Atypical neural activity during inhibitory processing in substance-naïve youth who later experience alcohol-induced blackouts.

Background: Alcohol-induced blackouts are associated with the development of alcohol abuse and dependence, so it is important to consider potential neurobiological risk factors for experiencing this problem prior to the onset of substance use. This study examines whether neural activity during inhibitory processing might be atypical in substance-naïve youth who later experience alcohol-induced blackouts.

Methods: We examined inhibitory processing during fMRI with a go/no-go task that requires withholding a prepotent response in substance-naïve youth who would later transition into heavy drinking (n=40) and youth who remain abstinent (n=20). After approximately 5 years of annual follow-up assessments, youth were classified as nondrinkers (n=20), and heavy drinking youth were classified as having experienced an alcohol-induced blackout (blackout+; n=20) or not (blackout-; n=20). Groups were matched on demographic variables, and youth who experienced blackouts were matched on follow-up substance use.

Results: Prior to initiating substance use, blackout+ youth showed greater activation during inhibitory processing than nondrinkers and blackout- youth in frontal and cerebellar brain regions. Mean activation during correct inhibitory responses relative to go responses in the left and right middle frontal gyri at baseline predicted future blackout experience, after controlling for follow-up externalizing behaviors and lifetime alcohol consumption.

Conclusions: Substance-naïve adolescents who later experience alcohol-induced blackouts show increased neural effort during inhibitory processing, as compared to adolescents who go on to drink at similar levels but do not experience blackouts and healthy, nondrinking controls, suggesting a neurobiological vulnerability to alcohol-induced memory impairments.