Priming Pharyngeal Motor Cortex by Repeated Paired Associative Stimulation: Implications for Dysphagia Neurorehabilitation

Background. Several stimulation parameters can influence the neurophysiological and behavioral effects of paired associative stimulation (PAS), a neurostimulation paradigm that repeatedly pairs a peripheral electrical with a central cortical (transcranial magnetic stimulation [TMS]) stimulus. This also appears to be the case when PAS is applied to the pharyngeal motor cortex (MI), with some variability in excitatory responses, questioning its translation into a useful therapy for patients with brain injury. Objective. To investigate whether repeated PAS in both “responders” and “nonresponders” could enhance cortical excitability in pharyngeal MI more robustly. Methods. Based on their responses after single PAS, healthy participants were stratified into 2 groups of “responders” and “nonresponders” and underwent 2 periods (60 minutes inter-PAS interval) of active and sham PAS in a randomized order. Neurophysiological measurements with single TMS pulses from pharyngeal motor representation were collected up to 90 minutes after the second PAS period. Results. Repeated PAS increased cortical excitability up to 95% at 60 minutes following the second PAS in both the “responders” and “nonresponders.” Moreover, cortical excitability in the “nonresponders” was significantly different after repeated PAS compared with single and sham application (P = .02; z = −2.2). Conclusions. Double dose PAS switched “nonresponders” to “responders.” These results are important for PAS application to dysphagic stroke patients who do not initially respond to a single application.