Brain-Derived Neurotrophic Factor – A Major Player in Stimulation-Induced Homeostatic Metaplasticity of Human Motor Cortex?

Claudia Mastroeni,Christine Klein,Norbert Brueggemann,Hartwig Roman Siebner,Ines Pohlmann,Vincenzo Rizzo,Christoph Ritter,Angelo Quartarone,Til Ole Bergmann,Robert Chen

doi:10.1371/journal.pone.0057957

Abstract

Repetitive transcranial magnetic stimulation (rTMS) of the human motor hand area (M1HAND) can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val66met polymorphism in the brain-derived neurotrophic factor (BDNF) gene. Here we used theta burst stimulation (TBS) to examine whether the BDNF val66met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS) usually inducing a lasting increase and continuous TBS (cTBS) a lasting decrease in corticospinal excitability. In three separate sessions, healthy val66met (n = 12) and val66val (n = 17) carriers received neuronavigated cTBS followed by cTBS (n = 27), cTBS followed by iTBS (n = 29), and iTBS followed by iTBS (n = 28). Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS) and increase (iTBS) in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val66met carriers and val66val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val66met polymorphism, our results do not support the notion that the BDNF val66met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND.

Highlights

The human motor cortex has a substantial potential to undergo plastic changes which may result in long-term potentiation (LTP)like increases or long-term depression (LTP)-like decreases in corticospinal excitability [1,2]
All subjects underwent three different interventions: continuous TBS (cTBS) followed by cTBS (c-cTBS), cTBS followed by Intermittent TBS (iTBS) (c-iTBS), and iTBS followed by iTBS (i-iTBS)
Apart from two subjects, all participants received three different combinations of theta burst stimulation (TBS) (Fig. 1): (i) cTBS followed by cTBS (c-cTBS), (ii) iTBS followed by iTBS, and (iii) cTBS followed by iTBS (c-iTBS)

Summary

Introduction

The human motor cortex has a substantial potential to undergo plastic changes which may result in long-term potentiation (LTP)like increases or long-term depression (LTP)-like decreases in corticospinal excitability [1,2]. Previous LTP hampers further synaptic potentiation and facilitates depression whereas previous LTD has the opposite effect. This mechanism keeps synaptic plasticity in a functional range (see discussion for details). Stimulation-induced LTP-like, LTD-like, or homeostatic plasticity can be readily assessed with single-pulse transcranial magnetic stimulation (TMS) by measuring changes in mean amplitude of the motor evoked potential (MEP) in contralateral hand muscles [14,15,16,17,18]

Methods

Results

Discussion

Conclusion