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Sex Differences in Scalp-to-Cortex Distance: Implications for Transcranial Magnetic Stimulation Efficacy in Alcohol
Kaitlin R Kinney1, Nathanial E Stewart1, Michiyah Kimber1
1Department of Translational Neuroscience, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Alcohol, Clinical & Experimental Research
|June 30, 2026
Summary
Individualized transcranial magnetic stimulation (TMS) dosing for alcohol use disorder (AUD) is crucial, as sex and age impact scalp-to-cortex distance and brain stimulation strength. Tailored strategies are needed, especially for older females.
Area of Science:
- Neuroscience
- Medical Imaging
- Neuromodulation
Background:
- Transcranial magnetic stimulation (TMS) shows promise for treating alcohol use disorder (AUD).
- Efficacy of TMS for AUD varies due to differences in scalp-to-cortex (STC) distance.
- Sex-specific craniofacial anatomy may influence STC variability, impacting TMS effectiveness.
Purpose of the Study:
- To investigate sex, age, and alcohol use severity effects on STC distance and electric field magnitude at key TMS targets in individuals with AUD.
- To determine if anatomical sex differences necessitate adjustments in TMS dosing for AUD treatment.
Main Methods:
- Acquired high-resolution MRI from 107 individuals with AUD (59 females, 48 males).
- Generated individualized finite-element head models using SimNIBS to compute STC distance and electric field strength.
- Analyzed data using linear mixed-effects models, assessing effects of sex, age, and AUDIT scores.
Main Results:
- Males exhibited greater STC distance than females, particularly at ventromedial prefrontal cortex (Fp1) and motor cortex (C3) targets.
- Higher alcohol use severity (AUDIT scores) correlated with increased STC distance.
- Electric field magnitude was lower at midline prefrontal targets and decreased with age, with a steeper decline observed in females.
Conclusions:
- Anatomical variations related to sex and age significantly affect TMS penetration depth and stimulation intensity in AUD.
- Individualized and sex-tailored TMS dosing strategies are recommended for optimizing AUD treatment.
- Midline prefrontal targets and older females may require particular attention due to potential reductions in TMS engagement.
