Four-pulse transcranial magnetic stimulation using multiple conditioning inputs. Normative MEP responses.

A four-pulse pattern of transcranial magnetic stimulation (TMS) was compared to traditional dual-pulse TMS for its ability to modulate motor cortical excitability. This novel pattern consisted of a three-pulse train of subthreshold conditioning pulses followed by a suprathreshold test pulse (i.e., SC-T). The intervals between these superconditioning (SC) pulses (1, 3, or 6 ms) and the follow-on test pulse (1, 3, 10, or 25 ms) were varied, and the resultant MEPs were compared to those elicited by: (1) single-pulse TMS; and (2) dual-pulse conditioning-test (C-T) TMS with either short (3 ms) or long (10 ms) intervals to elicit short-interval intracortical inhibition (SICI) or intracortical facilitation (ICF), respectively. Testing included abductor pollicis brevis (APB) and tibialis anterior (TA) in 15 neurologically normal adults. For superconditioning inputs, 10 ms test intervals caused especially strong facilitation of the test MEP, while 1 ms test intervals were particularly effective at causing inhibition of the test response. For both muscles and across all subjects, the most effective of the 12 SC-T inputs tested for causing either facilitation or inhibition was-with rare exception-superior to the dual-pulse TMS input for causing facilitation (i.e., ICF) or inhibition (i.e., SICI), while the overall magnitude of effect was more pronounced in APB compared to TA. Nevertheless, after normalization, the impact of a superconditioning input train on the test MEP was similar in APB and TA muscles, suggesting similar mechanisms of action. Limited findings from a single subject with amyotrophic lateral sclerosis (ALS) are included to further illustrate the potential advantages of using a train of conditioning pulses preceding a TMS test pulse to selectively investigate abnormal motor cortical excitatory and inhibitory circuitry.