Disruptions in the hierarchical organization of brain functional networks in individuals with psychotic and affective disorders indicate deficits in functional integration across psychiatric diseases, highlighting the role of attentional and sensory networks in disease processes.
Abstract
Individuals with psychosis and depression show widespread alterations in brain resting-state functional connectivity (rs-FC), affecting both sensory and higher-order brain regions. In this study, we investigate disruptions in the hierarchical organization of brain functional networks in individuals with psychotic and affective disorders. We derived functional brain gradients, low dimensional representations of rs-FC that capture cortical hierarchy, in a sample of 1071 (56.3% female) participants, including clinical high-risk for psychosis (CHR-P) individuals, recent-onset psychosis (ROP) patients, recent-onset depression (ROD) patients, and healthy controls (HC). We examined regional alterations, network-level alterations and functional differentiation and their relationship to clinical symptoms. In addition, we linked case-control differences to receptor expression maps to explore underlying neurobiological mechanisms. All clinical groups exhibited alterations in the visual-to-sensorimotor gradient, while only ROP patients showed alterations in the sensory-to-association gradient. CHR-P and ROP individuals exhibited lower values in the ventral attention network. Clinical groups combined showed higher values in the somatomotor network, a reduced gradient range and altered between-network dispersion. ROD patients showed reduced within-network dispersion in the attentional networks and a reduced range. Correlational analysis revealed weak associations of gradient measures with functioning, visual dysfunctions and cognition. Case-control differences showed associations to receptor expression maps, suggesting the involvement of neurotransmitter systems in these disruptions. Our findings reveal transdiagnostic and disease-specific alterations of hierarchical brain organization. These alterations indicate deficits in functional integration across psychiatric diseases, highlighting the role of attentional and sensory networks in disease processes.
Patients with psychosis and depression show widespread alterations in brain resting-state functional connectivity (rs-FC), affecting both sensory and higher-order brain regions. In this study, we investigate disruptions in the hierarchical organization of brain functional networks in patients with psychotic and affective disorders. We derived functional brain gradients, low dimensional representations of rs-FC that capture cortical hierarchy, in a large patient sample including clinical high-risk for psychosis (CHR-P) patients, recent-onset psychosis (ROP) patients, recent-onset depression (ROD) patients, and healthy controls (HC). We examined regional alterations, network-level alterations and functional differentiation and their relationship to clinical symptoms. In addition, we linked case-control differences to receptor expression maps to explore underlying neurobiological mechanisms. All patient groups exhibited alterations in the visual-to-sensorimotor gradient, while only ROP patients showed alterations in the association-to-sensory gradient. CHR-P and ROP patients exhibited lower values in the ventral attention network. Additionally, patients combined showed higher values in the somatomotor network, a reduced gradient range and altered between-network dispersion. ROD showed reduced within-network dispersion in the attentional networks and a reduced range. Correlational analysis revealed weak associations of gradient measures with functioning, visual dysfunctions and cognition. Furthermore case-control differences showed associations to receptor expression maps, suggesting the involvement of neurotransmitter systems in these disruptions. Our findings reveal transdiagnostic and disease-specific alterations of hierarchical brain organization. These alterations indicate deficits in functional integration across psychiatric diseases, highlighting the role of attentional and sensory networks in disease processes.
Hannah Hacker, L. Hoheisel, M. Buciuman et al.· Research Square· 0 citations
Abstract Background Schizophrenia (SZ) and bipolar disorder (BD) are common severe mental disorders. Although clear diagnostic boundaries exist between the two disorders, they share overlaps in certain clinical symptoms and abnormal brain network functions. Recent neuroimaging studies have shown both specific differences and common alterations in resting-state brain network functional connectivity (FC) between SZ and BD. However, direct or indirect comparative studies on the similarities and differences in whole-brain functional connectivity patterns between SZ and BD remain limited. This study aims to explore the abnormal functional connectivity features of SZ and BD using both network-level and edge-level functional connectivity analysis methods, providing insights into their neural underpinnings. Aims & Objectives Based on resting-state functional magnetic resonance imaging (fMRI) data from a Chinese population, this study compares brain functional connectivity patterns among SZ, BD, and healthy controls (HC) at both network-level and edge-level analyses. It investigates the specificity and commonality of brain network functional connectivity abnormalities in the two disorders and preliminarily explores the relationship between abnormal functional connectivity and clinical symptoms as well as cognitive impairment. Method A total of 45 SZ patients, 50 BD patients, and 57 HC participants were included in this study. General demographic information, clinical data, and resting-state fMRI data were collected. Network-level functional connectivity analysis was used to compare connectivity features within and between large-scale brain networks among the three groups. Logistic regression was employed to evaluate the predictive performance of functional connectivity features in distinguishing between the two disorders. Edge-level functional connectivity analysis was conducted for pairwise comparisons among SZ, BD, and HC to reveal whole-brain connectivity differences. Correlation analysis was performed to explore the relationship between abnormal edge-level functional connectivity indicators and clinical and cognitive symptom scores in SZ and BD. Results Both SZ and BD exhibited significant FC reductions within and between multiple brain networks, with SZ showing more extensive and severe FC abnormalities. In terms of differences in brain network connectivity abnormalities between SZ and BD, abnormal connectivity within the limbic network (LN) was a key feature distinguishing SZ from BD. Edge-level functional connectivity analysis revealed significant differences in the extent of impairment within the visual network (VN) between the two disorders. In terms of shared abnormal network patterns, weakened connectivity within the dorsal attention network (DAN) may serve as a potential indicator for distinguishing SZ and BD from HC. Networks commonly impaired in both disorders included the sensorimotor network (SMN), VN, and default mode network (DMN). The most significant FC reductions in both disorders were observed in the VN-SMN edges. In SZ, FC strength in the frontoparietal network (FPN)-DMN was significantly positively correlated with visual learning. Discussion & Conclusions Both SZ and BD exhibit abnormal reductions in resting-state brain network connectivity. Differences in limbic network connectivity hold potential diagnostic value for distinguishing between the two disorders, while attention network abnormalities reflect a shared pathological pattern. Additionally, some connectivity features are closely associated with cognitive function.
Y. Sun, Y. Xing, Q. Bo et al.· International Journal of Neu...· 0 citations
BACKGROUND
Functional/dissociative seizures (FDS) involve alterations in emotional processing, agency, self-monitoring, and motor control. Post-traumatic stress disorder (PTSD) involves brain systems related to emotional processing, salience detection, memory, and cognitive control. FDS and PTSD converge on several clinical and neurobiological dimensions-including trauma-related vulnerability, emotional processing, dissociation, and alterations involving limbic and regulatory networks-while producing markedly different clinical manifestations. However, it remains unclear which neural abnormalities reflect these shared dimensions and which may be more specifically associated with the emergence of functional seizures.
METHODS
The study included 25 FDS patients, 20 PTSD patients, and 23 healthy controls (HC) who underwent functional and structural 3T MRI. Functional connectivity between 12 predefined brain regions was analyzed using seed-to-voxel analysis. Cluster-based inference and Gaussian random field theory were applied with p-corrected <0.05 and p-uncorrected <0.001 thresholds. Cortical and subcortical structures, including specific hippocampal and amygdala subregions, were segmented using FreeSurfer, and volumes were expressed as mean ± SD.
RESULTS
FDS patients showed lower bilateral dentate gyrus volume (FDS: 142.75 ± 16.28, control: 157.75 ± 17.11, p-adj= 0.019) and greater left anterior cingulate cortical thickness (FDS: 2.85 ± 0.14, control: 2.75 ± 0.17, p-adj= 0.01). Compared with PTSD patients, FDS patients had lower right amygdala central nucleus (FDS: 39.81 ± 5.43, PTSD: 44.15 ± 4.15, p-adj= 0.01) and right pars orbitalis cortical thickness (FDS: 2.62 ± 0.19, PTSD: 2.75 ± 0.17, p-adj= 0.04). Hyperconnectivity was observed from the right hippocampus to the right temporoparietal junction (FDS vs. controls) and from the right insula to the orbitofrontal cortex (FDS vs. PTSD).
CONCLUSION
Anatomical and functional alterations were observed in FDS and PTSD groups versus HC and between FDS and PTSD groups. These findings suggest both shared and disorder-specific brain alterations in FDS and PTSD.
Clélia Galmiche, L. Tyvaert, P. Fauvé et al.· Seizure· 0 citations
BACKGROUND
Major depressive disorder (MDD) is highly prevalent and often complicated by anxiety symptoms, yet the neurobiological features associated with anxious depression remain incompletely characterized. The amygdala-prefrontal cortex (PFC) circuit, central to affect regulation, has been implicated in anxious depressive symptoms.
METHODS
We recruited 40 MDD patients and 69 healthy controls (HCs) from Tianjin Anding Hospital. All participants underwent resting-state functional magnetic resonance imaging(fMRI) and clinical assessments. Seed-based functional connectivity (FC) analyses were performed using the bilateral amygdala based on the Automated Anatomical Labeling (AAL) atlas. Group comparisons, partial correlations, and regression analyses tested associations between amygdala-based FC and HDRS-17 symptom dimensions, with subgroup analyses distinguishing MDD patients with and without anxiety.
RESULTS
Compared with HCs, MDD patients exhibited reduced FC between the right amygdala and prefrontal cortex, including the right middle frontal gyrus (MFG) and the left inferior frontal gyrus, triangular part (IFGtri) (GRF: voxel-level p < 0.001, cluster-level p < 0.05). Within the MDD group, higher right amygdala-MFG FC values were associated with HDRS-17 symptoms, including total scores and depressive and somatic symptom dimensions (r = 0.393, p = 0.020; r = 0.360, p = 0.033; r = 0.351, p = 0.039, uncorrected p). In exploratory subgroup analyses, right amygdala-MFG FC showed a positive association with HDRS-17 scores in MDD patients with anxiety (R2 = 0.280, F = 8.957, p = 0.006, Beta = 0.529, t = 2.993, p = 0.006); however, the FC × anxiety subgroup interaction did not reach statistical significance.
CONCLUSION
Our findings identify disrupted right amygdala-MFG connectivity as a potential neural correlate of symptom heterogeneity in MDD, particularly in patients with anxiety symptoms.
Chu-Hao Zhang, Li-Jun Wang, Wen-Jie Sun et al.· Neuroscience Letters· 0 citations
BACKGROUND
Although structural and functional alterations in borderline personality disorder (BPD) have been widely reported in neuroimaging studies, the findings remain heterogeneous. Emerging consensus suggests that these distributed alterations may converge on a common pathological network associated with BPD, providing a network-level framework for elucidating the neural basis of the disorder.
METHODS
We integrated findings from 96 publications covering 2325 patients with BPD and 2356 healthy controls across gray matter volume, task-induced activation, and resting-state activity modalities. Using the functional connectivity network mapping (FCNM) approach, we projected the reported alterations onto a large-scale functional connectome (n = 872) to localize brain alteration networks associated with BPD. We then evaluated the spatial relationship between these networks and 19 neurotransmitter distribution maps.
RESULTS
We identified three distinct networks. The gray matter volume alteration network involved the precentral/postcentral gyrus and temporal gyrus, predominantly within the somatomotor (12.24%) and subcortical networks (8.65%). The task-induced activation network was mainly located in the insula/putamen, primarily associated with the ventral attention network (18.83%). The resting-state network encompassed the superior frontal gyrus, precuneus, and angular gyrus, dominated by the default mode network (53.86%). The structural network exhibited spatial correlations with the serotonin transporter, while the task-induced network was associated with noradrenergic and cholinergic systems.
CONCLUSIONS
These findings suggest BPD might be characterized by structural deficits in somatic-emotional integration and functional dysregulation in salience detection and self-referential processing. This network-level framework helps address previously existing inconsistencies and suggests that these brain alterations may be related to specific neurotransmitters.
Leyi Zhang, Yiding Han, Y. Ou et al.· Journal of Affective Disorde...· 0 citations
Understanding functional connectivity alterations across manic, depressive, and remitted states of bipolar disorder (BD) remains an important challenge. In this cross-sectional study, we collected resting-state functional magnetic resonance imaging data from 117 BD patients, including manic BD patients (BipM: n = 38), depressive BD patients (BipD: n = 42), remitted BD patients (rBD: n = 37), and 35 healthy controls. We aimed to identify functional connectivity patterns associated with different BD episode states and shared alterations across groups, and to examine their normative reliability, heritability, and spatial correspondence with molecular and cellular brain maps. We identified shared altered connectivity patterns mainly involving ventral attention network-related regions, together with candidate state-associated patterns involving default-mode-related regions in BipM, frontoparietal/somatomotor/visual regions in BipD, and limbic-related regions in rBD. Using Human Connectome Project data, we further found that subsets of these selected connections showed normative test-retest reliability and heritability in healthy adults. Exploratory machine-learning analyses suggested that these patterns contained information related to BD episode-state classification and symptom variation, although the results require independent external validation. Spatial annotation analyses showed that the regional distribution of these connectivity patterns corresponded with normative neurotransmitter receptor, cell-type, and BD-related gene-expression maps. These findings suggest that BD episode states are associated with partially distinct and partially shared functional connectivity alterations. However, because the study was cross-sectional and single-center, and because the molecular analyses were based on normative spatial maps, the findings should be interpreted as exploratory state-associated network observations rather than causal mechanisms or validated clinical biomarkers.
Xiao-Bo Liu, Zhenqi Liu, Bin Wan et al.· Journal of Affective Disorde...· 0 citations
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