Hyperconnectivity of the lateral amygdala in long-term methamphetamine abstainers negatively correlated with withdrawal duration

Introduction: Several studies have reported structural and functional abnormalities of the amygdala caused by methamphetamine addiction. However, it is unknown whether abnormalities in amygdala function persist in long-term methamphetamine abstainers. Methods: In this study, 38 long-term male methamphetamine abstainers (>12 months) and 40 demographically matched male healthy controls (HCs) were recruited. Considering the heterogeneous nature of the amygdala structure and function, we chose 4 amygdala subregions (i.e., left lateral, left medial, right lateral, and right medial) as regions of interest (ROI) and compared the ROI-based resting-state functional connectivity (FC) at the whole-brain voxel-wise between the two groups. We explored the relationship between the detected abnormal connectivity, methamphetamine use factors, and the duration of withdrawal using correlation analyses. We also examined the effect of methamphetamine use factors, months of withdrawal, and sociodemographic data on detected abnormal connectivity through multiple linear regressions. Results: Compared with HCs, long-term methamphetamine abstainers showed significant hyperconnectivity between the left lateral amygdala and a continuous area extending to the left inferior/middle occipital gyrus and left middle/superior temporal gyrus. Abnormal connections negatively correlated with methamphetamine withdrawal time (r = −0.85, p < 0.001). The linear regression model further demonstrated that the months of withdrawal could identify the abnormal connectivity (β(adj) = −0.86, 95%CI: −1.06 to −0.65, p < 0.001). Discussion: The use of methamphetamine can impair the neural sensory system, including the visual and auditory systems, but this abnormal connectivity can gradually recover after prolonged withdrawal of methamphetamine. From a neuroimaging perspective, our results suggest that withdrawal is an effective treatment for methamphetamine.