title: Probing the Human Spinal Locomotor Circuits by Phasic Step-Induced Feedback and by Tonic Electrical and Pharmacological Neuromodulation.
abstract: The mammalian lumbar spinal cord experimentally isolated from supraspinal and afferent feedback input remains capable of expressing some basic locomotor function when appropriately stimulated. This ability has been attributed to spinal neural circuits referred to as central pattern generators (CPGs). In individuals with a severe spinal cord injury, rhythmic activity in paralyzed leg muscles can be generated by phasic proprioceptive feedback during therapist- or robotic-assisted stepping on a motorized treadmill. Here, we critically review to what extent the resulting motor output represents locomotor-like activity, and whether these motor patterns are the result of activation of CPGs, as commonly suggested in the literature. Attempts will be made to further delineate the pivotal roles played by mechanisms such as spinal proprioceptive reflexes and their alterations after spinal cord injury, the central excitability level, and by neurotransmitters critical for spinal locomotor activity. We will discuss the view that the muscle activity produced during assisted passive treadmill stepping is resulting from the entrainment of spinal reflex circuits by the cyclically generated proprioceptive feedback. We suggest that the activation of CPG circuits depends rather on the presence of a sustained tonic excitatory drive, as can be provided by electrical spinal cord stimulation, or by specific combinations of dopaminergic agonists, adrenergic/ dopaminergic precursors and/or 5-HT receptor agonists. Novel rehabilitation strategies using spinal cord stimulation and rhythmic-activity producing drugs during locomotor therapy will pave the way for clinically relevant advances in restoration of motor function in people with severe spinal cord injury.
authors.affiliation: Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna. Austria.
authors.forename: Ursula S
authors.initials: US
authors.lastname: Hofstoetter
authors.affiliation: The Graduate Center, City University of New York, NY. United States.
authors.forename: Maria
authors.initials: M
authors.lastname: Knikou
authors.affiliation: Department of Psychiatry and Neurosciences, Laval University, Québec City, Canada.
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Guertin
authors.affiliation: EPFL SV BMI UPCOURTINE, Station 19, 1015 Lausanne. Swaziland.
authors.forename: Karen
authors.initials: K
authors.lastname: Minassian
mesh_terms: D004599:Electric Stimulation Therapy; D025461:Feedback, Physiological / Q000187:drug effects*; D006801:Humans; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy
chemical_list: D018377:Neurotransmitter Agents
keywords: Central pattern generator; locomotion; neuromodulation; rehabilitation; spinal cord injury; spinal cord stimulation; spinal reflexes; treadmill stepping