Gastroenterology

Gastroenterology

Volume 141, Issue 3, September 2011, Pages 827-836.e3
Gastroenterology

Original Research
Clinical—Alimentary Tract
Val66Met in Brain-Derived Neurotrophic Factor Affects Stimulus-Induced Plasticity in the Human Pharyngeal Motor Cortex

https://doi.org/10.1053/j.gastro.2011.05.047Get rights and content

Background & Aims

Polymorphisms in brain-derived neurotrophic factor (BDNF) can affect brain and behavioral responses. However, little is known about the effects of a single nucleotide polymorphism (SNP) in BDNF, at codon 66 (the Val−Met substitution, detected in approximately 33% of the Caucasian population) on stimulation-induced plasticity in the cortico-bulbar system. We examined whether this SNP influenced outcomes of different forms of neurostimulation applied to the pharyngeal motor cortex.

Methods

Thirty-eight healthy volunteers were assessed for corticobulbar excitability after single-pulse, transcranial magnetic stimulation of induced pharyngeal electromyographic responses, recorded from a swallowed intraluminal catheter. Thereafter, volunteers were conditioned with pharyngeal electrical stimulation, or 2 forms of repetitive (1 and 5 Hz) transcranial magnetic stimulation (rTMS). Repeated measurements of pharyngeal motor-evoked potentials were assessed with transcranial magnetic stimulation for as long as 1 hour after the 3 forms of neurostimulation and correlated with SNPs at codon 66 of BDNF (encoding Val or Met).

Results

Pharyngeal electrical stimulation significantly increased the amplitude of motor-evoked potentials in individuals with the SNP that encoded Val66, compared to those that encoded Met66, with a strong GENOTYPE*TIME interaction (F8,112 = 2.4; P = .018). By contrast, there was a significant reduction in latencies of subjects with the SNP that encoded Met66 after 5-Hz rTMS (F3,60 = 4.9; P = .04). In addition, the expected inhibitory effect of 1-Hz rTMS on amplitude was not observed in subjects with the SNP that encoded Met66 in BDNF (F7,140 = 2.23; P = .035).

Conclusions

An SNP in human BDNF at codon 66 affects plasticity of the pharyngeal cortex to different forms of neurostimulation. Genetic analysis might help select specific forms of neurostimulation as therapeutics for patients with disorders such as dysphagic stroke.

Section snippets

Participants

Healthy volunteers for this study came from two sources, volunteers from the Dyne-Steele cohort with predetermined BDNF genotype24 and healthy volunteers who responded to the study advertisement. The former group were healthy older volunteers who were part of an ongoing cognitive genetic study undertaken by the University of Manchester, and were invited to take part in this study if they had normal swallowing function as per a validated swallowing questionnaire.25 Subjects from the latter group

Results

Age and sex distribution, baseline recordings for stimulation intensity of single-pulse TMS and MEP for both Val/Val and non-Val/Val subjects for the 3 experiments are shown in Table 1. In our study population, given the low prevalence of the Met66Met genotype, all non-Val/Val subjects were Val66Met heterozygotes.

Discussion

This study aimed to define the influence of the BDNFVal66Met polymorphism on functional flexibility/plasticity in the intact human pharyngeal motor cortex. Pharyngeal motor cortex was stimulated by transcranial magnetic stimulation that excited a polysynaptic descending pathway or pathways that activated motor neurons in the nucleus ambiguus leading to the recruitment of motor units in the pharyngeal muscles. The findings of this study suggest that the pharyngeal motor cortex's response to

Conclusions

We have shown that a common polymorphism of BDNF can exert contrasting effects on neurophysiological outcomes in experimentally induced plasticity paradigms in the intact human pharyngeal motor cortex with the implication that genotype profiling may improve bespoke rehabilitative tools for individual patients.

Acknowledgments

The authors would like to thank staff in CIGMR and the volunteers from the Dyne-Steele cohort.

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    Conflicts of interest The authors disclose no conflicts.

    Funding Grant support received from the Action Medical Research (Reference: A/P/1091); Biotechnology and Biological Sciences Research Council (BBSRC) (Reference BB.F02244101.1). The study was sponsored by the University of Manchester, UK, which did not have a role in the study design, in the collection, analysis, or interpretation of data.

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