BACKGROUND & AIMS: Coordinated delivery of peripheral and cortical stimuli (paired associative stimulation [PAS]) has been shown to induce plasticity in limb
motor cortex, however, its application in pharyngeal
motor cortex and the molecular mechanisms involved in human
neuroplasticity remain uncertain. Because
neuroplasticity appears to form the basis for functional recovery of digestive functions such as swallowing after
brain injury, the aim of this study was to characterize the induction of
cortical plasticity in human pharyngeal
motor cortex through PAS applied to pharyngeal
musculature and investigate the potential role of
glutamate in this process. METHODS: Fifteen healthy volunteers completed a series of experiments in which cortical excitability was assessed through pharyngeal
motor evoked potential amplitudes in response to
transcranial magnetic stimulation. The optimal parameters and interhemispheric interactions of PAS in the bilaterally represented pharyngeal system initially were investigated. Cortical
glutamate after PAS then was assessed with
magnetic resonance spectroscopy. RESULTS: The greatest increase in cortical pharyngeal excitability was seen if paired stimuli were separated by 100 ms (F[15,210] = 2.28; P < or = .05). Cortical excitability increased over 2 hours with analogous albeit lesser changes in the
contralateral hemisphere. A focal and transient reduction in
glutamate was found in the stimulated pharyngeal
motor cortex (F[1,12] = 21.9; P = .001), without changes in any other measured
brain metabolites. CONCLUSIONS: This study shows that PAS-induced plasticity in the human pharyngeal
motor system is both timing- and hemisphere-dependent and provides novel evidence for the potential role of
glutamate in modulating this effect.
