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Towards precision functional brain network mapping in Parkinson's disease
Neuroimage Clin. 2025 Dec 19;49:103935. doi: 10.1016/j.nicl.2025.103935. Online ahead of print.
ABSTRACT
BACKGROUND: Parkinson's disease (PD) is a complex neurodegenerative condition that leads to widespread disruption of large-scale brain networks and is further complicated by substantial individual variability in symptomology, progression rates, and treatment response. Consequently, the investigation of individual differences in networks measured via resting state functional connectivity (RSFC) may provide insight. However, most RSFC studies are unable to identify interindividual differences due to poor reliability and group average network definitions. "Precision" RSFC addresses these shortcomings through extended data collection, strict denoising, and individual network definition, but remains untested in PD.
OBJECTIVES: To evaluate the feasibility and reliability of precision RSFC studies in PD.
METHODS: We collected > 100 min of RSFC data from 20 PD and 10 healthy control participants. We evaluated the level of motion, reliability and stability of RSFC measures in each participant, as well as compared to a conventional 5 min of RSFC data. These measures were benchmarked against HC to evaluate comparability. In addition, we created individualized brain network measures in PD participants to establish feasibility in this population.
RESULTS: Using precision RSFC methods, the PD group produced reliable and stable measures of brain networks that were comparable in quality to healthy controls and substantially exceeded those derived from conventional approaches (whole-brain reliability: 5 min. r = 0.60 ± 0.06, 40 min. r = 0.88 ± 0.04; within-person stability: 5 min. r = 0.40 ± 0.08, 25 min. r = 0.68 ± 0.07; ps < 0.001). Individualized network maps in people with PD captured variation both from group-averaged templates and between individuals, including within motor-related networks.
CONCLUSION: Precision RSFC is feasible and reliable in individuals with PD. This approach holds promise for advancing personalized diagnostics and identifying brain-based biomarkers underlying clinical variability in PD.
PMID:41496387 | DOI:10.1016/j.nicl.2025.103935
Bridging the self to the world: resting-state functional connectivity of the temporoparietal junction in post-traumatic stress disorder and its dissociative subtype
Neuroimage Clin. 2025 Dec 2;49:103920. doi: 10.1016/j.nicl.2025.103920. Online ahead of print.
ABSTRACT
BACKGROUND: The temporoparietal junction (TPJ) is a cross-network hub involved in social cognition and attention, processes which are directly impacted by symptoms observed in clinical profiles of post-traumatic stress disorder (PTSD) and its dissociative subtype (PTSD + DS).
METHODS: Using SPM12 and CONN, seed-based TPJ resting-state functional connectivity patterns were analyzed in individuals with PTSD (n = 81), PTSD + DS (n = 49), and healthy controls (n = 54) using four seeds [right anterior TPJ (raTPJ), left anterior TPJ (laTPJ), right posterior TPJ (rpTPJ), left posterior TPJ (lpTPJ)]. Post-hoc graph theoretical analyses were performed for raTPJ connectivity in PTSD + DS and healthy controls.
RESULTS: As compared to healthy controls, PTSD + DS showed decreased raTPJ functional connectivity with critical anterior frontal lobe nodes involved in the ventral attention and social cognition networks (i.e., left ventrolateral and dorsomedial prefrontal cortices). PTSD showed decreased lpTPJ functional connectivity with the left superior parietal lobule as compared to healthy controls. When comparing PTSD to PTSD + DS, we observed increased bilateral TPJ functional connectivity with the cerebellum. Lastly, compared to healthy controls, both PTSD and PTSD + DS displayed decreased bilateral TPJ functional connectivity with the occipital lobe. Graph theoretical analyses revealed that PTSD + DS showed limited raTPJ involvement and instead more efficient neural communication between occipital lobe and frontal lobe structures as compared to healthy controls, suggesting a possible compensatory neural network in PTSD + DS.
CONCLUSIONS: These findings reveal disruptions in TPJ neural circuitry in PTSD and PTSD + DS, which may carry cascading effects on intersecting neural networks involving the TPJ. Implications for psychotherapeutic treatments targeting disembodiment and social cognition are discussed.
PMID:41496380 | DOI:10.1016/j.nicl.2025.103920
Decreased sleep is linked longitudinally and directionally to alterations in the brain's intrinsic functional architecture
Dev Cogn Neurosci. 2025 Dec 31;78:101668. doi: 10.1016/j.dcn.2025.101668. Online ahead of print.
ABSTRACT
Previous cross-sectional studies demonstrated that reduced sleep is associated with widespread changes in the brain's intrinsic functional architecture. The present study extends this work by clarifying links between sleep and the developing brain during adolescence both longitudinally (across two years) and directionally (does reduced sleep cause connectivity changes or are connectivity changes the cause of reduced sleep?). Our novel approach combines the Adolescent Brain Cognitive Development (ABCD) Study, a longitudinal observational study of 11,878 youth, and a second sample of 76 adult participants scanned after a typical night of sleep and after a sleep deprivation causal manipulation. First, in the ABCD dataset, we identified a robust and generalizable neurosignature of reduced sleep. Second, in an independent sample of ABCD participants, we demonstrate that greater reductions in sleep duration across two years are significantly related to greater expression of this neurosignature. Third, in the sleep deprivation dataset, we show that expression of the ABCD reduced sleep neurosignature is significantly increased within individuals following sleep deprivation, and that neurosignatures of reduced sleep from the two samples exhibit significant spatial correspondence. These results clarify links between sleep and the developing brain and provide novel evidence that changes in sleep produce characteristic brain functional connectivity changes across adolescence.
PMID:41496291 | DOI:10.1016/j.dcn.2025.101668
Predicting treatment response to transcutaneous auricular vagus nerve stimulation in patients with insomnia: resting-state functional connectivity based multivoxel pattern analysis
BMC Psychiatry. 2026 Jan 6;26(1):11. doi: 10.1186/s12888-025-07484-x.
ABSTRACT
BACKGROUND: The salience network, with the insula as its central hub, plays a pivotal role in the pathophysiology of primary insomnia (PI). Transcutaneous auricular vagus nerve stimulation (taVNS) shows therapeutic potential, its neural mechanisms and predictive biomarkers remain uncharacterized.
METHODS: In a double-blind trial, 67 PI patients (taVNS = 34, sham = 33) underwent clinical assessments and resting-state fMRI at baseline and after 4-week treatment. We analyzed:1)Treatment-induced changes in bilateral insula-cortical functional connectivity (FC); 2)Predictive value of baseline FC using support vector regression.
RESULTS: TaVNS group showed significantly improved clinical assessment compared with staVNS. Decreased rs-FCs were found between the left insula and areas involved in DMN(superior parietal gyrus, SPG), Visual/Auditory (superior occipital gyrus, SOG; middle occipital gyrus, MOG; calcarine and middle temporal gyrus, MTG) and cingulo-opercular network(middle frontal gyrus, MFG and cerebellum).In addition, decreased FC between left insula and left cerebellum correlated negatively with sleep disturbances score improvement (r = -0.502, p = 0.006, Bonferroni correction), while decreased FC between left insula and right SOG positively with sleep latency score (r = 0.391, p = 0.040,uncorrection). Baseline left insula-visual/auditory circuit FC can predicte taVNS treatment response in PI (r = 0.534, p = 0.002, 5000 permutation test).
CONCLUSIONS: TaVNS may alleviate PI symptoms by reducing FCs between the salience and task-positive networks and within the cingulo-opercular network to reduce visual-related overactivity and hypervigilance.The baseline functional connectivity in the left insula-visual/auditory circuit could act as a candidate biomarker for predicting taVNS treatment response, which enable the screen of therapy-responsive insomnia patients before treatment.
CLINICAL TRIALS REGISTRATION: Chinese Clinical Trial Registry (ChiCTR 1900022535, 2019-04-16).
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12888-025-07484-x.
PMID:41495721 | PMC:PMC12777391 | DOI:10.1186/s12888-025-07484-x
Whole-brain functional connectivity predicts ultra-high risk for psychosis status and level of functioning
Schizophrenia (Heidelb). 2026 Jan 6. doi: 10.1038/s41537-025-00685-z. Online ahead of print.
ABSTRACT
Resting-state functional magnetic resonance imaging (rs-fMRI) has offered insights into the neural mechanisms underlying psychosis, particularly when associated with clinically relevant features. 102 individuals at ultra-high risk for psychosis (UHR) and 105 matched healthy controls (HC) aged 18-40 underwent clinical and cognitive assessments and rs-fMRI at baseline. Using a recently developed prediction-based extension of the network-based statistics (NBS-predict), incorporating nested cross-validation, we tested the predictive power of functional connectivity estimated from rs-fMRI data, investigating diagnostic classification and prediction of level of functioning, estimated IQ, and UHR-symptoms. Hyper-connectivity predicted group with a classification accuracy of 0.58, p = 0.043, and hypo-connectivity predicted group with a classification accuracy of 0.59, p = 0.018. Hyper-connectivity in UHR-individuals was observed primarily in interhemispheric and cortico-thalamic connections, within networks that predicted poorer levels of functioning across groups. Hypo-connectivity in UHR-individuals was observed mainly in thalamic connections with posterior cingulate cortex, frontal medial, and precuneus, within networks that predicted higher level of functioning across groups. Post hoc analyses identified a significant groupwise interaction effect on the association between functional connectivity and level of functioning (ρ = 0.34, p < 0.001), with main nodes in the frontal medial regions connected across hemispheres. Within-group, no connections predicted level of functioning or UHR-symptoms. Whole-brain functional connectivity predicted UHR-status in hyper- and hypo-connected networks, with thalamus as a central integrative hub across networks. Connections that predicted level of functioning across groups were equivalent to the connections predicting UHR-status, hence capturing a neural correlate to a key clinical component of the UHR-status.
PMID:41495085 | DOI:10.1038/s41537-025-00685-z
Functional heterogeneity in non-suicidal self-injury across psychiatric disorders: neural and psychosocial correlates
Transl Psychiatry. 2026 Jan 6. doi: 10.1038/s41398-025-03802-9. Online ahead of print.
ABSTRACT
Non-suicidal self-injury (NSSI) is a common behavior among adolescents, particularly within psychiatric populations. While neurobiological and psychosocial risk factors have been extensively studied, the mechanisms underlying NSSI's heterogeneity remain unclear. This study investigated 304 hospitalized adolescents/young adults (16-25 years) with NSSI and comorbid psychiatric diagnoses (major depressive disorder [MDD], bipolar disorder [BD], eating disorders [ED]) using psychological assessments and resting-state fMRI data from 163 participants. Orthogonal projection non-negative matrix factorization of Ottawa Self-Injury Inventory responses identified two latent factors: self-related factor and social-related factor. The self-related factor correlated with amygdala-centered cortico-limbic emotional regulation networks and predominated in affective disorders (MDD/BD), while the social-related factor linked to frontoparietal cognitive control and frontotemporal social cognition networks, particularly in ED. Fuzzy C-means clustering revealed three NSSI functional subtypes, independent of diagnostic categories: self-subtype primarily driven by self-related functions, social-subtype influenced by both self-related and social-related functions with greater exposure to psychosocial risks, and non-specific subtype characterized by mixed motivations. No subtype was exclusively driven by social-related functions. The "self-social" dual-dimensional framework with distinct neural mechanisms demonstrated subtype-specific profiles in functional connectivity, psychosocial risk exposure, and clinical features. Self-related mechanisms primarily engaged emotional regulation circuits, whereas social-related mechanisms emphasize the role of psychosocial risk factors and cognitive-emotional circuits. These findings provide neural evidence for the functional heterogeneity of NSSI and highlight the need for personalized interventions. Treatments targeting emotion regulation may benefit all subtypes, individuals with prominent social-related motivations may additionally require interventions aimed at improving interpersonal functioning.
PMID:41495020 | DOI:10.1038/s41398-025-03802-9
Reduced functional connectome uniqueness on the whole brain and network levels as a clinically relevant and reproducible neuroimaging marker in major depressive disorder
J Affect Disord. 2026 Jan 4:121073. doi: 10.1016/j.jad.2025.121073. Online ahead of print.
ABSTRACT
BACKGROUND: Identifying reproducible neurobiological markers for Major Depressive Disorder (MDD) remains challenging due to methodological heterogeneity across neuroimaging studies. Functional connectome (FC) uniqueness, an individual-level metric derived from brain fingerprinting, quantifies the distinctiveness of intrinsic connectivity patterns and may offer a robust framework for biomarker discovery.
METHODS: We analyzed multi-site resting-state fMRI data from healthy controls (HC) and patients with Major Depressive Disorder (MDD), aged 19-37 years. Individual functional connectomes were constructed using 300 regions of interest grouped into 14 canonical networks. FC uniqueness was defined as the ratio of self-similarity (calculated as Pearson correlation between connectomes from the same individual across different time points) to similarity-to-others (calculated as Pearson correlations between an individual's connectome and those of other participants at the next timepoint). An FC uniqueness index greater than one indicates successful individual identification, referred to as fingerprinting accuracy.
RESULTS: Replicating prior studies, fingerprinting accuracy was highest at the whole-brain level, followed by the default mode and frontoparietal networks. MDD patients exhibited significantly lower FC uniqueness with pronounced reductions in frontoparietal and sensorimotor networks. Notably, reduced FC uniqueness was associated with higher PHQ-9 and BDI-II scores in this study.
LIMITATIONS: Comorbidity and age distribution differences may have introduced confounding effects.
CONCLUSIONS: Reduced FC uniqueness in frontoparietal and sensorimotor networks corelate with neurobiological organization in MDD and represents a reproducible, clinically interpretable neuroimaging marker with potential utility for diagnosis and stratification.
PMID:41494549 | DOI:10.1016/j.jad.2025.121073
Alterations in neurovascular coupling are present in adolescent patients with major depressive disorder: An integrated resting-state fMRI and arterial spin labeling study
J Affect Disord. 2026 Jan 4:121103. doi: 10.1016/j.jad.2025.121103. Online ahead of print.
ABSTRACT
BACKGROUND: Alterations in neuronal activity and cerebral hemodynamics have been reported in adolescent patients with major depressive disorder (MDD), possibly resulting in neurovascular decoupling; however, no neuroimaging evidence has confirmed this disruption. The aim of this study was to investigate the possible presence of neurovascular decoupling and its clinical implications in adolescent MDD patients via resting-state functional magnetic resonance imaging (fMRI) and arterial spin labeling (ASL) imaging.
METHODS: In this prospective single-center study, we recruited adolescent patients with MDD and age-matched healthy controls (HC) between December 2023 and October 2024 for a comprehensive multimodal MRI investigation. Adolescent MDD patients and HCs underwent resting-state fMRI and ASL imaging to calculate low-frequency fluctuation amplitude (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), degree centrality (DC) and cerebral blood flow (CBF). Across-voxel CBF-ALFF, CBF-fALFF, CBF-DC, and CBF-ReHo correlations were analyzed to evaluate global gray matter neurovascular coupling (NVC), and the regional NVC of the brain region was assessed with the CBF/ALFF, CBF/fALFF, CBF/DC, and CBF/ReHo ratios. Subsequently, Pearson's correlation analyses were conducted to explore the relationship between brain regions exhibiting significant differences in local NVC and clinical Hamilton Depression Scale (HAMD).
RESULTS: This study included 45 adolescent MDD patients (mean age: 16.88 ± 3.02years, male: 32) and 50 sex- and age-matched HCs (mean age: 16.90 ± 2.55years, male: 34). Compared with the HCs, the MDD patients presented lower across-voxel CBF-ALFF, CBF-fALFF, CBF-DC and CBF-ReHo correlations and a lower CBF/ALFF ratio in the right middle temporal gyrus (MTG) and angular gyrus (AG). The brain regions with reduced a CBF/ReHo ratio included the bilateral superior parietal lobule (SPL), the left superior frontal gyrus (SFG), and the left medial superior frontal gyrus (MSFG). The right AG and right MTG, with significant differences in the CBF/ALFF ratio in adolescent MDD patients, were negatively correlated with the clinical HAMD score. The CBF/ReHo ratios in the left MSFG and bilateral SPL were negatively correlated with HAMD scores in adolescent patients with MDD, whereas CBF/ReHo ratios in the left SFG were positively correlated with HAMD scores.
CONCLUSION: Adolescent patients with MDD presented alterations in NVC mainly in higher-order brain regions in key areas such as emotion regulation, executive function, and cognitive control. These findings provide new insights into the pathophysiology of adolescent MDD and potential imaging biomarkers for assessing cognitive performance in adolescent patients with MDD.
PMID:41494542 | DOI:10.1016/j.jad.2025.121103
Depression vulnerability involves brain activity and connectivity changes consistent with cholinergic deviancy
Neuroimage Clin. 2025 Dec 31;49:103941. doi: 10.1016/j.nicl.2025.103941. Online ahead of print.
ABSTRACT
Behavioral and imaging studies suggests that emotional biases in the perception of faces associated with major depression disorder (MD) may be embedded within a broader sensory processing deficit. Increased cortical acetylcholine in MD suggest that this deficit may be related to abnormal attention modulation of sensory areas. It is not clear, however, whether these problems are a manifestation of the disease or whether they precede symptom onset. To investigate this, we applied functional magnetic resonance imaging (fMRI) to look for brain activity changes that participants with a family risk of MD (N = 30) shared with participant with MD (N = 28), compared to matched controls (N = 28). Participants were scanned while performing gender categorization of sad, happy, and neutral face pictures, as well as during a state of rest. Task-related activity changes, shared by participants at risk of and suffering from MD, were mostly seen in the posterior brain: increased activity in dorsal attention and visual association cortex, and decreased in lower visual areas. The changes did not differ between neutral faces and faces expressing an emotion. The at risk and MD participants additionally showed increased functional connectivity between the dorsal attention clusters and the lingual gyrus, and decreased connectivity with the lateral occipital complex (LOC). Lastly, they also had in common increased functional connectivity of magnocellular basal forebrain seeds with LOC and visual association cortex. These changes are consistent with an acetylcholine-mediated change in attention-guided sensory processing of all environmental events, which is discernable even before the first MD episode.
PMID:41494451 | DOI:10.1016/j.nicl.2025.103941
Resting state functional connectivity patterns associate with alcohol use disorder characteristics: Insights from the triple network model
Neuroimage Clin. 2025 Dec 31;49:103939. doi: 10.1016/j.nicl.2025.103939. Online ahead of print.
ABSTRACT
Prolonged alcohol use results in neuroadaptations that mark more severe and treatment-resistant alcohol use. The goal of this study was to identify functional connectivity brain patterns underlying Alcohol Use Disorder (AUD)-related characteristics in fifty-five adults (31 female) who endorsed heavy alcohol use. We hypothesized that resting-state functional connectivity (rsFC) of the Salience (SN), Frontoparietal (FPN), and Default Mode (DMN) networks would reflect self-reported recent and lifetime alcohol use, laboratory-based alcohol seeking, urgency, and sociodemographic characteristics related to AUD. To test our hypothesis, we combined the triple network model (TNM) of psychopathology with a multivariate data-driven approach, regularized partial least squares (rPLS), to unfold concurrent functional connectivity (FC) patterns and their association with AUD-related characteristics. We observed three concurrent associations of interest: i) drinking and age-related cross communication between the SN and both the FPN and DMN; ii) family history density of AUD and urgency anticorrelations between the SN and FPN; and iii) alcohol seeking and sex-associated SN and DMN interactions. These findings provide an integrative interpretation for many individual findings reported in the literature relating functional connectivity signatures and AUD factors. Moreover, we identified a set of neural mechanisms and brain regions concomitant with AUD-related characteristics that can serve as potential treatment targets across clinical and preclinical models.
PMID:41494450 | DOI:10.1016/j.nicl.2025.103939
Neural Changes in Adolescents with Single Ventricle Congenital Heart Disease
Pediatr Cardiol. 2026 Jan 6. doi: 10.1007/s00246-025-04141-8. Online ahead of print.
ABSTRACT
Single ventricle heart disease (SVHD) adolescents show brain tissue injury in sites that mediate autonomic, mood, and cognition functions deficient in the condition, which may result from impaired neural interactions at resting state. However, it is unclear whether SVHD subjects have aberrant neural activities in those areas that can be examined with regional homogeneity (ReHo) measures, assessing local neural synchronization. We aimed to examine regional brain neural activity changes in SVHD compared to healthy controls using functional magnetic resonance imaging (fMRI). Resting fMRI data were collected from 27 SVHD and 31 controls using a 3.0-Tesla MRI scanner. Using the standard pre-processing steps, ReHo maps were calculated and transformed to z-scored maps, normalized to a common space, smoothed, and compared between groups (ANCOVA; qFDR corrected p ≤ 0.05; covariates: age and sex). Reduced ReHo appeared in brain sites, including the caudate, parietal cortex, frontal cortex, and amygdala, and increased ReHo emerged in the parietal cortex, insula, cerebellar vermis, hippocampus, para-hippocampal gyrus, cerebellar peduncles, and cerebellar cortex in SVHD over controls. SVHD adolescents show impaired neural synchronization at resting in areas involved in neurobehavior and cognition. The findings indicate the widespread impact on brain functional organization and may explain functional deficits observed in SVHD.
PMID:41493462 | DOI:10.1007/s00246-025-04141-8
Abnormal functional connectivity and structure-function coupling of the nucleus accumbens in patients with major depressive disorder
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2025 Sept 28;50(9):1579-1589. doi: 10.11817/j.issn.1672-7347.2025.250392.
ABSTRACT
OBJECTIVES: Major depressive disorder (MDD) is a common affective disorder with complex etiologies and largely unclear pathophysiological mechanisms. The nucleus accumbens (NAc) plays a central role in reward processing, motivational regulation, and emotional integration. Neuroimaging studies suggest that structural and functional abnormalities of the NAc are key contributors to the pathogenesis of MDD. However, the alterations in structure-function coupling (SFC) of the NAc in MDD remain poorly understood. This study aims to systematically investigate abnormal functional connectivity (FC) and SFC of the NAc in patients with MDD by integrating functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) techniques.
METHODS: A case-control design was adopted. Patients who met diagnostic criteria for a current depressive episode of MDD and had a 17-item Hamilton Rating Scale for Depression (HAMD-17) total score ≥17 were enrolled as the MDD group, while age-, sex-, and education-matched healthy controls (HCs) were included as the HC group. All participants underwent high-resolution T1-weighted structural imaging, resting-state fMRI, and DTI scanning using a 3.0T MR system. fMRI data preprocessing was performed using SPM12 (Statistical Parametric Mapping 12) and DPARSF (Data Processing Assistant for Resting-State fMRI), while DTI preprocessing was conducted using FSL (FMRIB Software Library). Based on the Brainnetome Atlas, the cerebral cortex was parcellated into 246 regions. FC values between bilateral NAc and the whole brain and the strength of structural connectivity (sSC) derived from probabilistic tractography were calculated. SFC values of bilateral NAc were computed using region-wise Spearman correlations between sSC and FC (ρ). A multiple linear regression model was constructed using FC as the dependent variable and age, gender, years of education, and head motion parameters as covariates, and corrected FC values were extracted from the regression residuals. Group differences in corrected FC values were assessed using independent-sample t-tests with false discovery rate (FDR) correction at a significance level of P<0.1. Analysis of covariance was used to compare SFC values between groups, controlling for age, gender, and years of education (a significance level of P<0.05). FC values showing significant intergroup differences and SFC values of bilateral NAc were correlated with HAMD-17 total scores using Spearman correlation analysis.
RESULTS: There were no significant differences between the MDD and the HC groups in gender (χ2=0.792, P=0.373), age (t=-0.930, P=0.292), or years of education (t=0.003, P=0.059). Compared with HCs, patients with MDD exhibited significantly increased FC in the following connections: BG.L.3 (left NAc)-IPL.R.4 (right inferior parietal lobule), BG.R.3 (right NAc)-IPL.R.4, BG.R.3-Tha.R.8 (right lateral prefrontal thalamus), and BG.R.3- MFG.R.4 (right middle frontal gyrus) (all FDR-corrected P<0.1). The SFC values of bilateral NAc were significantly reduced in the MDD group compared with the HC group (left: F=11.768, P=0.001; right: F=4.386, P=0.047). Spearman correlation analyses showed no significant associations between altered FC or bilateral NAc SFC values and HAMD-17 total scores in the MDD group (all P>0.05).
CONCLUSIONS: Patients with MDD exhibit enhanced NAc FC, predominantly between the NAc and cognition-related regions such as the inferior parietal lobule and middle frontal gyrus, suggesting imbalance between the reward circuit and cognitive regulatory networks. Moreover, the significantly reduced SFC of bilateral NAc indicated impaired structural-functional integration in MDD. These findings provide potential neuroimaging evidence supporting the involvement of the NAc in the pathophysiological mechanisms of MDD.
PMID:41492742 | PMC:PMC12740730 | DOI:10.11817/j.issn.1672-7347.2025.250392
Associations between subjective cognitive concern, brain network connectivity, and cognitive performance in cognitively normal older adults
Aging Brain. 2025 Dec 12;9:100155. doi: 10.1016/j.nbas.2025.100155. eCollection 2026.
ABSTRACT
Subjective Cognitive Decline (SCD) is the perception of a persistent decline in cognitive function and self-reported concerns over cognitive ability in older adults with normal objective cognitive performance. SCD is associated with increased Alzheimer's Disease (AD) risk and early AD pathology. The neurobiological underpinnings of SCD and cognitive or neural circuit alterations during SCD remain unclear. This study aimed to identify patterns of brain network functional connectivity that are associated with quantitative measures of cognitive concerns, and to examine how these functional patterns are related to performance in the cognitive domains of visual-spatial processing, attentional control, and working memory. This analysis combined data from three studies of cognitively healthy older adults which included a quantified assessment of cognitive concern severity, resting-state fMRI, and cognitive testing in the above domains. We examined brain network-to-network functional connectivity associated with self-rated cognitive concern severity, and then how the identified patterns relate to cognitive performance. Results showed that greater cognitive concern severity was associated with unique patterns of functional connectivity between the Default Mode Network and the Language and Salience Networks in older adults without objective cognitive impairment. While greater cognitive concern severity alone was associated with slower processing reaction time, these functional connectivity patterns were associated with faster processing reaction time. This suggests that these functional connectivity patterns may alter the relationship between cognitive concern severity and psychomotor slowing. These findings support that despite the perception of cognitive changes in older adults, normal cognitive performance may be maintained through functional connectivity changes in brain networks important to directing visual-spatial attention and processing.
PMID:41492384 | PMC:PMC12764441 | DOI:10.1016/j.nbas.2025.100155
Investigating the Causal Relationships Between Brain Imaging Phenotypes and Dementia and Its Subtypes: Comprehensive Analysis of Structural and Resting-State Functional Imaging
Psychogeriatrics. 2026 Jan;26(1):e70126. doi: 10.1111/psyg.70126.
ABSTRACT
BACKGROUND: Observational investigations have reported correlations between brain imaging-derived phenotypes (IDPs) and dementia, as well as dysfunctions in brain resting-state functional networks in dementia patients. However, the causal nature of these relationships remains largely unknown.
METHODS: Herein we applied bidirectional two-sample Mendelian randomisation analysis to infer the causal relationships between 587 IDPs (N = 33 224) and 191 brain resting-state functional networks (n = 34 691) with dementia and its sub-types (AD, PDD, FTD and DLB; n = 3024-216 771) using genetic variants-single nucleotide polymorphism (SNPs) as instrumental variables.
RESULTS: The forward MR identified 14 IDP phenotypes that are causally related to the risk of dementia, including frontotemporal dementia (FTD) and Lewy body dementia (DLB). For example, a decrease in the thickness of the right rostral middle frontal cortex was strongly associated with an increased risk of dementia. The reverse MR analysis revealed significant associations between 153 IDP phenotypes and the risk of FTD and DLB and between 73 rs-fMRI phenotypes and the risk of dementia and AD. For instance, a higher risk of DLB was associated with a decrease in FA in the right posterior thalamic radiation. Additionally, the risk of Alzheimer's disease dementia is causally associated with reduced connectivity in the default mode and salience networks.
CONCLUSIONS: We identified 14 IDPs causally associated with dementia or its subtypes. We also identified potential causal effects of FTD and DLB on 153 IDPs and dementia and AD on 73 rs-fMRI phenotypes. Our findings provide insights into the aetiology of dementia and highlight structural brain changes and functional network impairments throughout the disease process. Furthermore, these results contribute to the identification of potential imaging-based predictors and therapeutic targets for dementia.
PMID:41492205 | DOI:10.1111/psyg.70126
BOLD complexity characterizes glioblastoma survival via voxel-wise and localized sample entropy
J Neurooncol. 2026 Jan 5;176(2):151. doi: 10.1007/s11060-025-05361-x.
ABSTRACT
PURPOSE: Glioblastoma (GBM) is the most prevalent and lethal primary brain tumor. Non-invasive presurgical biomarkers are urgently needed to predict patients’ overall survival (OS). Here we demonstrated a nuanced prognostic tool using sample entropy to assess Blood-Oxygen-Level-Dependent (BOLD) complexity and predict survival outcome, which is computationally efficient, reproducible, robust to noise, and readily transferable across cohorts.
METHODS: Resting-state fMRI from 205 treatment-naïve GBM patients and 1148 cognitively stable healthy controls were evaluated. Sample entropy (SampEn), a complexity metric, was evaluated in relation to OS at four levels: whole brain voxel-wise, 15 resting state networks (RSNs), a 64-feature autoencoded latent space, and complexity dynamics along contrast-enhancing (CE) boundary.
RESULTS: GBM patients showed a significant reduction in global SampEn versus controls (p < 0.001). Among RSNs, medial temporal lobe (MTL) and basal ganglia (BGA) SampEn correlated inversely with OS (R² = 0.033 and 0.034; p = 0.008 and 0.006). The latent-space-dependent Cox risk score stratifies patients into high and low survival populations (p < 0.001). The number of SampEn peaks at the CE boundary also correlated negatively with OS (R² = 0.020, p = 0.037).
CONCLUSIONS: Voxel-wise SampEn revealed widespread loss of BOLD complexity in GBM. It identifies influences at RSNs and tumor-edge, characterizing survival. Latent space analysis revealed whole-brain SampEn characteristics, which provide a compact, data-driven biomarker that augments conventional Cox modelling and stratifies the patient survival. These findings show fMRI-derived SampEn measures are efficient and robust for risk stratification and mechanistic insight in glioblastoma.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11060-025-05361-x.
PMID:41491449 | PMC:PMC12769512 | DOI:10.1007/s11060-025-05361-x
Divergence unveils further distinct phenotypic traits of human brain connectomics fingerprint
iScience. 2025 Dec 1;29(1):114282. doi: 10.1016/j.isci.2025.114282. eCollection 2026 Jan 16.
ABSTRACT
The accurate identification of individuals from functional connectomes (FCs) is central to individualized neuro/psychiatric assessment. Traditional metrics (Pearson and Euclidean) fail to capture the non-Euclidean geometry of FCs, and geodesic metrics (affine-invariant and Log-Euclidean) require task- and scale-specific regularization and degrade in high-dimensional settings. To address these challenges, we propose the Alpha-Z Bures-Wasserstein divergence, a geometry-aware divergence for FC comparison that operates effectively without meticulous parameter tuning. Across Human Connectome Project tasks, scan lengths, and spatial resolutions, we benchmark Alpha-Z against classical and state-of-the-art manifold-based distances and quantify how varying regularization influences geodesic performance. Alpha-Z yields consistently higher identification rates, with pronounced advantages in rank-deficient regimes, and preserves performance across parcellations and conditions. We further verify generalization across resting-state and task fMRI under multiple parcellation schemes. These results position Alpha-Z as a reliable, robust, and scalable framework for functional connectivity analysis, improving sensitivity to cognitive and behavioral patterns and offering strong potential for individualized clinical neuroscience.
PMID:41488781 | PMC:PMC12757632 | DOI:10.1016/j.isci.2025.114282
Altered language-salience network connectivity in schizophrenia and differential associations with emotion regulation
Front Psychiatry. 2025 Dec 18;16:1695846. doi: 10.3389/fpsyt.2025.1695846. eCollection 2025.
ABSTRACT
INTRODUCTION: Emotion regulation is a key domain of social cognition, and its impairment contributes to poor psychosocial functioning in schizophrenia (SZ). The "Managing Emotions" (ME) branch of the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) is widely used to assess this ability, yet its neural correlates remain unclear.
METHODS: We examined resting-state functional connectivity (rsFC) associated with MSCEIT-ME performance in 56 patients with schizophrenia and 56 healthy controls matched for age, sex, and years of education. Seed-based correlation analyses focused on three large-scale networks previously implicated in emotion regulation: the salience network (SN), the language network (LN), and the ventral attention network (VAN). Between-group differences and brain-behavior relationships were tested while controlling for IQ scores on the Wechsler Abbreviated Scale of Intelligence (WASI). False discovery rate Benjamini-Yekutieli (FDR-BY) correction was applied to all analyses.
RESULTS: Patients with SZ scored significantly lower on the MSCEIT-ME compared to healthy subjects (HCs). Moreover, SZ patients exhibited reduced left-lateralized rsFC between SN and LN regions relative to HCs. These findings indicate altered language-salience connectivity in schizophrenia and show that, while connectivity is associated with emotion regulation ability in healthy individuals, no significant brain-behavior association was detected in patients. Therefore, the neural mechanisms underlying emotion regulation deficits in schizophrenia remain to be clarified.
CONCLUSION: Schizophrenia was characterized by altered left-lateralized language-salience connectivity. However, because no significant brain-behavior associations were found in patients, the neural basis of emotion-regulation deficits in schizophrenia remains unresolved, highlighting the need for network-level investigations in larger samples.
PMID:41488561 | PMC:PMC12756178 | DOI:10.3389/fpsyt.2025.1695846
From scales to circuits: integrating behavioral diagnosis and neural biomarkers for improved classification in disorders of consciousness
Front Neurosci. 2025 Dec 18;19:1725420. doi: 10.3389/fnins.2025.1725420. eCollection 2025.
ABSTRACT
INTRODUCTION: In this study, we propose a data-driven approach that integrates behavioral diagnosis with neuroimaging features to identify representative UWS and MCS patients from a large inpatient cohort.
METHODS: Clinical information was extracted using a subset of UWS patients with CRS-R scores ≤ 5. Neuroimaging biomarkers were established as the increased and decreased functional connectivity indices of anatomically defined regions covering the whole brain. The algorithm was implemented through an iterative refinement process that converged on a division of UWS and MCS patients into representative and excluded (or nonrepresentative) patient groups.
RESULTS: Thirty-one out of 58 UWS patients and 23 out of 30 MCS patients were identified as representative, with an average classification accuracy of 90.2% in differentiating between the two groups. In contrast, differentiating between excluded UWS patients (n = 27) and representative MCS patients (n = 23) and between all UWS (n = 58) and MCS (n = 30) patients produced average classification accuracies of 50.9 and 64.3%, respectively. Furthermore, altered DMN functional connectivity between representative UWS and MCS patients revealed a consistent pattern as shown in prior studies, while comparisons involving excluded patients did not.
DISCUSSION: These results highlight the value of integrating behavioral scores and neural connectivity features for DOC classification, providing a more coherent basis for downstream analysis and machine-learning applications in DOC classification.
PMID:41488324 | PMC:PMC12756502 | DOI:10.3389/fnins.2025.1725420
Effects of dance training on oxytocin secretion and neural activity in older adults with subjective cognitive decline
Innov Aging. 2025 Nov 14;10(1):igaf129. doi: 10.1093/geroni/igaf129. eCollection 2026.
ABSTRACT
BACKGROUND AND OBJECTIVES: Subjective cognitive decline (SCD) is a preclinical stage of mild cognitive impairment (MCI). Although dance training has been shown to be beneficial for mental health, cognitive function, and neural activity in older adults with MCI, its effect on SCD remains unclear. This study aimed to examine the effects of dance training on the aforementioned factors and on oxytocin secretion in older adults with SCD.
RESEARCH DESIGN AND METHODS: Participants (aged 65-84 years) were assigned to either the intervention group (n = 22) with a 12-week dance training program or the control group without any alternative training (n = 22). Apathy, depression, Montreal Cognitive Assessment scores, urinary oxytocin levels, and resting-state functional magnetic resonance imaging indices, including amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC), were evaluated pre- and post-intervention.
RESULTS: Compared to the control group, the intervention group exhibited significantly higher urinary oxytocin levels and significantly higher ALFF in the left medial orbitofrontal cortex post-intervention. Moreover, the intervention group showed more enhanced FC between the left medial orbitofrontal cortex and the left precuneus post-intervention than the control group. However, mental health or cognitive performance was not significantly different between the groups.
DISCUSSION AND IMPLICATIONS: Our results are particularly important in light of previous findings that older adults with SCD show a reduced FC between the medial orbitofrontal cortex and the precuneus, and that oxytocin levels are positively associated with the prefrontal-amygdala oxytocinergic circuit in socioemotional processing. Thus, dance training may contribute to socioemotional resilience-related neural and molecular adaptations in SCD.
PMID:41487488 | PMC:PMC12759060 | DOI:10.1093/geroni/igaf129
Altered resting-state sensorimotor network in patients with obsessive-compulsive disorder: An EEG study
J Affect Disord. 2026 Jan 1:121110. doi: 10.1016/j.jad.2025.121110. Online ahead of print.
ABSTRACT
BACKGROUND AND OBJECTIVE: Dysfunction in the cortical-striatal-thalamo-cortical circuit is considered a core pathological mechanism of obsessive-compulsive disorder (OCD) and may contribute to abnormalities in the sensorimotor network (SMN). Although altered SMN patterns in OCD have been reported using resting-state fMRI, SMN alterations remain underexplored in resting-state EEG (rsEEG). This study aimed to identify frequency-specific SMN alterations in patients with OCD compared to healthy controls (HCs) using rsEEG.
METHODS: Eyes-closed rsEEG were collected from 41 patients with OCD and 41 HCs. SMN was constructed by eight cortical regions and functional connectivity (FC) with the weighted phase-lag index across six frequency bands. Group differences in FC and strength were assessed using permutation testing. Correlation analysis was conducted between significantly altered measures and Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Machine learning-based classification was applied to assess the potential of SMN features as biomarkers for OCD.
RESULTS: In the theta band, FC between the left primary somatosensory cortex (S1) and the left supplementary motor area was significantly increased in OCD relative to HC. In the high alpha band, FCs between the left S1 and right primary motor cortex (M1), and between the left S1 and right premotor cortex (PMC), as well as local strength in the right PMC, were significantly increased in OCD. FCs between left S1 and right M1 in the high alpha band positively correlated with Y-BOCS. Classification accuracy was achieved at 78.05 %.
CONCLUSION: These findings suggest that rsEEG-derived SMN alterations may reflect neurophysiological mechanisms of OCD and serve as candidate biomarkers.
PMID:41483883 | DOI:10.1016/j.jad.2025.121110