Rat locomotor spinal circuits in vitro are activated by electrical stimulation with noisy waveforms sampled from human gait

Abstract

Noisy waveforms, sampled from an episode of fictive locomotion (FL) and delivered to a dorsal root (DR), are a novel electrical stimulating protocol demonstrated as the most effective for generating the locomotor rhythm in the rat isolated spinal cord. The present study explored if stimulating protocols constructed by sampling real human locomotion could be equally efficient to activate these locomotor networks in vitro. This approach may extend the range of usable stimulation protocols and provide a wide palette of noisy waveforms for this purpose. To this end, recorded electromyogram (EMG) from leg muscles of walking adult volunteers provided a protocol named ReaListim (Real Locomotion-induced stimulation) that applied to a single DR successfully activated FL. The smoothed kinematic profile of the same gait failed to do so like nonphasic noisy patterns derived from standing and isometric contraction. Power spectrum analysis showed distinctive low-frequency domains in ReaListim, along with the high-frequency background noise. The current study indicates that limb EMG signals (recorded during human locomotion) applied to DR of the rat spinal cord are more effective than EMG traces taken during standing or isometric contraction of the same muscles to activate locomotor networks. Finally, EMGs recorded during various human motor tasks demonstrated that noisy waves of the same periodicity as ReaListim, could efficiently activate the in vitro central pattern generator (CPG), regardless of the motor task from which they had been sampled. These data outline new strategies to optimize functional stimulation of spinal networks after injury.

Two Distinct Stimulus Frequencies Delivered Simultaneously at Low Intensity Generate Robust Locomotor Patterns

“…For neurorehabilitation purposes, optimizing the protocols of functional electrical stimulation to regain standing and gait after SCI is a primary goal of current research to improve efficacy and decrease potential side effects associated with strong electrical pulses (11,12). Our laboratory has recently discovered that noisy waveforms recorded from VRs of animals or extracted from the EMG of walking humans (13)(14)(15)(16), and applied to a single DR at low intensity, most effectively induce FL in the in vitro spinal cord. This study was, therefore, focused on understanding what protocols are most effective in activating the CPG using relatively weak afferent stimuli.…”

“…Thus, the protocol at 35 and 172 Hz represents the simplest protocol that still preserves the advantages of noisy waves (13)(14)(15)(16) and maximizes the benefits of afferent stimulation with variable inputs of weak strength (54,55). The selective efficacy of 35 1 172 Hz in inducing FL is not shared neither with a stereotyped train containing the same number of pulses nor with another train of two frequencies randomly selected in a comparable frequency domain.…”

“…In the attempt to enhance the efficacy of electrical stimulation and to lower the side-effects potentially associated with the use of strong current (11,12), new paradigms using stimuli reconstructed from sampled motor outputs recorded from ventral roots (VRs) and endowed with intrinsic variability have been observed to generate longer locomotor episodes (noisy waves; [13][14][15][16]. Nevertheless, translation of this approach to clinical use is limited by lack of suitable technology, as existing apparatus only deliver stereotyped impulses within a small frequency range (International Electrotechnical Commission directive 60601-2-10:2012).…”

Multilevel Analysis of Locomotion in Immature Preparations Suggests Innovative Strategies to Reactivate Stepping after Spinal Cord Injury

“…Noise-derived high variability of the stimulus per se is not sufficient to elicit FL, as a phasic component in the lower frequencies seems also to be required, as demonstrated by the ineffi- (Fig. 1C) or biosignals sampled during tonic muscle activation [174]. At the same time, FL could not even be induced by noise-free phasic input such as pure sinusoids (Fig.…”

“…noisy) patterns, obtained by sampling biosignals corresponding to rhythmic motor patterns in vitro or in vivo, from either a ventral root (VR, Fig. 1B), a muscle, or a single motoneuron [131,150,170,173,174]. The clear advantage of this approach relies on stimulation strength, which, unlike canonical electrostimulation, is much lower than the minimum one required to induce a reflex response (i.e., subthreshold).…”