A Magnetic Resonance Spectroscopy Study of Brain Glutamate in a Model of Plasticity in Human Pharyngeal Motor Cortex

Background & AimsCoordinated 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.MethodsFifteen 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.ResultsThe greatest increase in cortical pharyngeal excitability was seen if paired stimuli were separated by 100 ms (F[15,210] = 2.28; P ≤ .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.ConclusionsThis 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.