Effects of repetitive transcranial magnetic stimulation and trans-spinal direct current stimulation associated with treadmill exercise in spinal cord and cortical excitability of healthy subjects: A triple-blind, randomized and sham-controlled study.

Plínio Luna Albuquerque,Luís Augusto Mendes Fontes,Katia Monte-Silva,Mayara Campêlo,Thyciane Mendonça,Rodrigo De Mattos Brito,Tifei Yuan

doi:10.1371/journal.pone.0195276

Plínio Luna Albuquerque, Luís Augusto Mendes Fontes + Show 5 more

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https://doi.org/10.1371/journal.pone.0195276

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Abstract

Repetitive transcranial magnetic stimulation (rTMS) over motor cortex and trans-spinal direct current stimulation (tsDCS) modulate corticospinal circuits in healthy and injured subjects. However, their associated effects with physical exercise is still not defined. This study aimed to investigate the effect of three different settings of rTMS and tsDCS combined with treadmill exercise on spinal cord and cortical excitability of healthy subjects. We performed a triple blind, randomized, sham-controlled crossover study with 12 healthy volunteers who underwent single sessions of rTMS (1Hz, 20Hz and Sham) and tsDCS (anodal, cathodal and Sham) associated with 20 minutes of treadmill walking. Cortical excitability was assessed by motor evoked potential (MEP) and spinal cord excitability by the Hoffmann reflex (Hr), nociceptive flexion reflex (NFR) and homosynaptic depression (HD). All measures were assessed before, immediately, 30 and 60 minutes after the experimental procedures. Our results demonstrated that anodal tsDCS/treadmill exercise reduced MEP’s amplitude and NFR’s area compared to sham condition, conversely, cathodal tsDCS/treadmill exercise increased NFR’s area. High-frequency rTMS increased MEP’s amplitude and NFR’s area compared to sham condition. Anodal tsDCS/treadmill exercise and 20Hz rTMS/treadmill exercise reduced Hr amplitude up to 30 minutes after stimulation offset and no changes were observed in HD measures. We demonstrated that tsDCS and rTMS combined with treadmill exercise modulated cortical and spinal cord excitability through different mechanisms. tsDCS modulated spinal reflexes in a polarity-dependent way acting at local spinal circuits while rTMS probably promoted changes in the presynaptic inhibition of spinal motoneurons. In addition, the association of two neuromodulatory techniques induced long-lasting changes.

Highlights

Repetitive transcranial magnetic stimulation and trans-spinal direct current stimulation are safe and effective non-invasive tools involving the application of magnetic and electric fields to induce changes in the spinal cord and cortical excitability [1, 2].In humans, rTMS post-stimulation effects are widespread to cortical and subcortical areas [3] and depends on frequency, site of stimulation and coil position [4]
As far as we know, this is the first triple blind study that investigated the effects of different parameters of rTMS and trans-spinal direct current stimulation (tsDCS) in combination with physical exercise on the spinal cord and corticospinal excitability
The main result of this study is that anodal tsDCS plus treadmill induced a reduction of motor evoked potential (MEP)’s amplitude and nociceptive flexion reflex (NFR) area compared to sham stimulation/treadmill and reduced Hoffmann reflex (Hr) max/ M max ratio across the time up to 30 after stimulation offset

Summary

Introduction

Repetitive transcranial magnetic stimulation (rTMS) and trans-spinal direct current stimulation (tsDCS) are safe and effective non-invasive tools involving the application of magnetic and electric fields to induce changes in the spinal cord and cortical excitability [1, 2].In humans, rTMS post-stimulation effects are widespread to cortical and subcortical areas [3] and depends on frequency, site of stimulation and coil position [4]. Repetitive transcranial magnetic stimulation (rTMS) and trans-spinal direct current stimulation (tsDCS) are safe and effective non-invasive tools involving the application of magnetic and electric fields to induce changes in the spinal cord and cortical excitability [1, 2]. RTMS seems to induce changes in presynaptic inhibition in Ia afferents terminals; this way, few studies using high-frequency rTMS over the motor cortex showed a decrease of the Hoffmann reflex [5, 6] while low-frequency rTMS increased it [7]. TsDCS is another non-invasive tool capable of modulating central nervous system excitability through delivering a direct current (DC) over the spinal cord [2, 8]. Mice model, cathodal tsDCS increase corticospinal output through changes in neurotransmitters release at segmental level [11] and by the modulation of the corticospinal pathways conduction [12, 13]

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