Reduction of Continuous Theta Burst Stimulation-Induced Motor Plasticity in Healthy Elderly With COMT Val158Met Polymorphism

Abstract

ObjectiveTo delineate whether cortical plasticity induced by continuous theta burst stimulation (cTBS) differed according to catechol-O-methyltransferase (COMT) gene polymorphism in healthy older adults.MethodsEighteen healthy older volunteers (mean age 73.78±5.04; 12 females and 6 males) were recruited. Volunteers randomly assigned in either a sham-first or real cTBS first group participated in two separate TMS visits with at least a 2-day wash-out period. Genotyping was carried out at baseline by a separate researcher who was blinded. cTBS was delivered in a hot spot over M1 at an active motor threshold of 80%. Motor evoked potentials (MEPs) were obtained at 120% of the resting motor threshold before and after sham/cTBS.ResultsThe relative MEP to baseline was significantly decreased 0 and 10 minutes post-stimulation and increased 40 minutes post-stimulation, as compared with the sham condition. Immediately after cTBS, the Val/Val group had a significantly reduced relative MEP value, as compared with the MET carrier group.ConclusionIn healthy older persons, cTBS-induced motor plasticity was reduced in the COMT Val/Val group as compared with the 158Met carrier group.

Genetic influences on the variability of response to repetitive transcranial magnetic stimulation in human pharyngeal motor cortex

“…SNP rs6269 is functionally associated with hyperactivity/impulsivity, autism spectrum disorder, and major depressive disorder . Studies have shown that COMT may be associated with motor cortex reactivity and swallowing performance . Our results were, however, in contrast with previous findings that the presence of Met allele in BDNF Vat66Met polymorphism may suppress the expected inhibitory effects after 1 Hz rTMS .…”

“…Apart from swallowing performance, COMT gene may influence cortical excitability following NIBS . Witte et al found that carriers with homozygotes Met/Met for COMT along with homozygotes Val/Val for BDNF showed an increase in hand MEPs immediately after paired associative stimulation.…”

“…Both twin studies and studies in healthy participants have suggested that genetic predisposition may influence the excitability of the human motor cortex and subcortical structures . Individual variations in motor cortex excitability are strongly heritable .…”

“…The current study aimed to (a) examine the variability, if any, of the effects of 1 and 5 Hz rTMS paradigms delivered over pharyngeal motor cortex in the largest cohort of healthy participants to date and (b) explore possible associations between response to rTMS (1 and 5 Hz) paradigms and individual's genetic predispositions. We selected eight single nucleotide polymorphisms (SNP) from seven genes, a priori, based on previous relevant physiologic studies . Our hypothesis was that response variability to rTMS in the pharyngeal motor cortex would be predicted by genetic predisposition.…”

Interindividual variability in response to continuous theta-burst stimulation in healthy adults

“…However, the relatively small sample size of the present study limits the strength of the conclusions and warrants further replication in larger cohorts. It may also be important to obtain in those cohorts the results for other SNPs that have been found to influence cortical plasticity as measured by TMS, including catechol-O-methyltransferase ( COMT ) polymorphism that has been found to influence M1 cTBS responses (Lee et al, 2014) and to interact with the effect of BDNF polymorphism (Witte et al, 2012). …”