Abstracts

Rationale: Long intracortical inhibition (LICI) refers to the slow phase of GABAergic interneuron mediated suppression of pyramidal cells, occurring 100 to 300 milliseconds after interneuron activation. Physiologic measures of LICI may be useful biomarkers of disease and treatment response in epilepsy, where LICI is impaired. LICI can be measured in humans noninvasively with paired pulse transcranial magnetic stimulation (TMS). Recent advances allow TMS during EEG recording, a more direct and perhaps more sensitive measure of TMS effects than the conventional output measure for LICI, the motor evoked potential, assessed at a target muscle. Single pulses over motor cortex yield a reliable TMS evoked potential, a series of peaks which includes the prominent peak, the N100 but the modulation of these peaks by LICI is not well established. The aim of this study was to assess modulation of TMS evoked cortical potentials, particularly the N100, by LICI at the 250 msec interval, and to test reliability of these measurements. Methods: 11 healthy adult volunteers (7M:4F) underwent two sessions in which each received a random sequence of 50 supra-threshold single TMS pulses and 50 paired pulses (250 msec interval) over left motor cortex with 32 channel EEG and EMG recording of the right first dorsal interosseus, followed by 50 sham pulses. After controlling for artifacts by visual inspection, sham subtraction, and principal components analysis, responses over the Cz electrode were averaged to yield the TMS evoked potential. Results: Mean N100 amplitude after single pulses was -7.68 uV( 4.76), and after LICI250 was -3.70 uV( 4.63; p=0.03). The difference in amplitudes correlated with EMG measures of LICI (pearson s r=0.68). The P2 response (around 150 msec) was also modulated by LICI250 mean P2 amplitude after single pulses was 6.50 ( 5.18), and after LICI250 was -0.76( 0.84; p= 0.001). Earlier peaks showed no differences in amplitude or latency. Intraclass correlation (ICC) for N100 amplitude during the first and second sessions was 0.88. ICC for the N100 amplitude difference after single and LICI250 pulses between sessions was 0.85. Conclusions: Long intracortical inhibition suppresses the N100 peak of TMS evoked cortical potentials. The difference between N100 amplitude after single pulses and paired pulses (250 msec interval) can be measured with an excellent degree of reliability in healthy subjects. This represents a first step in developing TMS-EEG measures of cortical excitability as biomarkers of epilepsy and treatment response.