Department of Radiology, Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, PR China.
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.
Neuroimage. 2024 Nov 1;301:120883. doi: 10.1016/j.neuroimage.2024.120883. Epub 2024 Oct 9.
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 (P<0.05), with strong alterations in somatomotor regions (P<0.05) and moderate alterations in high-level association networks (P<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.
甲基苯丙胺（MA）使用障碍是一种慢性神经毒性脑疾病，其特征是强烈的渴望导致复发的风险很高。然而，渴望的神经生物学特征仍然不清楚，这限制了各种治疗方法的有效性。本研究使用了 62 名 MA 使用者和 57 名健康对照者（HC）的弥散 MRI（dMRI）扫描。对 MA 使用者进行了纵向随访，随访期间他们处于长期禁欲期（长期禁欲持续时间：347.52±99.25 天）。我们从因果关系的角度使用网络控制理论系统地量化了每个脑区对渴望相关状态转变的控制能力。通过多变量组比较和生物相关性分析研究了与渴望相关的结构改变（CSA）。使用转录组和神经化学分析阐明了 CSA 的神经机制。我们观察到，长期禁欲引起的结构改变显著影响了认知控制对外界信息的反应涉及的状态转换能量，这与渴望评分的变化相关（r ∼ 0.35，P <0.01）。我们的因果网络分析进一步支持了前额叶皮层（PFC）在渴望机制中的关键作用。值得注意的是，虽然 PFC 是渴望的核心，但 CSA 广泛分布在多个脑区（P<0.05），躯体运动区有强烈改变（P<0.05），高级联想网络有中度改变（P<0.05）。此外，转录组、化学化合物、细胞类型分析和分子成像共同强调了神经免疫通讯对人类渴望调节的影响。我们的研究结果提供了一个综合的、多尺度的视角，揭示了渴望的神经基础，并表明神经免疫信号可能是未来人类成瘾治疗的一个有前途的靶点。
