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

Abstract

AbstractHeroin addiction imposes a devastating toll on society, with little known about its neurobiology. Excessive salience attribution to drug over non-drug cues/reinforcers, with concomitant inhibitory control decreases, are common mechanisms underlying drug addiction. While inhibitory control alterations generally culminate in prefrontal cortex (PFC) hypoactivations across drugs of abuse, patterns in individuals with heroin addiction (iHUD) remain unknown. We used a stop-signal fMRI task designed to meet recent consensus guidelines in mapping inhibitory control in 41 iHUD and 24 age- and sex-matched healthy controls (HC). Despite group similarities in the stop-signal response time (SSRT; the classic inhibitory control measure), compared to HC, iHUD exhibited impaired target detection sensitivity (proportion of hits in go vs. false-alarms in stop trials) (p=.003). Additionally, iHUD exhibited lower anterior and dorsolateral PFC (aPFC, dlPFC) activity during successful vs. failed stops (the hallmark inhibitory control contrast). Higher dlPFC/supplementary motor area (SMA) activity was associated with faster SSRT specifically in iHUD, and higher aPFC activity with better target sensitivity across all participants (p<.05-corrected). Importantly, in iHUD, the lower the SMA and aPFC activity during inhibitory control, the shorter the time since last use and the higher the severity of dependence, respectively (p<.05-corrected). Taken together, results revealed lower perceptual sensitivity and hypoactivations during inhibitory control in cognitive control regions (e.g., aPFC, dlPFC, SMA) as associated with task performance and addiction severity measures in iHUD. Such neurobehavioral inhibitory control deficits may contribute to self-control lapses in heroin addiction, constituting targets for prevention and intervention efforts to enhance recovery.Significance statementHeroin addiction continues its deadly impact, with little known about its neurobiology. While behavioral and prefrontal cortical impairments in inhibitory control characterize addiction across drugs of abuse, these patterns have not been fully explored in heroin addiction. Here, we illustrate a significant behavioral impairment in target discrimination in individuals with heroin addiction compared to matched healthy controls. We further show lower engagement during inhibitory control in the anterior and dorsolateral prefrontal cortex (key regions that regulate cognitive control), as associated with slower stopping, worse discrimination, and addiction severity measures. Mapping the neurobiology of inhibitory control in heroin addiction for the first time, we identify potential treatment targets inclusive of prefrontal cortex-mediated cognitive control amenable for neuromodulation en route to recovery.