Abstracts

Rationale: nTMS is a method for focal noninvasive cortical stimulation where small intracranial electrical currents are generated by an extracranial fluctuating magnetic field. Resting motor threshold (rMT) is the minimal intensity required to activate a predetermined muscle group, and serves as a measure of motor cortex excitability. In children with epilepsy undergoing nTMS for presurgical planning, we tested whether rMT reflects (1) a measure of the developmental corticospinal tract (CST) trajectory as a function of hemispheric lateralization and proximity to seizure focus; (2) a gross measure of cortical functional maturity as indicated by verbal IQ. Methods: 138 patients (=23 y) with intractable focal epilepsy underwent nTMS for motor mapping to measure bilateral rMT. Only patients with rMT < 100% machine output were included. Comparisons between healthy and epileptic hemispheres were performed by a linear mixed-effects model to account for within-subject correlations, with age, lesion and age x lesion interaction as fixed-effects. Further analysis was performed using mixture modeling to detect clustering of rMT with respect to age per hemisphere, where Bayesian Information Criterion was used to choose number of clusters. For identified clusters, multiple regression analyses controlling for age examined the relationship between rMT and verbal IQ. Results: Patients without CST lesion show no rMT difference between epileptic and healthy hemispheres. Age is the major determinant of rMT, which decreases by ~7 V/m per year in childhood (p < .001); this maturational trajectory does not differ between hemispheres. Cluster analysis reveals two groups corresponding to (1) mature, minimal rMT after age ~15 y and (2) a progressive maturation from age 7 to 15 y. In a subgroup of patients (n=14) with CST injury in the epileptic hemisphere, average rMT in affected hemisphere is lower (p < .01). rMT for these patients decreases by ~9 V/m per year in the healthy hemisphere (R² = .57; p < .01), but does not change with age in the epileptic hemisphere (R²=.005; p=.82). The difference in maturational trajectory is significant between the two hemispheres (p < .01).In the mature, age 15 y group, there is a negative correlation between rMT and verbal IQ in the healthy hemisphere (R²=.31; p < .01), but not in the epileptic hemisphere (R²=.03; p=.39). Conclusions: Cortical excitability increases with age until ~15 y. We thus describe for the first time the rate and endpoint of CST maturation. Neither rate of maturation nor absolute rMT differ between healthy and epileptic hemispheres in patients with focal epilepsies without CST injury. However, unilateral CST injury corresponds to early CST maturation as indicated by low rMT and absent rMT trajectory in the epileptic hemisphere.. We also identify a negative correlation between rMT and verbal IQ in patients with mature CST excitability. Notably, this correlation is only in the healthy hemisphere, suggesting that focal seizures contribute to an uncoupling of CST maturation and regional cerebral function.