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OC-073 Evidence for genetic contribution to plasticity of the human swallowing motor system: the role of BDNF polymorphism
  1. V Jayasekeran1,
  2. N Pendleton2,
  3. G Holland1,
  4. A Payton3,
  5. S Jefferson1,
  6. B Ollier3,
  7. M Horan2,
  8. J Rothwell4,
  9. S Hamdy1
  1. 1Department of Gastrointestinal Sciences, School of Translational Medicine, London, UK
  2. 2Department of Clinical Gerontology, School of Translational Medicine, London, UK
  3. 3Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK
  4. 4Sobell Department of Neurophysiology, Institute of Neurology, University College London, London, UK

Abstract

Introduction A single nucleotide polymorphism (SNP) of brain-derived neurotrophic factor (BDNF) gene has been shown to influence neurological function. Transcranial magnetic stimulation (TMS) studies have suggested that the BDNF SNP producing a valine to methionine substitution can modulate plasticity in human motor cortex.1 ,2 This study aimed to determine if the SNP influences the outcome of two excitatory forms of neurostimulation applied to the swallowing motor system.

Methods Healthy subjects (n=22, 6 males, mean age 59) with predetermined BDNF SNP status (Val/Val or non-Val/Val), underwent bi-hemispheric single pulse TMS measurements of pharyngeal EMG responses recorded from a swallowed intra luminal catheter to assess corticobulbar excitability. Following baseline assessment with TMS, subjects received either pharyngeal electrical stimulation (PES) at 5 Hz, 75% of sensory threshold, for 10 minutes (n=16, 9 Val/Val and 7 non-Val/Val) or 250 pulses of 5 Hz repetitive TMS (rTMS) over the dominant pharyngeal motor cortex (n=22, 15 Val/Val and 7 non-Val/Val). Repeated measurements of the cortical excitability were assessed with TMS up to 60 minutes following the two interventions. Pharyngeal motor cortical excitability for the 2 BDNF SNP genotypes was compared using 2-way ANOVA.

Results PES significantly increased the amplitude of pharyngeal motor evoked potentials (MEPs) in the Val/Val group compared to the non-Val/Val group with a strong Genotype*Time interaction (F8112=2.4, p=0.018) (see Abstract 21). By contrast, there was a significant reduction in latencies of the non-Val/Val group after 5 Hz rTMS (Genotype∗Time interaction, F3,60=4.9, p=0.04). There was no significant difference in MEP latencies between groups following PES.

Conclusion SNPs of the BDNF gene predicts the degree of plasticity in the human swallowing motor system to differing forms of neurostimulation. Our results suggest that therapeutic response to swallowing interventions in pathology such as dysphagic stroke may be guided by BDNF genotype profiling.

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