Atypical Spatial Working Memory and Task-General Brain Activity in Adolescents with a Family History of Alcoholism

Background: Altered behavioral performance and brain activation during spatial working memory (SWM) tasks have been demonstrated in individuals with an alcohol use disorder (AUD). It is possible that alterations in processing during SWM may be present prior to initiation of heavy alcohol use in adolescents with a family history of AUDs (family history positive [FHP]) and therefore represent a premorbid neural phenotype that could increase risk for developing an AUD. The goal of our study was to investigate group differences in brain activation during a SWM task between FHP adolescents and adolescents with no family history of AUDs (family history negative [FHN]), as well as examine the relationship between brain activation and individual differences in family history density (FHD) of AUDs. Methods: Eighteen FHP and 16 gender and age-matched FHN participants completed a SWM and vigilance task while undergoing a functional magnetic resonance imaging (fMRI) scan. Results: There were no group differences in task performance. The FHN group demonstrated expected greater activation during the SWM than vigilance condition in the right middle frontal gyrus and dorsolateral prefrontal cortex, whereas the FHP group demonstrated comparable brain activation for both the more demanding and simple task conditions. Additionally, FHD was associated with greater activation of the right superior parietal cortex and less activation of the right cerebellum during the SWM task, but not during the vigilance task. Conclusions: Results suggest FHP adolescents demonstrate alterations in activation of prefrontal regions that are related more generally to the maintenance of top-down cognitive control and alterations in parietal and cerebellar regions that are specific to SWM. Alterations in top-down cognitive control may be a general risk factor for FHP adolescents, whereas SWM-specific alterations are seen as a function of family history loading.