Intensity-Dependent Effects of Low-Frequency Subthreshold rTMS on Primary Motor Cortex Excitability and Interhemispheric Inhibition in Elderly Participants: A Randomized Trial

Background Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) protocols targeting primary motor cortex (M1) are used in rehabilitation of neurological diseases for their therapeutic potential, safety, and tolerability. Although lower intensity LF-rTMS can modulate M1 neurophysiology, results are variable, and a systematic assessment of its dose effect is lacking. Objectives To determine the dose-response of LF-rTMS on stimulated and non-stimulated M1. Methods In a sham-controlled randomized double-blind crossover study the effect of LF-TMS protocols were determined in 20 right-handed older healthy participants. In 3 sessions, 1 Hz rTMS at 80% (rTMS 80 ), 90% (rTMS 90 ) of motor threshold or sham stimulation were applied to left upper extremity M1. Outcome measures were curve parameters of the stimulus-response curve (maximum motor evoked potential [MEP MAX ], slope and the intensity to evoke 50% MEP MAX ), short-interval intracortical inhibition (SICI), and interhemispheric inhibition (IHI). Results Within LF-rTMS sessions, rTMS 90 , increased MEP MAX in the stimulated M1. Furthermore, rTMS 90 , increased the slope in the non-stimulated M1. LF-rTMS effects on SICI were dependent on the participants’ baseline SICI, hemisphere, and intensity of conditioning pulse. Finally, rTMS 90 increased whereas rTMS 80 decreased IHI, for both IHI directions. These changes were dependent on baseline IHI and hemisphere and were no longer significant when baseline IHI was accounted for. Conclusions Intensity of subthreshold LF-rTMS has differential effects on excitation and inhibition of stimulated and non-stimulated M1. The effects were small and were only demonstrated within the LF-rTMS sessions but were not different when compared to sham. rTMS related changes in SICI and IHI were dependent on baseline level. ClinicalTrials.gov Identifier: NCT02544503, NCT01726218.