Females have shorter scalp-to-cortex distances and receive stronger TMS electrical fields: Implications for clinical treatment.

The strength of a given transcranial magnetic stimulation (TMS) pulse decays rapidly with distance. Male and female bone structure reliably differs by the shape of the frontal bone, mandible, and inion. Given the morphology of these structures constitutes much of the scalp-to-cortex distance (STCD), we hypothesized that females have shorter STCDs and thereby receive stronger TMS electrical field strengths, relative to males. Head models (n = 411; 197 female, 214 male) were constructed from MRIs of healthy participants (ages 18-90). STCD and peak electrical field strength were measured at 50 EEG 10-20 sites (SimNIBSv3.2). Linear models (bootstrapped and Benajamini-Hochberg multiple comparison-corrected) evaluated the influence of sex on STCD and electrical field strength. Females had significantly shorter STCDs at 27/50 sites and stronger TMS electrical fields at 18/50. When normalized by data collected at the motor cortex, females had significantly shorter STCD at 40/49 sites and stronger TMS electrical fields at 29/49 sites. The largest effect size differences were detected at the frontal, temporal, and occipital poles, and the cerebellum. Interestingly, STCD at the motor cortex was not different between sexes, suggesting the motor cortex-based dosing strategies produce unequal electrical fields between sexes. These data provide a mathematically grounded explanation for sex-differences in clinical outcome and may be relevant to other modalities that depend on electromagnetic signals (e.g., EEG, MEG).