Most recent paper

Int Neurourol J. 2026 Mar;30(1):63-72. doi: 10.5213/inj.2550210.105. Epub 2026 Mar 31.

ABSTRACT

PURPOSE: Changes in regional brain activity and functional connectivity (FC) in patients with neurogenic detrusor overactivity (NDO) following spinal cord injury (SCI) remain unclear. This study used resting-state functional magnetic resonance imaging (fMRI) to investigate regional brain activity and FC in NDO patients after SCI.

METHODS: Resting-state fMRI scans were obtained from 20 NDO patients after SCI and 20 healthy controls (HCs). Regional brain activity was measured using regional homogeneity (ReHo). Subsequently, a seed-based whole-brain FC analysis was performed using the regions with significantly different ReHo as seeds. Partial correlation analysis was conducted to examine the relationship between FC values and clinical scores in the NDO patients with SCI.

RESULTS: Compared to HC, patients with NDO exhibited significantly decreased ReHo in the right medial frontal gyrus (MFG). Furthermore, compared to HC, NDO patients demonstrated stronger FC between the seed (right MFG) and voxels in the left pyramis, right cerebellum posterior lobe, and left middle temporal gyrus. Weaker FC was observed between the seed (right MFG) and voxels in the right paracentral lobule. Correlation analyses revealed that the Overactive Bladder Symptom Score and urgency urinary incontinence scores were positively correlated with FC values between the right MFG and the left pyramis.

CONCLUSION: SCI-related NDO patients exhibit abnormalities in both regional brain activity and FC, with supraspinal connectivity deviation extent associated with the severity of lower urinary tract symptom. This study contributes to a better understanding of the potential supraspinal neural mechanisms underlying SCI-related NDO.

PMID:41942338 | DOI:10.5213/inj.2550210.105

Andrology. 2026 Apr 6. doi: 10.1111/andr.70233. Online ahead of print.

ABSTRACT

INTRODUCTION: Delayed ejaculation (DE) is a common sexual dysfunction with unclear neurobiological mechanisms. Few studies have explored its neural substrates using functional magnetic resonance imaging (fMRI), especially combining resting-state and task-state paradigms.

METHODS: Forty-two DE patients and 36 healthy controls (HCs) were enrolled. Clinical data (demographics, IIEF-5, GAD-7, PHQ-9, serum testosterone) and fMRI data (resting-state and visual sexual stimulation-induced task-state) were collected. Data were analyzed using regional homogeneity (ReHo), fractional amplitude of low-frequency fluctuations (fALFF), independent component analysis (ICA), and functional connectivity assessments.

RESULTS: Demographically, DE patients and HCs showed no differences in height, weight, or BMI (all p > 0.05), but DE patients had lower serum total testosterone, reduced IIEF-5 scores, and higher GAD-7/PHQ-9 ratings (all p < 0.05), with higher comorbidity of erectile dysfunction, anxiety, and depression. Resting-state fMRI revealed no significant voxel-wise differences in ReHo or fALFF between groups (all p > 0.05). However, during visual sexual stimulation, the two groups exhibited diametrically opposite responses in sensorimotor network regions. For ReHo, the bilateral precentral gyrus, postcentral gyrus, and rolandic operculum exhibited significant inhibition in DE patients (e.g., PoCG.L: T = -6.56) and robust activation in HCs (e.g., PoCG.L: T = 7.57). For fALFF, DE patients showed inhibition in these regions, including the supplementary motor area and the middle cingulate gyrus, whereas HCs activated them; post-correction, DE patients still showed significant inhibition in the left precentral/postcentral gyrus compared with the HC group. (e.g., PoCG.L: T = -4.44). ICA identified the parahippocampal gyrus (PHG) as a dual-functional hub-core node of the default mode network and cross-network connector-with disrupted functional connectivity to supplementary motor area, inferior parietal lobule, and temporal regions in DE patients.

CONCLUSIONS: DE is associated with stimulus-dependent neural dysregulation rather than inherent resting-state abnormalities. Inhibition of the sensorimotor network and PHG-centered connectivity disruption underlie DE's neurobiological basis, providing potential targets for clinical interventions.

PMID:41940829 | DOI:10.1111/andr.70233

Front Neurol. 2026 Mar 19;17:1756996. doi: 10.3389/fneur.2026.1756996. eCollection 2026.

ABSTRACT

BACKGROUND: High myopia (HM) is a common eye disorder which has become a public health problem globally. Previous neuroimaging studies demonstrated that HM is associated with brain structural abnormalities, whereas the spontaneous brain activity changes in HM are not well studied.

METHODS: 30 HM patients and 31 healthy controls were included in this study. The altered spontaneous brain activity in HM patients and their relationships with disease durations were explored, using amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF) and regional homogeneity (ReHo) methods based on resting-state functional MRI.

RESULTS: Compared with controls, HM patients showed significant increased ALFF in the left insula, hippocampus, increased fALFF in the right hippocampus, calcarine fissure, superior temporal gyrus, lingual gyrus, increased ReHo in the left middle frontal gyrus, calcarine fissure and right cingulate gyrus, and decreased ALFF, fALFF in the left inferior frontal gyrus (opercular part), left inferior parietal lobule respectively. Besides, the mean ALFF value of left hippocampus and the mean ReHo value of left middle frontal gyrus exhibited significantly positive correlations with disease duration, and the mean fALFF value of left inferior parietal lobule showed significantly negative correlations with disease duration.

CONCLUSION: HM patients associated with neural dysfunctions in the vision network, attention network and limbic system, which may implicate the presence of neurobiological changes involving deficits in sensorimotor, vision and limbic system in HM patients, providing early useful diagnostic biomarkers for HM as well.

PMID:41940298 | PMC:PMC13043415 | DOI:10.3389/fneur.2026.1756996

Front Neurol. 2026 Mar 20;17:1758013. doi: 10.3389/fneur.2026.1758013. eCollection 2026.

ABSTRACT

INTRODUCTION: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by involuntary motor and phonic tics, with diagnosis often delayed due to the 1-year symptom duration criterion. This study aimed to explore early neuroimaging biomarkers of TS in young children, by investigating spatiotemporal alterations in dynamic brain network connectivity in 4-6-year-old children with TS.

METHODS: This retrospective case-control study collected resting-state functional magnetic resonance imaging (fMRI) data from 24 children aged 4-6 years, including 12 drug-naive TS patients and 12 matched healthy controls (N group). Group Independent Component Analysis (GICA) and Independent Vector Analysis (IVA) were used to assess group differences in temporal and spatial dynamic functional network connectivity (FNC), respectively. Correlations between these connectivity alterations and Yale Global Tic Severity Scale (YGTSS) scores as well as disease duration were analyzed.

RESULTS: Statistically significant between-group differences were found in temporal dynamic FNC (p < 0.05), with marginal differences observed in spatial dynamic connectivity (p < 0.1), primarily involving the ventral default mode network (VDMN), primary visual network (PVN), and precuneus network (PCN). The N group showed a wider range and higher strength of FNC values, while the TS group exhibited abnormally enhanced connectivity in the insula region, which was positively correlated with disease duration.

DISCUSSION: This study revealed abnormal temporal and spatial dynamic brain network connectivity in young children at the early stage of TS, particularly in insula-related circuits. These findings provide novel insights into the early neuropathological mechanisms of TS and support the potential of dynamic FNC metrics as early imaging biomarkers for TS in young children.

PMID:41940292 | PMC:PMC13046543 | DOI:10.3389/fneur.2026.1758013

Front Neurol. 2026 Mar 20;17:1782025. doi: 10.3389/fneur.2026.1782025. eCollection 2026.

ABSTRACT

OBJECTIVE: This study aimed to investigate white matter microstructural damage, spontaneous brain activity, and functional connectivity alterations in patients with thyroid-associated ophthalmopathy (TAO) and visual impairment using multimodal MRI.

METHODS: Forty-five TAO patients with visual impairment and 32 healthy controls (HCs) underwent diffusion kurtosis imaging (DKI) and resting-state functional MRI (rs-fMRI). Microstructural changes along the visual pathway were quantified using fractional anisotropy (FA), mean kurtosis (MK), and mean diffusivity (MD). Regional spontaneous activity was assessed using the amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF), and seed-based functional connectivity (FC) analyses were employed. Group differences were examinded using two-sample t-tests with false discovery rate (FDR) correction (p < 0.05). Correlations between imaging parameters and clinical indicators were further analyzed.

RESULTS: Compared with HCs, the TAO group showed significantly decreased MK, FA, and MD values in the optic radiation, lateral geniculate body, optic tract, and optic nerve, with MK being the most markedly reduced one. Patients also exhibited increased ALFF in the right parahippocampal gyrus and decreased ALFF in the left calcarine fissure, as well as decreased fALFF in the left calcarine fissure and postcentral gyrus. Further analyses revealed decreased FC between the left calcarine fissure and the right lingual gyrus/middle frontal gyrus/bilateral postcentral gyri, and increased FC with the left supplementary motor area/fusiform gyrus. ALFF/fALFF in visual network-related regions correlated with proptosis and extraocular muscle thickening in TAO patients.

CONCLUSION: TAO is associated with white matter microstructural damage, aberrant spontaneous neural activity, and functional reorganization. The combination of DKI and rs-fMRI (ALFF/fALFF, FC) may provide comprehensively insights into central neuropathological mechanisms, providing a basis for early diagnosis and targeted intervention.

PMID:41940287 | PMC:PMC13046559 | DOI:10.3389/fneur.2026.1782025

Brain Commun. 2026 Mar 24;8(2):fcag106. doi: 10.1093/braincomms/fcag106. eCollection 2026.

ABSTRACT

Emerging evidence indicates that stroke may impair glymphatic function by disrupting cerebrospinal fluid clearance. The coupling between global blood-oxygen-level-dependent signals and cerebrospinal fluid flow has been proposed as a non-invasive biomarker of glymphatic activity. However, it remains unclear whether this coupling can be modulated through rehabilitation. This study investigated whether language therapy in patients with post-stroke aphasia enhances global blood-oxygen-level-dependent- cerebrospinal fluid coupling, thereby reflecting potential restoration of fluid-brain interaction. This longitudinal observational study was conducted at a single centre and included 20 patients with post-stroke aphasia and 35 age- and sex-balanced healthy controls. All participants underwent MRI scanning, including resting-state blood-oxygen-level-dependent and structural imaging. Among the post-stroke aphasia group, 14 patients completed both pre- and post-treatment assessments after undergoing a standardized 4-week speech-language therapy programme. The Western Aphasia Battery was used to quantify language deficits and monitor treatment-related changes. Global blood-oxygen-level-dependent-cerebrospinal fluid coupling was quantified using cross-correlation analysis across the whole brain and four predefined language-related resting-state networks. At baseline, patients exhibited significantly reduced global blood-oxygen-level-dependent-cerebrospinal fluid coupling compared to healthy controls (P < 0.05). Following therapy, coupling significantly increased within the language, salience and dorsal attention networks, whereas coupling within the default mode network significantly decreased (all P < 0.05). Notably, increased global blood-oxygen-level-dependent-cerebrospinal fluid coupling in specific networks was significantly correlated with improvements in targeted language functions, such as object naming, responsive naming and auditory word recognition (P < 0.05). These findings suggest that language rehabilitation enhances neurophysiological coupling between brain activity and cerebrospinal fluid flow, potentially reflecting restoration of fluid-brain interaction in post-stroke aphasia.

PMID:41940189 | PMC:PMC13049551 | DOI:10.1093/braincomms/fcag106

Imaging Neurosci (Camb). 2026 Apr 2;4:IMAG.a.1109. doi: 10.1162/IMAG.a.1109. eCollection 2026.

ABSTRACT

Transcranial direct current stimulation (tDCS) is a non-invasive form of neuromodulation. Previous work has shown that tDCS affects functional connectivity, typically assessed by comparing resting-state functional MRI (rs-fMRI) data collected before and after the intervention. This study focuses on the temporal dynamics of functional connectivity during tDCS. Additionally, electric field simulations are incorporated in functional connectivity analyses to gain more insights into the mechanism of action. Forty-seven healthy female volunteers were enrolled in a randomized, sham-controlled, cross-over design in which sham and active tDCS were administered to the left dorsolateral prefrontal cortex for 20 min at 1.5 mA. Functional connectivity analyses were performed on rs-fMRI data collected before, during, and after tDCS, using three seed regions in the brain: one under the anode, one under the cathode, and one at the brain region where the individual tDCS-induced electric field strength was highest. The rs-fMRI data collected during stimulation were divided into three time windows to obtain temporal information on functional connectivity during stimulation. Functional connectivity was assessed at the whole-brain level using seed-to-voxel analyses as well as within predefined resting-state networks. TDCS did not consistently change functional connectivity over time. On the whole-brain level, active tDCS did not affect functional connectivity during stimulation. After active stimulation, only the functional connectivity between the cathode and the postcentral gyrus was increased. At the network level, changes in functional connectivity were observed following both sham and active tDCS, indicating that these effects could not be specifically attributed to active stimulation. Future research should further investigate the relationship between tDCS-induced effects on functional connectivity and their potential links to clinical responses.

PMID:41938662 | PMC:PMC13047502 | DOI:10.1162/IMAG.a.1109

JAACAP Open. 2025 Nov 27;4(2):254-267. doi: 10.1016/j.jaacop.2025.11.008. eCollection 2026 Apr.

ABSTRACT

OBJECTIVE: The pathophysiology of attention-deficit/hyperactivity disorder (ADHD) is complicated by high rates of psychiatric comorbidities; thus, delineating unique vs shared functional brain perturbations is critical in elucidating illness pathophysiology. We investigated resting-state functional magnetic resonance imaging (rsfMRI)-complexity alterations among children with ADHD, oppositional defiant disorder (ODD), and obsessive-compulsive disorder (OCD), respectively, and comorbid ADHD, ODD, and OCD, within the cool and hot executive function (EF) networks.

METHOD: We leveraged baseline data from 9- to 10-year-old children in the Adolescent Brain and Cognitive Development (ABCD) Study. Data for children who singularly met all DSM-5 behavioral criteria for ADHD (n = 61), ODD (n = 38), and OCD (n = 48), respectively, were extracted, alongside data for children with comorbid ADHD, ODD, OCD, and/or other psychiatric diagnoses (n = 833). Data for a control sample of age-, sex-, and developmentally matched children were also extracted (N = 269). Voxel-wise sample entropy (SampEn) was computed using the LOFT Complexity Toolbox. Mean SampEn within all regions of interest (ROIs) of the EF networks was calculated for each participant. Hierarchical models with generalized estimating equations compared SampEn of comorbidity-free and comorbid ADHD, ODD, and OCD within the EF networks.

RESULTS: SampEn was reduced in comorbidity-free ADHD and ODD in overlapping regions of both EF networks compared with the healthy controls, including the bilateral superior frontal gyrus, anterior/posterior cingulate gyrus, and bilateral caudate (Wald statistic = 5.682-10.798, p < .05, and Benjamini-Hochberg [BH] corrected), with ADHD additionally affected in the right inferior/middle frontal gyrus and bilateral frontal orbital cortex (Wald statistic = 7.231-9.420, p < 0.05, and BH corrected). Among comorbid presentations, the presence of ADHD symptomatology was associated with significantly lower SampEn in every ROI (z = -3.973 to -2.235, p < .05, and BH corrected).

CONCLUSION: ADHD and ODD shared common impairments underlying the EF networks in the comorbidity-free presentations, with ADHD showing more widespread complexity reduction. When ADHD co-occurred with other psychiatric disorders, the reduction in SampEn extended beyond the regions affected in comorbidity-free ADHD, indicating that comorbidities amplify neural complexity deficits. In contrast, no significant SampEn alterations were observed in OCD, whether presented alone or in combination with ADHD.

PMID:41938226 | PMC:PMC13043473 | DOI:10.1016/j.jaacop.2025.11.008

J Affect Disord. 2026 Apr 3:121743. doi: 10.1016/j.jad.2026.121743. Online ahead of print.

ABSTRACT

Increasing attention has been paid to the nonlinear functional activity of human brain regions. This paper extends Chatterjee's correlation coefficient (CCC) method to model nonlinear relationships in brain functional networks explicitly. Specifically, the reliability and effectiveness comparisons between CCC and the Pearson correlation coefficient (PCC) are demonstrated using simulated data and two real resting-state functional magnetic resonance imaging (rs-fMRI) datasets: The Midnight Scan Club dataset and the UCLA dataset. The results demonstrate that CCC accounts for both linear and nonlinear dependencies and that its reliability is better than that of PCC. Additionally, from a whole-brain perspective, the number of connections in different brain regions was observed in the following order: bipolar disorder (BP) and healthy controls (HC) > adult attention-deficit/hyperactivity disorder (ADHD) and HC > schizophrenia (SZ) and HC. The commonalities among the three psychiatric disorders compared to HC were differences in occipital, default, cerebellum, and the regions connected to the occipital. Besides, using CCC: occipital performed classification best (AUC: 0.657) between ADHD and HC, and (AUC: 0.622) between BP and HC, but fronto_parietal performed classification best (AUC: 0.700) between SZ and HC. This method enhances sensitivity to group differences and may provide new insights for exploring functional networks based on fMRI in the future.

PMID:41936984 | DOI:10.1016/j.jad.2026.121743

Neurobiol Dis. 2026 Apr 3:107380. doi: 10.1016/j.nbd.2026.107380. Online ahead of print.

ABSTRACT

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy made a breakthrough in treating essential tremor (ET), but with variable tremor responses. This study employed support vector machine regression (SVR) to predict tremor response based on preoperative functional connectivity (FC) patterns.

METHODS: Fifty-six ET patients underwent unilateral MRgFUS thalamotomy and resting-state functional MRI (rs-fMRI). The Clinical Rating Scale for Tremor evaluated 12-month post-treatment responses. Two-sample t-tests identified disease-specific FC differences, which were used in SVR to predict responses. Model performance was evaluated using Pearson's correlation coefficient (r), mean squared error (MSE), and validated via permutation and cross-validation. Longitudinal rs-fMRI in 26 patients examined dynamic changes of the connection with the highest predictive contribution.

RESULTS: Patients demonstrated significant improvement in treated hand tremor at 12-month after thalamotomy (p < 0.001), with a mean improvement of 68%. While baseline tremor severity showed a significant negative correlation with treatment improvement (r = -0.37, p = 0.005), it failed to predict individual outcomes in regression models (linear regression: p = 0.98; SVR: p = 0.46). SVR identified a preoperative FC pattern that predicted tremor response (r = 0.38, p = 0.03; MSE = 0.05, p = 0.02). Longitudinal analysis demonstrated the restoration of the connection with the highest predictive contribution, which increased post-treatment (p = 0.005) and correlated with tremor improvement ratio (r = -0.49, p < 0.001).

CONCLUSION: Preoperative FC patterns predict tremor responses to MRgFUS in ET, serving as a potential imaging biomarker for personalized treatment planning.

PMID:41936873 | DOI:10.1016/j.nbd.2026.107380

J Affect Disord. 2026 Apr 2:121733. doi: 10.1016/j.jad.2026.121733. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the interaction between HPA-axis gene polymorphisms (FKBP5, NR3C1, AVPR1B, SLC1A3, SKA2) and brain functional alterations in adolescent depression.

METHODS: Between May 2021 and June 2024, 150 medication-naïve depressed adolescents and 44 healthy controls underwent HPA-axis SNP genotyping and resting-state fMRI scanning. Logistic regression was performed to evaluate SNP-depression associations, and chi-square tests were used to assess Hardy-Weinberg equilibrium (HWE) and genotype distributions. Imaging metrics (ALFF/fALFF/ReHo/FC) were analyzed via independent t-tests (group differences) and 2 × 2 ANOVA (diagnosis/genotype main effects + interaction) with FDR correction (p < 0.05), followed by depression score correlation analysis.

RESULTS: Among the examined HPA-axis gene polymorphisms, only SKA2-rs7208505 showed a significant association with depression, with G allele carriers exhibiting increased risk (OR = 1.751-2.321, p < 0.05), whereas NR3C1-rs41423247, AVPR1-rs28373064, FKBP5-rs9470080, and SLC1A3-rs2269272 showed no associations (all p > 0.05). Depressed adolescents exhibited elevated ALFF/ReHo in the right precentral gyrus (PreCG) /supplementary motor area (SMA) and increased sensorimotor network connectivity, but decreased ALFF in the cerebellum, angular gyrus, and precuneus (all p < 0.05, FDR-corrected). A Diagnosis×SKA2-rs7208505 interaction significantly modulated functional connectivity from right PreCG to bilateral inferior temporal and postcentral gyri (all p < 0.05, Bonferroni-corrected).

CONCLUSION: SKA2-rs7208505 was associated with adolescent depression, with the G allele conferring risk. A significant Diagnosis×SNP interaction was found for functional connectivity between the right PreCG and bilateral inferior temporal/postcentral gyri, indicating this SNP and brain functional alterations are linked to adolescent depression pathogenesis. These findings provide novel insights and support for early prevention and intervention strategies.

PMID:41935751 | DOI:10.1016/j.jad.2026.121733

Psychiatry Res. 2026 Mar 27;361:117126. doi: 10.1016/j.psychres.2026.117126. Online ahead of print.

ABSTRACT

OBJECTIVES: The purpose of this study was to investigate the changes of functional connectivity (FC) and its relationship with cognitive flexibility in patients with first-episode, treatment-naïve obsessive-compulsive disorder (OCD), using bilateral insula as seed regions.

METHODS: 45 OCD patients and 40 healthy controls (HC) were recruited to undergo a clinical symptom assessment, the Wisconsin Card Sorting Test (WCST), and rs-fMRI scans. Six seed regions in the bilateral insula were selected for whole-brain FC analyses. A two-sample t-test was utilized to compare the differences in FC between two groups. SPSS software was used to analyze the relationship between the strength of FC in different brain regions and cognitive flexibility in the OCD group using Pearson correlation.

RESULTS: Compared with the HC, FC between the left ventral anterior insula and left ventrolateral nucleus of thalamus was reduced in the OCD(p < 0.001), FC between the left dorsal anterior insula and right posterior central gyrus was increased (p < 0.001), and FC between the right dorsal anterior insula and right posterior central/middle temporal gyrus was increased (p < 0.001). FC between right dorsal anterior insula and right posterior central gyrus was significantly negatively correlated with cognitive flexibility(uncorrected p < 0.05). FC between left ventral anterior insula and left ventrolateral thalamus was positively correlated with cognitive flexibility(uncorrected p < 0.05). Finally, the FC between right dorsal anterior insula and right middle temporal gyrus was negatively correlated with cognitive flexibility (uncorrected p < 0.05).

CONCLUSION: Patients with OCD exhibit abnormal FC network involving insula, which are associated with cognitive flexibility, supporting a functional mechanism of cognitive inflexibility in OCD.

PMID:41935505 | DOI:10.1016/j.psychres.2026.117126

Phytomedicine. 2026 Mar 27;155:158127. doi: 10.1016/j.phymed.2026.158127. Online ahead of print.

ABSTRACT

BACKGROUND: Circadian rhythm disruption and chronic sleep deprivation are increasingly recognized as key contributors to depression, largely through gut-brain axis dysregulation and neuroinflammatory activation. IL-17A, a pro-inflammatory cytokine primarily derived from intestinal Th17 cells, has emerged as a pivotal mediator linking gut immune imbalance to central nervous system dysfunction.

PURPOSE: This study aimed to elucidate the gut-derived IL-17A-STAT3/RORγt signaling mechanism underlying sleep-deprivation-induced depression and to determine whether Schisandrin B, a lignan from Schisandra chinensis, can alleviate depressive phenotypes by restoring gut-brain axis homeostasis.

METHODS: Clinical analyses of plasma cytokines and metabolites were integrated with a mouse model of sleep-deprivation-induced depression. Behavioral tests, resting-state fMRI, gut microbiota 16S rDNA sequencing, Western blotting, ELISA, and network pharmacology with molecular docking were employed to comprehensively investigate neuroimmune, microbial, and neurofunctional alterations.

RESULTS: Patients with circadian rhythm disorder-related depression exhibited elevated IL-17A and systemic inflammatory cytokines, accompanied by metabolic dysregulation. Sleep-deprived mice showed depressive-like behaviors, intestinal barrier disruption, Th17/IL-17A pathway activation, and abnormal RS-fMRI activity in mood-regulating brain regions. Schisandrin B treatment markedly reversed these changes-restoring gut microbial balance, enhancing barrier integrity, suppressing IL-17A-driven inflammation, and normalizing neural function. Mechanistically, Schisandrin B inhibited STAT3 phosphorylation and RORγt expression, while targeting MAPK1 and GSK3β as key regulatory nodes.

CONCLUSION: This study identifies gut-derived IL-17A-STAT3/RORγt signaling as a mechanistic bridge between sleep deprivation and neuroinflammation, providing direct evidence for the immunological basis of circadian rhythm-related depression. By integrating multi-omics and neuroimaging validation, we demonstrate for the first time that Schisandrin B exerts antidepressant-like effects via coordinated modulation of the gut-brain-immune network. These findings highlight Schisandrin B as a promising natural immunomodulatory candidate for the treatment of mood disorders associated with disrupted circadian rhythms.

PMID:41935463 | DOI:10.1016/j.phymed.2026.158127

Biol Sex Differ. 2026 Apr 4. doi: 10.1186/s13293-026-00891-z. Online ahead of print.

ABSTRACT

BACKGROUND: Understanding the impact of biological sex on the functional organization and dynamics of the brain is crucial for elucidating sex-specific differences in cognitive functions and neuropsychiatric disorders. Systems neuroscience often models the brain as a network of interconnected brain regions with functional connectivity (FC), i.e., the correlation between signal time courses, serving as a measure of connection strength. FC matrices, here derived from resting-state functional magnetic resonance imaging (rs-fMRI), define a network graph that can be characterized by its level of module segregation or, inversely, integration. Such parameters can be generated for the full length of the acquired data (static) or for short periods implying dynamically changing brain states. We recently made the interesting observation in a separate study (N = 63) that measures of brain integration and segregation based on dynamic functional connectivity (dFC) data differed between sexes, while graph-based measures based on static FC (sFC) did not, which we investigated in more detail in this study.

METHODS: We preregistered a replication of our analysis from the small sample in N = 501 subjects of the Human Connectome Project dataset. We performed cross-sectional comparisons between sexes of the static rs-fMRI graph parameters modularity and global efficiency, as well as the dFC parameters state prevalence, mean dwell time, mean inter-state transition time, and variability derived from a two-state model. Additionally, we explored whether sex differences in 66 cognitive and behavioral parameters are mediated by the FC integration measure with the strongest sex effect.

RESULTS: All static and dynamic measures of integration/segregation showed higher levels of functional integration in males, with effect sizes up to 0.60 for the dFC parameter prevalence. For three of the 66 explored cognitive and behavioral parameters, we observed that the prevalence of the integrated state mediated the sex difference: dexterity, agreeableness, and self-reported aggression.

CONCLUSION: We found consistent evidence across two datasets that rs-fMRI-based measures of brain integration are increased in males. An exploratory analysis, which requires replication, suggests that such differences mediate personality differences. This study highlights that biological sex differences in brain functional organization may contribute to sex-typical behaviors.

PMID:41935261 | DOI:10.1186/s13293-026-00891-z

Neuroimage. 2026 Mar 31:121904. doi: 10.1016/j.neuroimage.2026.121904. Online ahead of print.

ABSTRACT

PURPOSE: Alzheimer's disease is characterized by progressive accumulation of hyperphosphorylated tau protein, which propagates in a prion-like manner along connected neuronal pathways. However, it remains unclear whether functional connectivity between gray and white matter (FCGW) can predict tau spread. This study aimed to determine the association between FCGW and tau deposition and to evaluate its value in predicting longitudinal tau spread.

METHODS: We integrated resting-state fMRI with cross-sectional and longitudinal tau-PET data from two independent cohorts. We assessed baseline associations between FCGW and tau deposition and then constructed an individual-level spreading model to predict longitudinal tau accumulation.

RESULTS: In both cohorts, FCGW showed a positive correlation with tau deposition. Model-simulated white-matter tau deposition was associated with clinical scales and predicted cognitive decline. The spreading model, which incorporated baseline tau-PET and the top 10% of gray and white matter, yielded the highest predictive performance for future tau accumulation.

CONCLUSION: FCGW captures key network pathways underlying tau spread in AD and improves prediction of future tau accumulation. These findings highlight the importance of FCGW in understanding tau propagation and support development of network-targeted therapeutic strategies.

PMID:41933844 | DOI:10.1016/j.neuroimage.2026.121904

J Affect Disord. 2026 Mar 31:121719. doi: 10.1016/j.jad.2026.121719. Online ahead of print.

ABSTRACT

Depressive symptoms frequently co-occur in individuals with Mild Cognitive Impairment (MCI) and are thought to accelerate neurodegenerative progression. However, the underlying neural mechanisms of Depressed MCI (DMCI) remain largely unclear. This study employed a multimodal resting-state functional magnetic resonance imaging (rs-fMRI) approach combined with advanced machine learning techniques, to systematically examine spontaneous brain activity patterns and topological organization differences among DMCI, non-depressed MCI (nDMCI), and non-depressed cognitively normal controls (nDCN). The research analyzed amplitude-based rs-fMRI measures and graph-theoretical features. Voxel-wise analyses and connectivity comparisons were conducted between groups. Additionally, classification tasks were performed using classical machine learning models and a graph reinforcement learning (GRL) model. DMCI individuals exhibited increased activity in the right insula and decreased amplitude of low-frequency fluctuation (ALFF) in the left calcarine cortex, along with heightened fractional ALFF (fALFF) and percent amplitude of fluctuation (PerAF) in the precuneus and parahippocampal regions. Graph metrics revealed disrupted global and local efficiency in nDMCI compared to nDCN. Using differential matrices, machine learning achieved optimal accuracies of 0.82 ± 0.15 (DMCI vs. nDMCI) and 0.84 ± 0.15 (DMCI vs. nDCN). Conversely, the GRL model for nDMCI vs. nDCN peaked at 0.66 ± 0.02 using full matrices, dropping to 0.60 ± 0.04 with filtering, indicating deep graph models require complete topological data for subtle differences. Rs-fMRI and graph learning approaches offer promising avenues for subtype classification, highlighting the hyperactivity of the right insula and the integrity of the whole-brain functional connectivity matrix as crucial potential biomarkers of early pathological changes.

PMID:41933620 | DOI:10.1016/j.jad.2026.121719

Neuroimaging Clin N Am. 2026 May;36(2):367-377. doi: 10.1016/j.nic.2025.11.004. Epub 2026 Jan 23.

ABSTRACT

Functional MRI (fMRI) is a noninvasive imaging technique used to map areas of the brain important for language, motor, and visual function before surgery. Language lateralization with fMRI has proven useful as a surrogate for direct memory testing in patients with epilepsy to help predict postoperative morbidity, with Wada testing remaining useful if at risk for global amnesia. Task-based and resting-state fMRI can play a role in the evaluation of patients with generalized epilepsy before disconnective surgery or neuromodulation.

PMID:41932783 | DOI:10.1016/j.nic.2025.11.004

Biol Psychiatry Cogn Neurosci Neuroimaging. 2026 Apr 1:S2451-9022(26)00090-X. doi: 10.1016/j.bpsc.2026.03.017. Online ahead of print.

ABSTRACT

BACKGROUND: In Tourette Disorder (TD), tics are frequently associated with impulsivity, yet the mechanisms linking these dimensions and their evolution during adolescence remain unclear. We combined behavioral, clinical, and receptor-enriched by target (REACT) functional connectivity imaging to examine tic severity and impulsivity over time in TD adolescents.

METHODS: 64 TD adolescents and 56 healthy controls completed a saccadic motor waiting impulsivity (WI) task and resting-state fMRI at baseline. TD participants were reassessed 15 months later. REACT was used to examine dopamine transporter (DAT) - and serotonin 1B receptor (5-HT1B)-weighted functional connectivity within fronto-striatal motor and limbic networks. Longitudinal analyses focused on within-TD changes and their associations with clinical measures.

RESULTS: Behaviorally, no differences emerged between groups, but within TD, higher WI was associated with greater global tic severity (YGTSS/100). Longitudinally, both tics (YGTSS/50 and /100) and WI improved significantly. Compared to controls, TD showed a higher functional connectivity between caudate and anterior cingulate cortex (ACC) on the left. Longitudinally, tic reduction (YGTSS/50) was linked to increased connectivity between nucleus accumbens (NAcc) - ventral tegmental area on the left; reduced WI correlated with a higher left caudate - subgenual ACC and bilateral putamen-supplementary motor area (SMA) connectivity. In TD versus controls, REACT showed elevated both DAT-weighted connectivity between the NAcc-SMA and 5-HT1B-weighted connectivity between the raphe-SMA. Longitudinally in TD, while 5-HT1B-weighted connectivity declined DAT-weighted connectivity remained stable.

CONCLUSIONS: Changes in motor and limbic fronto-striatal functional connectivity were associated with longitudinal improvements in tics and WI in TD adolescents.

PMID:41932579 | DOI:10.1016/j.bpsc.2026.03.017

J Affect Disord. 2026 Apr 1:121718. doi: 10.1016/j.jad.2026.121718. Online ahead of print.

ABSTRACT

BACKGROUND: While brain network dysfunction characterizes attention-deficit/hyperactivity disorder (ADHD), surface-based connectivity patterns underlying its clinical heterogeneity remain underexplored. Herein, we investigated surface-based complex network architecture alterations in medication-naïve children with combined (ADHD-C) and inattentive (ADHD-I) subtypes.

METHODS: Children with ADHD-C (n = 43), ADHD-I (n = 35), and healthy controls (HCs; n = 31) were recruited for a series of clinical examinations and resting-state fMRI. We utilized surface-based graph theoretical analysis (GTA) and functional connectivity (FC) to assess network topology, correlating imaging indices with clinical variables.

RESULTS: Significant intra- and inter-network FC disruptions emerged in children with ADHD, particularly in default mode (DMN), ventral attentional (VAN), and somatosensory-motor (SMN) networks. In particular, the ADHD-C group (vs HC) exhibited more FC abnormalities involving SMN and DMN, whereas the ADHD-I group (vs HC) showed slightly more abnormal FC between VAN and dorsal attentional network (DAN). Crucially, ADHD-C patients demonstrated significantly weaker intra-SMN and SMN-DMN connectivity than the ADHD-I group. Generally, children with ADHD showed diminished global modularity, assortativity, and disrupted left lateral prefrontal cortex (PFCl1_L) nodal centrality. Additionally, higher FRCQ scores were significantly associated with increased assortativity in ADHD. The hypo-connectivity linking the DMN (Default-PFC7_L) and SMN (SomMot27_L) was correlated with both higher SNAP-IV Hyperactivity/Impulsivity and Total scores.

CONCLUSION: These findings elucidate neural substrates associated with sensorimotor and attentional deficits across ADHD subtypes. Surface-based network profiling underscores the disorder's biological heterogeneity and advances the mechanistic understanding of its complex neurodevelopment.

PMID:41932505 | DOI:10.1016/j.jad.2026.121718

Addict Behav. 2026 Apr 1;179:108700. doi: 10.1016/j.addbeh.2026.108700. Online ahead of print.

ABSTRACT

BACKGROUND: Alcohol Use Disorder (AUD) is increasingly understood as a disorder of connectomic dysregulation. However, node-centric models fail to capture the brain's overlapping functional architecture. We employed an edge-centric framework to quantify functional diversity from overlapping communities and investigated its neurobiological basis in AUD.

METHODS: We analyzed resting-state fMRI data from 93 individuals with AUD and 91 matched healthy controls. We quantified nodal functional diversity using normalized entropy derived from overlapping edge communities. In this context, high diversity (entropy approaching 1) reflects flexible, multi-network engagement, while low diversity (entropy approaching 0) reflects functional specialization. A Partial Least Squares Discriminant Analysis (PLS-DA) identified the whole-brain functional diversity pattern maximizing group separation. This pattern was then correlated with normative neurotransmitter receptor and gene expression data.

RESULTS: A PLS component significantly separated the groups (p < 0.001). This pattern was defined by decreased functional diversity in the nucleus accumbens and globus pallidus, and increased functional generalization in the insula and inferior frontal gyrus. This AUD-related pattern was negatively predicted by D1 and NMDA receptor distributions and positively by the 5-HTT transporter. Spatially, this pattern correlated with genes enriched for "synapse structure" and "cellular responses to stress".

CONCLUSION: Our edge-centric approach identified a bidirectional reorganization of functional diversity in AUD. This pattern, reflecting a specialized striatum and generalized insula, is spatially anchored to core dopaminergic/glutamatergic receptor maps and genetic pathways for synaptic plasticity and cellular stress, highlighting functional diversity as a novel, multilevel biomarker for AUD.

PMID:41932004 | DOI:10.1016/j.addbeh.2026.108700