Focal epilepsy is associated with lesions confined to one cerebral hemisphere and may disrupt normal cortical maturation in childhood, though the timing and anatomical specificity of this disruption remain unclear. We examined inter-hemispheric differences in cortical function using resting motor threshold (RMT), the minimum stimulation intensity required to elicit a motor response in a resting muscle and an index of cortical excitability measured via transcranial magnetic stimulation (TMS). 

RMT data were analyzed from 154 individuals with focal epilepsy (ages 1-23 years). Generalized additive models characterized nonlinear age-related trends in RMT, motivating segmented (change-point) regression to estimate the age of maturational stabilization. Within-subject comparisons were performed between epileptic and healthy hemispheres. To assess anatomical specificity, regression models examined lesion-related RMT deviations and compared stabilization ages between corticospinal tract and frontal lobe lesions.

In healthy hemispheres, RMT stabilized at 10.81 years (95% CI [10.49, 11.12]) versus 13.68 years (95% CI [13.45, 13.91]) in epileptic hemispheres, reflecting a mean delay of 2.87 years (95% CI [2.48, 3.26], p < .001). Delays were greater in corticospinal tract lesions (4.16 years, 95% CI [3.98, 4.65], p < .001) than frontal lobe lesions (2.03 years, 95% CI [1.55, 2.52], p < .001). Corticospinal tract lesions were also associated with larger RMT deviations and later stabilization.

These findings demonstrate lesion-specific delays in cortical maturation, with particular vulnerability of the corticospinal tract. Improved characterization of maturation timing may inform earlier, targeted interventions to mitigate long-term motor and neurodevelopmental impairments.