Do Brain-Derived Neurotrophic Factor Genetic Polymorphisms Modulate the Efficacy of Motor Cortex Plasticity Induced by Non-invasive Brain Stimulation? A Systematic Review.

Ryoki Sasaki,Hideaki Onishi,Sho Kojima

doi:10.3389/fnhum.2021.742373

Abstract

Techniques of non-invasive brain stimulation (NIBS) of the human primary motor cortex (M1) are widely used in basic and clinical research to induce neural plasticity. The induction of neural plasticity in the M1 may improve motor performance ability in healthy individuals and patients with motor deficit caused by brain disorders. However, several recent studies revealed that various NIBS techniques yield high interindividual variability in the response, and that the brain-derived neurotrophic factor (BDNF) genotype (i.e., Val/Val and Met carrier types) may be a factor contributing to this variability. Here, we conducted a systematic review of all published studies that investigated the effects of the BDNF genotype on various forms of NIBS techniques applied to the human M1. The motor-evoked potential (MEP) amplitudes elicited by single-pulse transcranial magnetic stimulation (TMS), which can evaluate M1 excitability, were investigated as the main outcome. A total of 1,827 articles were identified, of which 17 (facilitatory NIBS protocol, 27 data) and 10 (inhibitory NIBS protocol, 14 data) were included in this review. More than two-thirds of the data (70.4–78.6%) on both NIBS protocols did not show a significant genotype effect of NIBS on MEP changes. Conversely, most of the remaining data revealed that the Val/Val type is likely to yield a greater MEP response after NIBS than the Met carrier type in both NIBS protocols (21.4–25.9%). Finally, to aid future investigation, we discuss the potential effect of the BDNF genotype based on mechanisms and methodological issues.

Highlights

Non-invasive brain stimulation (NIBS) to the primary motor cortex (M1) induces neural plasticity and is being used ubiquitously as a leading-edge neurorehabilitation tool
A total of 27 data obtained from 17 articles were extracted: iTBS, 10 data; anodal transcranial direct current stimulation (tDCS), 6 data; transcranial random noise stimulation (tRNS), 1 datum; paired-associative stimulation (PAS), 7 data; repetitive transcranial magnetic stimulation (rTMS), 2 data; and quadri-pulse stimulation (QPS), 1 datum
Considering that the glutamatergic and GABAergic activities in the M1 play an important role in the synaptic changes caused by NIBS (Liebetanz et al, 2002; Nowak et al, 2017; Bachtiar et al, 2018; Wischnewski et al, 2019), the decreased brain-derived neurotrophic factor (BDNF) secretion in the Met carriers may weaken M1 plasticity function via the NMDA- and GABAreceptor-dependent activities, producing smaller motorevoked potential (MEP) changes after NIBS than Val/Val carriers. These findings suggest that the weaker MEP changes observed in Met carriers after the facilitatory and inhibitory NIBS protocols (21.4–29.6% in all data) in this review are derived from decreased BDNF secretion

Summary

Introduction

Non-invasive brain stimulation (NIBS) to the primary motor cortex (M1) induces neural plasticity and is being used ubiquitously as a leading-edge neurorehabilitation tool. A clinical study reported that motor performance was improved in half of the patients with stroke who had motor deficits after 10 Hz repetitive transcranial magnetic stimulation (rTMS) (Ameli et al, 2009). These studies suggest that considerable interindividual heterogeneity exists in the capacity of individuals to induce M1 plasticity, both in healthy participants and in patients. Investigation of this issue is necessary to perform effective NIBS and improve motor performance in majority of the participants

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