title: Medial reward and lateral non-reward orbitofrontal cortex circuits change in opposite directions in depression.
abstract: The first brain-wide voxel-level resting state functional connectivity neuroimaging analysis of depression is reported, with 421 patients with major depressive disorder and 488 control subjects. Resting state functional connectivity between different voxels reflects correlations of activity between those voxels and is a fundamental tool in helping to understand the brain regions with altered connectivity and function in depression. One major circuit with altered functional connectivity involved the medial orbitofrontal cortex Brodmann area 13, which is implicated in reward, and which had reduced functional connectivity in depression with memory systems in the parahippocampal gyrus and medial temporal lobe, especially involving the perirhinal cortex Brodmann area 36 and entorhinal cortex Brodmann area 28. The Hamilton Depression Rating Scale scores were correlated with weakened functional connectivity of the medial orbitofrontal cortex Brodmann area 13. Thus in depression there is decreased reward-related and memory system functional connectivity, and this is related to the depressed symptoms. The lateral orbitofrontal cortex Brodmann area 47/12, involved in non-reward and punishing events, did not have this reduced functional connectivity with memory systems. Second, the lateral orbitofrontal cortex Brodmann area 47/12 had increased functional connectivity with the precuneus, the angular gyrus, and the temporal visual cortex Brodmann area 21. This enhanced functional connectivity of the non-reward/punishment system (Brodmann area 47/12) with the precuneus (involved in the sense of self and agency), and the angular gyrus (involved in language) is thus related to the explicit affectively negative sense of the self, and of self-esteem, in depression. A comparison of the functional connectivity in 185 depressed patients not receiving medication and 182 patients receiving medication showed that the functional connectivity of the lateral orbitofrontal cortex Brodmann area 47/12 with these three brain areas was lower in the medicated than the unmedicated patients. This is consistent with the hypothesis that the increased functional connectivity of the lateral orbitofrontal cortex Brodmann area 47/12 is related to depression. Relating the changes in cortical connectivity to our understanding of the functions of different parts of the orbitofrontal cortex in emotion helps to provide new insight into the brain changes related to depression.
authors.affiliation: 1 School of Mathematical Sciences and Centre for Computational Systems Biology, Fudan University, Shanghai, 200433, PR China.|2 Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai 200433, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.affiliation: 3 Department of Computer Science, University of Warwick, Coventry CV4 7AL, UK.|4 Oxford Centre for Computational Neuroscience, Oxford, UK.
authors.forename: Edmund T
authors.initials: ET
authors.lastname: Rolls
authors.affiliation: 5 Key Laboratory of Cognition and Personality (SWU), Ministry of Education, Chongqing, China.|6 Department of Psychology, Southwest University, Chongqing, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Qiu
authors.affiliation: 5 Key Laboratory of Cognition and Personality (SWU), Ministry of Education, Chongqing, China.|6 Department of Psychology, Southwest University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: 7 Department of Psychiatry, The First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning, PR China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Tang
authors.affiliation: 8 Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chu-Chung
authors.initials: CC
authors.lastname: Huang
authors.affiliation: 9 Institute of Neuroscience, Chongqing Medical University, Chongqing, China.|10 Chongqing Key Laboratory of Neurobiology, Chongqing, China.|11 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China.
authors.forename: XinFa
authors.initials: X
authors.lastname: Wang
authors.affiliation: 1 School of Mathematical Sciences and Centre for Computational Systems Biology, Fudan University, Shanghai, 200433, PR China.|2 Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai 200433, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 1 School of Mathematical Sciences and Centre for Computational Systems Biology, Fudan University, Shanghai, 200433, PR China.|2 Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai 200433, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.affiliation: 12 School of Information Science and Engineering, Fudan University, Shanghai, China.|13 KTH - Royal Institute of Technology, Sweden.
authors.forename: Lirong
authors.initials: L
authors.lastname: Zheng
authors.affiliation: 9 Institute of Neuroscience, Chongqing Medical University, Chongqing, China.|10 Chongqing Key Laboratory of Neurobiology, Chongqing, China.|11 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China.
authors.forename: JunCai
authors.initials: J
authors.lastname: Pu
authors.affiliation: 14 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Tsai
authors.affiliation: 8 Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan.|14 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Yang
authors.affiliation: 8 Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ching-Po
authors.initials: CP
authors.lastname: Lin
authors.affiliation: 7 Department of Psychiatry, The First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: 9 Institute of Neuroscience, Chongqing Medical University, Chongqing, China.|10 Chongqing Key Laboratory of Neurobiology, Chongqing, China.|11 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
authors.affiliation: 1 School of Mathematical Sciences and Centre for Computational Systems Biology, Fudan University, Shanghai, 200433, PR China jianfeng64@gmail.com xiepeng@cqmu.edu.cn fei.wang@yale.edu cplin@ym.edu.tw.|2 Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai 200433, PR China.|3 Department of Computer Science, University of Warwick, Coventry CV4 7AL, UK.|15 School of Mathematical Sciences, School of Life Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200433, PR China.|16 School of Life Sciences, Fudan University, Shanghai, 200433, PR China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Feng
mesh_terms: D000328:Adult; D015331:Cohort Studies; D063132:Connectome / Q000379:methods*; D003865:Major Depressive Disorder / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010296:Parietal Lobe / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012201:Reward; D012649:Self Concept
keywords: depression; functional connectivity; medial temporal lobe; orbitofrontal cortex; precuneus