Effects of Low-Frequency rTMS Preconditioning on Pharyngeal Electrical Stimulation-Induced Corticobulbar Excitability: A Randomised Crossover Study

Objectives: To determine whether preconditioning with 1 Hz repetitive transcranial magnetic stimulation (rTMS) alters the effect of subsequent pharyngeal electrical stimulation (PES) on corticobulbar excitability. Methods: Fourteen healthy adults completed three conditions in randomised order in a within-subject crossover design: C1, active 1 Hz rTMS followed by real PES; C2, sham 1 Hz rTMS followed by real PES; and C3, active 1 Hz rTMS followed by sham PES. Bilateral pharyngeal motor evoked potentials (PMEPs) and thenar motor evoked potentials (TMEPs) were recorded at baseline and at 0, 15, 30, 45, and 60 min post-PES. Results: C3 reduced dominant PMEP amplitude relative to its own baseline (overall −12.7%, 95% CI −22.7 to −2.7, p = 0.017). Adding PES after active rTMS raised amplitude relative to C3 (C1 versus C3 +39.5%, p = 0.008). C2 versus C3, which compares two different active protocols rather than isolating the effect of PES, also differed (+15.7%, p = 0.004). Only C1 increased above its own baseline (+26.8%, 95% CI +3.1 to +50.5, p = 0.029) whereas C2 did not (+3.0%, p = 0.525), but the direct C1 versus C2 contrast was not significant overall (+23.8%, 95% CI −5.4 to +52.9, p = 0.101) and reached nominal significance only at 45 min (+32.4%, unadjusted p = 0.023; Bonferroni p = 0.068). Sustained excitation across three or more consecutive timepoints occurred in 8/14 participants after C1, 4/14 after C2 and 0/14 after C3 (Cochran Q = 8.73, p = 0.011), although the direct C1 versus C2 comparison was not significant (exact McNemar p = 0.344). Non-dominant PMEP latency showed a condition effect (p = 0.034); non-dominant amplitude and thenar control responses did not. Conclusions: PES applied after inhibitory rTMS was associated with higher corticobulbar excitability than sham PES. Any additional benefit of preconditioning over PES alone remains exploratory and requires a larger trial.