title: A magnetic resonance spectroscopy study of brain glutamate in a model of plasticity in human pharyngeal motor cortex.
abstract: OBJECTIVE
  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.
authors.affiliation: Gastrointestinal Science, Salford Royal Hospital, Salford, United Kingdom.
authors.forename: Salil
authors.initials: S
authors.lastname: Singh
authors.forename: Satish
authors.initials: S
authors.lastname: Mistry
authors.forename: Samantha
authors.initials: S
authors.lastname: Jefferson
authors.forename: Karen
authors.initials: K
authors.lastname: Davies
authors.forename: John
authors.initials: J
authors.lastname: Rothwell
authors.forename: Stephen
authors.initials: S
authors.lastname: Williams
authors.forename: Shaheen
authors.initials: S
authors.lastname: Hamdy
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism*; D004558:Electric Stimulation; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009044:Motor Cortex / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D010609:Pharyngeal Muscles / Q000294:innervation*
chemical_list: D018698:Glutamic Acid