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Jonathan S. Calvert

Bio: Jonathan S. Calvert is an academic researcher from Mayo Clinic. The author has contributed to research in topics: Spinal cord injury & Neuromodulation (medicine). The author has an hindex of 10, co-authored 19 publications receiving 534 citations. Previous affiliations of Jonathan S. Calvert include Houston Methodist Hospital & University of Pittsburgh.

Papers
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Journal ArticleDOI
TL;DR: In a human subject with chronic paraplegia, a combination of epidural electrical stimulation and long-term rehabilitative training have culminated in the first report of unassisted, voluntary independent stepping in a paralyzed individual.
Abstract: Spinal sensorimotor networks that are functionally disconnected from the brain because of spinal cord injury (SCI) can be facilitated via epidural electrical stimulation (EES) to restore robust, coordinated motor activity in humans with paralysis1–3. Previously, we reported a clinical case of complete sensorimotor paralysis of the lower extremities in which EES restored the ability to stand and the ability to control step-like activity while side-lying or suspended vertically in a body-weight support system (BWS)4. Since then, dynamic task-specific training in the presence of EES, termed multimodal rehabilitation (MMR), was performed for 43 weeks and resulted in bilateral stepping on a treadmill, independent from trainer assistance or BWS. Additionally, MMR enabled independent stepping over ground while using a front-wheeled walker with trainer assistance at the hips to maintain balance. Furthermore, MMR engaged sensorimotor networks to achieve dynamic performance of standing and stepping. To our knowledge, this is the first report of independent stepping enabled by task-specific training in the presence of EES by a human with complete loss of lower extremity sensorimotor function due to SCI.

360 citations

Journal ArticleDOI
01 Apr 2017
TL;DR: This is the first time that the application of EES enabled all of these tasks in the same patient within the first 2 weeks (8 stimulation sessions total) of Ees therapy.
Abstract: We report a case of chronic traumatic paraplegia in which epidural electrical stimulation (EES) of the lumbosacral spinal cord enabled (1) volitional control of task-specific muscle activity, (2) volitional control of rhythmic muscle activity to produce steplike movements while side-lying, (3) independent standing, and (4) while in a vertical position with body weight partially supported, voluntary control of steplike movements and rhythmic muscle activity. This is the first time that the application of EES enabled all of these tasks in the same patient within the first 2 weeks (8 stimulation sessions total) of EES therapy.

166 citations

Journal ArticleDOI
TL;DR: The results suggest that the use of EES-evoked motor responses may guide intraoperative positioning of epidural electrodes to target spinal cord circuitry to enable motor functions after SCI.
Abstract: Epidural electrical stimulation (EES) of the spinal cord has been shown to restore function after spinal cord injury (SCI). Characterization of EES-evoked motor responses has provided a basic understanding of spinal sensorimotor network activity related to EES-enabled motor activity of the lower extremities. However, the use of EES-evoked motor responses to guide EES system implantation over the spinal cord and their relation to post-operative EES-enabled function in humans with chronic paralysis attributed to SCI has yet to be described. Herein, we describe the surgical and intraoperative electrophysiological approach used, followed by initial EES-enabled results observed in 2 human subjects with motor complete paralysis who were enrolled in a clinical trial investigating the use of EES to enable motor functions after SCI. The 16-contact electrode array was initially positioned under fluoroscopic guidance. Then, EES-evoked motor responses were recorded from select leg muscles and displayed in real time to determine electrode array proximity to spinal cord regions associated with motor activity of the lower extremities. Acceptable array positioning was determined based on achievement of selective proximal or distal leg muscle activity, as well as bilateral muscle activation. Motor response latencies were not significantly different between intraoperative recordings and post-operative recordings, indicating that array positioning remained stable. Additionally, EES enabled intentional control of step-like activity in both subjects within the first 5 days of testing. These results suggest that the use of EES-evoked motor responses may guide intraoperative positioning of epidural electrodes to target spinal cord circuitry to enable motor functions after SCI.

56 citations

Journal ArticleDOI
TL;DR: Over the past several years, the research field of spinal neuromodulation has generated promising results that hold potential to enable recovery of functions via epidural electrical stimulation (EES).
Abstract: Background Traumatic spinal cord injury (SCI) disrupts signaling pathways between the brain and spinal networks below the level of injury. In cases of severe SCI, permanent loss of sensorimotor and autonomic function can occur. The standard of care for severe SCI uses compensation strategies to maximize independence during activities of daily living while living with chronic SCI-related dysfunctions. Over the past several years, the research field of spinal neuromodulation has generated promising results that hold potential to enable recovery of functions via epidural electrical stimulation (EES). Methods This review provides a historical account of the translational research efforts that led to the emergence of EES of the spinal cord to enable intentional control of motor functions that were lost after SCI. We also highlight the major limitations associated with EES after SCI and propose future directions of spinal neuromodulation research. Results Multiple, independent studies have demonstrated return of motor function via EES in individuals with chronic SCI. These enabled motor functions include intentional, controlled movement of previously paralyzed extremities, independent standing and stepping, and increased grip strength. In addition, improvements in cardiovascular health, respiratory function, body composition, and urologic function have been reported. Conclusions EES holds promise to enable functions thought to be permanently lost due to SCI. However, EES is currently restricted to scientific investigation in humans with SCI and requires further validation of factors such as safety and efficacy before clinical translation.

54 citations

Journal ArticleDOI
TL;DR: The influence of spinal cord anatomy on the effects of epidural stimulation and the role of specific orientation of electrodes on the dorsal surface of the dura mater in relation to the dorsal roots are presented for the first time.
Abstract: In this study, the neuroanatomy of the swine lumbar spinal cord, particularly the spatial orientation of dorsal roots was correlated to the anatomical landmarks of the lumbar spine and to the magnitude of motor evoked potentials during epidural electrical stimulation (EES). We found that the proximity of the stimulating electrode to the dorsal roots entry zone across spinal segments was a critical factor to evoke higher peak-to-peak motor responses. Positioning the electrode close to the dorsal roots produced a significantly higher impact on motor evoked responses than rostro-caudal shift of electrode from segment to segment. Based on anatomical measurements of the lumbar spine and spinal cord, significant differences were found between L1-L4 to L5-L6 segments in terms of spinal cord gross anatomy, dorsal roots and spine landmarks. Linear regression analysis between intersegmental landmarks was performed and L2 intervertebral spinous process length was selected as the anatomical reference in order to correlate vertebral landmarks and the spinal cord structures. These findings present for the first time, the influence of spinal cord anatomy on the effects of epidural stimulation and the role of specific orientation of electrodes on the dorsal surface of the dura mater in relation to the dorsal roots. These results are critical to consider as spinal cord neuromodulation strategies continue to evolve and novel spinal interfaces translate into clinical practice.

37 citations


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Journal ArticleDOI
31 Oct 2018-Nature
TL;DR: Targeted spinal cord stimulation neurotechnologies that enabled voluntary control of walking in individuals who had sustained a spinal cord injury more than four years ago and presented with permanent motor deficits or complete paralysis despite extensive rehabilitation are introduced.
Abstract: Spinal cord injury leads to severe locomotor deficits or even complete leg paralysis. Here we introduce targeted spinal cord stimulation neurotechnologies that enabled voluntary control of walking in individuals who had sustained a spinal cord injury more than four years ago and presented with permanent motor deficits or complete paralysis despite extensive rehabilitation. Using an implanted pulse generator with real-time triggering capabilities, we delivered trains of spatially selective stimulation to the lumbosacral spinal cord with timing that coincided with the intended movement. Within one week, this spatiotemporal stimulation had re-established adaptive control of paralysed muscles during overground walking. Locomotor performance improved during rehabilitation. After a few months, participants regained voluntary control over previously paralysed muscles without stimulation and could walk or cycle in ecological settings during spatiotemporal stimulation. These results establish a technological framework for improving neurological recovery and supporting the activities of daily living after spinal cord injury.

599 citations

Journal ArticleDOI
TL;DR: Four patients with motor complete spinal cord injury, signifying no voluntary movement or sphincter function below the level of injury but including retention of some sensation, do not recover independent walking after intense locomotor treadmill training with weight support and simultaneous spinal cord epidural stimulation.
Abstract: Persons with motor complete spinal cord injury, signifying no voluntary movement or sphincter function below the level of injury but including retention of some sensation, do not recover independent walking. We tested intense locomotor treadmill training with weight support and simultaneous spinal cord epidural stimulation in four patients 2.5 to 3.3 years after traumatic spinal injury and after failure to improve with locomotor training alone. Two patients, one with damage to the mid-cervical region and one with damage to the high-thoracic region, achieved over-ground walking (not on a treadmill) after 278 sessions of epidural stimulation and gait training over a period of 85 weeks and 81 sessions over a period of 15 weeks, respectively, and all four achieved independent standing and trunk stability. One patient had a hip fracture during training. (Funded by the Leona M. and Harry B. Helmsley Charitable Trust and others; ClinicalTrials.gov number, NCT02339233 .).

383 citations

Journal ArticleDOI
TL;DR: In a human subject with chronic paraplegia, a combination of epidural electrical stimulation and long-term rehabilitative training have culminated in the first report of unassisted, voluntary independent stepping in a paralyzed individual.
Abstract: Spinal sensorimotor networks that are functionally disconnected from the brain because of spinal cord injury (SCI) can be facilitated via epidural electrical stimulation (EES) to restore robust, coordinated motor activity in humans with paralysis1–3. Previously, we reported a clinical case of complete sensorimotor paralysis of the lower extremities in which EES restored the ability to stand and the ability to control step-like activity while side-lying or suspended vertically in a body-weight support system (BWS)4. Since then, dynamic task-specific training in the presence of EES, termed multimodal rehabilitation (MMR), was performed for 43 weeks and resulted in bilateral stepping on a treadmill, independent from trainer assistance or BWS. Additionally, MMR enabled independent stepping over ground while using a front-wheeled walker with trainer assistance at the hips to maintain balance. Furthermore, MMR engaged sensorimotor networks to achieve dynamic performance of standing and stepping. To our knowledge, this is the first report of independent stepping enabled by task-specific training in the presence of EES by a human with complete loss of lower extremity sensorimotor function due to SCI.

360 citations

Journal ArticleDOI
TL;DR: Recent advances in biological and engineering strategies to augment neuroplasticity and/or functional recovery in animal models of SCI that are pushing toward clinical translation are summarized.
Abstract: Individuals with spinal cord injury (SCI) can face decades with permanent disabilities. Advances in clinical management have decreased morbidity and improved outcomes, but no randomized clinical trial has demonstrated the efficacy of a repair strategy for improving recovery from SCI. Here, we summarize recent advances in biological and engineering strategies to augment neuroplasticity and/or functional recovery in animal models of SCI that are pushing toward clinical translation. Advances in cellular regeneration and technical approaches to spinal cord repair are on the verge of being translated into clinical trials.

268 citations

Journal ArticleDOI
TL;DR: Simulations showed that burst stimulation and spatiotemporal stimulation profiles mitigate the cancellation of proprioceptive information, enabling robust control over motor neuron activity, demonstrating the importance of stimulation protocols that preserve proprioception information to facilitate walking with EES.
Abstract: Epidural electrical stimulation (EES) of the spinal cord restores locomotion in animal models of spinal cord injury but is less effective in humans. Here we hypothesized that this interspecies discrepancy is due to interference between EES and proprioceptive information in humans. Computational simulations and preclinical and clinical experiments reveal that EES blocks a significant amount of proprioceptive input in humans, but not in rats. This transient deafferentation prevents modulation of reciprocal inhibitory networks involved in locomotion and reduces or abolishes the conscious perception of leg position. Consequently, continuous EES can only facilitate locomotion within a narrow range of stimulation parameters and is unable to provide meaningful locomotor improvements in humans without rehabilitation. Simulations showed that burst stimulation and spatiotemporal stimulation profiles mitigate the cancellation of proprioceptive information, enabling robust control over motor neuron activity. This demonstrates the importance of stimulation protocols that preserve proprioceptive information to facilitate walking with EES.

220 citations