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 8 different preconditioned (1Hz and 5Hz) rTMS interventions with varying inter-rTMS intervals. Motor evoked potentials (MEPs) were measured before and for 60 minutes post-rTMS. Based on the changes in pharyngeal MEPs, the optimal preconditioned 1Hz and 5Hz rTMS protocols were then applied as interventions while assessing swallowing performance using a reaction time task. We found that 5Hz preconditioned with 1Hz rTMS with 30 minutes inter-rTMS interval induced the greatest increase on pharyngeal cortical excitability (F[1, 13]=21.244; p<0.001). By comparison, 1Hz preconditioned with 5Hz rTMS with 90 minutes inter-rTMS interval was most optimal for suppressing pharyngeal motor cortex (F[1, 13]=13.547; p=0.003). Behaviourally, swallowing accuracy was improved after preconditioned 5Hz rTMS (F[1,13]=10.109, p=0.007) and reduced after preconditioned 1Hz rTMS (F[1,13]=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.