Introduction nTMS is a focal noninvasive cortical stimulation method where small intracranial electrical currents are induced by an extracranial magnetic field. Resting motor threshold (rMT), the minimal nTMS intensity required to activate a muscle group, is an established corticospinal excitability metric. We previously identified that rMT decreases in childhood until age ~15y, when a mature, rMT endpoint is reached, and that rMT also correlates strongly with IQ. Now we test if these measures are differentially affected by sex in children with focal epilepsy

Methods rMT was measured in children (n=134, 71F) with focal epilepsy, in both hemispheres during presurgical functional motor mapping. IQ was measured in all subjects.

Results In girls (≤15y; n=56) rMT is lower in the epileptic hemisphere (p<10^-4), while in boys (≤15y; n=48), no such difference exists. Additionally, the rMT developmental trajectory does not differ between healthy and epileptic hemispheres in boys, but in girls this trajectory is absent in the epileptic hemisphere, reflecting early life rMT reduction to mature values. Lastly, IQ is higher in girls (p<10^-3). Notably, in the epileptic hemisphere, the negative correlation between IQ and rMT is absent in boys but maintained in girls (p<10^-3).

Conclusions Distinct rMT maturation patterns indicate that sex contributes to the degree that seizures and/or epileptogenesis affect nTMS-derived measures of corticospinal excitability, and to the magnitude of the cognitive burden of childhood epilepsy.