Jitter of corticospinal neurons during repetitive transcranial magnetic stimulation. Method and possible clinical implications

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) of the motor cortex activates corticospinal neurons mainly through the depolarization of cortico-cortical axons belonging to interneurons of superficial layers. OBJECTIVE: We used single-fiber electromyography (SFEMG) to estimate the "central jitter" of activation latency of interneural pools from one pulse of TMS to another. METHODS: We evaluated 10 healthy subjects and one patient with multiple sclerosis. By recording SFEMG evoked activity from the left first dorsal interosseous (FDI), we first used a standard repetitive electrical 3 Hz stimulation of the ulnar nerve at the wrist to calculate the mean consecutive difference from at least 10 different potentials. The same procedure was applied during 3 Hz repetitive TMS of the contralateral motor cortex. The corticospinal monosynaptic connection of the FDI and the selectivity of SFEMG recording physiologically justified the subtraction of the "peripheral jitter" from the whole cortico-muscular jitter, obtaining an estimation of the actual "central jitter." RESULTS: All subjects completed the study. The peripheral jitter was 28 μs ± 6 and the cortico-muscular jitter was 344 μs ± 97. The estimated central jitter was 343 ± 97 μs. In the patient the central jitter was 846 μs, a value more than twice the central jitter in healthy subjects. CONCLUSION: Current results demonstrate that the evaluation of the central component of the cumulative cortico-muscular latency variability in healthy subjects is feasible with a minimally invasive approach. We present and discuss this methodology and provide a "proof of concept" of its potential clinical applicability in a patient with multiple sclerosis.