title: Prefrontal dysconnectivity links to working memory deficit in first-episode schizophrenia.
abstract: Working memory (WM) deficit is a core feature of schizophrenia and is characterized by abnormal functional integration in the prefrontal cortex, including the dorsolateral prefrontal cortex (dLPFC), dorsal anterior cingulate cortex (dACC), and ventrolateral prefrontal cortex (vLPFC). However, the specific mechanism by which the abnormal neuronal circuits that involve these brain regions contribute to this deficit is still unclear. Therefore, this study focused on these regions and sought to answer which abnormal causal relationships in these regions can be linked to impaired WM in schizophrenia. We used spectral dynamic causal modeling to estimate directed (effective) connectivity between these regions based on resting-state functional magnetic resonance imaging data from healthy control (HC) subjects and patients with first-episode schizophrenia (FES). By comparing these effective connections in the controls and patients, we found that the effective connectivity from the dACC to the dLPFC and from the right dLPFC to the left vLPFC was weaker in the FES group than in the HC group. Furthermore, these effective connections displayed a positive correlation with WM performance in the HCs. However, in the FES patients, the effective connectivity from the dACC to the dLPFC was not correlated with WM performance, and the effective connectivity from the right dLPFC to the left vLPFC was negatively correlated with WM performance. These results could be explained by an aberrant top-down mechanism of WM processing and provide new evidence for the dysconnectivity hypothesis of schizophrenia.
authors.affiliation: Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Fang
authors.affiliation: Faculty of Psychological and Educational Sciences, Department of Experimental and Applied Psychology, Research Group of Biological Psychology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Luqi
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Yuanchao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Behavioral Science & Magnetic Resonance Imaging Research Center, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Shihao
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Jilin
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Radiology, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China. hlwang@whu.edu.cn.|Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China. hlwang@whu.edu.cn.
authors.forename: Huiling
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China. jiangtz@nlpr.ia.ac.cn.|Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China. jiangtz@nlpr.ia.ac.cn.|National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China. jiangtz@nlpr.ia.ac.cn.|CAS Center for Excellence in Brain Science, Institute of Automation, Chinese Academy of Sciences, Beijing, China. jiangtz@nlpr.ia.ac.cn.|Queensland Brain Institute, University of Queensland, Brisbane, Australia. jiangtz@nlpr.ia.ac.cn.
authors.forename: Tianzi
authors.initials: T
authors.lastname: Jiang
mesh_terms: D000208:Acute Disease; D001931:Brain Mapping / Q000379:methods; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology*; D008570:Memory, Short-Term / Q000502:physiology*; D009434:Neural Pathways / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D012146:Rest; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D055815:Young Adult
keywords: Effective connectivity; Resting-state fMRI; Schizophrenia; Spectral dynamic causal modeling; Working memory deficit