Metabolic and functional substrates of impulsive decision-making in individuals with heroin addiction after prolonged methadone maintenance treatment
Qian Lv,
Miao Zhang,
Haifeng Jiang,
Yilin Liu,
Shaoling Zhao,
Xiaomin Xu,
Wenlei Zhang,
Tianzhen Chen,
Hang Su,
Jiangtao Zhang,
Heqiu Wang,
Jianmin Zhang,
Yuanjing Feng,
Yongqiang Li,
Biao Li,
Min Zhao,
Zheng Wang
Affiliations
Qian Lv
Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; School of Psychological and Cognitive Sciences, Beijing Key Laboratory of Behavior and Mental Health, IDG/McGovern Institute for Brain Research, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China
Miao Zhang
Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Haifeng Jiang
Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
Yilin Liu
Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, China
Shaoling Zhao
Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, China
Xiaomin Xu
Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
Wenlei Zhang
Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
Tianzhen Chen
Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
Hang Su
Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
Jiangtao Zhang
Tongde Hospital of Zhejiang Province (Zhejiang Mental Health Center), Zhejiang Office of Mental Health, Hangzhou, China
Heqiu Wang
Tongde Hospital of Zhejiang Province (Zhejiang Mental Health Center), Zhejiang Office of Mental Health, Hangzhou, China
Jianmin Zhang
Tongde Hospital of Zhejiang Province (Zhejiang Mental Health Center), Zhejiang Office of Mental Health, Hangzhou, China
Yuanjing Feng
College of Information Engineering, Zhejiang University of Technology, Hangzhou, China
Yongqiang Li
College of Information Engineering, Zhejiang University of Technology, Hangzhou, China
Biao Li
Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding author at: Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Min Zhao
Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China; Corresponding author at: Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Zheng Wang
School of Psychological and Cognitive Sciences, Beijing Key Laboratory of Behavior and Mental Health, IDG/McGovern Institute for Brain Research, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China; Corresponding author at: Peking University, Beijing, China.
Elevated impulsivity has been frequently reported in individuals with opioid addiction receiving methadone maintenance therapy (MMT), but the underlying neural mechanisms and cognitive subprocesses are not fully understood. We acquired functional magnetic resonance imaging (fMRI) data from 37 subjects with heroin addiction receiving long-term MMT and 33 healthy controls who performed a probabilistic reversal learning task, and measured their resting-state brain glucose using fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET). Subjects receiving MMT exhibited significantly elevated self-reported impulsivity, and computational modeling revealed a marked impulsive decision bias manifested as switching more frequently without available evidence. Moreover, this impulsive decision bias was associated with the dose and duration of methadone use, irrelevant to the duration of heroin use. During the task, the switch-related hypoactivation in the left rostral middle frontal gyrus was correlated with the impulsive decision bias while the function of reward sensitivity was intact in subjects receiving MMT. Using prior brain-wide receptor density data, we found that the highest variance of regional metabolic abnormalities was explained by the spatial distribution of μ-opioid receptors among 10 types of neurotransmitter receptors. Heightened impulsivity in individuals receiving prolonged MMT is manifested as atypical choice bias and noise in decision-making processes, which is further driven by deficits in top-down cognitive control, other than reward sensitivity. Our findings uncover multifaceted mechanisms underlying elevated impulsivity in subjects receiving MMT, which might provide insights for developing complementary therapies to improve retention during MMT.
