Transcutaneous spinal direct current stimulation improves locomotor learning in healthy humans

Abstract

Background: Ambulation is an essential aspect of daily living and is often impaired after brain and spinal cord injuries. Despite the implementation of standard neurorehabilitative care, locomotor recovery is often incomplete. Objective: In this randomized, sham-controlled, double-blind, parallel design study, we aimed to determine if anodal transcutaneous spinal direct current stimulation (anodal tsDCS) could improve training effects on locomotion compared to sham (sham tsDCS) in healthy subjects. Methods: 43 participants underwent a single backwards locomotion training (BLT) session on a reverse treadmill with concurrent anodal (n=22) or sham (n=21) tsDCS. The primary outcome measure was speed gain measured 24 hours post-training. We hypothesized that anodal tsDCS+BLT would improve training effects on backward locomotor speed compared to sham tsDCS+BLT. A subset of participants (n=31) returned for two additional training days of either anodal (n=16) or sham (n=15) tsDCS and underwent (n=29) H-reflex testing immediately before, immediately after, and 30 minutes post-training over three consecutive days. Results: A single session of anodal tsDCS+BLT elicited greater speed gain at 24 hours relative to sham tsDCS+BLT (p=0.008, two-sample t-test, adjusted for one interim analysis after the initial 12 subjects). Anodal tsDCS+BLT resulted in higher retention of the acquired skill at day 30 relative to sham tsDCS+BLT (p=0.002) in the absence of significant group differences in online or offline learning over the three training days (p=0.467 and p=0.131). BLT resulted in transient down-regulation of H-reflex amplitude (Hmax/Mmax) in both test groups (p<0.0001). However, the concurrent application of anodal-tsDCS with BLT elicited a longer lasting effect than sham-tsDCS+BLT (p=0.050). Conclusion: TsDCS improved locomotor skill acquisition and retention in healthy subjects and prolonged the physiological exercise-mediated downregulation of excitability of the alpha motoneuron pool. These results suggest that this strategy is worth exploring in neurorehabilitation of locomotor function.

Backward locomotor treadmill training combined with transcutaneous spinal direct current stimulation in stroke: a randomized pilot feasibility and safety study

“…Past studies with direct current stimulation applied over the scalp suggest that anodal stimulation enhances the rate and retention of learned motor task ( Nitsche and Paulus, 2000 ; Reis et al , 2009 ; Fritsch et al , 2010 ; Kadosh et al , 2010 ; Dayan et al , 2013 ; Snowball et al , 2013 ). Likewise, a recent study from our group, albeit in young and neurologically intact individuals, demonstrated that anodal tsDCS over the thoracolumbar vertebra enhanced the acquisition rate and retention of the trained locomotor task ( Awosika et al , 2019 ).…”

“…Herein, we propose two potential explanations for this unexpected finding. Firstly, while anodal tsDCS at the spinal segmental level is understood to be facilitatory ( Winkler et al , 2010 ; Lamy et al , 2012 ; Awosika et al , 2019 ), its influence on ascending somatosensory pathways has been reported as inhibitory ( Cogiamanian et al , 2008 ; Truini et al , 2011 ; Lenoir et al , 2018 ), resulting in a phenomenon known as ‘anodal block’ ( Bhadra and Kilgore, 2004 ; Cogiamanian et al , 2012 ). Therefore, one possible explanation for our findings was that anodal tsDCS, in stroke patients, resulted in the inhibition of ascending sensory axons of the somatosensory pathway, which may have diminished the degree of proprioceptive feedback reaching supraspinal locomotor centres during BLTT ( Hao and Chen, 2011 ; Takakusaki, 2013 ; Clark et al , 2014 ; El-Basatiny and Abdel-Aziem, 2015 ; Schweizer et al , 2017 ; Takakusaki, 2017 ).…”

“…Supported by electrical current modelling ( Parazzini et al , 2014 ; Fregni et al , 2015 ; Fiocchi et al , 2016 ; Kuck et al , 2017 ), preclinical ( Zaghloul, 2014 , 2016 ; Weiguo et al , 2015 ), neurophysiologic ( Cogiamanian et al , 2012 ; Priori et al , 2014 ) and neuroimaging studies ( Schweizer et al , 2017 ), a growing body of literature suggests that tsDCS can modulate activity at multiple levels of the central nervous system, including the segmental spinal cord ( Winkler et al , 2010 ; Lamy et al , 2012 ; Hubli et al , 2013 ), ascending lemniscal and nociceptive pathways ( Cogiamanian et al , 2008 ; Cogiamanian et al , 2011 ; Truini et al , 2011 ), as well as cortical regions ( Bocci et al , 2014 , 2015 a , b , c ; Marangolo et al , 2017 ; Schweizer et al , 2017 ). In addition, a recent proof-of-concept study from our group, in young and neurologically intact individuals, found that anodal tsDCS applied over the lower thoracic region (T-11) concurrently with BLTT, increased the acquisition rate and retention of backward walking speed up to 2 weeks post-training ( Awosika et al , 2019 ). Therefore, this study explores if tsDCS could comparably enhance the effect of BLTT on forward walking in chronic stroke survivors.…”

Beyond the target area: an integrative view of tDCS-induced motor cortex modulation in patients and athletes

“…Finally, a novel and exciting mechanism of action has been recently proposed by Samaddar and co-workers [353]: they found that tsDCS also modulates the migration and proliferation of adult newly born spinal cells in mice, a cell population implicated in learning and memory; although the mechanisms are not fully understood, these findings suggest that tsDCS could be used, also in humans, as an early treatment to improve motor recovery in spinal cord lesions. In this connection, another study has confirmed that tsDCS increases locomotor skill acquisition and retention in healthy volunteers [354].…”

Cortical and Subcortical Effects of Transcutaneous Spinal Cord Stimulation in Humans with Tetraplegia

“…During the sham-TESS session, the electrodes were located in the same position, and the intensity of stimulation was set as the same intensity as used in TESS sessions and gradually decreased down to 0 in ϳ1 min. Similar sham stimulation procedures have been used successfully in previous neuromodulation studies using TESS to provide the initial sensation of stimulation without the subsequent effects (Murray et al, 2018;Awosika et al, 2019). During TESS without 5 kHz carrier frequency (tested on subjects listed as 1-8 on Table 1), single biphasic pulses (200 s duration) were delivered at a 30 Hz frequency (every 33.1 ms) for 20 min using the same intensity as described above.…”