Although nearly 90% of all regional GMVs show significant negative associations with alcohol intake, the most extensively affected regions included the frontal, parietal, and insular cortices, with changes also in temporal and cingulate regions. Associations are also marked in the brain stem, putamen, and amygdala. The share of variance explained by alcohol intake for these regions is smaller in size than for global GMV, suggesting that the latter results from an aggregation of many small effects that are widespread, rather than a localized effect that is limited to specific regions. Alcohol intake is further associated with poorer WM microstructure (lower FA and higher ISOVF and MD) in specific classes of WM tract regions. The commissural fibers (genu and body of the corpus callosum, bilateral tapetum), projection fibers (bilateral anterior corona radiata), associative bundles (fornix, fornix cres+stria terminalis, left inferior longitudinal fasciculus), and the bilateral anterior thalamic radiations show the most consistent associations with alcohol intake, with the fornix showing the strongest associations. The fornix is the primary outgoing pathway from the hippocampus50, and WM microstructural alterations in the fornix are consistently associated with heavy alcohol consumption and memory impairments3,51.
