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

Abstract

Recent studies have proposed therapeutic potential for repetitive transcranial magnetic stimulation (rTMS) in swallowing rehabilitation, yet its outcomes vary across individuals and studies. Such variability may be related to the brain state before stimulation. Metaplasticity is a higher order plasticity which regulates cortical response to plasticity changes. Studies have shown that preconditioning of the hand motor cortex could increase cortical capacity for neuroplastic change and enhance rTMS outcomes. We investigated, for the first time, the directional metaplastic properties in human pharyngeal motor cortex using preconditioned rTMS. We found that preconditioned rTMS with specific time intervals between preconditioning and conditioning rTMS had stronger stimulation effects in both swallowing neurophysiology and behaviour than that without preconditioning. Our results provide evidence for enhanced directional metaplasticity in pharyngeal motor cortex and new insights into its clinical application for dysphagia. 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 5Hz) rTMS interventions with varying inter-rTMS intervals. Motor evoked potentials (MEPs) were measured before and for 60min 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 rTMS preconditioned with 1Hz rTMS with 30min inter-rTMS interval induced the greatest increase on pharyngeal cortical excitability (F1,13 =21.244; P<0.001). By comparison, 1Hz rTMS preconditioned with 5Hz rTMS with 90min 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 5Hz rTMS (F1,13 =10.109, P=0.007) and reduced after preconditioned 1Hz 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.