title: Granger causality reveals a dominant role of memory circuit in chronic opioid dependence.
abstract: Resting-state magnetic resonance imaging has uncovered abnormal functional connectivity in heroin-dependent individuals (HDIs). However, it remains unclear how brain regions implicated in addictions are related in baseline state without conditioned cues in heroin dependent individuals during opioid maintenance treatment (HDIs-OMT). Previous connectivity analysis assessed the strength of correlated activity between brain regions but lacked the ability to infer directional neural interactions. In the current study, we employed Granger causality analysis to investigate directional causal influences among the brain circuits in HDIs-OMT and non-opioid users. The results revealed a weaker effective connectivity between the caudate nucleus implicated in mediating the reward circuit and other brain regions and also a weaker connectivity between the anterior cingulate cortex and medial prefrontal cortex implicated in mediating inhibitory control. Conversely, HDIs-OMT exhibited stronger effective connectivity between the hippocampus and amygdala implicated in mediating learning-memory, and the anterior cingulate cortex involved in mediating inhibitory control while the putamen mediated learned habits, suggesting that the hippocampus and amygdala may propel the memory circuit to override the control circuit and drive the learned habit in HDIs-OMT. Alterations in learning-memory and inhibitory control may contribute jointly and form a basis for relapse risk even after a period of heroin abstinence. Sustained neural effect of opioid dependence on methadone maintenance including hyperactivation in the memory circuit and impairment in the control circuit support the role of the memory circuitry in relapse and may help redefine targets for treatment.
authors.affiliation: School of Life Science and Technology, Xidian University, Xi'an, China.|Department of Psychiatry & McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Psychology, Renmin University of China, Beijing, China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Wen
authors.affiliation: School of Life Science and Technology, Xidian University, Xi'an, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Cai
authors.affiliation: School of Life Science and Technology, Xidian University, Xi'an, China.
authors.forename: Guanya
authors.initials: G
authors.lastname: Li
authors.affiliation: School of Life Science and Technology, Xidian University, Xi'an, China.|Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Psychiatry & McKnight Brain Institute, University of Florida, Gainesville, FL, USA.|Malcom Randall Veterans Affairs Medical Center, Gainesville, FL, USA.
authors.forename: Yi Edi
authors.initials: YE
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, Xidian University, Xi'an, China.
authors.forename: Jixin
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Life Science and Technology, Xidian University, Xi'an, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yuan
authors.affiliation: College of Mechanical and Electronic Engineering, Northwest A&F University, Yangling, China.
authors.forename: Jizheng
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Radiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Radiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA.
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Ding
authors.affiliation: Department of Psychiatry & McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Gold
authors.affiliation: Department of Psychiatry & McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors.forename: Gene-Jack
authors.initials: GJ
authors.lastname: Wang
mesh_terms: D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods*; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008875:Middle Aged; D009293:Opioid-Related Disorders / Q000150:complications* / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology; D011699:Putamen / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D012146:Rest
keywords: Granger causality; inhibitory control; learning-memory; opioid dependence; resting-state fMRI