The neural signature of impaired inhibitory control in individuals with heroin use disorder

Ceceli, Ahmet O.; King, Sarah; McClain, Natalie; Alia-Klein, Nelly; Goldstein, Rita Z. · 2022 · Crossref

DOI: 10.1101/2022.06.23.22276822

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Summary

This study investigates the neurobiological mechanisms of inhibitory control deficits in individuals with heroin use disorder (iHUD), a population for which neural signatures of addiction remain largely uncharacterized. While impaired response inhibition is a hallmark of substance use disorders generally, previous research has primarily focused on other drugs, often utilizing Go/No-Go tasks that fail to capture the competition between response initiation and suppression. To address this gap, the authors employed a stop-signal task (SST) during functional MRI (fMRI) scanning to map the neural correlates of inhibitory control in iHUD compared to healthy controls. The study included 41 inpatient iHUD participants and 24 age- and sex-matched healthy controls. Participants performed an SST designed according to recent consensus guidelines, requiring them to respond to directional arrows unless a stop signal appeared. Behavioral performance was assessed using stop-signal reaction time (SSRT) and signal detection sensitivity ($d'$). fMRI data were acquired using a 3.0 Tesla scanner and preprocessed using the fMRIPrep pipeline. Statistical analyses compared group differences in behavioral metrics and brain activity during the hallmark inhibitory control contrast (successful stops vs. failed stops), while also examining correlations between neural activity, behavioral performance, and addiction severity measures such as days since last use and dependence severity. Behaviorally, iHUD and healthy controls showed no significant difference in SSRT, indicating similar stopping latencies. However, iHUD exhibited significantly lower target detection sensitivity ($d'$), reflecting impaired discrimination between go and stop trials. Neuroimaging results revealed that iHUD had significantly lower activation in the anterior prefrontal cortex (aPFC) and dorsolateral prefrontal cortex (dlPFC) during successful inhibitions compared to controls. Within the iHUD group, higher dlPFC and supplementary motor area (SMA) activity was associated with faster SSRT, suggesting these regions are critical for stopping speed in this population. Furthermore, lower SMA activity correlated with shorter time since last heroin use, and lower aPFC activity correlated with higher severity of dependence. These findings identify a specific neurobehavioral signature of heroin addiction characterized by reduced perceptual sensitivity and hypoactivation in key cognitive control regions (aPFC, dlPFC, SMA). The results suggest that these neural deficits are linked to addiction severity and recent drug use, potentially contributing to self-control lapses in iHUD. By mapping these mechanisms for the first time in heroin addiction, the study highlights prefrontal cortex-mediated cognitive control as a potential target for neuromodulation therapies and intervention efforts aimed at enhancing recovery.

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• illicit drugs