BOLD Response During Spatial Working Memory in Youth With Heavy Prenatal Alcohol Exposure

Background: Prenatal alcohol exposure has been consistently linked to neurocognitive deficits and structural brain abnormalities in affected individuals. Structural brain abnormalities observed in regions supporting spatial working memory (SWM) may contribute to observed deficits in visuospatial functioning in youth with fetal alcohol spectrum disorders (FASDs). Methods: We used functional magnetic resonance imaging (fMRI) to assess the blood oxygen level dependent (BOLD) response in alcohol-exposed individuals during a SWM task. There were 22 young subjects (aged 10-18 years) with documented histories of heavy prenatal alcohol exposure (ALC, n = 10), and age- and sex-matched controls (CON, n = 12). Subjects performed a SWM task during fMRI that alternated between 2-back location matching (SWM) and simple attention (vigilance) conditions. Results: Groups did not differ on task accuracy or reaction time to the SWM condition, although CON subjects had faster reaction times during the vigilance condition (617 millisecond vs. 684 millisecond, p = 0.03). Both groups showed similar overall patterns of activation to the SWM condition in expected regions encompassing bilateral dorsolateral prefrontal lobes and parietal areas. However, ALC subjects showed greater BOLD response to the demands of the SWM relative to the vigilance condition in frontal, insular, superior, and middle temporal, occipital, and subcortical regions. CON youth evidenced less increased brain activation to the SWM relative to the vigilance task in these areas (p < 0.05, clusters > 1,664 mu l). These differences remained significant after including Full Scale IQ as a covariate. Similar qualitative results were obtained after subjects taking stimulant medication were excluded from the analysis. Conclusions: In the context of equivalent performance to a SWM task, the current results suggest that widespread increases in BOLD response in youth with FASDs could either indicate decreased efficiency of relevant brain networks, or serve as a compensatory mechanism for deficiency at neural and/or cognitive levels. In context of existing fMRI evidence of heightened prefrontal activation in response to verbal working memory and inhibition demands, the present findings may indicate that frontal structures are taxed to a greater degree during cognitive demands in individuals with FASDs.