Asymmetric Walkway: A Novel Behavioral Assay for Studying Asymmetric Locomotion

Behavioral assays are commonly used for the assessment of sensorimotor impairment in the central nervous system (CNS). The most sophisticated methods for ...

West Virginia University School of Medicine

The aim of this study was to produce a dynamic model of the spatiotemporal activation of ensembles of alpha motoneurons (MNs) in the cat lumbosacral spinal cord during the locomotor step cycle. The coordinates of MNs of 27 hindlimb muscles of the cat were digitized from transverse sections of spinal cord spanning the entire lumbosacral enlargement from the caudal part of L(4) to the rostral part of S(1) segments. Outlines of the spinal cord gray matter were also digitized. Models of the spinal cord were generated from these digitized data and displayed on a computer screen as three-dimensional (3-D) images. We compiled a chart of electromyographic (EMG) profiles of the same 27 muscles during the cat step cycle from previous studies and used these to modulate the number of active MNs in the 3-D images. The step cycle was divided into 100 equal intervals corresponding to about 7 ms each for gait of moderate speed. For each of these 100 intervals, the level of EMG of each muscle was used to scale the number of dots displayed randomly within the volume of the corresponding MN pool in the digital model. One hundred images of the spinal cord were thereby generated, and these could be played in sequence as a continuous-loop movie representing rhythmical stepping. A rostrocaudal oscillation of activity in hindlimb MN pools emerged. This was confirmed by computing the locus of the center of activation of the MNs in the 100 consecutive frames of the movie. The caudal third of the lumbosacral enlargement showed intense MN activity during the stance phase of locomotion. During the swing phase, the focus of activation shifted abruptly to the rostral part of the enlargement. At the stance-swing transition, a transient focus of activity formed in the most caudal part of the lumbosacral enlargement. This was associated with activation of gracilis, posterior biceps, posterior semimembranosus, and semitendinosus muscles. These muscles move the foot back and up to clear the ground during locomotion, a role that could be described as retraction. The spatiotemporal distribution of neuronal activity in the spinal cord during normal locomotion with descending control and sensory inputs intact has not been visualized before. The model can be used in the future to characterize spatiotemporal activity of spinal MNs in the absence of descending and sensory inputs and to compare these to spatiotemporal patterns in spinal MNs in normal locomotion.

Spatiotemporal activation of lumbosacral motoneurons in the locomotor step cycle.

In the absence of sensory input, the central nervous system can generate a rhythmical pattern of coordinated activation of limb muscles. Contracting muscles have spring-like properties. If synergistic muscles are co-activated in the right way, sustained locomotion can occur. What is the role of sensory input in this scheme? In this chapter we first discuss the implications of positive force feedback control in hindlimb extensor reflexes in the cat. We then raise the question of whether the sensory-evoked responses, which are modest in size and quite delayed in the stance phase, contribute to any significant extent. A locomotor model is used to show that when centrally generated activation levels are low, stretch reflexes can be crucial. However, when these levels are higher, stretch reflexes have a less dramatic role. The more important role for sensory input is probably in mediating higher level control decisions.

Sensory control of locomotion: reflexes versus higher-level control.

Goal-directed movements of the limbs involve the coordinated activation of dozens of muscles. The neural signals activating these muscles are organized at spinal and supraspinal levels, the end result being trains of action potentials delivered to muscles by ensembles of spinal motoneurons (MNs). A new modelling approach has allowed us to visualize the activity of MNs controlling cat hindlimb locomotion. This reveals a rostrocaudal oscillation of MN activity distributed over about 30 mm of the lumbosacral spinal cord. The coordination and topographical distribution of MN pools thus revealed put an interesting perspective on the restoration of motor function with regeneration and neuroprosthetic techniques. Recent progress in the area of intraspinal microstimulation (ISMS) is reviewed, including the synthesis of locomotor movements with a small number of implanted microwires, eliciting movements after a spinal transection and facilitating weak voluntary movements with subliminal ISMS. We suggest that neuroprostheses may be useful in maximizing the benefits of neural regeneration in the future.

Activation and coordination of spinal motoneuron pools after spinal cord injury.

Many laboratories have reported the successful regeneration of neurons across damaged portions of the spinal cord. Associated improvements in hindlimb locomotor movements have been attributed to the formation of functional neuronal connections with the locomotor central pattern generator (CPG). However, regenerating axons generally extend no more than 10 mm caudal to the lesion sites, terminating about 20 mm short of the lumbar segments thought to contain the CPG. It has therefore tacitly been assumed that the locomotor improvements arose from activation of propriospinal neurons relaying excitation to the CPG. Here we report a test of this assumption, which we call the propriospinal hypothesis. Intraspinal microstimulation (ISMS) was used to activate the putative propriospinal relay neurons. Approximately 2-3 wk after complete spinal cord transection at T8-T9 in rats, an array of six Pt-Ir microwires was chronically implanted in the intermediate and ventral gray matter of T10-T12 segments. ISMS pulse trains with amplitudes of 0.8-0.9 times threshold for activating axial muscles were delivered during open-field locomotor tests (BBB). ISMS significantly increased BBB scores over control tests, but did not produce limb coordination and weight bearing sufficient for locomotion. These results support the main assumption of the propriospinal hypothesis: that neuronal activity elicited in thoracic spinal segments caudal to a complete spinal cord transection may propagate caudally and activate the locomotor CPG.

Intraspinal stimulation caudal to spinal cord transections in rats. Testing the propriospinal hypothesis.

Conceptualizing the mammalian locomotor central pattern generator with modelling.

Simulations performed with neuromechanical models are providing insight into the neural control of locomotion that would be hard if not impossible to obtain in any other way. We first discuss the known properties of the neural mechanisms controlling locomotion, with a focus on mammalian systems. The rhythm-generating properties of central pattern generators (CPGs) are discussed in light of results indicating that cycle characteristics may be preset by tonic drive to spinal interneuronal networks. We then describe neuromechanical simulations that have revealed some basic rules of interaction between CPGs, sensory-mediated switching mechanisms and the biomechanics of locomotor movements. We posit that the spinal CPG timer and the sensory-mediated switch operate in parallel, the former being driven primarily by descending inputs and the latter by the kinematics. The CPG timer produces extensor and flexor phase durations, which covary along specific lines in a plot of phase- versus cycle-duration. We coined the term "phase-duration characteristics" to describe such plots. Descending input from higher centers adjusts the operating points on the phase-duration characteristics according to anticipated biomechanical requirements. In well-predicted movements, CPG-generated phase durations closely match those required by the kinematics, minimizing the corrections in phase duration required of the sensory switching mechanism. We propose the term "neuromechanical tuning" to describe this process of matching the CPG to the kinematics.

The neuromechanical tuning hypothesis.

Goal-directed locomotion, in particular in situations where there is a need to step over or around obstacles, is largely guided by visual information. To negotiate an obstacle successfully, subjects must first plan how to perform the movement and then must execute that plan. In cats, this information must also be stored and used to guide the hindlimbs, which are moved in the absence of direct visual input. Experiments in cats have shown that the motor cortex makes an important contribution to the execution of gait modifications and is involved both in specifying limb trajectory and, when necessary, where the paw will be placed. We suggest that, in both situations, subpopulations of pyramidal tract neurons in the motor cortex act to regulate the duration, level and timing of small groups of synergistic muscles, active at different times during the gait modification. However, the available evidence suggests that the motor cortex plays little role in the planning of these gait modifications. Instead, recent work suggests that the posterior parietal cortex (PPC) may contribute to this function. In agreement with this proposal, we have found that lesions to this structure lead to errors in forelimb placement in front of an advancing obstacle and may produce deficits in forelimb-hindlimb coordination. Single-unit recordings from neurons in the PPC support a role for the PPC in these two aspects of visually guided locomotion and further show that the signal in this structure might be limb-independent.

Cortical mechanisms involved in visuomotor coordination during precision walking.

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We tested the hypothesis that pyramidal tract neurons (PTNs) in the motor cortex contribute to the anticipatory postural adjustments (APAs) that precede the onset of a reach in the standing cat. We recorded the discharge activity of 151 PTNs in area 4 of the pericruciate cortex during reaches of both the contralateral and the ipsilateral limbs in an instructed delay task. A total of 70/151 PTNs were identified as showing an initial short-latency period of discharge following the Go signal. Linear regression analysis showed that in many of these PTNs the short-latency discharge was time-locked to the Go signal and temporally dissociated from the subsequent voluntary movement of the limb. The onset of the change in activity of most of those Go-related neurons that we could test (62/70) was temporally related to the onset of the change in the center of vertical pressure. In 33/70 PTNs, Go-related activity was observed only during contralateral reach, in 13/70 only during ipsilateral reach, and in 24/70 during movements of each limb; most of these latter cells (20/24) showed nonreciprocal changes in activity. Although 35/151 (23%) cells showed significant changes during the instructed delay period for reaches made with at least one of the limbs, only one neuron showed a significant reciprocal change during reaches with either limb. We suggest that the discharge characteristics of these PTNs are compatible with our hypothesis that the motor cortex contributes to the production of the APAs preceding movement.

A motor cortical contribution to the anticipatory postural adjustments that precede reaching in the cat.

We examined the contribution of the motor cortex to the control of intralimb coordination during reaching in the standing cat. We recorded the activity of 151 pyramidal tract neurons (PTNs) in the forelimb representation of three cats during a task in which the cat reached forward from a standing position to press a lever. We simultaneously recorded the activity of muscles in the contralateral forelimb acting around each of the major joints. Cell activity was recorded with and without the presence of an obstacle requiring a modification of limb trajectory. The majority of the PTNs (134/151, 89%) modulated their discharge activity at some period of the reach while 84/151 (56%) exhibited a significant peak or trough of activity as the limb was transported from its initial position to the lever. These phasic changes of activity were distributed sequentially throughout the transport phase. A cluster analysis of muscle activity in two of the cats showed the presence of five muscle synergies during this transport period. One of the synergies was related to the lift of the paw from the support surface, two to flexion of the limb and dorsiflexion of the paw, one to preparation for contact with the lever, and one to the transport of the entire limb forward; a sixth synergy was activated during the lever press. An analysis of the phase of cell activity with respect to the phase of activity of muscles selected to represent each of these synergies showed that different populations of PTNs were activated sequentially and coincidentally with each synergy. We suggest that this sequential activation of populations of PTNs is compatible with a contribution to the initiation and modulation of functionally distinct groups of synergistic muscles and ultimately serves to ensure the appropriate multiarticular, intralimb coordination of the limb during reaching.

Sequential activation of motor cortical neurons contributes to intralimb coordination during reaching in the cat by modulating muscle synergies.

The control of locomotion is a complex dynamic task solved with apparent ease by our body. How this is accomplished still remains an intriguing mystery. This chapter first describes classical and recent findings relevant to understanding the complexity of the question on the verge of several fields of neurophysiology, biomechanics, and computational neuroscience. Then, control of locomotion is analyzed with numerical simulations to reveal some basic characteristics responsible for modulation of the locomotor rhythm and high-level control of steering in the whole animal. In this study, the concept of a central pattern generator (CPG) for controlling locomotor rhythm first proposed by Brown was implemented in a "simple" model with bilateral half-center oscillators consisting of reciprocally organized integrators. The parameters of the CPG were determined by the process of optimization of its phase-duration characteristic that satisfies biomechanical requirements of the overground locomotion. The general finding of this study is that the modality of the control signal that drives CPGs for each limb corresponds to the desired speed of forward progression. This supports the idea that the descending and sensory feedback inputs to the spinal CPG are combined to produce a high-level control signal that sets forward velocity. The same mechanism may be responsible for the control of steering by generating a differential input of speed commands to different limbs.

Chapter 10--a hierarchical perspective on rhythm generation for locomotor control.

The neural control of locomotion involves a constant interplay between the actions of a central pattern generator (CPG) and sensory input elicited by bodily movement. With respect to the CPG, recent analysis of fictive locomotion has shown that durations of flexion and extension tend to covary along specific lines in plots of phase duration versus cycle duration. The slopes of these lines evidently depend on internal states that vary among preparations, but, within a preparation, remain rather steady from one sequence to the next. These relationships can be reproduced in a simple oscillator model having two pairs of preset parameters, suggesting that steady internal drives to flexor and extensor half-centers determine how phase durations covary. Regarding the role of sensory inputs, previous experiments have revealed state-dependent rules that govern phase-switching independently of the CPG rhythm. In addition, sensory input is known to modulate motoneuronal activation through stretch reflexes. To explore how sensory input combines with the locomotor CPG, we used a neuromechanical model with muscle actuators, proprioceptive feedback, sensory phase-switching rules, and a CPG. Interestingly, sequences of stable locomotion were always associated with phase durations that conformed to an extensor-dominated phase-duration characteristic (where extension durations vary more than flexion durations). This is the characteristic seen in normal animals, but not necessarily in fictive locomotion, where movement and associated sensory input are absent. This suggests that to produce the biomechanical events required for stability, an extensor-dominated phase-duration characteristic is required. In the model, when the preset CPG phase durations were well matched to coincide the biomechanical requirements, CPG-mediated phase switching produced stable cycles. When CPG phase durations were too short, phases switched prematurely and the model soon fell. When CPG phase durations were too long, sensory rules fired and overrode the CPG, maintaining stability. We posit that under normal circumstances, descending input from higher centers continually adjusts the operating point of the CPG on the preset phase-duration characteristic according to anticipated biomechanical requirements. When the predictions are good, CPG-generated phase durations closely match those required by the kinetics and kinematics, and little or no sensory adjustment occurs. We propose the term "neuromechanical tuning" to describe this process of matching the CPG to the biomechanical requirements.

Predictive and reactive tuning of the locomotor CPG.

Current diagnosis and treatment of movement impairment post-stroke is based on the subjective assessment of select movements by a trained clinical specialist. However, modern low-cost motion capture technology allows for the development of automated quantitative assessment of motor impairment. Such outcome measures are crucial for advancing post-stroke treatment methods. We sought to develop an automated method of measuring the quality of movement in clinically-relevant terms from low-cost motion capture. Unconstrained movements of upper extremity were performed by people with chronic hemiparesis and recorded by standard and low-cost motion capture systems. Quantitative scores derived from motion capture were compared to qualitative clinical scores produced by trained human raters. A strong linear relationship was found between qualitative scores and quantitative scores derived from both standard and low-cost motion capture. Performance of the automated scoring algorithm was matched by averaged qualitative scores of three human raters. We conclude that low-cost motion capture combined with an automated scoring algorithm is a feasible method to assess objectively upper-arm impairment post stroke. The application of this technology may not only reduce the cost of assessment of post-stroke movement impairment, but also promote the acceptance of objective impairment measures into routine medical practice.

Automated assessment of upper extremity movement impairment due to stroke.

Throughout the course of evolution there has been a parallel development of the complexity and flexibility of the nervous system and the skeletomuscular system that it controls. This development is particularly evident for the cerebral cortical areas and the transformation of the use of the upper limbs from a purely locomotor function to one including, or restricted to, reaching and grasping. This study addresses the issue of whether the control of reaching has involved the development of new cortical circuits or whether the same neurons are used to control both locomotion and reaching. We recorded the activity of pyramidal tract neurons in the motor cortex of the cat both during voluntary gait modifications and during reaching. All cells showed generally similar patterns of activity in both tasks. More specifically, we showed that, in many cases, cells maintained a constant temporal relationship to the activity of synergistic muscle groups in each task. In addition, in some cells the relationship between the intensity of the cell discharge activity and the magnitude of the EMG activity was equally constant during gait modifications and reaching. As such, the results are compatible with the hypothesis that the corticospinal circuits used to control reaching evolved from those used to precisely modify gait.

Sergiy Yakovenko

Neural Engineering Laboratory,
Biomedical Research Center,
Neural Engineering Laboratory, Biomedical Research Center

West Virginia University School of Medicine

Asymmetric Walkway: A Novel Behavioral Assay for Studying Asymmetric Locomotion

Sergiy Yakovenko

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Neural Engineering Laboratory,Biomedical Research Center,Neural Engineering Laboratory, Biomedical Research Center

West Virginia University School of Medicine

Asymmetric Walkway: A Novel Behavioral Assay for Studying Asymmetric Locomotion

Neural Engineering Laboratory,
Biomedical Research Center,
Neural Engineering Laboratory, Biomedical Research Center