Strength-Duration Relationship in Paired-pulse Transcranial Magnetic Stimulation (TMS) and Its Implications for Repetitive TMS

Background: Paired-pulse protocols have played a pivotal role in neuroscience research using transcranial magnetic stimulation (TMS). Stimulus parameters have been optimized over the years. More recently, pulse width (PW) has been introduced to this field as a new parameter, which may further fine-tune paired-pulse protocols. The relationship between the PW and effectiveness of a stimulus is known as the "strength-duration relationship". Objective: To test the "strength-duration relationship", so as to improve paired-pulse TMS protocols, and to apply the results to develop new repetitive TMS (rTMS) methods. Methods: Four protocols were investigated separately: short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), short-interval intracortical facilitation (SICF) and long-interval intracortical inhibition (LICI). First, various stimulus parameters were tested to identify those yielding the largest facilitation or inhibition of the motor evoked potential (MEP) in each participant. Using these parameters, paired-pulse stimulations were repeated every five seconds for 30 minutes (repetitive paired-pulse stimulation, rPPS). The after-effects of rPPS were measured using MEP amplitude as an index of motor-cortical excitability. Results: Altogether, the effect of changing PW was similar to that of changing the stimulus intensity in the conventional settings. The best parameters were different for each participant. When these parameters were used, rPPS based on either SICF or ICF induced an increase in MEP amplitude. Conclusions: PW was introduced as a new parameter in paired-pulse TMS. Modulation of PW influenced the results of paired-pulse protocols. rPPS using facilitatory protocols can be a good candidate to induce enhancement of motor-cortical excitability. (C) 2016 Elsevier Inc. All rights reserved.