Suprathreshold 0.3 Hz repetitive TMS prolongs the cortical silent period: potential implications for therapeutic trials in epilepsy

Objective: To investigate the after-effects of 0.3 Hz repetitive transcranial magnetic stimulation (rTMS) on excitatory and inhibitory mechanisms at the primary motor cortex level, as tested by single-pulse TMS variables. Methods: In 9 healthy subjects, we studied a wide set of neurophysiological and behavioral variables from the first dorsal interosseous before (Baseline), immediately after (Post 1), and 90 min after (Post 2) the end of a 30 min long train of 0.3 Hz rTMS delivered at an intensity of 115% resting motor threshold (RMT). Variables under investigation were: maximal M wave, F wave, and peripheral silent period after ulnar nerve stimulation; RMT, amplitude and stimulus–response curve of the motor evoked potential (MEP), and cortical silent period (CSP) following TMS; finger-tapping speed. Results: The CSP was consistently lengthened at both Post 1 and Post 2 compared with Baseline. The other variables did not change significantly. Conclusions: These findings suggest that suprathreshold 0.3 Hz rTMS produces a relatively long-lasting enhancement of the inhibitory mechanisms responsible for the CSP. These effects differ from those, previously reported, of 0.9–1 Hz rTMS, which reduces the excitability of the circuits underlying the MEP and does not affect the CSP. This provides rationale for sham-controlled trials aiming to assess the therapeutic potential of 0.3 Hz rTMS in epilepsy.