Reduced neural functional connectivity during working memory performance in methamphetamine use disorder

Methamphetamine misuse, a surging cause of morbidity and mortality worldwide, identifies Methamphetamine Use Disorder (MUD) as a critical public health problem. Treatment for MUD typically is sought during early abstinence when patients are experiencing cognitive difficulties that may hamper their engagement in treatment and recovery. Cognitive difficulties, particularly those that involve executive functions, likely reflect disruptions in neural functioning involving multiple brain areas and circuits. To extend knowledge in this area, we compared individuals with MUD (MUD group, n = 30) in early abstinence (3–11 days abstinent) with a healthy control group (HC, n = 33) on brain activation and network connectivity and topology, using functional magnetic resonance imaging (fMRI) during performance on an N-back working memory task. The N-back task involves the maintenance and manipulation of information in short-term memory and engages multiple neural processes related to executive functioning. The task was administered at two working-memory difficulty loads (1-back and 2-back). Compared with the HC group, the MUD group had worse task performance but no differences in task-related brain activation. Network-based statistics analyses, however, revealed that the MUD group exhibited less functional network connectivity at both difficulty loads of the N-back task than the HC group. Additional graph theory analyses showed that path lengths were longer, and clustering was lower across these networks, which also exhibited disrupted small-world properties in the MUD group. These results suggest a decoupling in network dynamics that may underlie deficits in cognition during early abstinence in MUD patients.