Recovery of inhibitory control prefrontal cortex function in inpatients with heroin use disorder: a 15-week longitudinal fMRI study

Abstract 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 [40.6±10.1 years; 7 (29.2%) women] and 24 age-/sex-matched HC [41.1±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±236 days by 65±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’ , 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’ [ 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’ 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. Key points Question Does inhibitory control brain function, a common impairment in drug addiction, recover with treatment in inpatient individuals with heroin use disorder (iHUD)? Findings In this longitudinal cohort study, 26 inpatient iHUD and 24 healthy controls (HC) performed a stop-signal task during functional MRI twice, separated by an average of 15 weeks. In the iHUD, we found lower anterior and dorsolateral prefrontal cortex (comprising the cognitive control network) signaling at baseline, which increased after 15 weeks of treatment, as associated with behavioral improvements. Meaning As the opioid epidemic continues, our results indicate potential therapeutic targets to enhance neural function underlying self-control in heroin addiction.