Regionally specific gray matter volume decreases in Alcohol Use Disorder: Implications for non-invasive brain stimulation treatment: Implications for non-invasive brain stimulation treatment.

BACKGROUND There is growing interest in neuromodulation-based therapeutics as tools for individuals with Alcohol Use Disorder (AUD). Through electromagnetic induction, techniques such as transcranial magnetic stimulation (TMS) can noninvasively depolarize cortical cells in the induced electrical field and monosynaptic afferents. The ability of TMS to modulate the brain is dependent upon 2 factors which may be compromised in individuals with AUD: 1) gray matter volume (GMV) at the site of stimulation and 2) scalp-to-cortex distance. This study tested the hypotheses that these aspects of neural architecture are compromised in AUD patients, and that, accordingly AUD patients may need a higher TMS dose in order to depolarize the cortex. METHODS High-resolution magnetic resonance images were acquired from 44 individuals with AUD and 44 age-matched healthy controls (n=88). Whole brain voxel-based morphometry was conducted. Subsequent region-of-interest analysis was performed at three EEG 10-20 sites commonly used in TMS for AUD: FP1 (left frontal pole), F3 (left DLPFC) and C3 (left motor cortex). Scalp-to-cortex distance and TMS electric fields were assessed at these EEG sites. RESULTS Individuals with AUD had significantly lower GMV in the bilateral orbitofrontal cortices, supramarginal gyri and the left DLPFC (voxel-threshold p<0.05, cluster-threshold p<0.05) as well as within all three TMS target locations (F1,264 =14.12, p=0.0002). There was no significant difference in scalp-to-cortex distance between the AUD and the healthy control group at any tested cortical location (F3,252 =1.906, p=0.129). CONCLUSIONS Individuals with AUD had significantly lower GMV in multiple areas of interest for TMS treatment, however these volumetric reductions did not impact scalp-to-cortex distance. Given previous studies which have shown that TMS-evoked changes in cortical and subcortical activity are dependent on GMV, these data suggest that individuals with AUD may need to be given higher doses of TMS in order to sufficiently modulate the neural circuits of interest.