Alcohol dependence is associated with impaired control over emotionally motivated actions, possibly associated with abnormalities in the frontoparietal executive control network and midbrain nodes of the reward network associated with automatic attention. To identify differences in the neural response to alcohol-related word stimuli, 26 chronic alcoholics (ALC) and 26 healthy controls (CTL) performed an alcohol-emotion Stroop Match-to-Sample task during functional MR imaging. Stroop contrasts were modeled for color-word incongruency (eg, word RED printed in green) and for alcohol (eg, BEER), positive (eg, HAPPY) and negative (eg, MAD) emotional word content relative to congruent word conditions (eg, word RED printed in red). During color-Stroop processing, ALC and CTL showed similar left dorsolateral prefrontal activation, and CTL, but not ALC, deactivated posterior cingulate cortex/cuneus. An interaction revealed a dissociation between alcohol-word and color-word Stroop processing: ALC activated midbrain and parahippocampal regions more than CTL when processing alcohol-word relative to color-word conditions. In ALC, the midbrain region was also invoked by negative emotional Stroop words thereby showing significant overlap of this midbrain activation for alcohol-related and negative emotional processing. Enhanced midbrain activation to alcohol-related words suggests neuroadaptation of dopaminergic midbrain systems. We speculate that such tuning is normally associated with behavioral conditioning to optimize responses but here contributed to automatic bias to alcohol-related stimuli.

Introduction:One of the most dramatic changes to sleep architecture across adolescence is a reduction in slow wave sleep, a stage of sleep dominated by slow delta (0.3 to <4Hz) waves. Concurrently, the brain undergoes a wealth of changes, including reductions in gray matter volume (GMV) and cortical thickness (CT) with advancing age across adolescence. Here we investigated whether age-related differences in GMV and CT accounted for the typically observed age-related differences in slow wave (delta) activity (SWA) in adolescents. Methods: 132 participants (59 male, 73 female; age range: 12-22 years) from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study were included in this cross-sectional analysis of baseline polysomnographic, electroencephalographic (EEG) and magnetic resonance imaging (MRI) data, which were collected at SRI International and the University of Pittsburgh. Mediation models, which controlled for site and supratentorial volume, were used to assess whether age-related differences in cortical brain structure accounted for age-related differences in SWA. We hypothesized that age would have a direct effect on SWA, but that age may also affect SWA indirectly due to its known influence on cortical thinning and gray matter volume decline. Results: Older compared with younger adolescents had less SWA, smaller GMV and/or CT, as shown previously. The direct effect of age on SWA explained 47% of the variance (p<0.001). In addition, significant indirect effects (p=0.01-0.001) of age on SWA via CT and GMV were identified for several, predominantly frontal, brain regions, with models explaining 50-54% of the variance. Conclusion: We identified that the significant association between age and SWA was partially mediated by age-related differences in brain structure. As reductions in GMV and CT may be indicative of synaptic pruning, these results suggest that diminished SWA in adolescence may largely be driven by synaptic pruning within a number of cortical brain regions. Support (If Any): AA021690 (DBC), AA021697 (AP+KMP), AA021696 (IMC+FCB) and NIH UL1TR001857.