Abstract
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 two factors, which may be compromised in individuals with AUD: (1) gray matter volume (GMV) at the site of stimulation and (2) scalp-to-cortex (STC) distance. This study tested the hypotheses that these aspects of neural architecture are compromised in AUD patients, and thus AUD patients may need a higher TMS dose 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). STC 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) and within all 3 TMS target locations, F (1, 264) = 14.12, p = 0.0002. There was no significant difference in STC distance between the AUD and the healthy control group at any tested cortical location, F (3, 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 STC distance. Given previous studies that have shown TMS-evoked changes in cortical and subcortical activity to be dependent on GMV, these data suggest that individuals with AUD may require higher doses of TMS to sufficiently modulate the neural circuits of interest.