Anterior Cingulate Cortex Metabolites and White Matter Microstructure: A Multimodal Study of Emergent Alcohol Use Disorder

Abstract

Multimodal imaging is increasingly used to address neuropathology associated with alcohol use disorder (AUD). Few studies have investigated relationships between metabolite concentrations and white matter (WM) integrity; currently, there are no such data in AUD. In this preliminary study, we used complementary neuroimaging techniques, magnetic resonance spectroscopy (MRS), and diffusion weighted imaging (DWI), to study AUD neurophysiology. We tested for relationships between metabolites in the dorsal anterior cingulate cortex (dACC) and adjacent WM microstructure in young adult AUD and control (CON) subjects. Sixteen AUD and fourteen CON underwent whole-brain DWI and MRS of the dACC. Outcomes were dACC metabolites, and diffusion tensor metrics of dACC-adjacent WM. Multiple linear regression terms included WM region, group, and region × group for prediction of dACC metabolites. dACC myo-inositol was positively correlated with axial diffusivity in the left anterior corona radiata (p < 0.0001) in CON but not AUD (group effect: p < 0.001; region × group: p < 0.001; Bonferroni-corrected). In the bilateral anterior corona radiata and right genu of the corpus callosum, glutamate was negatively related to mean diffusivity in AUD, but not CON subjects (all model terms: p < 0.05, uncorrected). In AUD subjects, dACC glutamate was negatively correlated with AUD symptom severity. This is likely the first integrative study of cortical metabolites and WM integrity in young individuals with AUD. Differential relationships between dACC metabolites and adjacent WM tract integrity in AUD could represent early consequences of hazardous drinking, and/or novel biomarkers of early-stage AUD. Additional studies are required to replicate these findings, and to determine the behavioral relevance of these results.