Abstracts

Rationale: Neuronavigated transcranial magnetic stimulation (nTMS) is a method for focal noninvasive cortical stimulation where small intracranial electrical currents are generated by an extracranial magnetic field. Resting motor threshold (rMT) is the minimal nTMS intensity required to activate a muscle group, and is an established measure of cortical excitability. We previously identified a motor cortex excitability maturational trajectory in children, and also found a strong correlation between the rMT and IQ. Now, in children undergoing nTMS for presurgical motor mapping, we test if cortical excitability maturation and its relationship to IQ are affected by focal epilepsy differentially in boys and girls. Methods: Children (n=186) with intractable epilepsy underwent nTMS motor mapping. Abductor pollicis brevis rMT was measured per hemisphere. Only patients with absent CST injury and a focal seizure onset zone were included (n=134, 71F). Intelligence tests were administered by a clinical neuropsychologist using age-appropriate Wechsler Scales, to obtain verbal and nonverbal IQ (VIQ, NVIQ) scores. Results: Age is the major determinant of rMT which decreases in childhood until age~15y, when a mature, minimal rMT (high cortical excitability) endpoint is reached. This maturational trajectory does not differ between healthy hemispheres of boys and girls (R²=.44, p<10^-4 R²=.33, p<10^-4). In young girls (=15y; n=56) rMT is significantly lower in the epileptic hemisphere than in the healthy hemisphere (123±36V/m v.175±67V/m, p<10^-4)--yet, in young boys (=15y; n=48) there is no such difference between hemispheres (158±60V/m v.159±64V/m, n.s.). Further, the rMT developmental trajectory in the epileptic hemisphere of girls is absent (Figure 1., R²=.0001, n.s.) reflecting premature rMT reduction to adolescent/adult values. In contrast, the rMT developmental trajectory is no different in the epileptic hemisphere (Figure 2.) than in the healthy hemisphere of boys. VIQ and NVIQ are higher for girls than for boys age=15y (VIQ 91.4±17.5 v.83.3±19.9, p<10^-3; NVIQ 90.7±18.0 v.72.1±16.3, p<10^-3). Last, whereas in the healthy hemisphere there is a strong negative correlation between IQ and rMT for both sexes (VIQ R²=.33 v.R²=.31, p<10^-4; NVIQ R²=.22 v.R²=.19, p<10^-3), in the epileptic hemisphere this correlation is absent in boys (VIQ R²=.01 NVIQ R²=.01, n.s) but is maintained in girls (VIQ R²=.22 NVIQ R²=.19, p<10^-3). Conclusions: Distinct rMT maturation patterns in boys and girls with focal epilepsy indicate that sex contributes to the degree to which seizures and/or epileptogenesis affect nTMS-derived measures of cortical excitability. Girls, but not boys, undergo accelerated motor cortex maturation in the setting of focal epilepsy.The higher IQ among girls in our cohort suggests preemptive closure of the critical period for cortical excitability maturation after epileptogenesis mitigates the burden of epilepsy on cognition. Thus, in children, sex may determine resiliency and susceptibility to developmental consequences of focal epilepsy. Funding: Boston Children's Hospital Translational Research Program, NIH NINDS R01NS088583, NIMH R01100186