Metaplasticity in swallowing system via cross-modal neurostimulation: A randomized crossover trial with magnetoencephalography.

The response to neurostimulation can be modulated based on the state of neural network activation prior to stimulation, a mechanism termed metaplasticity. In the swallowing system, preconditioning the pharyngeal motor cortex with non-invasive brain stimulation (NIBS) can induce metaplasticity. However, the effects of cross-modal neurostimulation, i.e. combined peripheral (pharyngeal electrical stimulation; PES) and central (transcranial direct current stimulation; tDCS) approaches, remain unknown. This study investigated the effects of PES preconditioned by tDCS on cortical activation of swallow-related network and swallowing behaviour. Twenty-one healthy volunteers (8 males, 13 females; mean age = 27.0 ± 4.8 years) participated in the study. They received, in randomized order across three separate visits, three experimental conditions in which PES (5Hz, 10 min) was preconditioned by (1) anodal tDCS (1 mA, 20 min), (2) cathodal tDCS (1.5 mA, 10 min), and (3) sham tDCS. Cortical activation of swallow-related network during "volitional" and "challenged" swallow tasks was measured using magnetoencephalography (MEG) at baseline and immediately post-intervention. Swallowing behaviour was assessed by submental electromyographic (EMG) measurements and timed water swallow test. Significant bilateral enhancement of cortical activation of swallow-related network during challenged swallow task was observed in the theta frequency following cathodal preconditioning (p = 0.042) and PES alone (p < 0.001). By contrast, anodal preconditioning significantly reduced swallow-related network activation in the alpha frequency (p = 0.037). There were no significant changes in swallowing behaviour across conditions. This is the first evidence of metaplasticity induced by cross-modal neurostimulation in the swallowing system. Future studies may focus on its clinical application in patients with neurogenic dysphagia.