An Initial Investigation of Disrupted Intracortical Myelin as a Novel Brain Marker of Alcohol Use Disorder

Abstract: Although disruption of cortical gray matter and white matter tracts are well-established markers of alcohol use disorder (AUD), this is the first study to examine the specific role of intracortical myelin (ICM; i.e., highly myelinated gray matter in deeper cortical layers) in AUD. The current study used a 3T MRI sequence optimized for high intracortical contrast to examine patterns of ICM-related MRI signal in 30 individuals with AUD and 33 healthy social drinkers. Secondary aims included exploring continuous associations with alcohol problem severity and examining sex differences. Surface-based analytic techniques were used to quantify ICM-related MRI signal for a priori region of interest analyses (20 bilateral regions) and exploratory vertex-wise analyses (using Cohen’s d). Although the distribution of ICM-related signal was generally comparable between groups, the AUD group exhibited significantly (p<.05) greater ICM-related MRI signal in precuneus, ventromedial prefrontal cortex, posterior cingulate, middle anterior cingulate, middle/posterior insula, dorsolateral prefrontal cortex, and posterior cingulate, among other regions (Cohen’s d = .50-.75, indicating medium magnitude effects). Significant positive correlations between ICM signal and AUD severity were found in several frontal, parietal, cingulate, and temporal regions (rs .25-.34). No sex differences in ICM were observed. These findings provide initial proof-of-concept for examining ICM in relation to AUD. Understanding the pathophysiological mechanisms of these associations (e.g., neuroinflammation) and the clinical relevance of ICM is warranted.