Alteration of H-reflex and MEP amplitude in the flexor carpi radialis muscle with transcutaneous spinal cord stimulation during static and leg cycling tasks in neurologically intact male and female humans

STUDY PURPOSE: Transcutaneous spinal cord stimulation (tSCS) is a novel, non-invasive approach used to activate and modulate spinal networks. tSCS facilitates upper extremity function, generates locomotor-like responses, and may facilitate sensorimotor recovery after neural injury when paired with rehabilitation interventions. However, one drawback of tSCS is that its underlying mechanisms of action are not well understood. It has been suggested recently that tSCS modulates spinal circuitry in a manner similar to epidural spinal cord stimulation. In this study, we investigated the ability of tSCS applied to the lumbar and cervical spinal cord to modulate cervical circuitry. We raised two questions in this study: 1) To what extent can the cervical circuitry of the spinal cord be modulated by tSCS as measured in the flexor carpi radialis (FCR) by Hoffmann (H-)reflex and motor evoked potential (MEP) amplitude? 2) Does providing tSCS at multiple segments of the spinal cord (lumbar and cervical combined) converge to alter excitability of H-reflex or MEP amplitude to a greater extent compared to either site alone? The neuromodulatory effects of tSCS were assessed during both a static task and relative to a leg cycling paradigm to determine if tSCS alters cervico-lumbar coupling. DATA COLLECTED: To explore the changes in amplitude of FCR H-reflexes and MEPs, 14 neurologically-intact participants completed the H-reflex (3 female, 11 male) and MEP (4 female, 10 male) assessments, with 11 completing both protocols. Because 3 individuals were excluded from MEP assessment due to possible contraindications to transcranial magnetic stimulation (TMS), 3 additional participants were recruited to complete only the MEP portion of the protocol. For each measure, participants completed two tasks that include a static task and leg cycling at a constant speed (?60 rpm). During each task, participants completed 4 tSCS conditions: (1) No tSCS, 2) tSCS active over the cervical spinal cord (Cervical); 3) tSCS active over the lumbar spinal cord (Lumbar); 4) tSCS active simultaneously on cervical and lumbar spinal cord (Combined). Thus, for each participant in each group 8 experimental conditions are available. Additionally, information about the level of background muscle activity, amplitude of evoked motor response (M-wave), maximum evoked motor response (Mmax), maximum MEP amplitude (MEPmax), peak muscle activation during a maximum voluntary contraction (MVC), and the amplitude of stimulation at the cervical and lumbar sites for each participant are included. The peak-to-peak amplitude of M-wave, H-reflex, and MEP, as well as baseline activity of the FCR muscle, were analyzed in a window of 400 ms (staring 100ms pre-stimulus, ending 300ms post-stimulus). A window of 100ms pre-stimulus (-100ms to 0ms relative to stimulus onset) was selected to calculate the baseline FCR and ECR EMG activity averaged over ten sweeps for each experimental condition. To obtain the value of pre-stimulus muscular contraction, the mean of the signal in this 100ms window was calculated and subtracted from the whole trace to remove any offset in the signal. The pre-stimulus background activity was then rectified and calculated as the mean activity in the 100ms window. The peak-to-peak amplitude of post-stimulus H-reflex, M-wave, and MEP were calculated by averaging ten sweeps per condition. The average values were then normalized to the value of Mmax for H-reflex measurements and to the value of MEPmax for MEP measurements, obtained in a separate trial immediately before the initiation of the testing conditions. The post-stimulus window of analysis for each evoked response was selected based on visual inspection. The FCR H-reflex was evoked by stimulating the median nerve using bipolar electrodes with 1ms square wave pulses. Transcranial magnetic stimulation was applied to the contralateral motor cortex using a double cone coil to elicit MEPs with a single monophasic pulse. Transcutaneous stimulation of the spinal cord was delivered by a constant current stimulator through two 2.5 cm round cathodic electrodes placed midline at C3-4 and C6-7, and T11 and L1 spinous processes. Two 5 × 10 cm rectangular electrodes were placed bilaterally over the iliac crests as anodes for the cervical tSCS while two additional anode electrodes were placed laterally for the lumbar tSCS. Muscle activity of four muscles in the left arm was recorded via electromyography (EMG) during each trial: FCR, extensor carpi radialis (ECR), biceps brachii (BB) and triceps brachii (TB). Muscle activity was recorded from surface Ag-AgCl electrodes placed on the muscle belly and recorded at a sampling rate of 2000Hz. All EMG signals were amplified 1000x during data collection and band-pass filtered from 30 to 1000 Hz. The EMG signals were used to record H-reflexes and MEPs from the FCR muscle. The amplitude of FCR H-reflexes, M-waves, and MEPs along with FCR/ECR pre-stimulus baseline activity were compared across different experimental conditions using repeated-measure ANOVA (rmANOVA). During the static task, the effects of condition (No tSCS, Cervical, Lumbar, and Combined) were compared for H-reflex, MEP, M-wave and baseline muscle activity with a 1 x 4 ANOVA. Similarly, during the cycling task, the effects of condition (Static No-tSCS, Cycle No-tSCS, Cycle Cervical, Cycle Lumbar, and Cycle Combined) were compared for H-reflex, MEP, M-wave, baseline muscle activity, and cycling cadence with a 1 x 5 ANOVA. Significant effects were followed by pairwise comparisons corrected by Tukey’s HSD adjustment for multiple comparisons. Differences with p ? 0.05 were accepted as statistically significant. This dataset represents a stand-alone data. DATA USAGE NOTES: This study demonstrates, for the first time, that tonic activation of spinal cord networks through multiple sites of tSCS provides a facilitation of both spinal reflex and corticospinal pathways.

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