Most recent paper

Neurobiol Dis. 2026 Jan 5:107264. doi: 10.1016/j.nbd.2026.107264. Online ahead of print.

ABSTRACT

Left-sided temporal lobe epilepsy (LTLE) causes bihemispheric dysfunctions in large networks and poor cognitive performance. To address possible compensatory mechanism in the resting-state we investigated the functional alteration in LTLE patients with histologically proven sclerosis in the left hippocampal CA1-field compared to healthy controls. Eight drug resistant LTLE-patients and eight sex and age matched healthy controls were included in the study. The patients' hemispherical language and verbal memory function was determined by intracarotid amytal testing. Additional cognitive abilities and depression-like symptoms were collected using standard questionnaires. 7 T-fMRI of the resting-state and graph-theoretical whole-brain analysis including hippocampal subfields enabled sensitive detection of highly specific resting-state modulations without predefinition of regions of interest. Graph-theoretical network parameter were correlated with patients' cognitive performance and depression-like symptoms. Functional connectivity of the hippocampus of LTLE patients was reduced interhemispheric and to the cortex. However, the whole-brain functional connectivity was strengthened, indicating a compensating mechanism for the above mentioned reduced hippocampus connectivity. The network's small-world index did not differ between groups. Graph-theoretical node-parameter were lateralized to the left hemisphere, reflecting interhemispheric neuroplasticity. A network component mediated by the left globus pallidus, the right inferior temporal gyrus and the left anterior corona radiata reinforced the functional connectivity between the impaired hippocampus and the bilateral cortex. The graph-theoretical resilience of the globus pallidus was correlated with improved depression-like symptoms. Therefore, we hypothesize, that the observed compensatory circuit reflects an allostatic adaptation of the brain to balance energy and disease-induced environmental stress rather than to improve cognitive impairments.

PMID:41500267 | DOI:10.1016/j.nbd.2026.107264

Alzheimers Dement. 2025 Dec;21 Suppl 2:e104870. doi: 10.1002/alz70856_104870.

ABSTRACT

BACKGROUND: White matter hyperintensities (WMH) often co-exist with β-amyloid (Aβ) and tau tangles in Alzheimer's disease (AD). However, the association of WMH, Aβ plaques, and tau tangles in AD remains elusive. Using two large datasets, this study comprehensively examined the relationship between regional WMH and longitudinal tau accumulation in AD.

METHOD: A total of 951 participants from the ADNI and A4 cohorts with Aβ-PET, fluid-attenuated inversion recovery images (FLAIR), and tau-PET data were included, with Resting-state functional MRI (RS-fMRI) available for a subset of participants. FLAIR images were segmented using a U-Net deep learning model to obtain regional WMH volumes. Tau propagation along connectivity patterns was assessed using connectivity-associated tau spread metrics derived for the whole cortex and specific cortical regions (βGlobal, βFrontal, βParietal, βTemporal, and βOccipital). We examined the associations between regional WMH, tau accumulation, and connectivity-associated tau spread. Additionally, two cortical tau subtypes were identified: "Occipital > Parietal" and "Parietal > Occipital", characterized by higher or lower occipital tau relative to parietal tau, and the impact of regional WMH on tau accumulation was assessed within these subtypes.

RESULT: Aβ+ individuals showed higher baseline levels and faster increases in total WMH compared to Aβ- individuals, but no differences were observed between T+ and T- individuals. Among Aβ+ individuals, temporal meta-ROI tau was not associated with faster WMH increases. However, greater total WMH was linked to accelerated temporal meta-ROI tau accumulation (Figure 1), although this relationship did not persist after controlling for Aβ. Greater occipital WMH was associated with faster tau accumulation in occipital regions, particularly the cuneus, and with increasing βOccipital, independent of Aβ (Figure 2). The "Parietal > Occipital" subtype exhibited more rapid tau progression than the "Occipital > Parietal" subtype. In contrast, higher WMH was linked to faster tau increases in the cuneus exclusively within the latter subtype (Figure 3).

CONCLUSION: Greater WMH burden, particularly in the occipital lobe, is associated with faster tau accumulation and spread in posterior cortical regions, independent of Aβ. These findings provide novel insights into understanding how vascular damages reflected by WMH contribute to cortical tau aggregation in the posterior cortical region of AD.

PMID:41499810 | DOI:10.1002/alz70856_104870

Alzheimers Dement. 2025 Dec;21 Suppl 2:e105952. doi: 10.1002/alz70856_105952.

ABSTRACT

BACKGROUND: Pathological tau spreads trans-synaptically in an activity-dependent manner. Previous findings support that tau spread can be measured in vivo in regions functionally connected to the entorhinal cortex (ERC). We hypothesized that the functional connectivity (FC) strength of the basal forebrain (BF), another site of early tau deposition, would also predict patterns of tau spread.

METHOD: We quantified flortaucipir tau-PET scans from unimpaired older adults in ADNI (n = 351) and the Berkeley Aging Cohort Study (BACS; n = 99). For ERC and BF regions of interest, seed-to-voxel functional connectivity (FC) networks were generated using resting-state fMRI in a partially overlapping BACS sample (n = 120) (Table 1). Outside-network ROIs were created by subtracting the target FC network from a gray-matter mask. Tau-PET SUVR and the proportion of suprathreshold voxels (>1.4 SUVR) in FC network and outside-network ROIs were compared with paired t-tests. Voxel-wise multiple regression analyses were used to measure the correlation between tau-PET in the ERC or BF and the cortex. We used these maps to explore their relationship with seed-to-voxel FC strength.

RESULT: FC of the ERC included the medial temporal, lateral temporal, and limbic regions, while FC of the BF included the insula, dorsal anterior cingulate, and limbic regions (Figure 1). Tau-PET uptake was significantly greater in both the ERC and BF FC network compared to outside the network, using both SUVRs and proportion of suprathreshold voxels as tau measures. When comparing FC networks to the outside-network ROIs, effects were greater for the ERC seed compared to BF (proportion of suprathreshold voxels: ERC d=0.85; BF d=0.49). In voxels across the cortex, the strength of FC to the ERC or BF was significantly correlated with the strength of cortical tau association to the ERC or BF (Figure 2).

CONCLUSION: Significantly greater tau-PET signal in the ERC and BF FC networks suggests that FC patterns of early tau accumulating regions predict pathological tau deposition across the cortex. The ERC seed provided stronger evidence for FC-mediated tau spread compared to BF. Future research will investigate whether amyloid and APOE4 carrier status moderate the relationship between FC and tau spread from these early tau regions.

PMID:41499672 | DOI:10.1002/alz70856_105952

Alzheimers Dement. 2025 Dec;21 Suppl 2:e104805. doi: 10.1002/alz70856_104805.

ABSTRACT

BACKGROUND: Amyloid-β (Aβ) and neurofibrillary tau deposition are two hallmark pathological proteins of Alzheimer's disease (AD) that accumulate through brain networks and drive cognitive decline. This study investigates whether the functional network abnormalities influence the Aβ-tau interactions and cognitive impairment in AD, which may provide more insightful perspectives in understanding the neural mechanisms and pathogenesis of AD.

METHOD: We divided the 190 participants from Shanghai Renji Hospital (68.6 ± 8.4 years, 62% female) into three groups, A-/T- (control group, N = 48), A+/T- (N = 121), and A+/T+ (N = 21), based on established global 18F-AV-45 amyloid PET thresholds and 18F-PI-2620 PET (tau PET) thresholds. All subjects underwent 18F-AV-45 PET, 18F-PI-2620 PET, resting state functional magnetic resonance imaging (fMRI) and T1-weighted MRI scans. Functional activity and functional network connectivity were determined using regional homogeneity (ReHo) and functional connectivity (FC) respectively.

RESULT: Participant demographics and summary descriptive statistics of the cognitive assessments and the PET data analyses are provide Table 1. The health control group (A-/T-, n = 48): The average age is 69.9 ± 8.3 years, with 62.5% being female. The mean education level is 10.1 ± 4.0 years. A+/T- Group (n = 121): The average age is 68.2 ± 8.9 years, with 60.0% being female. The mean education level is 10.4 ± 3.9 years. A+/T+ group(n = 21): The average age is 68.3 ± 5.0 years, with 71.4% being female. No significant difference was found for age and years of education across health control group and AD groups. We compared the brain's functional activity among A-/T- group, A+/T- group, and A+/T+ group, and we found that functional activity in some brain regions, such as bilateral cerebellum, right insula cortex, right precentral gyrus, right middle frontal gyrus, differed significantly among these forementioned three groups CONCLUSION: This study found significant differences in functional activity in brain regions such as the cerebellum, insula cortex, precentral gyrus, and middle frontal gyrus among control, A+/T-, and A+/T+ AD groups. These results suggest functional network abnormalities may influence Aβ-tau interactions and contribute to cognitive impairment in AD, shedding light on the neural mechanisms of the disease.

PMID:41499380 | DOI:10.1002/alz70856_104805

Alzheimers Dement. 2025 Dec;21 Suppl 2:e104964. doi: 10.1002/alz70856_104964.

ABSTRACT

BACKGROUND: The human brain is organized into macroscale functional networks that exhibit temporally synchronized spontaneous neural activity, known as functional connectivity (FC). Considering the high energetic cost of synaptic transmission (Tomasi et al. 2013, Aiello et al. 2015), hybrid imaging combining resting-state functional MRI (rsfMRI) with 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) offers a unique opportunity to study the relationship between FC and energy demands. Alzheimer's is associated with significant dissociation between regional metabolism and neural activity, particularly within functionally active network hubs (Marchitelli et al. 2018); however, other neurodegenerative disorders remain unexplored. Frontotemporal dementia (FTD) is a rare form of dementia marked by functional breakdown of the salience network (SN), which regulates appropriate responses to stimuli. Like Alzheimer's, we hypothesized that FTD would be characterized by functional/metabolic dissociation; however, network-level breakdown would be most evident in the SN given its role in the disease process.

METHOD: FDG-PET and rsfMRI were simultaneously collected on a Siemens Biograph mMR scanner from 18 controls and 20 behavioral-variant FTD (bvFTD) patients. FDG maps were converted into standardized uptake value ratio (SUVr). Local FC was quantified as Regional Homogeneity (ReHo), an fMRI metric reflecting regional synchronization of neural activity. Voxel-wise Spearman correlations were used to assess the relationship between ReHo and FDG-SUVr. Furthermore, inter-regional FC was measured with seed-based FC analysis. Group comparisons were made using 2-sample t-tests (p <0.05) while correcting for multiple comparisons.

RESULT: Reduced correlations between FDG and ReHo were found within the hubs of the SN in bvFTD, particularly bilateral anterior insula (AI) (Table). Analysis of inter-regional FC revealed diminished communication between the AI and other SN hubs (Table).

CONCLUSION: The disconnection between local FC and metabolism in the anterior insula (AI), coupled with disrupted intra-network communication within the SN, supports the hypothesis of insula being a primary target in FTD (Seeley, 2010). These findings indicate a critical role of FC/metabolism coupling in maintaining network integrity and suggests that its disruption may lead to progressive breakdown of the SN, contributing to the functional deficits characteristic of the disease.

PMID:41498439 | DOI:10.1002/alz70856_104964

Neuroimage Clin. 2025 Dec 25;49:103938. doi: 10.1016/j.nicl.2025.103938. Online ahead of print.

ABSTRACT

Accumulating evidence from neuroimaging studies has implicated widespread disruptions in brain connectivity in autism spectrum disorder (ASD), with altered connectivity patterns reported as early as infancy. However, it remains unexplored whether functional connectivity differences are evident prior to birth in the brain of fetuses who will later exhibit autistic traits in early childhood. In this study, we leveraged a longitudinal sample of 62 children with both quality-assured fetal brain resting-state MRI data and a parent-report measure of autistic traits at age 3 years. Enrichment analysis was employed to identify network pairs significantly correlated with autistic traits. Specificity analysis was conducted by additionally controlling for other childhood psychopathology. Our results demonstrated significant correlations between autistic traits and functional connectivity in the cingulate-left temporal and right prefrontal-left operculum network pairs in both the primary and specificity analyses. Visual network connectivity with prefrontal and opercular regions was also implicated. These network pairs demonstrated positive associations with autistic traits, indicating that stronger connectivity between these network pairs was associated with higher autistic traits. In contrast, weaker cerebellum-right operculum connectivity was associated with higher autistic traits, uniquely in the specificity analysis. This study provides the first in vivo evidence prospectively linking variation in functional network connectivity in the fetal brain to autistic traits in toddlerhood. These findings extend the current understanding of the prenatal brain origins of ASD and highlight the potential of fetal rs-fMRI as a tool to identify neural signatures related to social-emotional development and ASD likelihood.

PMID:41496390 | DOI:10.1016/j.nicl.2025.103938

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

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

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

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

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

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

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

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

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

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

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

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

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

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