Neural Variability and Cognitive Control in Individuals With Opioid Use Disorder
Authors: Jean Ye, Saloni Mehta, Hannah Peterson, Ahmad Ibrahim, Gul Saeed, Sarah Linsky, Iouri Kreinin, Sui Tsang, Uzoji Nwanaji-Enwerem, Anthony Raso, Jagriti Arora, Fuyuze Tokoglu, Sarah W. Yip, C. Alice Hahn, Cheryl Lacadie, Abigail S. Greene, R. Todd Constable, Declan T. Barry, Nancy S. Redeker, H. Klar Yaggi, Dustin Scheinost
Journal: JAMA Network Open (2025)

Opioid use disorder (OUD) impacts millions of people worldwide. Prior studies investigating its underpinning neural mechanisms have not often considered how brain signals evolve over time, so it remains unclear whether brain dynamics are altered in OUD and have subsequent behavioral implications. To characterize brain dynamic alterations and their association with cognitive control in individuals with OUD. This case-control study collected functional magnetic resonance imaging (fMRI) data from individuals with OUD and healthy control (HC) participants. The study was performed at an academic research center and an outpatient clinic from August 2019 to May 2024. Individuals with OUD were all recently stabilized on medications for OUD (<24 weeks). Recurring brain states supporting different cognitive processes were first identified in an independent sample with 390 participants. A multivariate computational framework extended these brain states to the current dataset to assess their moment-to-moment engagement within each individual. Resting-state and naturalistic fMRI investigated whether brain dynamic alterations were consistently observed in OUD. Using a drug cue paradigm in participants with OUD, the association between cognitive control and brain dynamics during exposure to opioid-related information was studied. Variations in continuous brain state engagement (ie, state engagement variability [SEV]) were extracted during resting-state, naturalistic, and drug-cue paradigms. Stroop assessed cognitive control. Overall, 99 HC participants (54 [54.5%] female; mean [SD] age, 31.71 [12.16] years) and 76 individuals with OUD (31 [40.8%] female; mean [SD] age, 39.37 [10.47] years) were included. Compared with HC participants, individuals with OUD demonstrated consistent SEV alterations during resting-state (99 HC participants; 71 individuals with OUD; F4,161 = 6.83; P < .001) and naturalistic (96 HC participants; 76 individuals with OUD; F4,163 = 9.93; P < .001) fMRI. Decreased cognitive control was associated with lower SEV during the rest period of a drug cue paradigm among 70 participants with OUD. For example, lower incongruent accuracy scores were associated with decreased transition SEV (ρ58 = 0.34; P = .008). In this case-control study of brain dynamics in OUD, individuals with OUD experienced greater difficulty in effectively engaging various brain states to meet changing demands. Decreased cognitive control during the rest period of a drug cue paradigm suggests that these individuals had an impaired ability to disengage from opioid-related information. The current study introduces novel information that may serve as groundwork to strengthen cognitive control and reduce opioid-related preoccupation in OUD.