Most recent paper

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

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

JMIR Med Inform. 2025 Sep 3;13:e72155. doi: 10.2196/72155.

ABSTRACT

BACKGROUND: Deep learning has demonstrated significant potential in advancing computer-aided diagnosis for neuropsychiatric disorders, such as migraine, enabling patient-specific diagnosis at an individual level. However, despite the superior accuracy of deep learning models, the interpretability of image classification models remains limited. Their black-box nature continues to pose a major obstacle in clinical applications, hindering biomarker discovery and personalized treatment.

OBJECTIVE: This study aims to investigate explainable artificial intelligence (XAI) techniques combined with multiple functional magnetic resonance imaging (fMRI) indicators to (1) compare their efficacy in migraine classification, (2) identify optimal model-indicator pairings, and (3) evaluate XAI's potential in clinical diagnostics by localizing discriminative brain regions.

METHODS: We analyzed resting-state fMRI data from 64 participants, including 21 (33%) patients with migraine without aura, 15 (23%) patients with migraine with aura, and 28 (44%) healthy controls. Three fMRI metrics-amplitude of low-frequency fluctuation, regional homogeneity, and regional functional connectivity strength (RFCS)-were extracted and classified using GoogleNet, ResNet18, and Vision Transformer. For comprehensive model comparison, conventional machine learning methods, including support vector machine and random forest, were also used as benchmarks. Model performance was evaluated through accuracy and area under the curve metrics, while activation heat maps were generated via gradient-weighted class activation mapping for convolutional neural networks and self-attention mechanisms for Vision Transformer.

RESULTS: The GoogleNet model combined with RFCS indicators achieved the best classification performance, with an accuracy of >98.44% and an area under the receiver operating characteristic curve of 0.99 for the test set. In addition, among the 3 indicators, the RFCS indicator improved accuracy by approximately 8% compared with the amplitude of low-frequency fluctuation. Brain activation heat maps generated by XAI technology revealed that the precuneus and cuneus were the most discriminative brain regions, with slight activation also observed in the frontal gyrus.

CONCLUSIONS: The use of XAI technology combined with brain region features provides visual explanations for the progression of migraine in patients. Understanding the decision-making process of the network has significant potential for clinical diagnosis of migraines, offering promising applications in enhancing diagnostic accuracy and aiding in the development of new diagnostic techniques.

PMID:40903006 | DOI:10.2196/72155

Front Neurol. 2025 Aug 18;16:1622274. doi: 10.3389/fneur.2025.1622274. eCollection 2025.

ABSTRACT

Cerebral small vessel disease (CSVD) has recently garnered extensive attention owing to its significant disease burden, insidious onset, and the absence of effective specific treatments. Poor lifestyle habits and chronic diseases are closely linked to its occurrence and development, eventually resulting in cognitive dysfunction. Therefore, improvement of lifestyle, stable blood pressure, effective glucose lowering, low-salt and low-fat diet, smoking cessation, moderate exercise and adequate sleep are the keys to preventing cognitive dysfunction in cerebral small-vessel disease. Early prevention and intervention are of significant clinical importance and social value, particularly as CSVD represents a major contributor to cognitive dysfunction in approximately 40 million elderly individuals worldwide. This comprehensive review integrates findings across four functional MRI techniques-diffusion tensor imaging (DTI), resting-state functional MRI (rs-fMRI), magnetic resonance spectroscopy (MRS), and arterial spin labeling (ASL)-to provide a holistic framework connecting structural abnormalities with functional deficits in CSVD. This paper aimed to cover four aspects: an overview of CSVD, the correlation between the clinical manifestations of CSVD and cognitive dysfunction, the neuroradiological features of CSVD, and the application of functional magnetic resonance imaging (fMRI) in CSVD patients with cognitive dysfunction. The integration of these complementary techniques offers unprecedented insights into disease mechanisms, enabling improved early diagnosis, establishment of reliable imaging biomarkers for monitoring disease progression, and development of tailored therapeutic strategies to slow or prevent cognitive decline in affected individuals.

PMID:40901662 | PMC:PMC12400868 | DOI:10.3389/fneur.2025.1622274

Dev Psychobiol. 2025 Sep;67(5):e70080. doi: 10.1002/dev.70080.

ABSTRACT

Early adversity is a well-established risk factor for psychopathology in youth. Contemporary taxonomies of adversity seek to distill the diverse stressors children face into meaningful categories of experience to enable more precise prediction of risk; however, few studies have tested these models using data-driven approaches in well-characterized, longitudinal samples. Here, we examined the latent structure of early stress across diverse domains of exposure, tested differential associations with psychopathology in adolescence, and investigated frontolimbic functional connectivity as a potential mediator. In a sample of 168 youth (Mage = 11.36), factor analyses identified two latent stress factors at baseline-"Parenting" and "Deprivation & Unpredictability"-and a single "Psychopathology" factor extracted from measures of mental health obtained 2 years later. While adverse parenting predicted greater psychopathology, exposure to threat emerged as the strongest predictor of adolescent mental health problems. High-dimensional regularized mediation analyses revealed that frontolimbic functional connectivity mediated the association between Threat and Psychopathology in girls but not in boys. These findings suggest that widely used dimensional models overlook key aspects of adversity, including sex-linked asymmetries across neurodevelopment and the distinct role of parenting-related stress. Refining adversity taxonomies across diverse samples and stress domains is crucial to advancing targeted interventions for youth mental health.

PMID:40898734 | DOI:10.1002/dev.70080

BMC Neurosci. 2025 Sep 2;26(1):57. doi: 10.1186/s12868-025-00979-z.

NO ABSTRACT

PMID:40898026 | DOI:10.1186/s12868-025-00979-z

Brain Res Bull. 2025 Aug 31:111534. doi: 10.1016/j.brainresbull.2025.111534. Online ahead of print.

ABSTRACT

Emotion regulation is crucial for maintaining normal social interactions and individual psychological health. Using transcranial magnetic stimulation (TMS) to modulate emotional regulation may be a powerful method for neurological or psychiatric disorders. However, TMS efficacy varies between protocols and individuals, with the brain's state during treatment being an often-overlooked factor. This study aimed to explore the influence of emotional brain state on TMS effects. Ninety-nine healthy participants were randomly assigned to three groups: one watched neutral film clips and received active TMS (neutral group), while the other two watched sadness film clips and received either active or sham TMS (sad and sham groups, respectively). The amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) were investigated using resting-state functional magnetic resonance imaging. Compared with the neutral group, the sad group showed different changes in neural activity (as measured by ALFF) in the right superior occipital gyrus and right middle frontal gyrus after TMS. In the neutral group, the ALFF change in the right superior occipital gyrus was correlated with the baseline FC between this region and the TMS target. Additionally, changes in neural activity in the right superior occipital gyrus and right middle frontal gyrus were related to changes in depression scale scores in the sad group. These findings may suggest that TMS during different emotional states can induce state-dependent alterations in neural activity. By combining emotional induction, TMS, and fMRI, this study offers a unique perspective on state-dependent effects and may improve TMS treatment outcomes.

PMID:40897293 | DOI:10.1016/j.brainresbull.2025.111534

Brain Cogn. 2025 Sep 1;189:106352. doi: 10.1016/j.bandc.2025.106352. Online ahead of print.

ABSTRACT

Rumination is closely associated with social anxiety and is considered a key cognitive factor in its onset and persistence. Both processes engage brain functions related to self-referential cognition and emotional regulation; however, the neural pathways linking rumination and social anxiety remain incompletely understood. Using resting-state neuroimaging data from 470 participants, we conducted voxel-based functional connectivity analysis focusing on the ventromedial prefrontal cortex (vmPFC), a key region implicated in self-referential processing and affective regulation. Results showed that functional connectivity between the anterior vmPFC and the left inferior frontal gyrus (IFG) and the right superior frontal gyrus (SFG) was significantly associated with both rumination and social anxiety, and mediated their association. Notably, functional connectivity related to social anxiety was primarily observed in the anterior rather than the posterior vmPFC, suggesting that social anxiety may be closely linked to heightened sensitivity to social value and reward cues. This study reveals the central role of the vmPFC in integrating self-related cognition and emotion regulation, demonstrating how its functional connectivity mediates the influence of rumination on social anxiety, thereby deepening our understanding of the neural mechanisms underlying social anxiety.

PMID:40897111 | DOI:10.1016/j.bandc.2025.106352

Front Psychiatry. 2025 Aug 14;16:1622162. doi: 10.3389/fpsyt.2025.1622162. eCollection 2025.

ABSTRACT

BACKGROUND: The causal or direct connectivity alterations of triple network including salience network (SN), central executive network (CEN), and default mode network (DMN) in tobacco use disorder (TUD) and the neurobiological features associated with smoking motivation are still unclear, which hampered the development of a targeted intervention for TUD.

METHOD: We recruited 93 male smokers and 55 male non-smokers and obtained their resting-state functional MRI (rs-fMRI) and smoking-related clinical scales. We applied dynamic causal modeling (DCM) to rs-fMRI to characterize changes of effective connectivity (EC) among seven major hubs from triple networks in TUD. Leave-one-out (LOO) cross-validation was used to investigate whether the altered EC could predict the smoking motivations (evaluated by Russell Reason for Smoking Questionnaire).

RESULTS: Compared with the control group, the TUD group displayed inhibitory extrinsic effective connectivity within SN. The abnormal ECs between networks were mainly characterized by uncoordinated switching between DMN and ECN activities in TUD individuals, with insula acting as a causal hub in this process. Moreover, increased EC from the right dorsolateral prefrontal cortex (R-DLPFC) and medial prefrontal cortex (MPFC) could predict the smoking motivations related to physical dependence.

CONCLUSIONS: This study revealed aberrant causal connectivity in triple network and clarified the potential neural mechanism of smoking behavior driven by physical dependence. These findings suggested that a network-derived indicator could be a potential bio-marker of TUD and help to identify the heterogeneity in the motivation of smoking behavior.

PMID:40896217 | PMC:PMC12392163 | DOI:10.3389/fpsyt.2025.1622162