Preconditioning human pharyngeal motor cortex enhances directional metaplasticity induced by repetitive transcranial magnetic stimulation.

Despite growing evidence that repetitive transcranial magnetic stimulation (rTMS) can be used as a treatment for dysphagia, its efficacy varies across individuals. Such variability may relate to the pre-stimulation state of neuronal activation. Previous studies found that preconditioning the hand motor cortex before rTMS could enhance stimulation outcomes through metaplasticity. No studies have investigated such mechanisms in human pharyngeal motor cortex. Therefore, we investigated the preconditioning effects of rTMS on swallowing neurophysiology and behaviour. Healthy adults were recruited for swallowing neurophysiological (n = 14) and behavioural (n = 14) experiments. They were first given eight different preconditioned (1 and 5 Hz) rTMS interventions with varying inter-rTMS intervals. Motor evoked potentials (MEPs) were measured before and for 60 min post-rTMS. Based on the changes in pharyngeal MEPs, the optimal preconditioned 1 Hz and 5 Hz rTMS protocols were then applied as interventions while assessing swallowing performance using a reaction time task. We found that 5 Hz rTMS preconditioned with 1 Hz rTMS with 30 min inter-rTMS interval induced the greatest increase on pharyngeal cortical excitability (F1,13  = 21.244; P < 0.001). By comparison, 1 Hz rTMS preconditioned with 5 Hz rTMS with 90 min inter-rTMS interval was most optimal for suppressing pharyngeal motor cortex (F1,13  = 13.547; P = 0.003). Behaviourally, swallowing accuracy was improved after preconditioned 5 Hz rTMS (F1,13  = 10.109, P = 0.007) and reduced after preconditioned 1 Hz rTMS (F1,13  = 14.108, P = 0.009) compared to sham. Thus, two optimal protocols for inducing functional metaplasticity in human pharyngeal motor cortex have been identified. These protocols appear superior to conventional rTMS and may be relevant to future clinical application in neurogenic dysphagia.