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

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.

Transcutaneous spinal direct current stimulation improves locomotor learning in healthy humans

“…This finding, together with the absence of group differences at the This study found that anodal-tsDCS prolonged the duration of H-reflex down-regulation following training relative to sham-tsDCS. Our data confirm prior studies showing that exercise such as BLT leads to transient down-regulation of the H reflex (77,78). We have shown that tsDCS can prolong the period of exercise-induced down-regulation of the H reflex, which may contribute to the behavioral gains during BLT (79).…”

“…From a kinematic point of view, changes in step length related to improved confidence with training was a likely contributor to speed improvements (64,(80)(81)(82). From a mechanistic angle, previously reported tsDCS influences on H-reflex modulation (77,78,83) impacts speed and symmetry of locomotion and modulates H-reflex post-activation (20), central nociceptive signal transmission (15,21) possibly contributing to speed improvements as well. Alternatively, tsDCS could have modified cortical plasticity underlying motor learning through modulation of somatosensory and motor (16,21) evoked potentials as well as interhemisperic inhibition (22,23).…”

“…The mechanical advantage this normal pattern of modulation offers for propelling forward walking would likely be detrimental for BLT. Our results cannot determine whether the prolongation of H-reflex down-regulation by anodal-tsDCS resulted from action on local spinal circuits or modulators of presynaptic inhibition of inputs to alpha-motor neurons (61,78). Future studies will be needed to evaluate the mechanisms of H-reflex down-regulation from anodal-tsDCS during BLT and the contribution of other cortical and subcortical regions, as well as the effects of aging.…”

Variability in cTBS Aftereffects Attributed to the Interaction of Stimulus Intensity With BDNF Val66Met Polymorphism

“…However, we believe the lack of a sham-control condition does not undermine the main findings. Prior work that has included a sham-control arm, but did not investigate genetic moderators of rTMS response, demonstrates that cortical excitability changes in the expected direction following real, but not sham, stimulation (e.g., Todd et al, 2009;Albuquerque et al, 2018), suggesting that the effects of rTMS on MEP amplitudes are not due to order effects (i.e., prior elicitation of MEPs via single-pulse TMS) and/or placebo effects. Regarding the BDNF polymorphism, studies have shown that MEPs decrease to a greater extent for homozygous Val carriers when compared to Val66Met carriers in the absence of repetitive NIBS protocols (e.g., motor learning tasks; e.g., Kleim et al, 2006); however, the current study did not include a voluntary motor (learning) component.…”

Does Compression Sensory Axonopathy in the Proximal Tibia Contribute to Noncontact Anterior Cruciate Ligament Injury in a Causative Way?—A New Theory for the Injury Mechanism

“…Accordingly, it appears that the more efficient is the energy-generating capacity of these mitochondria, the higher is the resistance to mechano-energetic lesions at the terminals of these sensory neurons. It is noteworthy that proprioceptive training not only enhances the neuro-energetic capacity and plasticity of the proprioceptive system at the terminals of the peripheral sensory nerves, but likely at spinal and supraspinal levels as well [ 30 , 139 , 140 , 141 ]. It is important to emphasize the findings of Dargo et al [ 138 ] again that more training or more added components to the programs were not leading to better outcome.…”