Heroin 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.

The authors have declared no competing interest.

This work was supported by 1R01AT010627 to RZG.

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