Trevor Drew

Cortical and brainstem control of locomotion

While a basic locomotor rhythm is centrally generated by spinal circuits, descending pathways are critical for ensuring appropriate anticipatory modifications of gait to accommodate uneven terrain. Neurons in the motor cortex command the changes in muscle activity required to modify limb trajectory when stepping over obstacles. Simultaneously, neurons in the brainstem reticular formation ensure that these modifications are superimposed on an appropriate base of postural support. Recent experiments suggest that the same neurons in the same structures also provide similar information during reaching movements. It is suggested that, during both locomotion and reaching movements, the final expression of descending signals is influenced by the state and excitability of the spinal circuits upon which they impinge.

Locomotor role of the corticoreticular–reticulospinal–spinal interneuronal system

In vertebrates, the descending reticulospinal pathway is the primary means of conveying locomotor command signals from higher motor centers to spinal interneuronal circuits, the latter including the central pattern generators for locomotion. The pathway is morphologically heterogeneous, being composed of various types of inparallel-descending axons, which terminate with different arborization patterns in the spinal cord. Such morphology suggests that this pathway and its target spinal interneurons comprise varying types of functional subunits, which have a wide variety of functional roles, as dictated by command signals from the higher motor centers. Corticoreticular fibers are one of the major output pathways from the motor cortex to the brainstem. They project widely and diffusely within the pontomedullary reticular formation. Such a diffuse projection pattern seems well suited to combining and integrating the function of the various types of reticulospinal neurons, which are widely scattered throughout the pontomedullary reticular formation. The corticoreticular-reticulospinal-spinal interneuronal connections appear to operate as a cohesive, yet flexible, control system for the elaboration of a wide variety of movements, including those that combine goal-directed locomotion with other motor actions.

Contributions of the motor cortex to the control of the hindlimbs during locomotion in the cat

Although the corticospinal tract is not essential for the production of the basic locomotor rhythm in cats, it does contribute to the regulation of locomotion, particularly in situations in which there is a requirement for precise control over paw placement or limb trajectory. Lesions of the dorsolateral funiculi at the low thoracic level (T(13)) that completely interrupted both the cortico- and rubrospinal pathways produced long-term deficits in locomotion on a level surface. These deficits included a paw-drag that was probably caused both by a loss of cortico- and rubrospinal input to motoneurones controlling distal muscles as well as by a change in the relative timing of muscles acting around the hip and knee. Smaller lesions produced similar deficits from which the cats recovered relatively quickly. Cats with the largest lesions of the dorsolateral funiculi were unable to modify their gait sufficiently to step over obstacles attached to the treadmill belt even 3-5 months postlesion. These results imply that the medial pathways, the reticulo- and vestibulospinal pathways, are unable to fully compensate for damage to the lateral pathways. Single unit recordings from identified pyramidal tract neurones (PTNs) within the hindlimb representation of the primary motor cortex (area 4) showed that a substantial proportion of neurones (67%) significantly increased their discharge frequency when the cats modified their gait to step over obstacles attached to the treadmill belt. Of those PTNs that showed increased activity during the swing phase, populations of neurones were activated at different times. A large proportion of PTNS discharged early in swing, in phase with knee flexors such as the semitendinosus. Others discharged slightly later, in phase with the activity of ankle flexors, such as tibialis anterior, while still others discharged at the end of swing, in phase with digit dorsiflexors, such as the extensor digitorum brevis. We suggest that different populations of cortical neurones may specifically modify the activity of selected groups of close synergistic muscles during different parts of the swing phase. We further suggest that these modifications are mediated, in part, by groups of interneurones that are involved in determining the base locomotor rhythm. This provides a means by which the changes specified by the descending signal from the motor cortex may be smoothly, and appropriately, incorporated into the locomotor cycle.

Cortical mechanisms involved in visuomotor coordination during precision walking

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.

Muscle synergies during locomotion in the cat: a model for motor cortex control

It is well established that the motor cortex makes an important contribution to the control of visually guided gait modifications, such as those required to step over an obstacle. However, it is less clear how the descending cortical signal interacts with the interneuronal networks in the spinal cord to ensure that precise changes in limb trajectory are appropriately incorporated into the base locomotor rhythm. Here we suggest that subpopulations of motor cortical neurones, active sequentially during the step cycle, may regulate the activity of small groups of synergistic muscles, likewise active sequentially throughout the step cycle. These synergies, identified by a novel associative cluster analysis, are defined by periods of muscle activity that are coextensive with respect to the onset and offset of the EMG activity. Moreover, the synergies are sparse and are frequently composed of muscles acting around more than one joint. During gait modifications, we suggest that subpopulations of motor cortical neurones may modify the magnitude and phase of the EMG activity of all muscles contained within a given synergy. Different limb trajectories would be produced by differentially modifying the activity in each synergy thus providing a flexible substrate for the control of intralimb coordination during locomotion.

Neurons in the pontomedullary reticular formation signal posture and movement both as an integrated behavior and independently

We have previously suggested that the discharge characteristics of some neurons in the pontomedullary reticular formation (PMRF) are contingent on the simultaneous requirement for activity in both ipsilateral flexor muscles and contralateral extensors. To test this hypothesis we trained cats to stand on four force platforms and to perform a task in which they were required to reach forward with one forelimb or the other and depress a lever. As such the task required the cat to make a flexion movement followed by an extension in the reaching limb while maintaining postural support by increasing extensor muscle tonus in the supporting limbs. We recorded the activity of 131 neurons from the PMRF of three cats during left, ipsilateral reach. Of these, 86/131 (66%) showed a change in discharge frequency prior to the onset of activity in one of the prime flexor muscles and 43/86 (50%) showed a bimodal pattern of discharge in which activity decreased during the lever press. Among the remaining cells, 28/86 (33%) showed maintained activity throughout the reach and the lever press. Most cells showed a broadly similar pattern of discharge during reaches with the right, contralateral limb. We suggest these results support the view that a population of neurons within the PMRF contributes to the control of movement in one forelimb and the control of posture in the other forelimb as a coordinated unit. Another population of neurons contributes to the control of postural support independently of the nature of the activity in the reaching limb.

Chapter 31 Locomotor Performance and Adaptation after Partial or Complete Spinal Cord Lesions in the Cat

Publisher Summary Much of the information on the role of various structures of the central nervous system (CNS) in the regulation of different aspects of locomotion in the cat comes from the studies based on microstimulation, unit recordings, or acute ablations. Less attention has been paid to the performance and functional reorganization of locomotor control after chronic lesions of these central structures. In part, this may be because interpretation of the results of such studies is problematic in that it has to take into consideration the fact that the consequences of the lesion on the expression of the remaining functions are a mixture of deficits due to the removed structures and due to compensation by other structures. Nevertheless, some indication of the degree of compensation can be obtained by comparing the short- and long-term locomotor performance. In the short term, the deficits represent the uncompensated state and give some indication of the normal role of a given structure in the control of locomotion. Later, after the maximal compensation has taken place, the remaining permanent behavioral deficits give a fair indication of the essential contributions of the ablated structures and the limits of other structures to replace, totally or in part, the function of the missing structures. This chapter summarizes the results of the different studies in which the locomotor performance of chronically instrumented cats was documented before and after either partial or complete spinal lesions. It discusses some of the kinematic and electromyographic (EMG) changes that occur during ordinary treadmill locomotion and briefly describes how these lesioned cats adapt their locomotion to more demanding situations (slopes, tilts, and obstacles). Finally, it correlates these changes with the current knowledge on the function of different supra-spinal structures in the control of locomotion obtained from unit recording and microstimulation studies.

Organization of the projections from the pericruciate cortex to the pontomedullary brainstem of the cat: a study using the anterograde tracer Phaseolus vulgaris-leucoagglutinin.

The anterograde tracer Phaseolus vulgaris‐leucoagglutinin (PHA‐L) was used to study the distribution and density of the projections that originate from four identified subdivisions of the pericruciate cortex (namely, the forelimb and hind limb representations of area 4, area 6aβ, and area 6aγ) and that terminate in the pontomedullary brainstem in the cat. Injections of PHA‐L in all areas of the pericruciate cortex labelled numerous fibers and their terminal swellings in the brainstem. The major target regions of all four cortical areas were the pontine nuclei and the pontomedullary reticular formation (PMRF). Injections into both the forelimb and hind limb representations of area 4 and into area 6aβ resulted in a dense pattern of terminal labelling in restricted regions of the medial and lateral parts of the ipsilateral pontine nuclei. The labelling following the area 6aβ injection was spatially distinct from that seen following the area 4 injections. Injections into the forelimb representation of area 4 as well as into area 6aβ and 6aγ resulted in the labelling of numerous terminal swellings bilaterally in the PMRF; in contrast, there were few labelled terminal swellings in the PMRF following injections into the hind limb representation of area 4. Terminal swellings on individual corticoreticular fibers were far less densely aggregated than those in the pontine nuclei. The dense pattern of innervation to restricted regions of the pontine nuclei supports previous suggestions that the corticopontine projections retain a high degree of topographical specificity that could be used in the control of discrete voluntary movements. In contrast, the more diffuse pattern of the projections to the PMRF may facilitate the selection and activation of the complex postural patterns that accompany voluntary movement. J. Comp. Neurol. 389:617–641, 1997.

Application of circular statistics to the study of neuronal discharge during locomotion

An application of circular statistics is described which permits one to readily and efficiently describe neuronal discharge patterns recorded during locomotion. The method can be adapted to any data which are normally plotted as post-event histograms (PEHs) and can also be used to describe the pattern of electromyographic (EMG) activity during the step cycle. Data can be objectively classified with respect to both the mean direction and amplitude of their discharge, as well as to the variability (angular deviation) of that discharge. In addition, the Rayleigh test for directionality can be used to determine whether cells are modulated or unmodulated. Finally, the ability to describe each cells discharge as a single vector allows the data from several different neurones to be displayed on a single figure and provides an efficient method for comparing the discharge of a population of cells under two or more different conditions.

Visuomotor coordination in locomotion

This article reviews the recent literature concerning the role of visual information in the control of locomotion with an emphasis on the neurophysiological mechanisms that underlie visually triggered, voluntary, gait modifications. Data are presented to show how these gait modifications may be encoded by the motor cortex, and how they may interact with the basic locomotor rhythm.