation linked to atogepant treatment. A deeper understanding of the observed central changes may help to clarify the mechanisms underlying anti-CGRP therapies for migraine.

PMID:42712363 | PMC:PMC13549835 | DOI:10.3389/fneur.2026.1824731

Neuro Oncol. 2026 Sep 8:noag223. doi: 10.1093/neuonc/noag223. Online ahead of print.

ABSTRACT

BACKGROUND: Glioblastoma (GBM) is traditionally viewed as disrupting brain network connectivity. Recent evidence of tumor-neuron synaptic interactions suggests gliomas may actively engage with the brain. We hypothesized that GBM tumors contain functionally distinct intratumoral subregions that differentially couple with resting-state networks (RSNs) and carry prognostic significance.

METHODS: We applied fuzzy c-means clustering to resting-state fMRI data from 190 GBM patients to identify and count the number of intratumoral functional subregions. We used the participation ratio, a PCA-derived measure of signal dimensionality, as a continuous variable complement to cluster number. Cluster-level BOLD time series were correlated with seven canonical RSNs and compared to tumor location-matched voxels in 347 healthy subjects. Associations with survival and preoperative seizures were evaluated using Kaplan-Meier analysis, restricted mean survival time (RMST), multivariable Cox proportional hazards modeling, and multivariable logistic regression.

RESULTS: Fifty-two of 190 GBMs exhibited multiple intratumoral functional clusters. Multi-cluster tumors were associated with longer survival and higher seizure prevalence. Elevated RSN coupling was more prevalent in multi-cluster tumors as compared to single-cluster tumors, with elevated coupling strongly predicting multi-cluster status. Distinct clusters often showed preferential coupling to different RSNs.

CONCLUSIONS: A subset of GBM contains functionally distinct subregions that selectively engage large-scale brain networks, a pattern associated with favorable survival and increased seizure risk. These findings support a model in which certain tumors function as active participants within neurovascular networks, indicating a novel network-integrated subtype of GBM with implications for prognosis and disease staging.

PMID:42711254 | DOI:10.1093/neuonc/noag223

Exp Neurol. 2026 Sep 8:115991. doi: 10.1016/j.expneurol.2026.115991. Online ahead of print.

ABSTRACT

STUDY OBJECTIVES: Our primary objective was to characterize the mechanism that underlies fine motor deficits in Pediatric obstructive sleep apnea (POSA) using a preclinical mouse model of the disease. Our goal was to use a systematic approach to characterize neuroanatomical lesions in POSA mice and identify potential molecular drivers of the fine motor changes in this preclinical model of POSA.

METHODS: We used our established mouse model of POSA to characterize fine motor deficits using four approaches: a) neurobehavioral deficiencies in motor function with a focus on fine versus gross motor skills; b) resting state functional magnetic resonance imaging (rs-fMRI) as well as diffusion tension imaging (DTI); c) immunostaining of oligodendrocyte markers using a lineage tracing mouse, and d) the oligodendrocyte transcriptome using single-nucleus RNA sequencing.

RESULTS: POSA mice showed deficits in fine motor function without changes in gross motor function when compared with controls. DTI showed no significant differences between groups in gross motor tractography; however, rs-fMRI revealed region-to-region connection differences in POSA mice. Immunostaining showed fewer oligodendrocyte progenitor cells with no reduction in mature oligodendrocytes in POSA mice as compared to controls. The oligodendrocyte transcriptome in POSA mice identified many upregulated and downregulated genes involved in oligodendrocyte function and differentiation.

CONCLUSIONS: Consistent with neurological findings in POSA, these POSA mice showed deficits in fine motor skills. The molecular mechanism for the disruption of neuronal circuits involved the loss of developmental myelination, which may contribute to fine motor impairments in POSA.

PMID:42710774 | DOI:10.1016/j.expneurol.2026.115991