Importance: Heroin addiction and related mortality impose a devastating toll on society, with little known about the neurobiology of this disease or its treatment. Poor inhibitory control is a common manifestation of prefrontal cortex (PFC) impairments in addiction, and its potential recovery following treatment is largely unknown in heroin (or any drug) addiction. Objective: To study inhibitory control brain activity in iHUD and HC, before and after 15 weeks of inpatient treatment in the former. Design: A longitudinal cohort study (11/2020-03/2022) where iHUD and HC underwent baseline and follow-up fMRI scans. Average follow-up duration: 15 weeks. Setting: The iHUD and HC were recruited from treatment facilities and surrounding neighborhoods, respectively. Participants: Twenty-six iHUD [mean=40.6, sd=10.1 years; 7 (29.2%) women] and 24 age-/sex-matched HC [mean=41.1, sd=9.9 years; 9 (37.5%) women]. Intervention: Following the baseline scan, inpatient iHUD continued to participate in a medically-assisted program for an average of 15 weeks [abstinence increased from an initial 183 (sd=236) days by 65 (sd=82) days]. The HC were scanned at similar time intervals. Main Outcomes and Measures: Behavioral performance as measured by the stop-signal response time (SSRT), target detection sensitivity (d-prime, proportion of hits in go vs. false-alarms in stop trials), and brain activity (blood-oxygen level dependent signal differences) during successful vs. failed stops in the stop signal task. Results: As we previously reported, at time 1 and as compared to HC, iHUD exhibited similar SSRT but impaired d-prime [t(38.7)=2.37, p=.023], and lower anterior and dorsolateral PFC (aPFC, dlPFC) activity (p<.001). Importantly, at time 2, there were significant gains in aPFC and dlPFC activity in the iHUD (group*session interaction, p=.002); the former significantly correlated with increases in d-prime specifically in iHUD (p=.012). Conclusions and Relevance: Compared to HC, the aPFC and dlPFC impairments in the iHUD at time 1 were normalized at time 2, which was associated with individual differences in improvements in target detection sensitivity. For the first time in any drug addiction, these results indicate a treatment-mediated inhibitory control brain activity recovery. These neurobehavioral results highlight the aPFC and dlPFC as targets for intervention with a potential to enhance self-control recovery in heroin addiction.

The authors have declared no competing interest.

This work was supported by T32DA053558 to AOC, R01DA048094 to EG, and R01AT010627 to RZG.

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The Icahn School of Medicine at Mount Sinai institutional review board approved study procedures, and all participants provided written informed consent.

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All data produced in the present study are available upon reasonable request to the authors.