Signatures of alcohol use in the structure and neurochemistry of insular cortex: a correlational study

RATIONALE: Insular cortex supports the representation of motivational feelings through the integration of interoceptive information concerning bodily physiology. Compromised insular integrity is implicated in alcohol and drug use disorders. Alcohol-associated insular dysfunction may arise through aberrant glutamatergic neurotransmission associated with selective neuronal death and atrophy. OBJECTIVE: In a sample of alcohol users, we combined magnetic resonance spectroscopy (MRS) with voxel and surface-based morphometry (VBM, SBM) to test the hypothesis that the neurochemical and structural properties of the insula relate to alcohol use. METHODS: Twenty-three healthy individuals were characterized by measures of alcohol use and subjective craving. Right mid-insula glutamate/glutamine (Glx) and total N-acetylaspartate/N-acetyl-aspartylglutamate (TNAA) concentrations were measured using MRS. Right insular structure was quantified using VBM and SBM parameters. We tested for predictive associations between these neuroimaging and behavioral/psychometric measures using Bayesian statistics. RESULTS: Reduced insular Glx concentration was associated with increased alcohol compulsions and, to a lesser extent, with greater alcohol use severity. Anecdotal evidence for a negative relationship between alcohol use severity and levels of insular gyrification was also observed. CONCLUSIONS: This study is, to date, the first characterization of the neurochemical and morphological integrity of insular cortex in alcohol users. Our data seem to reveal a negative relationship between alcohol use and the neurochemical and structural integrity of the insula, a critical substrate for motivational behavior. These neurobiological characteristics might contribute to loss of control toward compulsive drinking with prolonged and excessive alcohol use. KEYWORDS: Addiction; Alcohol use; Craving; Insula; Interoception; Magnetic resonance spectroscopy; Voxel/surface-based morphometry