P 79. Effects of brain derived neurotrophic factor polymorphism on cortical excitability measured by transcranial magnetic stimulation

Abstract

Variation in the brain derived neurotrophic factor (BDNF) gene affects neural plasticity. With the commonly studied single nucleotide polymorphism (SNP) BDNF Val66Met, the Met allele is associated with reduced plasticity. However, little is known about the baseline excitability measures of rarer form Met/Met compared to other forms and the response to plasticity and metaplasticity protocols using transcranial magnetic stimulation (TMS). To investigate the effects of the BDNF Val66Met SNP on motor cortex excitability, inhibition, facilitation, plasticity and metaplasticity. From 177 healthy volunteers we selected 7 subjects with the rare (around 5–10% of population) Met/Met genotype and compared them to 9 age-and gender-matched Val allele carriers on various excitability measures using TMS. Motor threshold, recruitment curves, short and long interval intracortical inhibition (SICI and LICI), short interval intracortical facilitation (SICF) and time courses of these circuits were studied. Potentiation [high frequency rTMS and paired associative stimulation at 25 ms latency (PAS25)] and depression (low frequency rTMS and PAS10) protocols as well as interactions of these plasticity protocols (metaplasticity) were studied with sessions separated at least by a week (6 sessions in total). Met/Met subjects showed higher motor threshold (61.7 ± 8.6% stimulator output compared to 48.7 ± 9.5; p = 0.01), and less steep recruitment curves (significant main effects and interaction for BDNF genotype and TMS intensity). There was no significant difference between the groups in terms of intracortical inhibitory circuits, the time course and recruitment curves for SICI/LICI. There was a trend for reduced facilitation at the peaks (1.5, 3 and 4 ms) for SICF in Met/Met compared to non-Met/Met subjects. For plasticity protocols, there was significantly higher potentiation of MEP amplitude with high frequency rTMS (main effects of BDNF genotype) and a trend of greater MEP depression with PAS10 in non-Met/Met subjects. No difference was noted in the other plasticity and metaplasticity protocols. Met/Met subjects had higher motor threshold, less steep MEP recruitment curves and reduced peaks of SICF, implying lower cortical excitability compared to non-Met/Met genotypes. This decreased excitability in Met/Met subjects is associated with less potentiation induced by high frequency rTMS. Our study is ongoing and more subjects are being recruited to compare the three BDNF genotypes (Met/Met, Val/Met and Val/Val genotypes) of subjects. Support by Canadian Institutes of Health Research.