Abstract
Neurorecovery from locomotor training is well established in human spinal cord injury (SCI). However, neurorecovery resulting from combined interventions has not been widely studied. In this randomized clinical trial, we established the tibialis anterior (TA) flexion reflex modulation pattern when transcranial magnetic stimulation (TMS) of the primary motor cortex was paired with transcutaneous spinal cord (transspinal) stimulation over the thoracolumbar region during assisted step training. Single pulses of TMS were delivered either before (TMS-transspinal) or after (transspinal-TMS) transspinal stimulation during the stance phase of the less impaired leg. Eight individuals with chronic incomplete or complete SCI received at least 20 sessions of paired stimulation during assisted step training. Each session consisted of 240 paired stimuli delivered over 10-min blocks for 1 h during robotic-assisted step training with the Lokomat6 Pro®. Body weight support, leg guidance force and treadmill speed were adjusted based on each participant’s ability to step without knee buckling or toe dragging. Both the early and late TA flexion reflex remained unaltered after TMS-transspinal and locomotor training. In contrast, the early and late TA flexion reflexes were significantly depressed during step** after transspinal-TMS and locomotor training. Reflex changes occurred at similar slopes and intercepts before and after training. Our findings support that targeted brain and spinal cord stimulation coupled with locomotor training reorganizes the function of flexion reflex pathways, which are a part of locomotor networks, in humans with varying levels of sensorimotor function after SCI.
Trial registration number NCT04624607; Registered on November 12, 2020.
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We thank all participants and their care givers for their commitment during participation in the research study.
Funding
This study was supported by the Spinal Cord Injury Research Board (SCIRB) of the New York State Department of Health (NYSDOH), Wadsworth Center (Grants C32095GG, C33276GG), and, in part, by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), under grant number R01HD100544 awarded to Maria Knikou. Funding sources were not involved in study design, data collection, data analysis, data interpretation, or decision to publish.
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MK: conception and design of research, interpreted results of experiments and wrote first draft of manuscript. TP, MZ, MK: performed experiments. MZ: analyzed data, prepared figures. TP, MZ and MK: edited and revised manuscript. TP, MZ and MK: approved final version of manuscript.
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The study was approved by the Institutional Review Board of the City University of New York (IRB no. 2017-0261). All participants gave informed consent before study enrollment and participation.
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Communicated by Francesco Lacquaniti.
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Pulverenti, T.S., Zaaya, M. & Knikou, M. Brain and spinal cord paired stimulation coupled with locomotor training affects polysynaptic flexion reflex circuits in human spinal cord injury. Exp Brain Res 240, 1687–1699 (2022). https://doi.org/10.1007/s00221-022-06375-x
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DOI: https://doi.org/10.1007/s00221-022-06375-x