A Magnetic Resonance Spectroscopy Study of Brain Glutamate in a Model of Plasticity in Human Pharyngeal Motor Cortex
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 ≤ .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.
Abbreviations used in this paper: CEP, cerebral evoked potentials, EMG, electromyography, ISI, interstimulus interval, LTP, long-term potentiation, MRS, magnetic resonance spectroscopy, MT, motor threshold, NAA, N-acetyl aspartate, NMDA, N-methyl-D-aspartate, PAS, paired associative stimulation, PMEP, pharyngeal motor evoked potential, TMS, transcranial magnetic stimulation
Drs Singh and Mistry conducted the studies, analyzed the data, and helped write the article. Drs Jefferson and Davies helped analyze the MRS data. Professors Rothwell and Williams helped to conceptualize the study, interpret data analysis, and helped to write the article. Dr Hamdy conceptualized the study, helped in data interpretation, and in the writing of the article.
The authors disclose the following: This work was funded in part by grants from the Medical Research Council (S.S., S.M., S.H., J.R., and S.W.), The Wellcome Trust (S.H., S.M., and S.W.), and the Stroke Association (S.J.).
PII: S0016-5085(08)02040-4
doi:10.1053/j.gastro.2008.10.087
© 2009 AGA Institute. Published by Elsevier Inc. All rights reserved.
