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

Introduction Methamphetamine use disorder (MUD) represents a significant public health crisis characterized by neurobiological abnormalities. While neurofunctional variations across abstinence stages are documented, brain connectivity patterns associated with abstinence duration remain poorly characterized. Objectives In this cross-sectional study, we characterized brain connectivity patterns associated with abstinence duration in MUD. We hypothesized that whole-brain functional connectivity patterns would covary with abstinence duration in MUD. Methods In this cross-sectional study, we aimed to apply connectome-based predictive modeling (CPM) to resting-state functional magnetic resonance imaging (fMRI) data from MUD participants to identify abstinence-duration-associated connectivity patterns (Figure 1A). These patterns were validated in a separate, heterogeneous sample (Figure 1B). We subsequently conducted exploratory analyses to compare connectivity strength between MUD participants and healthy comparison subjects (HCs; Figure 1C) and examine connectivity variations across abstinence stages (<1 month, 1-3 months, 3-6 months, and 6-24 months) (Figure 1D). Results Applying connectome-based predictive modeling with leave-one-out cross-validation to resting-state functional connectivity data from MUD participants 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 < .001) (Figure 2), validated in an independent cohort ( N =48, r = 0.41, P < .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 (Figure 2). Exploratory analyses revealed systematic variation in strength, with healthy comparison subjects exhibiting intermediate connectivity relative to short-term (<1 month) versus prolonged (6–24 months) abstinent MUD individuals (Figure 3). Image 1: Image 1: Long description. Image 2: Image 2: Long description. Image 3: Image 3: Long description. Conclusions In summary, this cross-sectional study identified abstinence-duration-associated connectivity patterns that covary with time abstinent from methamphetamine. Connectivity strength within these patterns demonstrated a significant association with abstinence duration across cohorts, revealing systematic variation along the abstinence continuum. These findings suggest dynamic neurofunctional reorganization during sustained abstinence from methamphetamine use. Disclosure of Interest None Declared