Most recent paper

Eur Neuropsychopharmacol. 2025 Dec 12;103:112738. doi: 10.1016/j.euroneuro.2025.11.015. Online ahead of print.

ABSTRACT

Abnormal functional connectivity (FC) has been consistently associated with bipolar disorders (BD). Classical FC analyses assume stationarity of brain interactions, although connectivity actually varies over time. Here, we examined alterations in dynamic functional network connectivity (dFNC) in BD, their associations with symptom severity and global functioning, and potential differences between bipolar disorder type I (BD1) and type II (BD2). In this case-control study, we investigated dFNC in 57 patients with BD (29 BD1, 28 BD2) and 43 healthy controls (HCs). Most patients were euthymic at scanning (∼86 %), with only a minority showing residual depressive or hypomanic/mixed symptoms. Resting-state fMRI data were decomposed with spatially constrained independent component analysis and analyzed using a sliding-window approach. Meta-state metrics-number of meta-states, transitions, total distance, and span-were derived and compared across groups. Correlations with clinical measures and Global Assessment of Functioning (GAF) scores were tested. Dynamic metrics (number of meta-states, state transitions, and total distance) were reduced in BD relative to HCs, with the greatest reduction in BD1, followed by BD2. State span did not differ between groups. Across the BD sample, higher GAF scores were positively associated with greater dynamic fluidity, whereas no significant associations emerged with standard symptom scales. In conclusion, BD is characterized by a graded disruption of the spatio-temporal dynamics of large-scale brain networks, most pronounced in BD1. Reduced neural flexibility is linked to poorer global functioning, suggesting that dFNC meta-state metrics may provide clinically relevant markers of illness burden in bipolar disorder.

PMID:41391397 | DOI:10.1016/j.euroneuro.2025.11.015

Neuroimage. 2025 Dec 12:121647. doi: 10.1016/j.neuroimage.2025.121647. Online ahead of print.

ABSTRACT

Infra-Low-Frequency Neurofeedback (ILF-NFB), an EEG-based intervention, integrates specific electrode placements with "classic" frequency band (FB; 1-35 Hz) and infra-low-frequency (ILF; <0.1 Hz) components. Despite increasing clinical use, systematic studies of their individual and combined effects on neurophysiology remain limited. To address this gap, we conducted three randomized, sham-controlled, double-blind crossover studies (each with 40 healthy volunteers) examining FB-Only (Study 1), ILF-Only (Study 2), and combined FB&ILF (Study 3) protocols. The primary outcome was a functional connectivity multivariate pattern analysis (fc-MVPA) of resting-state fMRI data, using false discovery rate (FDR)-corrected thresholds (p<0.05) at voxel and cluster levels. Exploratory analyses included post-hoc seed-to-voxel analyses (Bonferroni-corrected, p-FWE<0.0083), psychophysiological measures (heart rate variability [HRV], respiration), and neurofeedback state questionnaires. For FB-Only and ILF-Only, fc-MVPA interaction effects did not survive FDR correction. For study with combined FB&ILF, fc-MVPA revealed significant interaction effects ([Post-Pre Verum] vs. [Post-Pre Sham]), identifying clusters in parietal, occipital, and cingulate regions. Post-hoc seed-to-voxel analyses using the fc-MVPA clusters as seeds suggested that FB&ILF increased connectivity between posterior midline/parieto-occipital regions and the right dorsolateral prefrontal cortex; no significant changes were observed in sham conditions. HRV showed a significant interaction effect only in the FB&ILF study. Questionnaires revealed greater perceived controllability and signal causation in Verum vs. Sham for FB-Only and FB&ILF, but not ILF-Only. Verum ILF-Only improved concentration and well-being, though participants also reported increased nervousness and sleepiness post-session. Overall, our findings indicate that the combined FB&ILF application induces robust connectivity and autonomic changes, providing initial evidence to support clinical ILF-NFB effects and warranting further mechanistic studies.

PMID:41391628 | DOI:10.1016/j.neuroimage.2025.121647

Transl Psychiatry. 2025 Dec 13. doi: 10.1038/s41398-025-03774-w. Online ahead of print.

ABSTRACT

Why some individuals are resilient to trauma while others develop psychopathology remains a baffling question in mental health research. Trauma-related conditions like post-traumatic stress disorder (PTSD), major depressive disorder (MDD), and anxiety disorders affect millions worldwide, emphasizing the need to understand the neural mechanisms that underlie these divergent outcomes. Through the use of ultra-high field (UHF) 7 T imaging, this study sought to investigate how thalamic functional connectivity differentiates resilience from vulnerability in trauma-exposed individuals. To that end, UHF 7 T resting-state functional magnetic resonance imaging (rs-fMRI) was applied to a group of 46 refugees from the Levant region, including 23 symptomatic (PTSD, MDD, or anxiety disorders) and 23 asymptomatic participants. Using the CONN toolbox, we conducted seed-to-voxel analyses focused on the thalamic subregions defined by the Human Brainnetome Atlas. Our results revealed significant connectivity alterations in the right medial prefrontal thalamus (mPFtha), the lateral prefrontal thalamus (lPFtha), and the occipital thalamus (Otha). Symptomatic individuals exhibited hyperconnectivity between the thalamic subregions and the somatosensory, visual, and cerebellar networks, along with reduced inter-thalamic connectivity, suggesting emotional dysregulation and hypervigilance. In contrast, asymptomatic participants displayed increased inter-thalamic connectivity and hypoconnectivity with these networks, reflecting efficient sensory integration and emotion regulation. Reduced inter-thalamic connectivity was found to correlate with lower resilience, underscoring the importance of effective thalamic communication for emotional stability. Taken together, our findings suggest that thalamic dysregulation contributes to vulnerability, while increased inter-thalamic connectivity fosters resilience through better sensory and emotion regulation. Thus, this study affords valuable insights into potential neural targets for interventions, which may help enhance resilience in trauma-exposed populations.

PMID:41390440 | DOI:10.1038/s41398-025-03774-w

Psychiatry Res Neuroimaging. 2025 Dec 8;356:112108. doi: 10.1016/j.pscychresns.2025.112108. Online ahead of print.

ABSTRACT

AIM: Mental time travel (MTT) is a cognitive capacity to mentally re-experience past events and anticipate future possibilities. Self-related MTT events have stronger vividness and sense of experience than events related to others, i.e., the "self-advantage effect". This effect is diminished in individuals with high schizotypal traits (HST) who are at risk for schizophrenia. However, the neural correlates of this effect remain unclear. The present study aimed to examine this issue through resting-state functional magnetic resonance imaging (rs-fMRI).

METHODS: Thirty-nine individuals with HST and 38 individuals with low schizotypal traits (LST) were recruited. They completed the self/other-related MTT task and underwent rs-fMRI scanning.

RESULTS: In HST, the "self-advantage effect" on specificity was positively correlated with functional connectivity (FC) between the right precuneus and bilateral frontal pole, left temporal pole, and the posterior cingulate cortex, whereas this association was negative in individuals with LST. Additionally, the "self-advantage effect" on emotional intensity was negatively associated with FC between the left precuneus and middle cingulate cortex in HST, but positively associated in LST.

CONCLUSIONS: People with HST have altered association patterns between the "self-advantage effect" in MTT and resting-state FC. The "self-advantage effect" in MTT may be a potential target for intervention in the schizophrenia spectrum.

PMID:41389534 | DOI:10.1016/j.pscychresns.2025.112108

Psychiatry Res Neuroimaging. 2025 Dec 8;356:112104. doi: 10.1016/j.pscychresns.2025.112104. Online ahead of print.

ABSTRACT

OBJECTIVE: This double-blind randomized controlled trial aimed to investigate the effects of high-definition transcranial direct current stimulation (HD-tDCS) on degree centrality (DC) in the cerebellum and empathy in patients with schizophrenia.

METHODS: Forty-five patients with schizophrenia were randomly assigned to either active stimulation group (n=24) or sham stimulation group (n=21). Both groups underwent HD-tDCS targeting the left dorsolateral prefrontal cortex (DLPFC). Resting-state fMRI scan, the Positive and Negative Syndrome Scale (PANSS) and Chinese version of the Interpersonal Reactivity Index (IRI-C) were applied at baseline and post-intervention. Degree centrality (DC) analysis and functional connectivity (FC) analysis were performed to identify changes in brain. Correlations between neural and behavioral alterations were examined.

RESULTS: After intervention, the active stimulation group showed a significant increase in DC in the right posterior cerebellum compared with their own baseline, whereas no such change was observed in the sham group. Exploratory analysis revealed enhanced FC between the right posterior cerebellum and right hippocampus in the active group post-intervention. Clinically, the active group exhibited significant reductions in total PANSS scores and positive symptom scores relative to baseline. A potential positive correlation was noted between the increased right posterior cerebellar DC and improved empathetic concern in the active group.

CONCLUSION: HD-tDCS over the left DLPFC emerges as a promising targeted intervention for schizophrenia, capable of modulating cerebellar functional integration (as reflected by improved DC) and alleviating clinical symptoms.

PMID:41389533 | DOI:10.1016/j.pscychresns.2025.112104

BMC Med. 2025 Dec 13. doi: 10.1186/s12916-025-04577-y. Online ahead of print.

ABSTRACT

BACKGROUND: Verbal fluency impairment is a common cognitive deficit in epilepsy that further increases the burden of the disease. Current anti-seizure medications mainly target seizure control but rarely improve cognition and may even worsen it in the patients. Neuromodulation has shown potential to control seizures and improve cognition simultaneously by stimulating specific nuclei or neural circuits, but the precise targets for verbal fluency deficits remain unclear, particularly in patients unaffected by anti-seizure medication. Therefore, investigating the neural mechanisms in newly diagnosed epilepsy (NDE) patients is essential for developing targeted interventions. This study aimed to explore brain network abnormalities and their relationship with verbal fluency deficits in NDE patients.

METHODS: One hundred NDE patients and 54 matched healthy controls were recruited and underwent resting-state functional magnetic resonance imaging (fMRI). Independent component analysis was used to assess whole-brain network functional connectivity (FC). Verbal fluency was evaluated using character and semantic verbal fluency tests (VFTs). Correlation and mediation analyses were conducted to examine the relationships among clinical features, verbal fluency, and FC.

RESULTS: Compared with healthy controls, NDE patients exhibited hypo-intra-network FC in the medial visual, auditory, and lateral sensorimotor networks. Correlation analysis showed that FC in the left auditory network, including the left inferior frontal gyrus (IFG) and superior temporal gyrus (STG), was significantly associated with the VFT scores in the NDE patients. Notably, the FC of IFG and STG within the left auditory network mediated the relationship between seizure frequency and verbal fluency deficits.

CONCLUSIONS: These findings indicate that NDE patients exhibit widespread dysfunction in perceptual networks. Abnormal FC of IFG and STG within the left auditory network serves as a neural substrate linking seizure burden to verbal fluency deficits. These insights provide a foundation for future interventions targeting network-level dysfunction in patients with epilepsy.

PMID:41387880 | DOI:10.1186/s12916-025-04577-y

BMC Infect Dis. 2025 Dec 12. doi: 10.1186/s12879-025-12273-8. Online ahead of print.

NO ABSTRACT

PMID:41387784 | DOI:10.1186/s12879-025-12273-8

Psychopharmacology (Berl). 2025 Dec 12. doi: 10.1007/s00213-025-06981-x. Online ahead of print.

ABSTRACT

RATIONALE: Cannabis is one of the most widely used psychoactive drugs in the United States, yet its long-term effects on brain function remain poorly understood. Prior resting-state functional connectivity (rsFC) studies have yielded inconsistent findings, likely due to variability in cannabis use thresholds, a predominant focus on younger populations, and region-of-interest (ROI)-based approaches limited to a small number of a priori brain regions.

OBJECTIVES: We aimed to address these limitations by examining rsFC across the entire brain using an atlas-based, whole-brain, ROI-to-ROI approach in a middle-aged sample (mean age = 41.64 years) of individuals with chronic cannabis use (CCU) and a demographically matched group of controls who did not use cannabis or other illicit substances. Based on the known neuroanatomical distribution of type 1 cannabinoid receptors (CB1Rs), we hypothesized that regions with high CB1R density would be the most affected. However, given our whole-brain approach, we were also sensitive to other regions that may exhibit altered connectivity.

METHODS: Using the Automated Anatomical Labeling (AAL) atlas, we computed rsFC matrices across 116 brain regions in 22 adults with CCU and 23 demographically matched controls.

RESULTS: The CCU group showed decreased rsFC (pFDR< .05) between the right cerebellar Crus II and the left pars triangularis, bilateral pars orbitalis, left superior frontal gyrus, left middle temporal gyrus, and left inferior temporal gyrus compared with the control group. The CCU group also had lower rsFC (pFDR < .05) between the right cerebellar Crus I and the left pars triangularis compared with controls.

CONCLUSIONS: Our findings revealed disrupted rsFC between cerebellar and prefrontal-temporal regions in the CCU group. This study advances the literature by using an atlas-based, whole-brain, ROI-to-ROI approach in a middle-aged sample with sustained cannabis use. Future studies should integrate neuropsychological assessments and task-based paradigms to understand how such alterations in rsFC affect behavioral outcomes.

PMID:41384975 | DOI:10.1007/s00213-025-06981-x

Rheumatology (Oxford). 2025 Nov 27:keaf628. doi: 10.1093/rheumatology/keaf628. Online ahead of print.

ABSTRACT

OBJECTIVES: The neural mechanisms underlying salience network (SN) dysfunction in SLE remain unclear. This study applied a comprehensive multimodal approach to characterize SN abnormalities in SLE patients.

METHODS: We analysed the resting-state fMRI data from 76 SLE patients and 68 healthy controls using four complementary approaches: functional gradient mapping of brain organization, dynamic functional connectivity (dFC) and static functional connectivity (sFC) analyses of SN interactions with the sensorimotor (SMN) and default mode (DMN) networks, gene enrichment profiling combined with predictive modelling, and neurotransmitter system mapping.

RESULTS: SLE patients revealed distinct alterations in brain functional network organization, showing reduced gradient values in both the SN and frontoparietal control network along with compressed gradient distance between the SN and SMN. sFC analyses revealed a decreased coupling between the SN and DMN but an enhanced sFC between the SN and SMN. The dFC analysis showed a significantly higher fractional occupations in the states with lower information integration in SLE. These network abnormalities are correlated with complement levels of C3, the most abundant component of the complement system. The SN gradient abnormalities were associated with specific molecular indicators, including enrichment in synaptic and protein-binding genes with WFDC1 as the strongest predictor, and showed significant relationships with 5-HT2A receptor expression patterns.

CONCLUSION: Our study identifies a convergent mechanism in which complement-mediated inflammation, and serotonergic signalling alterations may collectively contribute to SN dysregulation in SLE. These findings provide new insights into potential biomarkers and therapeutic targets for SLE-related neural dysfunction.

PMID:41384855 | DOI:10.1093/rheumatology/keaf628

Front Psychiatry. 2025 Nov 26;16:1689119. doi: 10.3389/fpsyt.2025.1689119. eCollection 2025.

ABSTRACT

BACKGROUND: The amygdala-hippocampal complex (AHC) plays a central role in the neural mechanisms underlying Internet Gaming Disorder (IGD), particularly in emotional regulation, memory processing, and reward-related functions. However, the dynamic interactions between the AHC and large-scale brain networks, and their relationship with cognitive performance in IGD, remain poorly understood.

METHODS: A total of 123 adolescents (66 with IGD and 57 healthy controls) underwent resting-state functional magnetic resonance imaging (fMRI). Temporal fluctuations in AHC connectivity were assessed using dynamic functional network connectivity (dFNC) analysis. Correlation and mediation analyses were conducted to investigate the relationship between aberrant AHC-related dFNC and cognitive function.

RESULTS: Three distinct connectivity states were identified, each characterized by unique network configurations. In State 2, dFNC strength between the AHC and both the attentional network (ATN) and visual network (VN) was positively correlated with T scores of the MATRICS Consensus Cognitive Battery (MCCB). Further mediation analysis revealed that weakened dFNC between the AHC and VN regions, particularly the calcarine sulcus and cuneus, served as a mediator linking cognitive impairment to the internet addiction severity of IGD.

CONCLUSION: These findings suggest that aberrant dynamic connectivity of the AHC, particularly its disrupted interaction with VN, may underlie the cognitive impairments in adolescents with IGD. This study provides novel insights into the neurobiological basis of behavioral addiction and highlights the importance of dynamic network analysis in elucidating its underlying pathology.

PMID:41383994 | PMC:PMC12689908 | DOI:10.3389/fpsyt.2025.1689119

bioRxiv [Preprint]. 2025 Dec 1:2025.11.26.690332. doi: 10.1101/2025.11.26.690332.

ABSTRACT

Numerous studies report that BOLD fMRI signal variance (SD BOLD ) decreases with age. However, these associations may partly reflect cardiovascular contributions to the BOLD signal. For example, heart rate variability (HRV) has been positively associated with Resting State Fluctuation Amplitude (RSFA), which captures low frequency components of BOLD fMRI variability. HRV is also negatively associated with age, which could potentially confound age-SD BOLD associations. Yet, limited research has examined HRV-SD BOLD associations or tested within-person HRV-SD BOLD coupling using sliding window analyses of simultaneous HRV and SD BOLD . We analyzed resting-state fMRI data from two independent Midlife in the United States (MIDUS) samples: Core at M3 (n=115) and Refresher at MR1 (n=101). Partial Least Squares (PLS) analyses revealed significant positive HRV-SD BOLD associations (Core: permutation p=0.018; Refresher: permutation p<0.001). Whole brain age-SD BOLD PLS associations were non-significant via permutation tests across several models (Core: permutation p=0.201; Refresher: permutation p=0.121). We found age-related decreases in SD BOLD across ∼70% of voxels in both samples. Concordance analyses showed 67-69% of brain voxels exhibited negative age-SD BOLD but positive HRV-SD BOLD relationships, suggesting that regions showing age-related decreases in SD BOLD also showed HRV-related increases in SD BOLD . Sliding-window analyses demonstrated robust positive within-person associations between person-centered HRV and SD BOLD via different HRV metrics: SDNN (Core: p < 0.001; Refresher: p < 0.001), RMSSD (Core: p = 0.072; Refresher: p = 0.009), and low frequency (Core: p < 0.001; Refresher: p < 0.001), with non-significant effects of high frequency (Core: p = 0.516; Refresher: p = 0.12) HRV. Thus, regardless of baseline levels, windows with higher HRV corresponded to higher SD BOLD , suggesting that cardiovascular factors partially explain age-SD BOLD associations and HRV may mechanistically influence SD BOLD . These results suggest that controlling for HRV, especially low-frequency HRV or SDNN, may be necessary when analyzing SD BOLD to isolate neural effects.

PMID:41383773 | PMC:PMC12694588 | DOI:10.1101/2025.11.26.690332

Neuroprotection. 2025 Jan 7;3(1):104-115. doi: 10.1002/nep3.70. eCollection 2025 Mar.

ABSTRACT

BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating disease characterized by autoimmune attacks on myelin sheaths. Its deleterious effects may be reversed by remyelination, a process that restores the integrity of myelin sheaths and, consequently, neuronal function. However, the functional implications of demyelination and remyelination in MS, as well as the potential impact of therapeutic interventions, remain incompletely understood. We used noninvasive longitudinal resting-state functional magnetic resonance imaging in a cuprizone murine model of demyelination to investigate these unsolved questions.

METHODS: Three groups of (n = 6) animals were studied. A control group was fed with standard food for 5 weeks while two treatment groups (cuprizone and clemastine) suffered progressive demyelination by feeding them with 2% cuprizone. At Week 5 (W5), all animals returned to the standard diet and studied for another 5-week period to compare controls vs spontaneous (cuprizone group) vs clemastine-aided (clemastine group) remyelination group. Group clemastine was treated with this antihistaminic (oral gavage) during the remyelination period (Weeks 5-10). Anatomical magnetic resonance imaging (T2w-MRI) and resting state functional MRI (rs-FMRI) studies were conducted on weeks W0, W2, W5 (maximal demyelination) W7 and W10 (remyelination). MRI images were processed with the FMRIB Software Library, involving seed-free functional imaging and seed-based correlation. This study uses the t-test and the D'Agostino-Pearson normality test to make an assessment.

RESULTS: The principal findings of our research include: (1) cuprizone-treated animals suffer an initial phase of elevated connectivity at Week 2 with respect to controls, transitioning to reduced connectivity at Week 5; (2) different temporal trajectories across brain regions, reflecting varying susceptibility to demyelination; (3) while spontaneous remyelination normalizes connectivity in most networks at Week 10 (5 weeks after ceasing cuprizone intoxication), the thalamocortical axis exhibits lasting disruption even 6 months after normalization of diet; and (4) on the contrary, clemastine-aided remyelination re-establishes normal thalamocortical connectivity at 6 months after demyelination.

CONCLUSION: This approach provides insights into the dynamic processes of demyelination and remyelination, informing the development of more effective interventions for MS.

PMID:41383521 | PMC:PMC12486909 | DOI:10.1002/nep3.70

Br J Dermatol. 2025 Jun 27;193(Supplement_1):ljaf085.380. doi: 10.1093/bjd/ljaf085.380.

ABSTRACT

Atopic dermatitis (AD) is a T helper 2-mediated inflammatory condition, resulting in erythematous and pruritic skin. Patients with AD often have chronic itching, leading to subsequent scratching, which further damages the skin and exacerbates cutaneous inflammation. Patients with AD often experience severe itching-scratching behaviour at night, leading to poor sleep quality. Chronic sleep disturbances during early childhood may alter brain development and neural connectivity, contributing to the increased risk of neuropsychological problems in patients with AD. In Mind & Skin, we aim to understand how inflammation and itch experienced by patients with AD can affect sleep, functional connectivity and cognitive function. Adolescent patients with AD were recruited from paediatric allergy and dermatology clinics, whereas healthy controls were recruited from patients' healthy siblings or through internal newsletters. Resting-state functional magnetic resonance imaging (fMRI) scans were acquired from the participants. The participants also completed a series of cognitive tasks using the Maudsley Attention and Response Suppression task battery to assess their attention, motor and cognitive inhibition, and time perception. Eighteen adolescent patients with AD with a range of disease severities (median age 15 years, range 12-18) and nine healthy controls (median age 15 years, range 12-16) were recruited for the study. The patients with AD had a median Eczema Area and Severity Index score of 4.45 (range 0.8-30.9). Sixteen resting-state networks were identified from fMRI analysis. The patients with AD, relative to healthy controls, had significant increases in functional connectivity within the somatosensory motor network, likely associated with chronic itching-scratching behaviours. The patients with AD exhibited reduced functional connectivity between the visual cortex and the temporoparietal network compared with healthy controls. The cohort with AD also showed decreased performance in the Simon (cognitive interference inhibition) and time discrimination tasks compared with healthy controls. The temporoparietal junction (TPJ) has been suggested to be a multisensory integration hub and is crucial for visual-spatial attention to external stimuli. Enhanced somatosensory connectivity in AD may disrupt TPJ-visual connectivity, potentially affecting selective visual-spatial attention and contributing to reduced ability in the Simon task. Our preliminary findings provide insights into the neurocognitive effects of the chronic itch-scratch behaviours associated with AD and how they may be associated with changes in brain network connectivity. These insights highlight the need for a multidisciplinary approach to address the dermatological and neurodevelopmental impacts of AD, with future studies aimed at identifying targeted interventions that mitigate these specific cognitive difficulties and improve quality of life.

PMID:41382893 | DOI:10.1093/bjd/ljaf085.380

Brain Res Bull. 2025 Dec 9:111681. doi: 10.1016/j.brainresbull.2025.111681. Online ahead of print.

ABSTRACT

BACKGROUND: Neuropsychological tests provide standardized cognitive assessment but have limited ecological validity. Virtual reality (VR) creates immersive environments, better reflecting real-world cognitive performance. Although impaired VR performance correlates with early cognitive decline, its neural mechanisms remain unclear in non-demented elders. This study investigates fMRI biomarkers linked to VR performance to identify neural predictors of cognitive decline.

METHODS: 24 non-demented older adults, including cognitively normal (CN) and mild cognitive impairment (MCI), completed baseline resting-state fMRI and immersive VR tasks combining physical and cognitive demands (dog walking, mountain climbing, drone protection). VR performance score (VRS) was quantified via entropy weight method. We analyzed relationships between VRS, neuropsychological scores, and resting-state functional connectivity (FC).

RESULTS: VRS significantly correlated with MoCA visuospatial/executive scores (p = 0.015). Whole-brain FC analysis revealed a strong association between VRS and FC between the left anterior cingulate cortex (ACC) and left paracentral lobule (PCL) in the overall sample (adjusted p = 1.94 × 10⁻⁶), present in CN but absent in MCI. Stepwise regression confirmed this FC as the significant VRS predictor in CN (R² = 0.599, p < 0.001).

CONCLUSION: Immersive VR performance reflects visuospatial/executive function and is predicted by left ACC-PCL connectivity, serving as a neuroimaging biomarker for real-world cognition that complements traditional assessments. Practically, this biomarker requires validation in larger longitudinal cohorts.

PMID:41380786 | DOI:10.1016/j.brainresbull.2025.111681

Brain Res Bull. 2025 Dec 9:111682. doi: 10.1016/j.brainresbull.2025.111682. Online ahead of print.

ABSTRACT

The heterogeneity of basal ganglia (BG) atrophy in temporal lobe epilepsy (TLE) has not been fully elucidated. This study employed a multimodal fusion framework to examine the potential heterogeneity of BG atrophy among TLE patients. 89 patients diagnosed with TLE were recruited. Structural magnetic resonance imaging (sMRI), resting - state functional magnetic resonance imaging (fMRI), consensus clustering (CC), and neuroimaging - transcriptomic approaches were integrated to explore the structural and functional alterations in the BG and their molecular mechanisms. Canonical correlation analysis (CCA) was employed to investigate the associations between MRI features and clinical characteristics. An individualized prediction model was constructed to facilitate clinical decision-making. CC identified a significant subgroups of BG atrophy in TLE: widespread BG atrophy (TLE-Cluster1, TLE-C1). In TLE-C1, the functional connectivity between the BG and cortical regions associated with sensation, emotion, and memory was notably enhanced. These patients additionally exhibited more severe cognitive impairment as well as higher degrees of anxiety and depression. Transcriptomic analysis established a connection between the heterogeneity of BG atrophy and specific gene expression patterns that were enriched in biological processes such as synaptic function, neurostructural development, and learning and memory. Further analyses uncovered a positive correlation between the gray matter volume of BG and cognitive performance. A classifier based on a Neural Network (NNET) predicted cognitive function with an area under curve (AUC) of 0.983. This study characterizes BG atrophy heterogeneity in TLE, its molecular mechanisms, and clinical relevance, offering insights for personalized diagnosis and management.

PMID:41380785 | DOI:10.1016/j.brainresbull.2025.111682

Front Neurosci. 2025 Nov 25;19:1675610. doi: 10.3389/fnins.2025.1675610. eCollection 2025.

ABSTRACT

OBJECTIVE: This study aims to utilize multimodal neuroimaging techniques to simultaneously analyze global topological properties of white matter structural networks and resting-state functional networks in aMCI patients, comparing them with healthy controls. By conducting independent and integrative analyses of topological impairments in both networks, we seek to systematically characterize the multimodal network disruption patterns in aMCI.

METHODS: 45 aMCI patients and 42 healthy adults from the First Affiliated Hospital of Heilongjiang University of Chinese Medicine in Harbin, Heilongjiang Province, China, were enrolled. A case-control cross-sectional study was conducted. DTI and rs-fMRI data were collected for all participants. Global topological properties of structural and functional networks were constructed using PANDA and dpabi software and were calculated via graph-theoretical analysis in GRETNA software, followed by statistical comparisons between groups.

RESULTS: In patients with aMCI, the small-world (C p , aC p , Lambda, aLambda) of the WM structural network were significantly higher than those in the HC group; Rich-club nodes showed redistribution, and the Rich-club coefficient was decreased; aE loc was significantly increased; the Assortativity index (r < 0) indicated disassortativity; the Hierarchy index (b > 0) exhibited a significant decrease in b within the sparsity range of 0.39∼0.4; the synchronization coefficient (s) was significantly reduced at sparsity levels ranging from 0.28 to 0.30. For the functional network, the small-world index aL p in the aMCI group was significantly lower than that in the HC group; Rich-club nodes showed redistribution, and the Rich-club coefficient was increased within a certain Degree range; aE g was significantly increased; the Assortativity index (r > 0) indicated assortativity; the Hierarchy index (b > 0) was observed within a specific sparsity range.

CONCLUSION: We identified a "structure-function dissociation" in aMCI, where the structural network suffers from fragmentation and hub disruption, while the functional network compensates through rigid, hyper-localized reorganization with elevated local efficiency. This divergence reveals a core pathological mechanism of the disease.

PMID:41378344 | PMC:PMC12685844 | DOI:10.3389/fnins.2025.1675610

bioRxiv [Preprint]. 2025 Dec 1:2025.11.26.690831. doi: 10.1101/2025.11.26.690831.

ABSTRACT

The Risk Reduction for Alzheimer's Disease (rrAD) trial included 513 cognitively normal, sedentary, hypertensive older adults (aged 60 to 85 years) with dementia risk factors. We utilized 420 high-quality baseline resting-state functional MRI (rs-fMRI) scans from this cohort to develop a functional atlas tailored for aging populations. Typical rs-fMRI atlases derived from healthy young adults do not account for age-related changes, such as cortical atrophy, enlarged ventricles, and altered connectivity. To address this gap, we created a cohort-specific MNI-adjacent anatomical template, rrAD420, using SPM12's DARTEL registration. In this space, we derived a comprehensive functional atlas using both group independent component analysis (GICA) and probabilistic functional mode decomposition (PROFUMO). The rrAD420 atlas offers detailed representations of Resting-State Network (RSN) connectivity, encompassing unique configurations and overlapping interactions. It features two Default-Mode Network (DMN)-specific seed-based maps (DMN24 with cerebellum, DMN18 without) and data-driven components resembling the major RSNs. Furthermore, PROFUMO allowed for the identification of multimodal and combinatory networks, capturing connections within and between RSNs. While optimized for hypertensive older adults, the rrAD420 atlas serves as a versatile tool for broader aging populations, aiding in the study of neurodegenerative processes and biomarker discovery.

PMID:41377509 | PMC:PMC12687787 | DOI:10.1101/2025.11.26.690831

Front Neurol. 2025 Nov 25;16:1675066. doi: 10.3389/fneur.2025.1675066. eCollection 2025.

ABSTRACT

OBJECTIVE: Temporal lobe epilepsy (TLE) is a common form of drug-resistant epilepsy often treated with surgical interventions, including laser interstitial thermal therapy (LITT). However, patient-specific factors influencing LITT outcomes remain unclear. This retrospective study aimed to identify pre-operative resting-state functional MRI (rs-fMRI) patterns associated with seizure freedom following LITT in mesial TLE.

METHODS: We analyzed rs-fMRI data from 28 patients with mesial TLE who underwent LITT, classifying them into seizure-free (SF) and not seizure-free (NSF) groups based on 12-month post-operative outcomes. Independent component analysis (ICA) was used to identify subject-specific brain networks, and generalized linear models (GLM) were employed to assess associations between pre-operative spatial patterns of ICA-derived functional connectivity (FC) and surgical outcomes, controlling for clinical variables.

RESULTS: Significant differences in brain ICA-derived FC patterns were observed between SF and NSF groups, with SF exhibiting more locally distributed ICA-derived FC patterns around the mesial temporal lobe, including the posterior orbitofrontal cortex (OFC) and anterior parahippocampal gyrus (PHG). In contrast, NSF demonstrated more diffusely distributed ICA-derived FC patterns encompassing the insula and thalami.

SIGNIFICANCE: These findings highlight the potential of pre-operative rs-fMRI as a prognostic tool for identifying TLE patients more likely to benefit from LITT. Further validation in larger cohorts is warranted to confirm these results and optimize patient selection for surgical interventions.

PMID:41376770 | PMC:PMC12685642 | DOI:10.3389/fneur.2025.1675066

Neuroimage Clin. 2025 Nov 30;49:103919. doi: 10.1016/j.nicl.2025.103919. Online ahead of print.

ABSTRACT

Alterations in brain network centrality are key features of Alzheimer's disease (AD) and may offer insights into the disruption of network organization underlying cognitive decline. We introduce a novel centrality metric, DomiRank, to characterize dominance-driven connectivity patterns in the human brain network, using a multi-center MRI dataset comprising 809 participants. Compared with conventional metrics, DomiRank centrality showed greater sensitivity in detecting AD-related network disruptions, particularly within the cingulate gyrus, precuneus, and subcortical hubs such as the basal ganglia-regions critical for cognition. Regional DomiRank alterations were significantly correlated with clinical cognitive scores, indicating their potential relevance to disease severity. Gene enrichment analysis revealed that areas with reduced DomiRank centrality were enriched for genes involved in synaptic signaling and neuronal communication, suggesting molecular mechanisms underlying network vulnerability. These findings highlight DomiRank centrality as a promising biomarker for characterizing network disorganization in AD, linking changes in brain connectivity with underlying molecular processes.

PMID:41371028 | DOI:10.1016/j.nicl.2025.103919

Age Ageing. 2025 Nov 28;54(12):afaf353. doi: 10.1093/ageing/afaf353.

ABSTRACT

BACKGROUND: Although cerebrovascular reactivity (CVR) correlates with cognitive performance in neurodegenerative conditions, the age-related spatial patterns of CVR alterations and their relationships with grey matter (GM) atrophy and cognition are underexplored.

METHODS: In this cross-sectional study, 301 cognitively unimpaired participants (181 younger, 18-34 years; 120 older: 60-89 years) underwent multi-echo resting-state functional magnetic resonance imaging (fMRI) for CVR measurement. Voxel-wise t-tests compared regional CVR between age groups, with significant clusters defined as regions of interest (ROIs). Mediation analyses examined regional GM atrophy as a mediator of the ageing-CVR relationships within ROIs. Multivariable linear regression and restricted cubic spline analyses evaluated the association between ROI-CVR and cognition in older adults.

RESULTS: Compared with younger adults, older adults showed lower CVR primarily in the temporal, basal ganglia, cingulate, brainstem and cerebellum regions, while higher CVR in the frontal, parietal, occipitotemporal, thalamus and caudate regions. Regional GM atrophy partially mediated age-related CVR increases in the right frontal pole (P = .004) and fusiform/lingual gyrus (P = .001), as well as age-related CVR reduction in bilateral brainstem/cerebellum vermis 45 (P < .001). The proportions mediated were 55.9%, 56.6% and 79.2%, respectively. Among older adults, six ROI-CVRs were associated with executive function, exhibiting linear or nonlinear relationships.

CONCLUSIONS: Resting-state CVR demonstrated regionally heterogeneous age-related decreases or increases, partly mediated by GM atrophy. In older adults, CVR in age-sensitive regions was selectively associated with executive function through linear and nonlinear patterns. Cerebrovascular ageing may involve region-specific vascular adaptations and macrostructural-microvascular (GM-CVR) interactions. Region- and range-dependent CVR could serve as a biomarker for executive function changes.

PMID:41370625 | DOI:10.1093/ageing/afaf353