Extensive spontaneous plasticity of corticospinal projections after primate spinal cord injury.

Although axonal regeneration after CNS injury is limited, partial injury is frequently accompanied by extensive functional recovery. To investigate mechanisms underlying spontaneous recovery after incomplete spinal cord injury, we administered C7 spinal cord hemisections to adult rhesus monkeys and analyzed behavioral, electrophysiological and anatomical adaptations. We found marked spontaneous plasticity of corticospinal projections, with reconstitution of fully 60% of pre-lesion axon density arising from sprouting of spinal cord midline-crossing axons. This extensive anatomical recovery was associated with improvement in coordinated muscle recruitment, hand function and locomotion. These findings identify what may be the most extensive natural recovery of mammalian axonal projections after nervous system injury observed to date, highlighting an important role for primate models in translational disease research

A Computational Model for Epidural Electrical Stimulation of Spinal Sensorimotor Circuits

Epidural electrical stimulation (EES) of lumbosacral segments can restore a range of movements after spinal cord injury. However, the mechanisms and neural structures through which EES facilitates movement execution remain unclear. Here, we designed a computational model and performed in vivo experiments to investigate the type of fibers, neurons, and circuits recruited in response to EES. We first developed a realistic finite element computer model of rat lumbosacral segments to identify the currents generated by EES. To evaluate the impact of these currents on sensorimotor circuits, we coupled this model with an anatomically realistic axon-cable model of motoneurons, interneurons, and myelinated afferent fibers for antagonistic ankle muscles. Comparisons between computer simulations and experiments revealed the ability of the model to predict EES-evoked motor responses over multiple intensities and locations. Analysis of the recruited neural structures revealed the lack of direct influence of EES on motoneurons and interneurons. Simulations and pharmacological experiments demonstrated that EES engages spinal circuits trans-synaptically through the recruitment of myelinated afferent fibers. The model also predicted the capacity of spatially distinct EES to modulate side-specific limb movements and, to a lesser extent, extension versus flexion. These predictions were confirmed during standing and walking enabled by EES in spinal rats. These combined results provide a mechanistic framework for the design of spinal neuroprosthetic systems to improve standing and walking after neurological disorders

Electrical spinal cord stimulation must preserve proprioception to enable locomotion in humans with spinal cord injury

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

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

Human walking along a curved path. I. Body trajectory, segment orientation and the effect of vision

Task‐related characteristics of gait and segment orientation during natural locomotion along a curved path have been described in order to gain insight into the neural organization of walking. The locomotor task implied continuous deviation from straight‐ahead, thereby requiring continuous adjustment of body movement to produce and assist turn‐related torques. Performance was compared to straight‐ahead locomotion. Subjects easily reproduced both trajectories with eyes open (EO). The actual‐to‐required trajectory difference increased blindfolded (BF), more so during turning. Stride length was unchanged for the outer but decreased for the inner leg. The feet anticipated subsequent body rotation by pivoting toward the inner side of the curve at heel strike. A shift of body centre of mass and trunk roll toward the inner side accompanied turning. The head turned more than dictated by the heading change, and the absolute range of yaw oscillation increased. Head yaw anticipated body yaw by ≈ 200 ms. Despite the minor effect of vision on the behaviour of all other segments, a difference in head pitch occurred between EO and BF; with EO, the head was flexed (P < 0.01), as to look at the path, while pitch was negligible with BF. In general, the changes in the amplitude of head, trunk and feet movements proved to be well related to the kinematics of the steering body, and constituted a sort of basic library of motor synergie

Human walking along a curved path. II. Gait features and EMG patterns

We recorded basic gait features and associated patterns of leg muscle activity, occurring during continuous body progression when humans walked along a curved trajectory, in order to gain insight into the nervous mechanisms underlying the control of the asymmetric movements of the two legs. The same rhythm was propagated to both legs, in spite of inner and outer strides diverging in length (P < 0.001). There was a phase lag in limb displacement between the inner and outer leg of 7% of the total cycle duration (P = 0.0001). Swing velocity was greater for outer than inner foot (P < 0.001). The duration of the stance phase diminished and increased in the outer and inner leg (P < 0.01), respectively, and was associated with trunk leaning toward the inside of the path. Muscle activity was not dramatically altered during curved walking. The amplitude of soleus burst during stance increased in the outer (P < 0.05) and decreased in the inner leg (P < 0.05), without changes in timing. Tibialis anterior activity increased in both legs during the swing phase (P < 0.05); it was advanced on the outer and delayed on the inner side (P < 0.01; 2% of the cycle). The peroneus longus burst decreased in both legs, but more in the inner than the outer leg, and lasted longer in the inner leg at the onset of swing. Closing the eyes did not affect the gait pattern and muscle activity during turning. The command to walk along a curved path may exploit the basic mechanisms of the spinal locomotor generator, thereby limiting the computational cost of turnin

Tuning of a basic coordination pattern constructs straight-ahead and curved walking in humans.

We tested the hypothesis that common principles govern the production of the locomotor patterns for both straight-ahead and curved walking. Whole body movement recordings showed that continuous curved walking implies substantial, limb-specific changes in numerous gait descriptors. Principal component analysis (PCA) was used to uncover the spatiotemporal structure of coordination among lower limb segments. PCA revealed that the same kinematic law accounted for the coordination among lower limb segments during both straight-ahead and curved walking, in both the frontal and sagittal planes: turn-related changes in the complex behavior of the inner and outer limbs were captured in limb-specific adaptive tuning of coordination patterns. PCA was also performed on a data set including all elevation angles of limb segments and trunk, thus encompassing 13 degrees of freedom. The results showed that both straight-ahead and curved walking were low dimensional, given that 3 principal components accounted for more than 90% of data variance. Furthermore, the time course of the principal components was unchanged by curved walking, thereby indicating invariant coordination patterns among all body segments during straight-ahead and curved walking. Nevertheless, limb- and turn-dependent tuning of the coordination patterns encoded the adaptations of the limb kinematics to the actual direction of the walking body. Absence of vision had no significant effect on the intersegmental coordination during either straight-ahead or curved walking. Our findings indicate that kinematic laws, probably emerging from the interaction of spinal neural networks and mechanical oscillators, subserve the production of both straight-ahead and curved walking. During locomotion, the descending command tunes basic spinal networks so as to produce the changes in amplitude and phase relationships of the spinal output, sufficient to achieve the body turn

Neck Muscle Vibration and Spatial Orientation During Stepping in Place in Humans

Unilateral long-lasting vibration was applied to the sternomastoid muscle to assess the influence of asymmetric neck proprioceptive input on body orientation during stepping-in-place. Blindfolded subjects performed 3 sequences of 3 trials, each lasting 60 s: control, vibration applied during stepping (VDS), and vibration applied before stepping (VBS). VDS caused clear-cut whole body rotation toward the side opposite to vibration. The body rotated around a vertical axis placed at about arm's length from the body. The rotation did not begin immediately on switching on the vibrator. The delay varied from subject to subject from a few seconds to about 10 s. Once initiated, the angular velocity of rotation was remarkably constant (about 1°/s). In VBS, at the beginning of stepping, subjects rotated for a while as if their neck were still vibrated. At a variable delay, the direction of rotation reversed, and the effects were opposite to those observed during VDS. Under no condition did head rotation, head roll, or lateral body tilt accompany rotation. The results confirm and extend the notion that the neck proprioceptive input plays a major role in body orientation during locomotion. The body rotation does not seem to depend on the same mechanisms that modify the erect posture; rather, the asymmetric neck input would seem to modify the egocentric body-centered coordinate syste

Apparatus to apply forces in a three-dimensional space

The present invention relates to a robotic system useful to unload an object/person from its weight. The robotic system is useful in locomotor rehabilitation programs and allows the manipulation of forces in a three-dimensional space with far lower actuator requirements and a much higher precision than prior-art systems. The apparatus combines passive and active elements to minimize actuation requirements while still keeping inertia to a minimum and control precision to a maximum. It requires minimal actuators and at the same time has a low inertia