Edge-centric Brain Connectome Representations Reveal Increased Brain Functional Diversity of Reward Circuit in Patients with Major Depressive Disorder.
Authors
Affiliations (7)
Affiliations (7)
- Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan, China; Mental Health Center, Taihe Hospital, Hubei University of Medicine, Shiyan, China. Electronic address: [email protected].
- Mental Health Center, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
- Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
- Mental Health Center, Taihe Hospital, Hubei University of Medicine, Shiyan, China; The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.
- Huaxi Magnetic Resonance Research Center (HMRRC), West China Hospital of Sichuan University, Chengdu, China; Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
- Huaxi Magnetic Resonance Research Center (HMRRC), West China Hospital of Sichuan University, Chengdu, China; The Turner Institute for Brain and Mental Health, School of Psychological Sciences and Monash Biomedical Imaging, Monash University, Clayton, Australia.
- Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan, China. Electronic address: [email protected].
Abstract
Major depressive disorder (MDD) has been increasingly understood as a disorder of network-level functional dysconnectivity. However, previous brain connectome studies have primarily relied on node-centric approaches, neglecting critical edge-edge interactions that may capture essential features of network dysfunction. This study included resting-state functional MRI data from 838 MDD patients and 881 healthy controls (HC) across 23 sites. We applied a novel edge-centric connectome model to estimate edge functional connectivity and identify overlapping network communities. Regional functional diversity was quantified via normalized entropy based on community overlap patterns. Neurobiological decoding was performed to map brain-wide relationships between functional diversity alterations and patterns of gene expression and neurotransmitter distribution. Comparative machine learning analyses further evaluated the diagnostic utility of edge-centric versus node-centric connectome representations. Compared with HC, MDD patients exhibited significantly increased functional diversity within the prefrontal-striatal-thalamic reward circuit. Neurobiological decoding analysis revealed that functional diversity alterations in MDD were spatially associated with transcriptional patterns enriched for inflammatory processes, as well as distribution of 5-HT1B receptors. Machine learning analyses demonstrated superior classification performance of edge-centric models over traditional node-centric approaches in distinguishing MDD patients from HC at the individual level. Our findings highlighted that abnormal functional diversity within the reward processing system might underlie multi-level neurobiological mechanisms of MDD. The edge-centric connectome approach offers a valuable tool for identifying disease biomarkers, characterizing individual variation and advancing current understanding of complex network configuration in psychiatric disorders.