Investigating the Effects of Controllable Pulse Parameter Transcranial Magnetic Stimulation on Neurophysiological and Clinical Response

Abstract

Repetitive transcranial magnetic stimulation (rTMS) is an established non-invasive neuromodulation technique used to alter cortical excitability and treat various neurological and psychiatric disorders. However, individual response variability and hardware limitations to biphasic pulses restrict its efficacy. Controllable pulse parameter TMS (cTMS) enables delivery of monophasic pulses at high frequency, potentially offering improved neurophysiological and clinical outcomes. This thesis aimed to compare the effects of 10 Hz monophasic (cTMS) and biphasic (rTMS) stimulation on corticospinal excitability in healthy individuals, and to evaluate the therapeutic efficacy of cTMS in individuals with fibromyalgia (FM). In Study 1, twenty-six healthy individuals each underwent a session of 10 Hz monophasic, biphasic, and sham stimulation. Motor evoked potentials (MEPs) were recorded before and after each intervention. In Study 2, twenty-eight individuals with FM received either 10 sessions of cTMS or placebo stimulation over two weeks. Outcomes included pain intensity, quality of life, corticospinal excitability, and short-interval intracortical inhibition (SICI). In Study 1, no significant differences were observed between monophasic, biphasic, or sham stimulation, and similar proportions of participants showed facilitation of MEPs following real stimulation. Baseline MEP amplitude predicted response to biphasic, but not monophasic stimulation. Also, BDNF genotype did not influence outcomes. In Study 2, there were no differences in pain intensity, SICI, MEPs, or quality of life between cTMS and placebo stimulation. Additionally, the proportion of responders (defined as >30% pain reduction) was equivalent between the cTMS and placebo groups (n=4). These findings suggest that monophasic stimulation does not outperform biphasic stimulation in modulating corticospinal excitability in healthy individuals. Moreover, cTMS did not provide any clinical advantage over placebo stimulation in individuals with FM. Further investigation is needed to refine cTMS protocols, optimize stimulation parameters, clarify mechanisms underlying individual variability, and tailor interventions to response profiles to enhance both neurophysiological and clinical outcomes.