Most recent paper

Front Public Health. 2025 Aug 21;13:1630294. doi: 10.3389/fpubh.2025.1630294. eCollection 2025.

ABSTRACT

OBJECTIVE: To investigate the neural and molecular correlates of occupational burnout in nurses by integrating resting-state fMRI (rs-fMRI), clinical assessments, brain-wide gene expression, and neurotransmitter atlases.

METHODS: Fifty-one female nurses meeting burnout criteria and 51 matched healthy controls underwent 3 T rs-fMRI. We analyzed fractional amplitude of low-frequency fluctuations (fALFF) and seed-based functional connectivity (FC), correlating findings with burnout (emotional exhaustion [EE], depersonalization [DP], and personal accomplishment [PA]). The fALFF t-map was spatially correlated with Allen Human Brain Atlas gene expression (followed by gene ontology enrichment) and neurotransmitter system maps.

RESULTS: Nurses with burnout exhibited significantly decreased precuneus fALFF and reduced precuneus-right dorsolateral prefrontal cortex (DLPFC) FC compared to controls. The fALFF in the precuneus negatively correlated with EE and DP, and positively correlated with PA, while reduced precuneus-DLPFC FC negatively correlated with EE. Genes spatially associated with fALFF alterations were enriched in pathways involving neuronal excitability, synaptic organization, stress response, and immune modulation. The fALFF alteration pattern also spatially correlated with serotonin, norepinephrine, γ-aminobutyric acid, glutamate, and endocannabinoid system distributions.

CONCLUSION: Nurse burnout features precuneus hypoactivity and precuneus-DLPFC hypoconnectivity, linked to EE and DP severity. Associated molecular signatures implicate altered neuronal excitability, stress/immune pathways, and multiple neurotransmitter systems. The precuneus-DLPFC circuit and identified molecular pathways represent potential targets for interventions against burnout.

PMID:40917413 | PMC:PMC12408554 | DOI:10.3389/fpubh.2025.1630294

Hum Brain Mapp. 2025 Sep;46(13):e70342. doi: 10.1002/hbm.70342.

ABSTRACT

Perinatal stroke is a vascular injury occurring early in life, often resulting in motor deficits (hemiplegic cerebral palsy/HCP). Comorbidities may also include poor neuropsychological outcomes, such as deficits in memory. Previous studies have used resting state functional MRI (fMRI) to demonstrate that functional connectivity (FC) within hippocampal circuits is associated with memory function in typically developing controls (TDC) and in adults after stroke, but this is unexplored in perinatal stroke. Investigating links with visual memory function has the potential to inform prognosis and personalized cognitive rehabilitation strategies. This study aimed to quantify FC within hippocampal circuits of children and adolescents with perinatal stroke and associations with visual memory. We hypothesized that FC would differ between participant groups (AIS, PVI, TDC) and hemispheres (left vs. right stroke), and would correlate with visual memory function. Participants aged 6-19 years with HCP and MRI-confirmed unilateral perinatal stroke (n = 30) arterial ischemic stroke (AIS), n = 38 periventricular venous infarction (PVI) were recruited through the Alberta Perinatal Stroke Project and compared to n = 43 TDC. Resting fMRI volumes (150 volumes, TR/TE = 2000/30 ms, voxels 3.6 mm isotropic, 36 axial slices) were processed to compute FC values between memory-related seeds (including bilateral hippocampi) using a standard pipeline in the CONN toolbox. Seed-to-voxel and seed-to-seed analyses computed FC with each hippocampus. Hemispheric and group differences in FC were examined. A subset of stroke participants (n = 46) completed visual memory testing via CNS Vital Signs (CNSVS), a computerized neurocognitive test battery. Partial correlations assessed associations between FC and visual memory function, factoring out age. We found hemispheric differences in FC within each group. Participants with left perinatal stroke showed greater FC between the hippocampus and lateral prefrontal cortex in the lesioned compared to non-lesioned hemisphere. TDCs had higher hippocampal FC when compared to the lesioned hemisphere of stroke groups. For participants with right hemisphere stroke, associations were observed between hippocampal FC and visual memory function. We describe differences in bilateral hippocampal functional connectivity in children and adolescents with perinatal stroke that are associated with visual memory function. Our findings suggest that developmental plasticity may occur in the non-lesioned hippocampus after perinatal stroke. These findings may inform our understanding of how visual memory function is affected after early unilateral brain injury and facilitate the development of novel therapies for individuals affected by perinatal stroke.

PMID:40916901 | DOI:10.1002/hbm.70342

J Neuroimaging. 2025 Sep-Oct;35(5):e70087. doi: 10.1111/jon.70087.

ABSTRACT

BACKGROUND AND PURPOSE: Socioeconomic determinants of health impact childhood development and adult health outcomes. One key aspect is the physical environment and neighborhood where children live and grow. Emerging evidence suggests that neighborhood deprivation, often measured by the Area Deprivation Index (ADI), may influence neurodevelopment, but longitudinal and multimodal neuroimaging analyses remain limited.

METHODS: We examined the association between childhood neighborhoods and brain white matter (WM) microstructural integrity using a large, demographically representative cohort from the Adolescent Brain Cognitive Development Study. We analyzed the relationship between ADI and MRI metrics of WM microstructural integrity and resting-state funtional magnetic resonance imaging (rs-fMRI) connectivity in children with data at baseline (mean age of 9.9 years) and follow-up (mean age 12.0 years), with a sample size of n = 2615.

RESULTS: Children living in poorer neighborhoods (higher ADI) showed lower brain WM microstructural integrity at baseline and follow-up, even after adjusting for age, sex, race/ethnicity, head size, body mass index, parental education, and income levels. This reduced microstructure was seen in critical tracts, such as the superior longitudinal fasciculus, corpus callosum, and the uncinate. Additionally, baseline and follow-up rs-fMRI analysis revealed that children living in poorer neighborhoods had decreased connectivity within the retrosplenial-temporal network and between higher-order networks, such as the cingulo-opercular network.

CONCLUSIONS: These findings highlight the influence of neighborhood socioeconomic disadvantage on both WM microstructural integrity and functional brain connectivity in the preadolescent brain. Children from more deprived neighborhoods showed reduced integrity in key WM tracts and disrupted connectivity within and between higher-order networks.

PMID:40916058 | DOI:10.1111/jon.70087

Neuroimage. 2025 Sep 5:121443. doi: 10.1016/j.neuroimage.2025.121443. Online ahead of print.

ABSTRACT

Functional magnetic resonance imaging (fMRI) opens a window on observing spontaneous activities of the human brain in vivo. However, the high complexity of fMRI signals makes brain functional representations intractable. Here, we introduce a state decomposition method to reduce this complexity and decipher individual brain functions at multiple levels. Briefly, brain dynamics are captured by temporal first-order derivatives and spatially divided into 'state sets' at each time point based on the velocity and direction of change. This approach transforms the original signals into discrete series consisting of four fundamental states, which efficiently encode individual-specific information. Subsequently, we designed a suite of state-based metrics to quantify regional activities and network interactions. Compared with conventional representations such as resting-state fluctuation amplitude and Pearson's functional connectivity, the state-based representations serve as more discriminative 'brain fingerprints' for individuals and produce reproducible spatial patterns across heterogeneous cohorts (n = 1,015). Regarding functional organization, our proposed profiles extend previous representations into nonlinear domains, revealing not only the canonical default-mode dominant pattern but also patterns dominated by the attention network and basal ganglia. Moreover, we demonstrate that personal phenotypes (such as age and gender) can be decoded from regional representations with high accuracy. The equivalence between state series outperforms other existing network representations in predicting individual fluid intelligence. Overall, this framework establishes a foundation for enriching the repertoire of brain functional representations and enhancing the power of brain-phenotype modeling.

PMID:40915552 | DOI:10.1016/j.neuroimage.2025.121443

Biol Psychiatry Cogn Neurosci Neuroimaging. 2025 Sep 5:S2451-9022(25)00261-7. doi: 10.1016/j.bpsc.2025.08.013. Online ahead of print.

ABSTRACT

BACKGROUND: Late-life depression (LLD) is associated with negative outcomes including high rates of recurrence and cognitive decline. However, the neurobiological changes influencing such outcomes in LLD are not well understood. Disequilibrium in large-scale brain networks may contribute to LLD-related cognitive decline.

METHODS: Never-depressed older adults and participants in early remission from LLD were recruited as part of the REMBRANDT study. At study entry, participants completed a resting-state fMRI scan and neuropsychological testing and were subsequently monitored over two years for depression recurrence. Using a previously described algorithm, recurring whole-brain states of spatial co-activation were identified by k-means consensus clustering. Co-occurring network state properties from never-depressed participants (n = 40) were then compared to LLD participants who remained in remission (n = 50) or experienced depression recurrence (n = 33).

RESULTS: A three-network solution overlapping anatomically with the Default Mode Network, Cognitive Control Network, and Anterior Salience Network best explained recurring network states. Compared with never-depressed older adults, participants who remitted from LLD exhibited decreased network resilience and altered transitions between networks. Stability of specific networks were associated with baseline clinical and neuropsychological markers in never-depressed and sustained remission participants but were blunted for participants who experienced depression recurrence.

CONCLUSIONS: Collectively, these data suggest that LLD alters dynamic network stability lasting into remission. Furthermore, stability of specific networks states is associated with clinical and neuropsychological markers which may predict the likelihood of a recurrent episode of LLD.

PMID:40915537 | DOI:10.1016/j.bpsc.2025.08.013

Sleep Med. 2025 Aug 21;136:106741. doi: 10.1016/j.sleep.2025.106741. Online ahead of print.

ABSTRACT

OBJECTIVE: This multicenter study aimed to investigate resting-state brain functional alterations in patients with type 2 diabetes mellitus (T2DM) comorbid with obstructive sleep apnea (OSA), and to elucidate the underlying neural mechanisms.

METHODS: A total of 139 participants were enrolled from two centers, including 48 healthy controls (HCs), 46 T2DM patients, and 45 T2DM with OSA patients. Resting-state functional magnetic resonance imaging (rs-fMRI) was used to assess brain function using degree centrality (DC), amplitude of low-frequency fluctuation (ALFF), and seed-based functional connectivity (FC). Group comparisons were conducted, and partial correlation analyses were performed with clinical and neuropsychological measures.

RESULTS: Compared with HCs group, the T2DM group showed significantly lower ALFF values in the right parahippocampal gyrus, which were negatively correlated with fasting glucose levels. Compared with the T2DM group, the T2DM with OSA group exhibited significantly lower DC values in the left medial superior frontal gyrus, and lower ALFF values in the bilateral medial superior frontal gyrus and the left middle frontal gyrus. Additionally, FC between the left medial superior frontal gyrus and the left middle frontal gyrus was higher, whereas FC between the left middle frontal gyrus and the right middle temporal gyrus, as well as the right rectus gyrus, was lower. These functional alterations were closely associated with the Montreal Cognitive Assessment (MoCA) scores and oxygen desaturation index (ODI).

CONCLUSION: The findings reveal widespread brain functional abnormalities in patients with T2DM and in those with comorbid T2DM and OSA, particularly within the frontal and temporal networks. These alterations are strongly associated with hyperglycemia, intermittent hypoxia, and cognitive impairment. These findings offer novel imaging-based insights into the neural mechanisms underlying brain dysfunction in patients with coexisting T2DM and OSA, and underscore the clinical importance of implementing integrated interventions in this population to mitigate the risk of cognitive decline.

PMID:40913917 | DOI:10.1016/j.sleep.2025.106741

CNS Neurosci Ther. 2025 Sep;31(9):e70602. doi: 10.1111/cns.70602.

ABSTRACT

OBJECTIVES: Unruptured brain arteriovenous malformations (AVMs) typically do not cause aphasia, even when the traditional language areas are affected by the nidus. We attempted to elucidate its language reorganization mechanism by analyzing the alterations in functional connectivity using functional connectivity (FC) and track-weighted static functional connectivity (TW-sFC) approaches.

METHODS: This cross-sectional study prospectively enrolled patients with AVMs involving left-hemisphere language areas and healthy controls. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging scans. Conventional FC analysis was used to investigate the spatially segregated functional connectivity in the gray matter, and the TW-sFC method was applied to explore the functional connectivity constrained by the white matter.

RESULTS: 34 AVM patients with lesions involving the left cerebral hemisphere and 27 healthy subjects were included. FC analysis findings revealed decreased FC intensity between the left-hemisphere language-associated regions and their right-hemisphere homologs in AVM patients. Additionally, increased FC intensity was observed between the anterior cingulate cortex (ACC) and the language-related areas in bilateral cerebellar hemispheres (lobule VIII, VIIb, Crus I, and Crus II). The TW-sFC results demonstrated increased intensity in multiple right-hemisphere fiber bundles, the left anterior thalamic radiation (ATR) and the callosum.

CONCLUSIONS: Three factors may contribute to maintaining intact language function in AVM patients, including the weakened inhibitory effect from the left dominant cerebral hemisphere over the right cerebral hemisphere leading to activation of the potential language functions of the right cerebral hemisphere (inter-cerebral connection reorganization), the functional upregulation of the cerebral language areas by cerebellar language-related brain regions via ACC (cerebrocerebellar connection reorganization), as well as the enhanced functions of the brain areas surrounding the lesion in the left cerebral hemisphere (intracerebral connection reorganization).

TRIAL REGISTRATION: This study is registered in the Chinese Trial Registry (clinical trial number: ChiCTR1900020993).

PMID:40913349 | DOI:10.1111/cns.70602

bioRxiv [Preprint]. 2025 Aug 28:2025.08.24.671805. doi: 10.1101/2025.08.24.671805.

ABSTRACT

Ethnic identity refers to how individuals perceive and experience themselves in the context of social groups, racial background, or culture (Phinney & Ong., 2007). Ethnic identity is positively associated with psychological well-being (Rivas-Drake et al., 2014) and negatively associated with depression and anxiety (Forstmeier et al., 2021). Those with strong ethnic identity may display resiliency to the negative effects of discrimination on psychological well-being (Urzúa et al., 2021). Phinney's model describes four profiles for how people put effort into, participate in, and reflect upon their ethnic identity (Phinney, 1989). Despite prior work addressing ethnic identity and psychosocial outcomes (for review, see Meca et al., 2023), few studies have considered its neurobiological underpinnings. In the current study, we identified profiles of ethnic identity among participants in The Adolescent Brain Cognitive Development Study (ABCD Study) using latent profile analysis. Next, we examined resting state functional connectivity differences across observed profiles and assessed the moderating effects of perceived discrimination. Results indicated heightened cingulo-parietal (CPAR) network connectivity among adolescents with highly diffuse ethnic identities; among moderately achieved ethnic identities, perceived discrimination moderated the association between ethnic identity and CPAR connectivity. We discuss how these findings may be related to attentional shift, error monitoring, autobiographical memory, and social judgements.

PMID:40909580 | PMC:PMC12407776 | DOI:10.1101/2025.08.24.671805

J Affect Disord. 2025 Sep 3:120238. doi: 10.1016/j.jad.2025.120238. Online ahead of print.

ABSTRACT

Functional network connectivity (FNC) among large-scale brain networks-including the default mode (DMN), frontoparietal (FPN), and salience (SN) networks-have been increasingly implicated in transdiagnostic features of mental health disorders. In this study, we examined FNC patterns among the DMN, FPN, SN, and nine additional large-scale networks using resting-state functional MRI (rs-fMRI) data from 7760 adolescents (ages 10-13) from the Adolescent Brain Cognitive Development (ABCD) study. We investigated whether altered connectivity among these networks was associated with symptoms of social anxiety, as reported by caregivers at the two-year follow-up visit. Bayesian multiple regression revealed small, positive associations between social anxiety symptoms and FNC between the SN and cingulo-opercular network (β = 0.038, 95 % HDI = [0.003, 0.073]), the SN and retrosplenial temporal network (β = 0.031, 95 % HDI = [0.001, 0.061]), and the DMN and dorsal attention network (β = 0.046, 95 % HDI = [0.008, 0.085]). Female sex was also associated with greater social anxiety (β = 0.073, 95 % HDI = [0.026, 0.119]). These results highlight specific patterns of FNC that may serve as early neurobiological markers of social anxiety during adolescent development, offering insight into the network-level mechanisms that underlie risk for social anxiety in youth. SIGNIFICANCE STATEMENT: By analyzing resting-state fMRI data from 7760 adolescents, we identified small, positive effects of salience network-cingulo-opercular network and salience network-retrosplenial temporal network connectivity on social anxiety, and a small, positive effect of default mode network-dorsal attention network connectivity. These findings highlight the role of salience and default mode network dynamics in shaping adolescent social anxiety risk. With growing interest in transdiagnostic approaches to mental health, our results provide novel evidence that network-level variations can represent a core risk factor for social anxiety during early adolescence. This work suggests that functional network connectivity could yield clinically relevant biomarkers for early identification and targeted interventions for social anxiety in adolescence.

PMID:40912322 | DOI:10.1016/j.jad.2025.120238

Psychiatry Res Neuroimaging. 2025 Aug 31;353:112062. doi: 10.1016/j.pscychresns.2025.112062. Online ahead of print.

ABSTRACT

The neural correlates of treatment-resistant depression (TRD) are not fully elucidated. Brainstem functional connectivity (FC) in TRD has rarely been investigated, despite the assumed role of several brainstem nuclei in depression. 23 patients and 23 sex- and age-matched healthy controls underwent resting-state functional MRI. Seed-based connectivity (SBC) was calculated for 37 brainstem seeds with motor and arousal functions. Correlations between significant FC and somatic symptom severity were computed. FC of dorsal raphe nucleus, locus coeruleus, cuneiform nucleus and periaqueductal gray to the precentral and postcentral gyrus was increased. The anterior division of the mesencephalic reticular formation showed increased FC to left frontal pole, left superior frontal gyrus and middle temporal gyrus, whereas its lateral division showed decreased FC to frontal orbital and insular cortex, compared to healthy subjects. FC of bilateral locus coeruleus to bilateral postcentral gyrus were positively correlated with depressive symptoms and the intensity of somatic symptoms. We found increased FC between brainstem and sensorimotor and frontal cortical regions in TRD patients compared to healthy controls. Increased brainstem-cortical FC appeared to be linked with depressive and somatic symptom severity.

PMID:40912103 | DOI:10.1016/j.pscychresns.2025.112062

J Psychiatr Res. 2025 Sep 3;190:490-498. doi: 10.1016/j.jpsychires.2025.09.001. Online ahead of print.

ABSTRACT

OBJECTIVE: Bipolar depression with mixed features (BD-MF) is a distinct subtype of bipolar disorder (BD), characterized by emotional instability, impulsivity, and an elevated risk of suicide. However, its neurobiological mechanisms remain poorly understood. This study aims to investigate these mechanisms in BD-MF patients using resting-state fMRI.

METHODS: A total of 208 adolescents and young adults with bipolar depression episodes and 169 healthy controls (HC) were recruited. The final analysis included 78 patients with BD-MF, 110 patients with bipolar depression without mixed features (BD-nMF), and 164 HC. The patients were classified according to DSM-5 criteria. Clinical assessments were conducted using the Hamilton Depression Rating Scale-17 (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), and Young Mania Rating Scale (YMRS). Resting-state fMRI was analyzed using the mean fractional amplitude of low-frequency fluctuations (mfALFF) to identify functional abnormalities, and correlations between mfALFF values and clinical symptoms were examined.

RESULTS: BD-MF patients exhibited significantly increased mfALFF values in the right precuneus, left inferior parietal lobule, and right middle frontal gyrus compared to BD-nMF and HC (P < 0.05, FDR corrected). Hyperactivation of the right precuneus correlated with mixed features (r = 0.364, P < 0.001) and agitation scores (r = 0.275, P < 0.001). Left inferior parietal lobule activity correlated with suicide scores (r = 0.241, P < 0.001), and right middle frontal gyrus hyperactivation correlated with mixed features (r = 0.293, P < 0.001).

CONCLUSIONS: This study identified significant increases in brain activity in the right precuneus, left inferior parietal lobule, and right middle frontal gyrus in BD-MF patients. These regions may serve as potential neuroimaging biomarkers for BD-MF, with their activation patterns correlating with mixed features, agitation, and suicide risk. Future research should explore the temporal dynamics and clinical relevance of these changes to enhance diagnostic and therapeutic strategies.

PMID:40912055 | DOI:10.1016/j.jpsychires.2025.09.001

medRxiv [Preprint]. 2025 Aug 29:2025.08.27.25334547. doi: 10.1101/2025.08.27.25334547.

ABSTRACT

OBJECTIVE: Methylphenidate is effective in reducing ADHD symptoms in the short term, but long-term benefits are inconsistent, possibly due to the development of tolerance. Moreover, little is known about its sustained effects on brain functional connectivity. We examined whether a 4-month methylphenidate treatment leads to sustained alterations in resting-state functional connectivity, and whether acute brain responses to methylphenidate decrease after treatment, as a potential marker of neurobiological tolerance.

METHOD: This is a secondary analysis of the ePOD-MPH RCT in which 50 boys and 49 men with ADHD were randomized to methylphenidate or placebo. Resting-state fMRI data were collected before, and one week after, a 4-month treatment period. At both visits, participants were scanned before and after an acute oral methylphenidate challenge. We computed whole-brain and default mode network (DMN) global efficiency, and DMN-whole-brain connectivity strength.

RESULTS: In adults, methylphenidate (but not placebo) led to sustained increases in whole-brain efficiency (p=0.01) and DMN-whole-brain connectivity strength (p=0.03). No significant effects were observed in children (all p>0.17). Exploratory analyses indicated that whole-brain efficiency increases related to decreasing cognitive performance in methylphenidate-treated children, but improving performance in placebo-treated children, suggesting treatment-dependent moderation (p<0.01). Acute connectivity responses remained stable in adults across visits (all p>0.15), but increased in children, regardless of treatment (all p<0.04).

CONCLUSION: Four months of methylphenidate treatment led to sustained functional connectivity changes in adults with ADHD, without evidence of neurobiological tolerance. These findings emphasize the importance of studying longer treatment durations, considering that methylphenidate treatments typically span multiple years.

PMID:40909826 | PMC:PMC12407672 | DOI:10.1101/2025.08.27.25334547

Res Sq [Preprint]. 2025 Aug 27:rs.3.rs-7303216. doi: 10.21203/rs.3.rs-7303216/v1.

ABSTRACT

Background Neurocognitive impairment (NCI) is a common comorbidity among aging people with HIV (PWH), despite effective antiretroviral therapy (ART). Processing speed is often the earliest affected cognitive domain and may be linked to disrupted functional brain network organization. This study investigated whether the balance of segregation and integration in large-scale functional networks is associated with processing speed in middle-aged and older PWH. Methods In a prospective, cross-sectional study, 26 virologically suppressed PWH aged ≥ 50 years underwent neuropsychological testing and resting-state functional MRI (rs-fMRI). Functional brain networks were constructed using a 300-node cortico-subcortical parcellation. System segregation index and node-level participation coefficient (PC) were calculated to quantify the global and local balance between integration and segregation, respectively. Associations with age-adjusted Wechsler Adult Intelligence Scale (WAIS-III) Symbol Search (WAISsys) T-scores were assessed using regression and correlational analyses. Results Higher system segregation within associative networks was significantly associated with better WAISsys T-scores (β = 0.544, p = 0.004), whereas segregation in sensorimotor networks was not. The majority of nodal PC values were negatively correlated with WAISsys T-scores, indicating that lower processing speed was associated with less segregated and more integrated connectivity. Nodes showing the strongest negative associations with WAISsys T-scores were disproportionately located in the default mode and frontoparietal networks. Conclusions In middle-aged and older PWH, greater segregation within associative networks is linked to better processing speed. Disruptions in network segregation and modularity, especially in cognitive control systems, may be associated with processing speed deficits despite viral suppression. These findings highlight the importance of functional brain network topology and organization as a potential biomarker for cognitive aging in HIV.

PMID:40909788 | PMC:PMC12408012 | DOI:10.21203/rs.3.rs-7303216/v1

Res Sq [Preprint]. 2025 Aug 26:rs.3.rs-7200801. doi: 10.21203/rs.3.rs-7200801/v1.

ABSTRACT

Stress-related conditions disrupt cognition and emotion regulation and can result in psychiatric illness, but the neural circuit-level changes that can explain these broad effects remain unclear. To address this issue, we paired population-grounded discovery with out-of-sample testing. Using resting-state fMRI from > 14,000 healthy adults in the UK Biobank, we derived connectivity profiles tied to cognition (reaction time, numeric memory), and proxies of emotion dysregulation (neuroticism, anhedonia). We then applied the profiles to a trauma-exposed cohort (N = 306) to assess symptom relevance. Associations with stress, anxiety, and depression concentrated in a subset of circuit motifs, two of which recurred: (1) hyperintegration between the default mode and control/limbic interfaces, as well as (2) hypointegration between the default mode and visual interfaces, both tracked higher symptom burden. Static and dynamic analyses converged on the precuneus as a critical hub: stronger precuneus-visual coupling and greater occupancy of a precuneus-engaged dynamic state were related to lower symptoms, whereas the opposing state was related to higher burden. This novel hybrid approach-discover-then-project-thus yielded interpretable markers of circuit dysfunction that generalized to post-trauma psychopathology. Furthermore, the approach identified the precuneus as a potential target for mechanistically informed interventions.

PMID:40909772 | PMC:PMC12407995 | DOI:10.21203/rs.3.rs-7200801/v1

Front Hum Neurosci. 2025 Aug 20;19:1650178. doi: 10.3389/fnhum.2025.1650178. eCollection 2025.

ABSTRACT

INTRODUCTION: Auditory verbal hallucinations are one of the most prevalent positive symptoms associated with schizophrenia. The superior and middle temporal gyri have been demonstrated to play a role in auditory and language perception. Dysfunction in the temporal cortex has been associated with the development of psychosis. The aim of the present study was to explore the functional connectivity and laterality of superior and middle temporal gyri in patients with auditory verbal hallucinations.

METHODS: Resting-state functional magnetic resonance imaging data was obtained from a total of 105 subjects including 63 healthy controls and 42 patients diagnosed with schizophrenia experiencing auditory verbal hallucinations. A comparative analysis was conducted to assess the functional connectivity of the superior and middle temporal gyri bilaterally.

RESULTS: The comparison between the two groups revealed several significant differences in the resting-state functional connectivity of the superior and middle temporal gyri in patients with auditory verbal hallucinations as compared to healthy controls. The aberrant connections were focused on the anterior part of the right superior temporal gyrus and the posterior part of the left one, as well as in the posterior division of the right middle temporal gyrus and both anterior and posterior divisions of the left middle temporal gyrus.

DISCUSSION: The observed dysconnectivity between the named subdivisions of the temporal lobe and cortical and subcortical structures suggests that the aberrant connectivity and brain lateralization may be related to the etiopathogenesis of schizophrenia and auditory verbal hallucinations.

PMID:40909394 | PMC:PMC12405222 | DOI:10.3389/fnhum.2025.1650178

Front Neurosci. 2025 Aug 20;19:1581884. doi: 10.3389/fnins.2025.1581884. eCollection 2025.

ABSTRACT

OBJECTIVE: This study aims to investigate the effects of Type 2 Diabetes Mellitus (T2DM) on brain function in patients with Obstructive Sleep Apnea (OSA) using Regional Homogeneity (ReHo) combined with seed-based Functional Connectivity (FC) methods.

MATERIALS AND METHODS: 46 OSA patients, 38 OSA with T2DM patients, and 34 healthy controls (HC) were prospectively recruited. Clinical data were collected from all participants, and neuropsychological testing was performed using the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and Epworth Sleepiness Scale (ESS). Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected, and ReHo combined with seed-based FC analysis was used to assess brain function differences among the three groups. Finally, partial correlation analysis was conducted to investigate the relationship between clinical variables and imaging metrics ofthe differential brain regions.

RESULTS: Compared to HCs group, the OSA group showed increased ReHo in the left occipital gyrus, and decreased ReHo in the right fusiform gyrus and left cerebellum region 8. Furthermore, FC between the left occipital gyrus and left cerebellum region 8, as well as between the right fusiform gyrus and left cerebellum region 3, was significantly decreased. Partial correlation analysis revealed a significant negative correlation between ReHo in the right fusiform gyrus and the Oxygen Desaturation Index (ODI), and a significant positive correlation between FC in the left cerebellum region 8 and MMSE scores. Compared to the OSA group, the OSA with T2DM group exhibited decreased ReHo in the left occipital gyrus, with increased FC between the left occipital gyrus and left thalamus. Partial correlation analysis showed that ReHo in the left occipital gyrus was significantly negatively correlated with the Insulin Resistance Index (IRI), while FC in the left thalamus was negatively correlated with MoCA scores and positively correlated with hemoglobinA1c (HbA1c) levels.

CONCLUSION: T2DM affects brain function in OSA patients, further exacerbating cognitive burden. These findings provide valuable insights into the neuropathological mechanisms ofT2DM in OSA and support the development of objective neuroimaging biomarkers.

PMID:40909136 | PMC:PMC12405157 | DOI:10.3389/fnins.2025.1581884

J Affect Disord. 2025 Sep 2:120214. doi: 10.1016/j.jad.2025.120214. Online ahead of print.

ABSTRACT

BACKGROUND: Evidence demonstrated that frontostriatal disruption may result in anhedonia in major depressive disorder (MDD). However, limited research examined the correlations of frontostriatal connectivity and anhedonia, especially in first-episode, treatment-naïve major depressive disorder.

METHOD: Resting-state functional magnetic resonance imaging (rs-fMRI) was obtained from 44 first-episode, treatment-naïve young adult patients with MDD and 50 healthy controls (HCs). Seed-based functional connectivity and Granger causality analysis were computed to examine, respectively, functional connectivity and directional effective connectivity related to frontostriatal circuit. Association between functional and effective connectivity of frontostriatal and severity of anhedonia was investigated.

RESULTS: MDD patients showed higher levels of anhedonia than healthy controls. Compare to healthy individuals, subjects with MDD exhibited simultaneously increased functional and effective connectivity in ventral striatum and medial prefrontal cortex (MPFC). Additionally, we observed decreased functional connectivity between superior ventral striatum and precuneus, and reduced effective connectivity from inferior parietal lobule to ventral striatum in patients with MDD. Correlation analysis manifested functional connectivity between superior ventral striatum and MPFC was positively correlated with severity of anhedonia in MDD group.

CONCLUSIONS: Our observation verified dysfunction in functional and effective connectivity between ventral striatum and MPFC in patients with major depression. Our study suggested that anhedonia was closely linked to altered ventral striatum and MPFC connectivity, highlighting the importance of ventral striatum-MPFC connectivity in pathophysiological mechanism of MDD.

PMID:40907719 | DOI:10.1016/j.jad.2025.120214

Neurology. 2025 Sep 23;105(6):e213677. doi: 10.1212/WNL.0000000000213677. Epub 2025 Sep 4.

ABSTRACT

BACKGROUND AND OBJECTIVES: Cerebrovascular reactivity (CVR) is an indicator of cerebrovascular health, and its signature in familial frontotemporal dementia (FTD) remains unknown. The primary aim was to investigate CVR in genetic FTD using an fMRI index of vascular contractility termed resting-state fluctuation amplitudes (RSFAs) and to assess whether RSFA differences are moderated by age. A secondary aim was to study the relationship between RSFA and cognition.

METHODS: Participants included presymptomatic and symptomatic C9orf72, GRN, and MAPT pathogenic variation carriers, along with noncarriers, from the prospective Genetic FTD Initiative cohort study. Cross-sectional differences in CVR were assessed using both component-based and voxel-level RSFA maps. To study disease progression-related effects, the moderating effect of age on differences between genetic status groups was analyzed using generalized linear models. The influence of RSFA, and its interaction with genetic status, on participants' cognitive function was also examined. All models were adjusted for sex, handedness, and scanning site and false discovery rate-corrected at p < 0.05.

RESULTS: A total of 284 presymptomatic and 124 symptomatic sequence variation carriers, and 265 noncarriers, were included in the analysis (mean age 48.17 years, 55% female). Across the sample, symptomatic carriers exhibited lower RSFA and a greater age-related RSFA decline predominantly in the medial frontal (-0.07 standard units, p = 0.046, 95% CI -0.13 to -0.01) and posterior parietal (-0.06 standard units, p = 0.048, 95% CI -0.12 to 0.01) cortex, compared with presymptomatic carriers and noncarriers. RSFA was inversely correlated with age (-0.43 standard units, p < 0.001, 95% CI -0.48 to -0.37) and positively associated with cognitive function (0.09 standard units, p = 0.008, 95% CI 0.04-0.15), particularly in the prefrontal cortex, in sequence variation carriers across the sample, independent of disease stage.

DISCUSSION: CVR impairment in genetic FTD has a predilection for the middle frontal and posterior cortex, and its preservation may yield a cognitive benefit for at-risk individuals. Although findings do not provide causality and warrant replication, they support the notion that vascular dysfunction in familial FTD may be a target for biomarker identification and disease-modifying efforts.

PMID:40906975 | DOI:10.1212/WNL.0000000000213677

Soc Cogn Affect Neurosci. 2025 Sep 4:nsaf087. doi: 10.1093/scan/nsaf087. Online ahead of print.

ABSTRACT

Sensitivity to the social environment is linked to suicidal ideation in adolescence, and little research has examined variance in neural functioning that may underlie this sensitivity and increase risk. Neural-based pathways to suicidal ideation are likely mediated by subjective experiences of the social environment. Loneliness is associated with both salience network connectivity and suicidal ideation. This longitudinal study tested whether greater salience network functional integration (ie, global efficiency) in early adolescence, which may underlie hypervigilance to social experiences, predicts risk for future suicidal ideation via loneliness. Participants (N = 96; Mage=12.94) completed a fMRI scan to measure resting-state salience network functional integration. Loneliness, suicidal ideation, and a sociometric measure of adolescents' real-world peer environment were assessed over several years. Greater salience network global efficiency was associated with suicidal ideation two years later via higher levels of loneliness approximately one year later, particularly for girls. Across boys and girls, the effect of salience network global efficiency on loneliness appeared stronger for youth experiencing relatively larger decreases in peer acceptance over the prior year. While findings should be interpreted as preliminary given the sample size, they suggest a possible social-developmental pathway from early-adolescent salience network integration to future vulnerability for loneliness and suicidal thinking.

PMID:40905679 | DOI:10.1093/scan/nsaf087

Front Neurol. 2025 Aug 19;16:1608371. doi: 10.3389/fneur.2025.1608371. eCollection 2025.

ABSTRACT

BACKGROUND: Ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD), is linked to neuropsychiatric comorbidities and changes in brain connectivity through the brain-gut axis. Resting-state functional MRI (RS-fMRI) offers a non-invasive approach to examining these neural alterations; however, no comprehensive review has compiled findings specific to UC.

OBJECTIVE: This review summarizes RS-fMRI studies to characterize functional connectivity (FC) alterations and methodological approaches in UC patients compared to healthy controls (HCs) and other inflammatory bowel disease (IBD) subtypes.

METHODS: Literature searches were performed in Ovid, PubMed, Google Scholar, and EMBASE (up to July 2025) using keywords: resting-state fMRI, RS-FMRI, ulcerative colitis, and UC. Few studies meeting the inclusion criteria (human participants, UC diagnosis, RS-fMRI analysis) were reviewed.

KEY FINDINGS: Seven studies were included in this review. UC patients show disrupted FC in the salience, cerebellar, visual, default mode, and dorsal attention networks. Reduced hippocampal activity is linked to working memory deficits, while increased FC in corticolimbic areas (e.g., caudate anterior, cingulate) correlates with active inflammation. Grey matter volume decreases in cerebellar regions and increases in parahippocampal regions. Sex-specific differences in FC are observed, especially in the visual and attention networks. Altered FC patterns are associated with the severity of anxiety, depression, and stress. UC exhibits distinct neural signatures compared to CD.

IMPLICATIONS: RS-fMRI uncovers UC-specific neural phenotypes, advancing the mechanistic understanding of brain-gut interactions. These findings highlight potential biomarkers for neuropsychiatric comorbidities and support the use of integrated fMRI in clinical assessments. Future research should focus on longitudinal studies, larger cohorts, and AI-enhanced analytics to clarify causality and identify therapeutic targets.

PMID:40904825 | PMC:PMC12402898 | DOI:10.3389/fneur.2025.1608371