Drug use severity is linked to more cross-communication between brain networks.

Reward and cognitive brain networks may be less efficient with severe opioid use.

Naltrexone treatment for opioid use disorder did not alter network segregation.

Salience network segregation may support positive emotions in opioid use disorder.

Opioid use disorder (OUD) is associated with altered brain network connectivity, particularly in the fronto-parietal, default mode, and salience networks. Brain efficiency is maximized when networks are distinct (‘segregated’) yet maintain partial connectivity with other networks (‘integrated’). ‘Brain network segregation’ quantifies this balance by comparing the functional connectivity of nodes within and between networks. Previous research found lower brain network segregation in people with cognitive impairment, alcohol use disorder, and older age. We hypothesized that recent drug use severity in people with OUD would relate to reduced brain network segregation.

Forty treatment-seeking adults with OUD (72.5 % male) completed resting-state functional magnetic resonance imaging. We grouped 264 brain regions into 10 networks, categorized as “association” (higher-order cognition) or “sensorimotor” (sensory and motor) networks. Regression analysis tested the relation between drug use severity and brain network segregation of association and sensorimotor categories and specific networks. Partial correlations explored the effects of cognition (IQ and working memory), mood, and affect.

Drug use severity predicted lower brain network segregation of the association networks, particularly the fronto-parietal and salience networks, but not the default mode network. The relation between drug use severity and lower segregation of the sensorimotor networks depended on age. In exploratory analyses, positive affect related to greater salience network segregation.

An altered balance of connectivity within and between brain networks may correspond with drug use severity, particularly in cognitive and salience-detection networks. Lower brain network segregation may indicate accelerated brain aging and be a target for OUD treatment.

Opioids

Brain network segregation

Resting-state fMRI

Graph theory

© 2025 The Authors. Published by Elsevier B.V.