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Graph-level contrastive learning with self-aware and cross-sample topology augmentation for brain disorder diagnosis using rs-fMRI
Neural Netw. 2025 Nov 27;196:108379. doi: 10.1016/j.neunet.2025.108379. Online ahead of print.
ABSTRACT
Resting-state functional MRI (rs-fMRI) is widely used for diagnosing and analyzing brain disorders. However, existing fMRI studies have shown that learning-based approaches depend heavily on labeled training data, which is difficult to obtain due to the substantial time and effort required for annotation in clinical settings. To address these challenges, we propose GCSC-TA (Graph-level Contrastive Learning with Self-aware and Cross-sample Topology Augmentation) for brain disorder diagnosis and analysis using rs-fMRI. The proposed GCSC-TA generates two complementary augmented brain networks for each subject by introducing self-aware and cross-sample topology augmentations. This dual-view strategy enhances the identification of individual-specific features and also amplifies inter-subject functional heterogeneity. Moreover, we designed a min-max contrastive loss function to accommodate augmented brain networks, overcoming the limitations of traditional projection-based methods while performing graph-level contrastive learning on the original integrity of the brain topology structure. Extensive experiments on a private Major Depressive Disorder (MDD) dataset and the publicly available Autism Spectrum Disorder (ABIDE) dataset demonstrate the superior classification performance of GCSC-TA over several state-of-the-arts. Furthermore, GCSC-TA also identifies abnormal brain connectivity patterns associated with MDD and ASD, thereby advancing the interpretability and clinical utility of rs-fMRI for clinical diagnosis.
PMID:41349174 | DOI:10.1016/j.neunet.2025.108379
A neural signature for gastrointestinal symptoms in depression: insula-gastric connectivity predicts symptom severity
Front Psychiatry. 2025 Nov 19;16:1672148. doi: 10.3389/fpsyt.2025.1672148. eCollection 2025.
ABSTRACT
BACKGROUND: Gastrointestinal (GI) symptoms are a common and burdensome dimension of major depressive disorder (MDD), yet their neurobiological underpinnings are poorly understood. It is unclear how the brain's processing of visceral signals relates to the subjective experience of GI distress in depression. We aimed to identify a neural substrate for GI symptoms by examining functional connectivity (FC) between the insula and a network defined by gastric rhythms.
METHODS: We first identified a gastric-related seed in the posterior insula (GD-pINS) using a large normative dataset of 652 healthy adults. Subsequently, 100 MDD patients-stratified into groups with (GD; n=58) and without (NGD; n=42) GI symptoms-and 80 healthy controls (HCs) were recruited. Using resting-state fMRI, we analyzed FC between the GD-pINS and the gastric network (GN). Group differences, clinical correlations, and the utility of FC features for patient classification via a support vector machine (SVM) were assessed.
RESULTS: Compared to HCs, MDD patients as a whole showed reduced GD-pINS to GN connectivity. Paradoxically, GD patients exhibited relatively stronger connectivity than NGD patients. This symptom-specific enhancement was driven by pathways connecting the posterior insula to the secondary somatosensory cortex (SII). The strength of this insula-SII connection was positively correlated with GI symptom severity. An SVM classifier using these connectivity features distinguished between GD and NGD patients with high accuracy (AUC = 0.82).
CONCLUSIONS: Our findings reveal a distinct neural signature for GI distress in depression, characterized by aberrant connectivity within an insula-somatosensory circuit. This circuit, which shows relative enhancement in symptomatic patients against a backdrop of globally reduced connectivity, may reflect a mechanism of somatosensory amplification. It represents a potential biomarker for patient stratification and a novel target for therapeutic intervention.
PMID:41346640 | PMC:PMC12673926 | DOI:10.3389/fpsyt.2025.1672148
Genetic contribution to intrinsic functional connectivity underlying general intelligence: evidence from adult twin study
Brain Commun. 2025 Nov 21;7(6):fcaf461. doi: 10.1093/braincomms/fcaf461. eCollection 2025.
ABSTRACT
Resting-state functional connectivity has been linked to intelligence, and twin studies suggest that these associations may be influenced by genetic factors. To investigate this relationship, we analysed behavioural and resting-state functional magnetic resonance imaging data from young adult twins in the Human Connectome Project. General intelligence was assessed based on ten cognitive task performances. The results showed a positive correlation in both identical and fraternal twins, indicating a similarity of general intelligence among twin pairs. For the resting-state functional connectivity analysis, we conducted two approaches. In the first approach, twins were randomly assigned to two separate groups, ensuring that each pair was split between the groups. We then applied a connectome-based predictive method separately for identical and fraternal twins to predict general intelligence. Specifically, a predictive model was trained using one group's functional connectivity and then applied to its co-twin group to predict their general intelligence. Significant prediction was recorded in identical twins but not in fraternal twins, suggesting a high level of similarity of intelligence-related functional connectivity among identical twins. In the second approach, we aimed to quantify the intelligence similarity using the resting-state functional connectivity. To implement this, we generated models to predict the difference in general intelligence in twin pairs, where a smaller difference indicates a greater degree of similarity. The results showed that only the intelligence difference in identical twins was successfully predicted, where the default mode network showed a significant contribution, suggesting a higher neural basis for intelligence similarity in identical twins. Together, these findings demonstrate that functional connectivity patterns associated with intelligence extend across genetically identical twins. More broadly, they highlight the default mode network role in intelligence similarity and illustrate the utility of predictive modelling as a complementary framework to classical twin analyses.
PMID:41346464 | PMC:PMC12674170 | DOI:10.1093/braincomms/fcaf461
Vitamin D-linked vulnerability and functional connectivity alterations in the superior frontal gyrus contributing to cognitive impairment in Parkinson's disease
Front Aging Neurosci. 2025 Nov 19;17:1657723. doi: 10.3389/fnagi.2025.1657723. eCollection 2025.
ABSTRACT
BACKGROUND AND AIMS: Forecasting specific factors influencing cognitive impairment (CI) in Parkinson's disease (PD) patients can improve clinical outcomes. This study aims to identify brain areas vulnerable to vitamin D deficiency and assess functional integrity in PD patients with and without CI.
METHODS: Thirty-four PD patients [14 with CI (PD-CI), 20 with normal cognition (PD-NC)] and 21 healthy controls (HCs) underwent serum vitamin D testing, T1-weighted MRI, and resting-state functional MRI (rs-fMRI). Voxel-based morphometry (VBM) was used to compare gray matter volume (GMV) between PD patients and HCs. Whole-brain multiple regression analyses, adjusted for age and sex, identified GMV regions associated with vitamin D levels. Resting-state functional connectivity (FC) analyses were performed using vitamin D-related regions as seeds. Correlation and multivariate regression analyses, adjusted for Hoehn and Yahr stage and age, assessed relationships among FC, cognitive performance, and vitamin D levels.
RESULTS: Compared with HCs, PD patients exhibited significant GMV loss, affecting widespread brain regions including the middle frontal gyrus (MFG), superior frontal gyrus (SFG), and hippocampus. Region of interest (ROI)-based analysis revealed that vitamin D levels were associated with GMV in the bilateral MFG and SFG (r = -0.406, p = 0.021). These findings suggest that the MFG and SFG are vulnerable regions in PD patients linked to vitamin D levels. To assess the impact of abnormal vitamin D levels on relevant resting-state networks, clusters encompassing the bilateral SFG were used as ROIs. The intrinsic connectivity network of the vulnerable area, using the bilateral SFG as seed regions, revealed abnormal functional connectivity with several brain networks, including the visual network, the default mode network, the executive control network, the sensorimotor network, and the memory network. Abnormal FC values within the SFG functional network were associated with disease severity, cognitive dysfunction, and vitamin D levels (p < 0.05). Multi-model regression analyses revealed that connectivity in the left SFGmed network was negatively associated with CI in PD, with vitamin D levels showing a potential protective effect.
CONCLUSION: The SFG is associated with vitamin D levels in PD patients, and disruptions in its structural and functional connectivity may link to CI. Future longitudinal studies are necessary to confirm these associations and explore the potential impact of vitamin D supplementation on cognitive function in PD.
PMID:41346436 | PMC:PMC12673341 | DOI:10.3389/fnagi.2025.1657723
Dysfunctional default mode and visual networks underlie cognitive deficits in dementia with Lewy bodies: a resting-state fMRI study
Front Aging Neurosci. 2025 Nov 19;17:1630826. doi: 10.3389/fnagi.2025.1630826. eCollection 2025.
ABSTRACT
OBJECTIVE: To characterize abnormal functional connectivity in dementia with Lewy bodies (DLB) and its association with cognitive impairment using resting-state functional magnetic resonance imaging (rs-fMRI).
METHODS: Sixty-eight DLB patients and 38 age-, sex-, and education-matched healthy controls underwent neuropsychological assessments (MoCA, MMSE) and rs-fMRI. Imaging analyses included seed-based functional connectivity (sFC), independent component analysis (ICA), regional homogeneity (ReHo), fractional amplitude of low-frequency fluctuations (fALFF), and graph-theoretical network metrics (small-worldness, global/local efficiency).
RESULTS: DLB patients exhibited significantly reduced FC in the default mode network (DMN) and visual network, including PCC-AG (P < 0.001) and PCC-mPFC (P < 0.001). ReHo and fALFF indicated decreased local neural synchronization and low-frequency activity in the posterior occipital lobe (fALFF: P = 0.004), angular gyrus (fALFF: P = 0.001), left temporal pole (fALFF: P < 0.001), left parietal (ReHo: P < 0.001), and posterior cerebellar lobe (ReHo: P < 0.001). Graph theory revealed impaired global network topology in DLB, with decreased small-worldness (P < 0.001) and global efficiency (P < 0.001). PCC-AG connectivity positively correlated with the MoCA total score (r = 0.53, P < 0.001), attention (r = 0.46, P < 0.001), executive (r = 0.41, P < 0.001), and language function (r = 0.34, P < 0.001). Posterior occipital fALFF and left parietal ReHo showed significant positive correlations with multiple cognitive domains, including visuospatial ability (r = 0.34, P < 0.001 for fALFF; r = 0.42, P < 0.001 for ReHo) and memory (r = 0.45, P < 0.001 for fALFF; r = 0.27, P = 0.006 for ReHo). A combined model of PCC-AG connectivity, fALFF, and small-worldness predicted 42% of MoCA variance (R 2 = 0.42, P < 0.001).
CONCLUSION: DLB is characterized by DMN and visual network dysfunction, disrupted local neural activity, and impaired global network integration. These rs-fMRI metrics may serve as potential biomarkers for cognitive deficits in DLB.
PMID:41346435 | PMC:PMC12673660 | DOI:10.3389/fnagi.2025.1630826
Brain metabolic-functional (de)coupling from health to glioma dysfunction
Commun Biol. 2025 Dec 4. doi: 10.1038/s42003-025-09181-7. Online ahead of print.
ABSTRACT
The interplay between brain metabolism and function supports the brain's adaptive capacity in cognitively demanding processes. Prior work has linked glucose metabolism to resting-state fMRI activity, but often overlooks both hemodynamic confounders in the BOLD signal and the brain's dynamic nature. To address this, we employed a novel effective connectivity decomposition, separating symmetric partial covariance, capturing "true" statistical dependencies between regions, from antisymmetric differential covariance, reflecting directional brain flow. In 42 healthy subjects, we show that partial covariance corresponds to metabolic connectivity across regions, while node directionality relates to standardized uptake value ratio, a proxy for local glucose consumption. We subsequently tested the sensitivity of detected couplings in 43 glioma patients, identifying disruptions in both local and network-level effective-metabolic interactions that varied with tumor anatomical location. Our findings provide novel insights into the coupling between brain metabolism and functional dynamics at rest, advancing understanding of healthy and pathological brain states.
PMID:41345236 | DOI:10.1038/s42003-025-09181-7
Neural Mechanisms Underlying the Depression-reducing Effects of Mindfulness-Based Stress Reduction in University Students: A Rs-fMRI Study
Biol Psychol. 2025 Dec 2:109174. doi: 10.1016/j.biopsycho.2025.109174. Online ahead of print.
ABSTRACT
Depression constitutes a major global public health burden, with university students exhibiting a disproportionately high prevalence of depressive symptoms. Although Mindfulness-Based Stress Reduction (MBSR) has demonstrated efficacy in alleviating depressive symptomatology, its underlying neurobiological mechanisms remain incompletely understood. This randomized controlled trial investigated neural activity changes and functional connectivity alterations of MBSR's depression-reducing effects in university students using resting-state functional magnetic resonance imaging (rs-fMRI). Forty-two healthy university students were randomly assigned to either an 8-week MBSR intervention or a control group. Clinical outcomes were assessed using the Depression Anxiety Stress Scales-21, and rs-fMRI data were acquired to examine regional brain activity and functional connectivity. Results demonstrated that MBSR participants exhibited greater improvements in depression scores compared to the control group. Neuroimaging analyses indicated that MBSR intervention led to reduced Amplitude of Low-Frequency Fluctuations (ALFF), fractional ALFF, and Regional Homogeneity in the right middle cingulate cortex (MCC). Furthermore, seed-based functional connectivity analysis demonstrated decreased connectivity between the right MCC and regions involved in emotional regulation and self-referential processing, including the left hippocampus and bilateral precuneus, in the MBSR group relative to controls. Furthermore, changes in MCC-hippocampus and MCC-precuneus functional connectivity were negatively correlated with improvements in depression scores. These findings provide novel evidence that MBSR promotes adaptive neural reorganization, characterized by reduced activity and altered functional connectivity within the MCC-centric emotional regulation network, providing mechanistic insight into for its depression-reducing effects in subclinical populations and supporting the neural efficiency hypothesis.
PMID:41344637 | DOI:10.1016/j.biopsycho.2025.109174
Abnormal dynamic connectivity patterns in self-limited epilepsy with centrotemporal spikes
Brain Res Bull. 2025 Dec 2:111669. doi: 10.1016/j.brainresbull.2025.111669. Online ahead of print.
ABSTRACT
OBJECTIVE: To characterize the dynamic functional network connectivity (dFNC) patterns in children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and to uncover potential abnormalities in neural regulation and related functional impairments.
MATERIALS AND METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 61 children with SeLECTS and 69 healthy controls (HCs). Independent component analysis (ICA), the sliding window approach and hidden markov modeling (HMM) were employed to systematically investigate potential differences in dFNC properties between the two groups.
RESULTS: The dFNC analysis identified four dynamic states, with State 1 occurring most frequently. State 1 and State 3 represented two polarized connectivity patterns, with State 1 characterized by weak/negative connections and State 3 by widespread strong connections. In both states, children with SeLECTS showed significantly reduced connectivity within the dorsal attention network (DAN) compared with HCs (p < 0.001, FDR-corrected). In the connectivity-balanced State 2, children with SeLECTS showed significantly reduced fractional windows (p = 0.009) and mean dwell time (p = 0.018) compared with HCs, whereas no significant differences were observed in State 4. In addition, temporal variability of functional connectivity between the DAN and visual network (VIS) was significantly reduced in SeLECTS (p < 0.001, FDR-corrected), and this variability was positively correlated with full-scale intelligence quotient (FIQ) (p < 0.05). HMM results from another dynamic perspective further confirmed and echoed the above abnormalities.
CONCLUSION: This study revealed abnormal dynamic connectivity patterns of brain networks in children with SeLECTS from a multidimensional dynamic perspective. These macroscopic abnormalities may reflect an underlying excitation-inhibition imbalance in neural networks and provide new insights into brain functional reorganization and the potential neurobiological mechanisms of SeLECTS.
PMID:41344618 | DOI:10.1016/j.brainresbull.2025.111669
Structure-function coupling alterations in adolescent depression correlate with neurotransmitter systems and cell-type-specific transcriptomics
Prog Neuropsychopharmacol Biol Psychiatry. 2025 Dec 2:111573. doi: 10.1016/j.pnpbp.2025.111573. Online ahead of print.
ABSTRACT
BACKGROUND: Adolescent major depressive disorder (AMDD) emerges during a period of significant neurobiological reorganization, yet its specific pathophysiological mechanisms remain poorly understood. This study investigated structural-functional brain coupling (SC-FC coupling) in AMDD and its relationship with neurotransmitter systems and molecular profiles.
METHODS: We examined 107 adolescents with AMDD and 78 healthy controls. Participants underwent multimodal neuroimaging (DTI, resting-state fMRI), clinical assessment, and cognitive testing. We analyzed regional SC-FC coupling abnormalities and their associations with neurotransmitter distributions. Gene expression profiles underlying coupling alterations were examined through partial least squares regression with Allen Human Brain Atlas data. Cell-type enrichment analysis was performed using established transcriptomic references, and developmental expression trajectories were mapped using BrainSpan developmental transcriptome atlas through CSEA tool.
RESULTS: AMDD was characterized by decoupling in the default mode network and hypercoupling in somatomotor networks. These alterations demonstrated significant potential for diagnostic classification (AUC = 0.83-0.85) and correlated with clinical symptom severity. The spatial distribution of coupling alterations was significantly associated with multiple neurotransmitter systems, most robustly with dopaminergic and serotonergic markers. At the transcriptomic level, these alterations were correlated with distinct gene expression profiles, which were further linked to cell-type-specific signatures: genes associated with decoupled regions were enriched in neuronal lineages, while those associated with hypercoupled regions showed enrichment in glial cells.
CONCLUSIONS: These findings suggest that SC-FC alterations in AMDD are linked to neurotransmitter systems and cell-type-specific gene expression. These associations may reflect developmentally sensitive mechanisms that could inform age-appropriate intervention strategies for adolescent depression.
PMID:41344601 | DOI:10.1016/j.pnpbp.2025.111573
Subtyping Autism Spectrum Disorder With a Population Graph-Based Dual Autoencoder: Revealing Two Distinct Biotypes
CNS Neurosci Ther. 2025 Dec;31(12):e70675. doi: 10.1002/cns.70675.
ABSTRACT
AIM: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by significant heterogeneity in clinical symptoms and underlying neurobiology. This study aimed to identify distinct ASD biotypes and uncover their neurobiological underpinnings using a novel graph-based subtyping approach.
METHODS: Resting-state fMRI and clinical data from 443 males with ASD (17.22 ± 8.63 years) were analyzed. We proposed a population graph-based dual autoencoder for subtyping (PG-DAS), a deep clustering framework that integrates imaging data and nonimaging data to extract deep features for biotype identification. Statistical analyses were conducted to compare clinical scores and functional connectivity patterns between biotypes. Correlation analyses examined the associations between intra- and internetwork connectivity and clinical symptoms. Predictive modeling using support vector regression assessed the ability of network connectivity to predict clinical scores.
RESULTS: Two distinct ASD biotypes were identified. ASD1 exhibited significantly lower clinical scores and reduced network integration, characterized by weaker intra- and internetwork connectivity, particularly in core networks such as the cingulo-opercular network, linked to communication symptom scores. In contrast, ASD2 exhibited greater network segregation, with internetwork connectivity in sensorimotor-related networks correlating with total symptom scores. Predictive modeling further revealed biotype-specific brain-behavior associations, with ASD1 and ASD2 showing positive correlations with social and communication scores, respectively.
CONCLUSION: This study underscores the critical role of biotype-specific brain network patterns in understanding ASD heterogeneity. The proposed PG-DAS framework proved effective in ASD subtyping and holds promise for broader applications in exploring other neuroheterogeneous disorders.
PMID:41340232 | DOI:10.1002/cns.70675
Multidimensional structural-functional coupling uncovers network dysregulation and predicts binge-eating severity in bulimia nervosa
BMC Med. 2025 Dec 3;23(1):675. doi: 10.1186/s12916-025-04556-3.
ABSTRACT
BACKGROUND: Bulimia nervosa (BN) is a severe psychiatric disorder characterized by dysregulated eating behaviors and impaired cognitive-emotional control. Despite increasing recognition of brain network dysfunction in BN, the interplay between structural connectivity (SC) and functional connectivity (FC), termed SC-FC coupling, remains poorly understood. This study aimed to comprehensively characterize SC-FC coupling alterations in BN using multimodal neuroimaging and to evaluate the predictive value for disordered eating behaviors.
METHODS: This study enrolled 79 patients with BN and 69 healthy controls who underwent high-resolution structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and resting-state functional MRI (rs-fMRI). Functional and structural connectomes were constructed using the Schaefer-400 atlas. SC-FC coupling was quantified using eight biologically grounded similarity and communication metrics. A multivariate linear modeling framework was applied to estimate region-specific coupling profiles. Group comparisons and ridge regression-based leave-one-out cross-validation were used to identify altered coupling and predict symptom severity.
RESULTS: The global topological properties of the SC and FC networks were preserved in BN. However, patients exhibited significantly reduced degree centrality and nodal efficiency in the inferior frontal gyrus within the FC network. SC-FC coupling, quantified using the matching index (MI), showed widespread regional alterations in BN, particularly within the default mode, control, and attention networks. Seventeen brain parcels demonstrated significant group differences in MI-based coupling (false discovery rate (FDR)-corrected, p < 0.05), with both hypercoupling and hypocoupling observed. Findings were parcellation-robust (Glasser-360 replication; Dice = 0.93 vs. Schaefer-400). Moreover, coupling features moderately predicted binge-eating frequency (r = 0.24, p < 0.001), but not questionnaire-based emotional or behavioral scores.
CONCLUSIONS: In BN, macroscale white-matter organization is preserved, yet focal prefrontal functional decentralization and widespread, parcellation-robust SC-FC coupling changes invisible to single-modality analyses were observed. Multidimensional SC-FC coupling provides a sensitive neurobiological marker that explains clinically relevant variance in binge-eating behavior, highlighting its potential as a target for personalized diagnosis and intervention in BN.
PMID:41340129 | DOI:10.1186/s12916-025-04556-3
The Addiction Neurocircuitry and Resting-State Functional Connectivity in Cannabis Use Disorder: An fMRI Study
Addict Biol. 2025 Dec;30(12):e70105. doi: 10.1111/adb.70105.
ABSTRACT
Cannabis use disorder (CUD) affects ~22-million people globally and is characterised by difficulties in cutting down and quitting use, but the underlying neurobiology remains unclear. We examined resting-state functional connectivity (rsFC) between regions of interest (ROIs) of the addiction neurocircuitry and the rest of the brain in 65 individuals with moderate-to-severe CUD who reported attempts to cut down or quit, compared to 42 controls, and explored the association between rsFC and cannabis exposure and related problems, to elucidate potential drivers of rsFC alterations. The CUD group showed greater rsFC than controls between ROIs implicated in reward processing and habitual substance use (i.e., nucleus accumbens, putamen and pallidum) and occipito/parietal areas implicated in salience processing and disinhibition. Putamen-occipital rsFC correlated with levels of problematic cannabis use and depression symptoms. CUD appears to show neuroadaptations of the addiction neurocircuitry, previously demonstrated in other substance use disorders.
PMID:41339716 | DOI:10.1111/adb.70105
Assessment of the relationship between spatial navigation impairment and dynamic functional connectivity in individuals with subjective cognitive decline across different traditional Chinese medicine constitutions
Zhonghua Nei Ke Za Zhi. 2025 Dec 1;64(12):1226-1234. doi: 10.3760/cma.j.cn112138-20250707-00395.
ABSTRACT
Objective: To investigate the relationship between alterations in dynamic functional connectivity (dFC) and spatial navigation abilities in individuals with subjective cognitive decline (SCD) across different Traditional Chinese Medicine (TCM) constitutions. Methods: Seventy-five participants with SCD, comprising 34 individuals with balanced constitutions and 41 individuals with biased constitutions, were recruited from the Affiliated Drum Tower Hospital of Nanjing University Medical School between August 2022 and January 2025. The participants underwent TCM constitution assessment, spatial navigation ability testing, and neuropsychological scale evaluation. Additionally, each participant was assessed using 3.0 T resting-state functional magnetic resonance imaging (rs-fMRI) and high-resolution T1-weighted imaging scans. Based on prior research, 20 spatial navigation-related regions of interest (ROIs) were defined. Afterwards, rs-fMRI time series were segmented using a sliding time window approach before calculating the dFC within the spatial navigation brain network. Results: Compared to the balanced constitution group, the biased constitution SCD group showed significantly lower scores on the Mini-Mental State Examination (MMSE) (z=-3.05, P=0.002) and the Auditory Verbal Learning Test (AVLT) measures: immediate recall (z=-2.12, P=0.035), short-delay recall (z=-2.22, P=0.026), long-delay recall (z=-2.88, P=0.004), cued recall (z=-2.91, P=0.004), and recognition (z=-2.20, P=0.028). They also exhibited significantly higher average error distances in ego-allocentric navigation (z=-2.28, P=0.023), egocentric navigation (z=-2.31, P=0.021), and delayed navigation (z=-2.02, P=0.043). Participants with SCD who had a biased constitution also demonstrated significantly reduced dFC between the left parahippocampal gyrus (PHG) and left prefrontal cortex (PFC) (t=2.43), right precuneus and right retrosplenial cortex (RSC) (t=2.96), and left inferior parietal lobule (IPL) and left hippocampus (t=2.42) (all P<0.05, Bonferroni-corrected). Conversely, the dFC was significantly increased between the right PHG and left PFC (t=-2.29, P<0.05, Bonferroni-corrected). Significant correlations were also found in participants with SCD who had biased constitutions: the dFC between the left PHG and left PFC positively correlated with the egocentric navigation average total error (r=0.34, P=0.030) and negatively correlated with the visuospatial memory cognitive domain (r=-0.35, P=0.026); the dFC between the left IPL and left hippocampus negatively correlated with the egocentric navigation average total error (r=-0.32, P=0.043); and the dFC between the right PHG and left PFC positively correlated with the delayed navigation average total error (r=0.33, P=0.037). The area under the ROC curve for the combined differences in cognitive assessments, spatial navigation behavior, and navigation-related brain network dFC was 0.966 in predicting biased constitution versus balanced constitution in participants with SCD. Conclusions: Individuals with SCD and biased constitutions demonstrated poorer spatial navigation ability, possibly due to altered dFC within the spatial navigation brain network. Furthermore, the integrated model based on spatial navigation behaviors and dFC exhibited a high predictive value in distinguishing between individuals with SCD who had balanced and biased constitutions.
PMID:41338558 | DOI:10.3760/cma.j.cn112138-20250707-00395
A multimodal neuroimaging dataset for investigating speech perceptual normalization
Sci Data. 2025 Dec 3;12(1):1893. doi: 10.1038/s41597-025-06183-2.
ABSTRACT
A central challenge in speech perception is the lack of a one-to-one mapping between acoustic patterns and linguistic interpretations. This is often resolved through intrinsic normalization, where acoustic cues mutually influence each other's categorization. Notably, segmental (e.g., consonants, vowels) and suprasegmental (e.g., tone) features overlap temporally during speech perception, giving rise to complex interactions across linguistic and acoustic levels. However, the neural basis of these interactions remains underexplored due to a lack of integrated neuroimaging datasets designed for this purpose. This dataset presents a multimodal neuroimaging resource comprising structural MRI (sMRI), resting-state fMRI (rs-fMRI), categorization task-based fMRI, diffusion MRI (dMRI), and behavioral data from 28 participants (14 females, mean age 20.79 ± 1.52 years). Each participant completed two separate two-alternative forced-choice categorization tasks using 7 × 7 consonant-tone and vowel-tone continua. This resource is uniquely valuable for its explicit design to capture interactions between segmental and suprasegmental features, enabling researchers to explore neural representations, functional connectivity, and white matter correlates of speech normalization processes.
PMID:41339578 | DOI:10.1038/s41597-025-06183-2
Characterization of 'Local' Functional Network Connectivity in 4D Spatial Dynamic fMRI Networks
Annu Int Conf IEEE Eng Med Biol Soc. 2025 Jul;2025:1-4. doi: 10.1109/EMBC58623.2025.11253471.
ABSTRACT
The use of functional magnetic resonance imaging (fMRI) to map brain activity through functional network connectivity (FNC) has become a focal point in research. Most studies focus on static or dynamic FNC between predefined spatial network nodes, neglecting the possibility of time-varying dynamics within these spatial networks. While recent methods estimate voxel-level spatial dynamic networks, no approach has explored FNC between these spatial dynamic networks. In this study, we propose a novel method for examining FNC within spatially dynamic brain networks using human resting-state fMRI (rsfMRI) data. This method enables the calculation of network-specific FNC across (localized) voxel subsets. We applied this technique to the baseline dataset of 100 participants from the large-scale Adolescent Brain and Cognitive Development (ABCD) study. We first show our voxel-based FNC approach successfully replicates traditional static FNC results, demonstrating similar significant modularity in both the static FNC (sFNC) and global voxel FNC (GvFNC) matrices. The key advancement of our approach, however, lies in its ability to investigate local FNC within different voxel subsets. The findings reveal a reduction in anticorrelations within the average local voxel FNC (LvFNC) as the voxel inclusion rate decreases.
PMID:41337285 | DOI:10.1109/EMBC58623.2025.11253471
Neural Mechanisms of Post-Stroke Anomic Aphasia: Insights from fMRI-Based Machine Learning Categorical Features
Annu Int Conf IEEE Eng Med Biol Soc. 2025 Jul;2025:1-5. doi: 10.1109/EMBC58623.2025.11253918.
ABSTRACT
Anomic aphasia is a subtype of aphasia, characterized by impaired naming functions while other language abilities remain relatively intact. However, due to the relatively mild symptoms, patients with anomic aphasia are often prone to misdiagnosis or underdiagnosis, which may delay treatment and intervention. This study employed resting-state functional magnetic resonance imaging (rs-fMRI) and machine learning techniques to classify anomic aphasia and differentiate it from post-stroke non-aphasic subjects, while also investigating the neural mechanisms underlying its manifestation. Brain imaging analysis techniques, including fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and the Laterality Index (LI), were used to analyze data from 95 subjects to reveal significant differences in brain activity between anomic aphasia subjects and post-stroke non-aphasic subjects. Subsequently, these imaging-derived features were used to train and validate machine learning classifiers. Among the classifiers tested, the Multilayer Perceptron (MLP) achieved an accuracy of 94.74% in distinguishing between the two groups. Collectively, our findings highlight the potential of automated methods based on neuroimaging and machine learning in assisting clinicians to enhance diagnostic efficiency for anomic aphasia, enabling the early detection of symptoms and timely intervention.Clinical Relevance- Subjects with anomic aphasia exhibited increased rightward activation in regions such as the superior frontal gyrus and inferior frontal gyrus, coupled with reduced activation in the inferior parietal lobule and superior temporal gyrus.
PMID:41337239 | DOI:10.1109/EMBC58623.2025.11253918
A Novel Graph Neural Network Framework for Brain Age Prediction
Annu Int Conf IEEE Eng Med Biol Soc. 2025 Jul;2025:1-4. doi: 10.1109/EMBC58623.2025.11254083.
ABSTRACT
Alzheimer's disease (AD) is a neurodegenerative disorder that causes cognitive decline, and early detection remains a challenge. Resting-state functional MRI (rs-fMRI) has shown potential for identifying early AD signs by analyzing brain connectivity. In this study, we propose a Hierarchical GCN-Transformer Network (HGTNet) for brain age prediction using rs-fMRI data. Through experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, we demonstrate that, compared to traditional machine learning and deep learning methods, the combination of Graph Convolutional Networks (GCN) and Transformer architecture enhances the model's ability to capture complex brain interactions. Our model's more accurate brain age predictions provide a valuable step in identifying early neurodegenerative changes, aiding in the better intervention and management of Alzheimer's disease.
PMID:41337145 | DOI:10.1109/EMBC58623.2025.11254083
MAD-Net: Morphometric-Attentive Diffusion Network for Predicting Longitudinal Infant Brain Functional Connectivity
Annu Int Conf IEEE Eng Med Biol Soc. 2025 Jul;2025:1-5. doi: 10.1109/EMBC58623.2025.11252645.
ABSTRACT
Resting-state functional MRI (rs-fMRI) data analysis provides essential insights into early neurodevelopment through longitudinal assessment of functional connectivity (FC) patterns in infant brains, which may help uncover critical biomarkers for developmental monitoring. However, due to challenges in acquiring high-quality functional MRI (fMRI) data in infants, such as strong motion artifacts, short scan durations, and participant compliance, longitudinal FC of infants remain scarce, which significantly hampers the capacity to systematically investigate early functional brain development. To address this challenge, we propose MAD-Net, a novel diffusion model that predicts longitudinal FC from morphometric features derived from structural MRI (sMRI). Our framework integrates classifier-free guidance with a cross-modal attention mechanism, enabling the dynamic fusion of morphometric features and developmental age constraints during the diffusion process. A shared triplet encoder learns robust feature representations from longitudinal data, while a U-Net-based architecture ensures precise conditioning on individual morphometry and target age. We evaluate MAD-Net on 386 longitudinal infant fMRI scans and demonstrate its superior performance in FC prediction compared to state-of-the-art methods. By integrating diffusion-based learning, structural priors, and age-dependent constraints, MAD-Net represents a significant advancement in neuroimaging-based functional network reconstruction. The code is available at https://github.com/IPMI-NWU/MAD-Net.
PMID:41336914 | DOI:10.1109/EMBC58623.2025.11252645
Widespread Spatiotemporal Patterns of Functional Brain Networks in Longitudinal Progression of Alzheimer's Disease
Annu Int Conf IEEE Eng Med Biol Soc. 2025 Jul;2025:1-7. doi: 10.1109/EMBC58623.2025.11251603.
ABSTRACT
Alzheimer's Disease (AD) is characterized by progressive functional network disruptions that precede cognitive decline, yet traditional functional connectivity analyses often fail to capture transient network instabilities critical for early diagnosis. This study investigates the role of Quasi-Periodic Patterns (QPPs) in identifying disease-related connectivity changes across longitudinal stable disease stages (sNC, sMCI, sDAT) and transitioning (uNC, pMCI) AD cohorts using resting-state fMRI data from the Alzheimer's Disease Neuroimaging Initiative. By integrating QPP occurrences with intrinsic connectivity networks (ICNs), we assessed network integrity across disease stages, with statistical significance evaluated using the Kruskal-Wallis test and Dunn's test for post-hoc analysis. Results revealed a progressive decline in functional connectivity integrity, with early impairments in subcortical and executive function networks in stable groups, followed by widespread disconnection in higher cognition, sensorimotor, and visual networks at later stages. Transitioning AD groups exhibited earlier disruptions in visual and cerebellar networks, suggesting their potential as early biomarkers for disease onset. The occurrence of QPPs decreased significantly with disease progression, indicating an increase in functional disconnection. These findings highlight the synergy between QPPs and ICNs as a dynamic and sensitive biomarker framework for AD progression. Future research should further explore this integration within multimodal imaging and clinical diagnostic frameworks to enhance early detection and intervention strategies.
PMID:41336827 | DOI:10.1109/EMBC58623.2025.11251603
Dynamic Inter-Modality Source Coupling Reveals Sex Differences in Brain Connectivity in Children: A Multimodal MRI Study of the ABCD Dataset
Annu Int Conf IEEE Eng Med Biol Soc. 2025 Jul;2025:1-4. doi: 10.1109/EMBC58623.2025.11252770.
ABSTRACT
In this study, we introduce Dynamic Inter-Modality Source Coupling (dIMSC), an extension of our earlier Inter-Modality Source Coupling (IMSC) method. While IMSC evaluated the coupling between source-based morphometry (SBM) from structural MRI (sMRI) and static functional network connectivity (sFNC) from resting-state fMRI (rs-fMRI), dIMSC incorporates the temporal dimension by linking SBM with dynamic functional network connectivity (dFNC). Using data from the Adolescent Brain Cognitive Development (ABCD) study, we applied dIMSC to examine brain connectivity and evaluate sex differences in children aged 9-11. Our analysis revealed significant sex-specific patterns: males exhibited stronger positive coupling in the putamen and hippocampus, while females showed stronger coupling in the superior parietal lobule and anterior cingulate cortex. On average, 27.12% of timecourses exhibited positive coupling, 46.63% neutral coupling, and 26.25% negative coupling, reflecting a balanced alignment between structural and functional features. Sex differences were also observed in neutral and negative coupling groups, with males demonstrating stronger coupling in the caudate and middle cingulate gyrus, and females in the cerebellum and inferior parietal lobule. These findings suggest distinct developmental trajectories in brain network organization between sexes, potentially reflecting sex-specific adaptations in functional integration and compensatory mechanisms. The dIMSC method advances our earlier work by enabling time-sensitive analysis of brain structure-function coupling, providing a powerful framework for investigating neurodevelopmental processes and their implications for cognitive and behavioral outcomes.Clinical RelevanceThis study identifies sex-specific patterns in brain connectivity during childhood, offering insights that could inform sex-tailored diagnostic and therapeutic approaches for neurodevelopmental disorders.
PMID:41336665 | DOI:10.1109/EMBC58623.2025.11252770