Unconstrained three-dimensional reaching in Rhesus monkeys

To better understand normative behavior for quantitative evaluation of motor recovery after injury, we studied arm movements by non-injured Rhesus monkeys during a food-retrieval task. While seated, monkeys reached, grasped, and retrieved food items. We recorded three-dimensional kinematics and muscle activity, and used inverse dynamics to calculate joint moments due to gravity, segmental interactions, and to the muscles and tissues of the arm. Endpoint paths showed curvature in three dimensions, suggesting that maintaining straight paths was not an important constraint. Joint moments were dominated by gravity. Generalized muscle and interaction moments were less than half of the gravitational moments. The relationships between shoulder and elbow resultant moments were linear during both reach and retrieval. Although both reach and retrieval required elbow flexor moments, an elbow extensor (triceps brachii) was active during both phases. Antagonistic muscles of both the elbow and hand were co-activated during reach and retrieval. Joint behavior could be described by lumped-parameter models analogous to torsional springs at the joints. Minor alterations to joint quasi-stiffness properties, aided by interaction moments, result in reciprocal movements that evolve under the influence of gravity. The strategies identified in monkeys to reach, grasp, and retrieve items will allow the quantification of prehension during recovery after a spinal cord injury and the effectiveness of therapeutic interventions

Biodegradable scaffolds promote tissue remodeling and functional improvement in non-human primates with acute spinal cord injury

Grégoire Courtine, Isabel Laura Vollenweider

Tissue loss significantly reduces the potential for functional recovery after spinal cord injury. We previously showed that implantation of porous scaffolds composed of a biodegradable and biocompatible block copolymer of Poly-lactic-co-glycolic acid and Poly-L-lysine improves functional recovery and reduces spinal cord tissue injury after spinal cord hemisection injury in rats. Here, we evaluated the safety and efficacy of porous scaffolds in non-human Old-World primates (Chlorocebus sabaeus) after a partial and complete lateral hemisection of the thoracic spinal cord. Detailed analyses of kinematics and muscle activity revealed that by twelve weeks after injury fully hemisected monkeys implanted with scaffolds exhibited significantly improved recovery of locomotion compared to non-implanted control animals. Twelve weeks after injury, histological analysis demonstrated that the spinal cords of monkeys with a hemisection injury implanted with scaffolds underwent appositional healing characterized by a significant increase in remodeled tissue in the region of the hemisection compared to non-implanted controls. The number of glial fibrillary acidic protein immunopositive astrocytes was diminished within the inner regions of the remodeled tissue layer in treated animals. Activated macrophage and microglia were present diffusely throughout the remodeled tissue and concentrated at the interface between the preserved spinal cord tissue and the remodeled tissue layer. Numerous unphosphorylated neurofilament H and neuronal growth associated protein positive fibers and myelin basic protein positive cells may indicate neural sprouting inside the remodeled tissue layer of treated monkeys. These results support the safety and efficacy of polymer scaffolds in a primate model of acute spinal cord injury. A device substantially similar to the device described here is the subject of an ongoing human clinical trial. (C) 2017 Elsevier Ltd. All rights reserved.

2017

Spatiotemporal Maps of Proprioceptive Inputs to the Cervical Spinal Cord During Three-Dimensional Reaching and Grasping

Beatrice Barra, Marco Capogrosso, Sara Conti, Nathan Antoine Greiner, Auke Ijspeert, Pierre Charles Marie Kibleur, Shravan Tata Ramalingasetty

Proprioceptive feedback is a critical component of voluntary movement planning and execution. Neuroprosthetic technologies aiming at restoring movement must interact with it to restore accurate motor control. Optimization and design of such technologies depends on the availability of quantitative insights into the neural dynamics of proprioceptive afferents during functional movements. However, recording proprioceptive neural activity during unconstrained movements in clinically relevant animal models presents formidable challenges. In this work, we developed a computational framework to estimate the spatiotemporal patterns of proprioceptive inputs to the cervical spinal cord during three-dimensional arm movements in monkeys. We extended a biomechanical model of the monkey arm with ex-vivo measurements, and combined it with models of mammalian group-Ia, Ib and II afferent fibers. We then used experimental recordings of arm kinematics and muscle activity of two monkeys performing a reaching and grasping task to estimate muscle stretches and forces with computational biomechanics. Finally, we projected the simulated proprioceptive firing rates onto the cervical spinal roots, thus obtaining spatiotemporal maps of spinal proprioceptive inputs during voluntary movements. Estimated maps show complex and markedly distinct patterns of neural activity for each of the fiber populations spanning the spinal cord rostro-caudally. Our results indicate that reproducing the proprioceptive information flow to the cervical spinal cord requires complex spatio-temporal modulation of each spinal root. Our model can support the design of neuroprosthetic technologies as well as in-silico investigations of the primate sensorimotor system.

IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC2020

Performance of locomotion and foot grasping following a unilateral thoracic corticospinal tract lesion in monkeys (Macaca mulatta)

Grégoire Courtine

Six adult monkeys (Macaca mulatta) received a unilateral lesion of the lateral corticospinal tract (CST) in the thoracic spinal cord. Prior to surgery, the animals were trained to perform quadrupedal stepping on a treadmill, and item retrieval with the foot. Whole body kinematics and electromyogram (EMG) recordings were made prior to, and at regular intervals over a period of 12 weeks after the CST lesion. After 1 week of recovery, all monkeys were able to walk unaided quadrupedally on the treadmill. The animals, however, dragged the hindpaw ipsilateral to the lesion along the treadmill belt during the swing phase and showed a significant reorganization of the spatiotemporal pattern of hindlimb (HL) and forelimb (FL) displacements. The inability to appropriately trigger the swing phase resulted in an increase in the cycle duration and stride length of both HLs. The stance duration decreased in the ipsilateral HL, and increased in the contralateral HL and both FLs. Consequently, there was a dramatic disruption of interlimb and intralimb coupling that was reflected in the limb kinematic and EMG patterns. The CST lesion completely abolished the ability of the monkeys to retrieve items with the foot ipsilateral to the lesion and significantly disrupted the level of performance of the contralateral HL during the first 2 weeks post-lesion. Interestingly, selected HL muscles remained almost quiescent when the monkeys attempted to retrieve items, but were unsuccessful with the affected foot at 1 week post-lesion, whereas the capacity to activate the same muscles was preserved, although reduced, during stepping. Spatial and temporal parameters of gait, kinematics, and EMG patterns recorded during locomotion generally converged toward control values over time, but significant differences persisted up to 12 weeks post-lesion. Although some control was recovered over the distal foot musculature, fine foot grasping remained significantly impaired at the end of the testing period. These findings demonstrate that the CST pathway from the brain normally makes an important contribution to interlimb and intralimb coordination during basic locomotion, and to muscle activation to produce dexterous foot digit movements in the monkey. Furthermore, the present study indicates that the primate has the ability to rapidly accommodate locomotor performance, and to a lesser degree fine foot motor skills, to a reduction in supraspinal control. Identification of the neural substrates mediating the rapid recovery of motor function following injury to the primate spinal cord could provide insight into developing repair strategies to augment functional recovery from neuromotor impairments.

2005