Abstracts

Rationale: Trancranial magnetic stimulation (TMS) a noninvasive, focal brain stimulation tool activates brain regions functionally connected to the primary motor cortices, which maximally express the ictal discharge. In this study, we report our (preliminary) results of attempting to elicit paroxysmal responses with repetitive TMS (rTMS) at different frequencies in both epileptic and control groups. Methods: Eight lightly anesthetized adult baboons (5 epileptics; 3 controls) underwent rTMS at stimulation frequencies of 3 Hz, 5 Hz, 10 Hz and 15 Hz. TMS pulses were delivered to each subject s primary motor cortex (M1) at 120% motor threshold for a total of 300 TMS pulses over a period of 90 seconds. The baboons were sedated using intravenous ketamine (5-6 mg/kg/hr) and paralyzed with vecuronium (0.1-0.3 mg/kg); the order of rTMS frequencies was randomized in each session. Scalp EEG recordings (Nihon-Kohden, Japan) were performed in order to evaluate any occurrence of epileptiform activity (ictal or interictal) triggered by rTMS. Electrodes were placed according to the Standard 10-20 International Electrode Placement System, and included FP1, FP2, T1, T2, O1 and O2, ground and reference electrodes, with electrode impedances of less than 10 micro-ohms. A board-certified clinical neurophysiologist reviewed all EEG recordings for epileptiform activity. Results: Spontaneous generalized, interictal epileptic discharges (IEDs) were recorded in all five of the epileptic baboons prior to the rTMS study. No IEDs were noted in the EEG recordings of the 3 asymptomatic, control baboons prior to rTMS. We performed over 40 rTMS imaging studies in eight baboons, with each animal exposed to at least five rTMS protocols (greater than 1500 TMS pulses) per imaging session. Following every TMS pulse there was interference with the recording for about 3-5 seconds. Ringing artifacts were noted after 15 Hz stimulation in one epileptic baboon. Afterdischarges (2-3 for less than 2 seconds) were noted in one of five epileptic animals after continuous 3 and 5 Hz stimulation, which was morphologically distinct from the baboon s IEDs; no afterdischarges were observed in the control animals. No ictal discharges were recorded after any of the stimuli for any of the animals. Ictal and/or interictal discharges are likely to be generalized in this model and should have been recognized even by a limited set up. Conclusions: Our study demonstrates that suprathreshold, high-frequency rTMS may be used to safely activate the motor cortex, even in subjects with a history of epilepsy. After delivering over 1500 TMS pulses in a single session, there was a very low risk of inducing a seizure as long as higher rTMS frequencies are delivered with longer intertrain intervals. Further studies are needed to investigate the parameters responsible for minimizing (or maximizing) the risk of seizure induction using rTMS.