title: The Fault Lies on the Other Side: Altered Brain Functional Connectivity in Psychiatric Disorders is Mainly Caused by Counterpart Regions in the Opposite Hemisphere.
abstract: Many psychiatric disorders are associated with abnormal resting-state functional connectivity between pairs of brain regions, although it remains unclear whether the fault resides within the pair of regions themselves or other regions connected to them. Identifying the source of dysfunction is crucial for understanding the etiology of different disorders. Using pathway- and network-based techniques to analyze resting-state functional magnetic imaging data from a large population of patients with attention deficit hyperactivity disorder (239 patients, 251 controls), major depression (39 patients, 37 controls), and schizophrenia (69 patients, 62 controls), we show for the first time that only network-based cross-correlation identifies significant functional connectivity changes in all 3 disorders which survive correction. This demonstrates that the primary source of dysfunction resides not in the regional pairs themselves but in their external connections. Combining pathway and network-based functional-connectivity analysis, we established that, in all 3 disorders, the counterparts of pairs of regions in the opposite hemisphere contribute 60-76% to altered functional connectivity, compared with only 17-21% from the regions themselves. Thus, a transdiagnostic feature is of abnormal functional connectivity between brain regions produced via their contralateral counterparts. Our results demonstrate an important role for contralateral counterpart regions in contributing to altered regional connectivity in psychiatric disorders.
authors.affiliation: Centre for Computational Systems Biology, Fudan University, Shanghai 200433, PR China Fudan University - Jinling Hospital Computational Translational Medicine Center, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory for Neuro Information, University of Electronic Science and Technology of China, School of Life Science and Technology, Chengdu 610054, PR China.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Kendrick
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, PR China Fudan University - Jinling Hospital Computational Translational Medicine Center, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, PR China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Lu
authors.affiliation: Centre for Computational Systems Biology, Fudan University, Shanghai 200433, PR China Fudan University - Jinling Hospital Computational Translational Medicine Center, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, PR China Department of Computer Science, University of Warwick, Coventry, UK.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Feng
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods; D003865:Major Depressive Disorder / Q000503:physiopathology; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D001523:Mental Disorders / Q000503:physiopathology*; D009415:Nerve Net / Q000503:physiopathology; D009434:Neural Pathways / Q000503:physiopathology; D012559:Schizophrenia / Q000503:physiopathology
keywords: cross-correlation; functional connectivity alteration; mental disorders; partial correlation; resting-state functional brain network