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.