Brain connectivity patterns associated with duration of abstinence in methamphetamine use disorder

Abstract

Methamphetamine use disorder (MUD) is a substantial public health crisis characterized by neurobiological abnormalities. Although neurofunctional variations across abstinence stages are documented, brain connectivity patterns associated with abstinence duration remain poorly characterized. In this cross-sectional study, we characterize brain connectivity patterns associated with abstinence duration in MUD. We hypothesize that whole-brain functional connectivity patterns would covary with abstinence duration in MUD. Applying connectome-based predictive modeling with leave-one-out cross-validation to resting-state functional connectivity data from participants with MUD stratified by abstinence duration (<1 month, 1–3 months, 3–6 months, 6–24 months; total N = 85), we identified patterns significantly associated with abstinence duration (r = 0.51, P < 0.001), validated in an independent cohort (N = 48, r = 0.41, P < 0.004). These patterns comprised positive components showing strengthened within-network connectivity in motor/sensory, subcortical and medial frontal networks, and enhanced between-network connectivity involving motor/sensory, cerebellum/brainstem and subcortical networks, and negative components demonstrating reduced connectivity between motor/sensory and default mode networks, as well as among motor/sensory, medial frontal and visual association networks. Exploratory analyses revealed systematic variation in strength, with healthy comparison individuals exhibiting intermediate connectivity relative to individuals who were short-term (<1 month) versus prolonged (6–24 months) MUD-abstinent. Our findings reveal cross-sectional associations between abstinence duration and brain connectivity in MUD.