title: fMRI and MRS measures of neuroplasticity in the pharyngeal motor cortex.
abstract: BACKGROUND
  Paired associative stimulation (PAS), is a novel non-invasive technique where two neural substrates are employed in a temporally coordinated manner in order to modulate cortico-motor excitability within the motor cortex (M1). In swallowing, combined pharyngeal electrical and transcranial-magnetic-stimulation induced beneficial neurophysiological and behavioural effects in healthy subjects and dysphagic stroke patients. Here, we aimed to investigate the whole-brain changes in neural activation during swallowing using functional magnetic resonance imaging (fMRI) following PAS application and in parallel assess associated GABA changes with magnetic resonance spectroscopy (MRS).
  
  
  METHODS
  Healthy adults (n=11, 38±9years old) were randomised to receive real and sham PAS to the 'stronger' motor cortex pharyngeal representation, on 2 separate visits. Following PAS, event-related fMRI was performed to assess changes in brain activation in response to water and saliva swallowing and during rest. Data were analysed (SPM8) at P<.001. MRS data were acquired using MEGA-PRESS before and after the fMRI acquisitions on both visits and GABA concentrations were measured (AMARES, jMRUI).
  
  
  RESULTS
  Following real PAS, BOLD signal changes (group analyses) increased at the site of stimulation during water and saliva swallowing, compared to sham PAS. It is also evident that PAS induced significant increases in BOLD signal to contralateral (to stimulation) hemispheric areas that are of importance to the swallowing neural network. Following real PAS, GABA:creatine ratio showed a trend to increase contralateral to PAS.
  
  
  CONCLUSIONS
  Targeted PAS applied to the human pharyngeal motor cortex induces local and remote changes in both primary and non-primary areas for water and saliva tasks. There is a possibility that changes of the inhibitory neurotransmitter, GABA, may play a role in the changes in BOLD signal. These findings provide evidence for the mechanisms underlying the beneficial effects of PAS on the brain swallowing network.
authors.affiliation: Centre for Gastrointestinal Sciences, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, University of Manchester, Clinical Sciences Building, Salford Royal Hospital (part of the Manchester Academic Health Sciences Centre (MAHSC)), Eccles Old Road, Salford M6 8HD, UK. Electronic address: emilia.michou@manchester.ac.uk.
authors.forename: Emilia
authors.initials: E
authors.lastname: Michou
authors.affiliation: Centre for Imaging Science, Manchester Academic Health Sciences Centre, University of Manchester, Oxford Road, M13 9PT, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Williams
authors.affiliation: Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, Melbourne, Victoria, Australia; Department of Anatomy and Neuroscience, Melbourne University, Melbourne, Victoria, Australia.
authors.forename: Rishma
authors.initials: R
authors.lastname: Vidyasagar
authors.affiliation: Neuroscience and Psychiatry Unit, Manchester Academic Health Sciences Centre, University of Manchester, Oxford Road, M13 9PT, UK.
authors.forename: Darragh
authors.initials: D
authors.lastname: Downey
authors.affiliation: Centre for Gastrointestinal Sciences, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, University of Manchester, Clinical Sciences Building, Salford Royal Hospital (part of the Manchester Academic Health Sciences Centre (MAHSC)), Eccles Old Road, Salford M6 8HD, UK.
authors.forename: Satish
authors.initials: S
authors.lastname: Mistry
authors.affiliation: FM Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA; The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Richard A E
authors.initials: RA
authors.lastname: Edden
authors.affiliation: Centre for Gastrointestinal Sciences, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, University of Manchester, Clinical Sciences Building, Salford Royal Hospital (part of the Manchester Academic Health Sciences Centre (MAHSC)), Eccles Old Road, Salford M6 8HD, UK.
authors.forename: Shaheen
authors.initials: S
authors.lastname: Hamdy
mesh_terms: D000328:Adult; D001931:Brain Mapping; D003679:Deglutition; D004576:Electromyography; D019054:Evoked Potentials, Motor; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009044:Motor Cortex / Q000378:metabolism / Q000502:physiology*; D009473:Neuronal Plasticity; D010609:Pharyngeal Muscles / Q000502:physiology*; D050781:Transcranial Magnetic Stimulation; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005680:gamma-Aminobutyric Acid
keywords: Cortex; GABA; Neuroplasticity; Paired associative stimulation; Pharynx; Swallowing