UC San Diego

Background : Many adolescents engage in heavy alcohol use. From existing literature it is difficult to disentangle whether brain abnormalities are a consequence of heavy drinking, a preexisting risk factor for initiation of alcohol use, or both. Methods: This study uses longitudinal functional magnetic resonance imaging (fMRI) data from 12 to 16 year-olds (N=40) imaged prior to the onset of drinking, then again approximately three years later after half transitioned to heavy drinking (80 total scans). Heavy drinkers and non-users were matched on baseline and follow-up developmental and risk factors. A repeated measures group x time ANOVA on a priori specified regions of interest was conducted to determine if youth who initiated heavy drinking evidenced a change in activation pattern, as compared to youth who remained non- drinkers. Regions showing divergent activation among initiators of heavy drinking were examined for correspondence with neuropsychological measures of VWM and attention among the heavy drinkers (n=20) in regression analyses. Results : As hypothesized, significant group x time interactions were found in the right inferior parietal lobule (cluster size: 810[mu]L, p=.005; [eta]²=.23) and left medial frontal gyrus (cluster size: 1431[mu]L, p=.003; [eta]²=.19). For both interactions, heavy drinkers showed significantly less blood oxygen level dependent (BOLD) response contrast to high relative to low working memory loads at baseline that increased after the onset of heavy drinking, as compared to controls. Contrary to hypotheses, BOLD response contrast and its change over time were not related to follow-up neuropsychological performance. Discussion: Adolescents who initiated heavy drinking had different brain activation compared to non-drinkers prior to the onset of drinking, suggesting brain activation patterns could be a risk factor for future substance use. Over time, adolescent heavy drinkers exhibited less efficient and mature processing of information. While brain activation did not correlate with behavioral measures, continued heavy use during this important developmental period could compromise neural networks. This investigation helps clarify the effect of alcohol use on brain functioning during adolescence, and aids in understanding whether abnormalities in VWM response among adolescent drinkers follow the initiation of alcohol involvement or predate the onset of drinking