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The Mechanistic Basis for Successful Spinal Cord Stimulation to Generate Steady Motor Outputs.

ABSTRACT: Electrical stimulation of the spinal cord is a promising rehabilitation intervention to restore/augment motor function after spinal cord injury (SCI). Combining sensory feedback with stimulation of remaining motor circuits has been shown to be a prerequisite for the functional improvement of SCI patients. However, little is known about the cellular mechanisms potentially underlying this functional benefit in the injured spinal cord. Here, we combine computer simulations with an isolated whole-tissue adult mouse spinal cord preparation to examine synaptic, cellular, and system potentials measured from single motoneurons and ventral roots. The stimulation protocol included separate and combined activation of the sensory inputs (evoked by dorsal root stimulation) and motor inputs (evoked by stimulation of spinal cord tissue) at different frequencies, intensities, and neuromodulatory states. Our data show that, while sensory inputs exhibit short-term depression in response to a train of stimulation, motor inputs exhibit short-term facilitation. However, the concurrent activation of both inputs elicits a stronger and steadier motor output. This effect is enhanced by the application of pharmacological neuromodulators. Furthermore, sensorimotor excitatory postsynaptic potentials (EPSPs) summate sublinearly (i.e., their combination produces an excitatory potential smaller than the sum of the excitatory potentials they would individually produce). However, ventral root compound action potentials (CoAPs) summate supralinearly generating much higher outputs. Computer simulations revealed that the contrasting summation and disproportionality in plasticity between the excitatory postsynaptic potentials (EPSPs) and CoAPs result from the motoneuronal firing threshold acting as an amplitude-selective filter. Together, these results provide the mechanistic basis for the cellular processes contributing to the generation of steady motor outputs using spinal stimulation. This data has great potential to guide the design of more effective stimulation protocols in SCI patients.

SUBMITTER: Mahrous AA

PROVIDER: S-EPMC6698793 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Mechanistic Basis for Successful Spinal Cord Stimulation to Generate Steady Motor Outputs.

Mahrous Amr A AA Mousa Mohamed H MH Elbasiouny Sherif M SM

Frontiers in cellular neuroscience 20190809

Electrical stimulation of the spinal cord is a promising rehabilitation intervention to restore/augment motor function after spinal cord injury (SCI). Combining sensory feedback with stimulation of remaining motor circuits has been shown to be a prerequisite for the functional improvement of SCI patients. However, little is known about the cellular mechanisms potentially underlying this functional benefit in the injured spinal cord. Here, we combine computer simulations with an isolated whole-ti ...[more]

PMID: 31456665

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Project description:BackgroundTranscutaneous spinal cord stimulation (tSCS) is a non-invasive modality in which electrodes can stimulate spinal circuitries and facilitate a motor response. This review aimed to evaluate the methodology of studies using tSCS to generate motor activity in persons with spinal cord injury (SCI) and to appraise the quality of included trials.MethodsA systematic search for studies published until May 2021 was made of the following databases: EMBASE, Medline (Ovid) and Web of Science. Two reviewers independently screened the studies, extracted the data, and evaluated the quality of included trials. The electrical characteristics of stimulation were summarised to allow for comparison across studies. In addition, the surface electromyography (EMG) recording methods were evaluated.ResultsA total of 3753 articles were initially screened, of which 25 met the criteria for inclusion. Studies were divided into those using tSCS for neurophysiological investigations of reflex responses (n = 9) and therapeutic investigations of motor recovery (n = 16). The overall quality of evidence was deemed to be poor-to-fair (10.5 ± 4.9) based on the Downs and Black Quality Checklist criteria. The electrical characteristics were collated to establish the dosage range across stimulation trials. The methods employed by included studies relating to stimulation parameters and outcome measurement varied extensively, although some trends are beginning to appear in relation to electrode configuration and EMG outcomes.ConclusionThis review outlines the parameters currently employed for tSCS of the cervicothoracic and thoracolumbar regions to produce motor responses. However, to establish standardised procedures for neurophysiological assessments and therapeutic investigations of tSCS, further high-quality investigations are required, ideally utilizing consistent electrophysiological recording methods, and reporting common characteristics of the electrical stimulation administered.

Project description:Deficient ankle control after incomplete spinal cord injury (iSCI) often accentuates walking impairments. Transcutaneous electrical spinal cord stimulation (tSCS) has been shown to augment locomotor activity after iSCI, presumably due to modulation of spinal excitability. However, the effects of possible excitability modulations induced by tSCS on ankle control have not yet been assessed. This study investigated the immediate (i.e., without training) effects during single-sessions of tonic tSCS on ankle control, spinal excitability, and locomotion in ten individuals with chronic, sensorimotor iSCI (American Spinal Injury Association Impairment Scale D). Participants performed rhythmic ankle movements (dorsi- and plantar flexion) at a given rate, and irregular ankle movements following a predetermined trajectory with and without tonic tSCS at 15 Hz, 30 Hz, and 50 Hz. In a subgroup of eight participants, the effects of tSCS on assisted over-ground walking were studied. Furthermore, the activity of a polysynaptic spinal reflex, associated with spinal locomotor networks, was investigated to study the effect of the stimulation on the dedicated spinal circuitry associated with locomotor function. Tonic tSCS at 30 Hz immediately improved maximum dorsiflexion by +4.6° ± 0.9° in the more affected lower limb during the rhythmic ankle movement task, resulting in an increase of +2.9° ± 0.9° in active range of motion. Coordination of ankle movements, assessed by the ability to perform rhythmic ankle movements at a given target rate and to perform irregular movements according to a trajectory, was unchanged during stimulation. tSCS at 30 Hz modulated spinal reflex activity, reflected by a significant suppression of pathological activity specific to SCI in the assessed polysynaptic spinal reflex. During walking, there was no statistical group effect of tSCS. In the subgroup of eight assessed participants, the three with the lowest as well as the one with the highest walking function scores showed positive stimulation effects, including increased maximum walking speed, or more continuous and faster stepping at a self-selected speed. Future studies need to investigate if multiple applications and individual optimization of the stimulation parameters can increase the effects of tSCS, and if the technique can improve the outcome of locomotor rehabilitation after iSCI.

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The Mechanistic Basis for Successful Spinal Cord Stimulation to Generate Steady Motor Outputs.

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The Mechanistic Basis for Successful Spinal Cord Stimulation to Generate Steady Motor Outputs.

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