Neuroscience of inhibition for addiction medicine

Abstract

A core deficit in drug addiction is the inability to inhibit maladaptive drug-seeking behavior. Consistent with this deficit, drug-addicted individuals show reliable cross-sectional differences from healthy non-addicted controls during tasks of response inhibition accompanied by brain activation abnormalities as revealed by functional neuroimaging. However, it is less clear whether inhibition-related deficits predate the transition to problematic use, and, in turn, whether these deficits predict the transition out of problematic substance use. Here, we review longitudinal studies of response inhibition in children/adolescents with little substance experience and longitudinal studies of already-addicted individuals attempting to sustain abstinence. Results show that response inhibition, and its underlying neural correlates, predict both substance use outcomes (onset and abstinence). Neurally, key roles were observed for multiple regions of the frontal cortex (e.g., inferior frontal gyrus, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex). In general, less activation of these regions during response inhibition predicted not only the onset of substance use, but interestingly, also better abstinence-related outcomes among individuals already addicted. The role of subcortical areas, although potentially important, is less clear because of inconsistent results and because these regions are less classically reported in studies of healthy response inhibition. Overall, this review indicates that response inhibition is not simply a manifestation of current drug addiction, but rather a core neurocognitive dimension that predicts key substance use outcomes. Early intervention in inhibitory deficits could have high clinical and public health relevance.

Functional neural changes following behavioral therapies and disulfiram for cocaine dependence.

“…Namely, pre-morbid functional abnormalities may confer vulnerability to SUDs and drugs may have acute and prolonged effects on brain function, and some drug-induced abnormalities may persist through prolonged abstinence. Therefore, abstinence may not return individuals to pre-substance-use-disorder baselines, and pre-morbid baselines may be suboptimal treatment targets as they may not represent ‘normalizations’ of functional activity relative to healthy non-drug-users with low SUD-vulnerability (see (Moeller, Bederson, Alia-Klein, & Goldstein, 2016) for review of changes with substance-use onset and predictors of treatment outcome). These complexities underline the limits of using healthy case-comparisons to derive treatment targets and reinforce the importance of testing treatment-related change within substance abusers and relating these changes to treatment mechanisms.…”

Exercise as a Sex-Specific Treatment for Substance Use Disorder

“…For example, acute aerobic exercise (cycling) decreased drug-craving in women and men undergoing residential treatment for methamphetamine use disorder (19), and chronic aerobic exercise (8-week treadmill interval training) decreased measures of depression in men and women undergoing residential treatment for an illicit substance use disorder (i.e., heroin, amphetamine, cannabis; 18). Recent studies have also shown that aerobic exercise during abstinence can offset deficits in inhibitory control (19–20) that have been linked to relapse (60). …”

Sex differences in guanfacine effects on stress-induced stroop performance in cocaine dependence

“…For example, sex differences have been observed in physiologic and neuroendocrine response to stress and drug cue (Back et al, 2005; Fox and Sinha, 2009) as well as in neural responses regulatory behaviors including inhibitory control, cognitive flexibility and self control (Moeller et al, 2016; Potenza et al, 2012). Notably, these are all measures that have been associated with high risk of relapse and treatment outcomes (Back et al, 2005; Daughters et al, 2009; Fox and Sinha, 2009; Moeller et al, 2016; Sinha et al, 2006; Van Dam et al, 2014). Furthermore, while executive functions such as response inhibition and self control are critical for successful clinical outcome and relapse prevention (Aharonovich et al, 2006; Aharonovich et al, 2003), these functions are known to be most compromised under stress and cue reactivity states.…”