Opioid Use Disorder is Associated with Lower Resting-State Brain Network Segregation

Background: Opioid use disorder (OUD) is associated with a wide range of cognitive, affective, and motivational impairments, suggesting a disruption of large-scale brain systems that support diverse domains of functioning. Resting-state brain network segregation quantifies the degree of functional specialization within brain networks, is age-related, has been linked to brain glucose metabolism, and has been shown to be reduced in substance use disorders. We examined brain network segregation in individuals with OUD and non-OUD controls and tested associations with the duration of opioid use. Methods: Resting-state functional MRI data were collected from 149 individuals with OUD and 126 non-OUD controls. Functional connectivity was computed between brain regions assigned to functionally specialized networks supporting higher-order "association" or "sensorimotor" processes. For each network, segregation was quantified as the extent to which within-network connectivity exceeded between-network connectivity. Results: Individuals with OUD demonstrated lower segregation of the association and sensorimotor networks than non-OUD controls. Within the OUD group, more years of opioid use was associated with lower segregation of the association network, but not the sensorimotor network. Conclusions: OUD is characterized by overall lower resting-state brain network segregation. More years of opioid exposure was associated with lower association-network segregation, consistent with there being cumulative effects of chronic opioid use on large-scale brain organization, though causation could not be examined in this cross-sectional dataset. These findings identify altered network segregation as a potential neurobiological marker of OUD and suggest that restoration of brain network specialization is a measurable target of OUD treatment and potentially recovery.