Sex Differences in Scalp‐to‐Cortex Distance: Implications for Transcranial Magnetic Stimulation Efficacy in Alcohol Use Disorder

INTRODUCTION: Transcranial magnetic stimulation (TMS) is a promising intervention for alcohol use disorder (AUD), yet its efficacy varies widely. Scalp-to-cortex (STC) distance influences the strength of the induced electric field, and preliminary evidence suggests sex-specific craniofacial anatomy may contribute to STC variability. However, the implications of anatomical sex differences for TMS dosing in AUD remain unclear. This study examined whether STC distance and modeled electric field magnitude differ by sex, age, and alcohol use severity across common TMS targets. METHODS: High-resolution structural magnetic resonance imaging was acquired from 107 individuals with AUD (59 females, 48 males). Individualized finite-element head models were generated using SimNIBS to calculate STC distance and electric field strength at four cortical targets: medial prefrontal cortex (Afz), dorsolateral prefrontal cortex (F3), ventromedial prefrontal cortex (Fp1), and motor cortex (C3). Linear mixed-effects models assessed the effects of sex, age, and Alcohol Use Disorders Identification Test (AUDIT) score. RESULTS: STC distance differed significantly across sites and was larger in males than in females, with sex differences strongest at Fp1 and C3. No sex differences were observed at Afz or F3. Higher AUDIT scores predicted greater STC distance independent of age. Electric field magnitude varied significantly across sites, with reduced values at midline regions (Afz, Fp1) relative to lateral sites (F3, C3). Electric field magnitude did not differ by sex overall. Age was associated with lower estimated electric field magnitude at the cortical surface. Exploratory sex-stratified analyses indicated a steeper age-related decline in females, particularly at medial prefrontal targets. CONCLUSIONS: Sex-specific and age-related anatomical differences influence cortical depth and effective stimulation strength in individuals with AUD. These findings highlight the need for individualized and potentially sex-tailored TMS dosing strategies, particularly for midline prefrontal targets and for older females who may be more vulnerable to reduced TMS engagement.