Influence of BDNF Val66Met polymorphism on excitatory-inhibitory balance and plasticity in human motor cortex

Objective: While previous studies showed that the single nucleotide polymorphism (Val66Met) of brain derived neurotrophic factor (BDNF) can impact neuroplasticity, the influence of BDNF genotype on cortical circuitry and relationship to neuroplasticity remain relatively unexplored in human. Methods: Using individualised transcranial magnetic stimulation (TMS) parameters, we explored the influence of the BDNF Val66Met polymorphism on excitatory and inhibitory neural circuitry, its relation to I-wave TMS (ITMS) plasticity and effect on the excitatory/inhibitory (E/I) balance in 18 healthy individuals. Results: Excitatory and inhibitory indexes of neurotransmission were reduced in Met allele carriers. An E/ I balance was evident, which was influenced by BDNF with higher E/I ratios in Val/Val homozygotes. Both long-term potentiation (LTP-) and depression (LTD-) like ITMS plasticity were greater in Val/Val homozygotes. LTP-but not LTD-like effects were restored in Met allele carriers by increasing stimulus intensity to compensate for reduced excitatory transmission. Conclusions: The influence of BDNF genotype may extend beyond neuroplasticity to neurotransmission. The E/I balance was evident in human motor cortex, modulated by BDNF and measurable using TMS. Given the limited sample, these preliminary findings warrant further investigation. Significance: These novel findings suggest a broader role of BDNF genotype on neurocircuitry in human motor cortex. (c) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Automated summary

Using individualized transcranial magnetic stimulation (TMS) parameters, this study found that the single nucleotide polymorphism (Val66Met) of brain derived neurotrophic factor (BDNF) can influence neuroplasticity and neurotransmission. The research also observed a higher excitatory/inhibitory (E/I) balance ratio in Val/Val homozygotes compared to Met allele carriers.