Neuro-immune communication at the core of craving-associated brain structural network reconfiguration in methamphetamine users
Yanyao Du,
Jiaqi Zhang,
Dan Cao,
Wenhan Yang,
Jin Li,
Deying Li,
Ming Song,
Zhengyi Yang,
Jun Zhang,
Tianzi Jiang,
Jun Liu
Affiliations
Yanyao Du
Department of Radiology, Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, PR China
Jiaqi Zhang
Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, PR China; School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing 100049, PR China
Dan Cao
Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, PR China
Wenhan Yang
Department of Radiology, Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, PR China
Jin Li
School of Psychology, Capital Normal University, Beijing 100048, PR China
Deying Li
Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, PR China; School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing 100049, PR China
Ming Song
Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, PR China
Zhengyi Yang
Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, PR China
Jun Zhang
Hunan Judicial Police Academy, Changsha, Hunan 410138, PR China
Tianzi Jiang
Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, PR China; School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing 100049, PR China; Center for Excellence in Brain Science and Intelligence Technology, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, PR China; Xiaoxiang Institute for Brain Health and Yongzhou Central Hospital, Yongzhou 425000, Hunan Province, PR China; Corresponding authors.
Jun Liu
Department of Radiology, Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, PR China; Clinical Research Center for Medical Imaging in Hunan Province, Changsha, Hunan 410011, China; Department of Radiology Quality Control Center, Changsha, Hunan 410011, China; Corresponding authors.
Methamphetamine (MA) use disorder is a chronic neurotoxic brain disease characterized by a high risk of relapse driven by intense cravings. However, the neurobiological signatures of cravings remain unclear, limiting the effectiveness of various treatment methods. Diffusion MRI (dMRI) scans from 62 MA users and 57 healthy controls (HC) were used in this study. The MA users were longitudinally followed up during their period of long-term abstinence (duration of long-term abstinence: 347.52±99.25 days). We systematically quantified the control ability of each brain region for craving-associated state transitions using network control theory from a causal perspective. Craving-associated structural alterations (CSA) were investigated through multivariate group comparisons and biological relevance analysis. The neural mechanisms underlying CSA were elucidated using transcriptomic and neurochemical analyses. We observed that long-term abstinence-induced structural alterations significantly influenced the state transition energy involved in the cognitive control response to external information, which correlated with changes in craving scores (r ∼ 0.35, P <0.01). Our causal network analysis further supported the crucial role of the prefrontal cortex (PFC) in craving mechanisms. Notably, while the PFC is central to the craving, the CSAs were distributed widely across multiple brain regions (PFDR<0.05), with strong alterations in somatomotor regions (PFDR<0.05) and moderate alterations in high-level association networks (PFDR<0.05). Additionally, transcriptomic, chemical compounds, cell-type analyses, and molecular imaging collectively highlight the influence of neuro-immune communication on human craving modulation. Our results offer an integrative, multi-scale perspective on unraveling the neural underpinnings of craving and suggest that neuro-immune signaling may be a promising target for future human addiction therapeutics.
