Review PaperNeural control of locomotion; Part 1: The central pattern generator from cats to humans
Introduction
Understanding how such seemingly `simple' and automated movements, such as walking and running, are controlled forms a main challenge for modern neuroscience. Somehow the central nervous system (CNS) is able to coordinate which joint has to be moved, how far and at what time. Such movements can only be made properly if a set of biomechanical requirements are met using a pattern of electrical signals sent along the nerves to activate the appropriate set of muscles. Furthermore, the locomotor movements are continuously adapted when obstacles are encountered, thereby ensuring the smooth progression of the ongoing movement. Hence, out of a large flow of sensory input from the periphery the system is able to select the most optimal context-specific information and to incorporate this information into the executed movements.
This task is simplified by the remarkable organization of neural networks, specialized in repeating particular actions over and over again. For many species the cyclical patterns needed for walking, respiration, mastication or other rhythmical activities, are generated by such neural networks. For locomotion one usually refers to the term central pattern generator (CPG) to indicate a set of neurons responsible for creating a motor pattern, “regardless of whether all aspects of the motor pattern of the intact animal are produced or some part is missing” [1]. It should be emphasized indeed that `pattern' is used here in a broad sense to indicate alternating activity in groups of flexors and extensors. Hence it is not implied that an overground walking animal would use exactly the same pattern of muscle activation as the one seen, for example, in `fictive locomotion'. In the latter case the animal is motionless but shows an activation pattern which resembles the one seen in `normal' gait. During normal overground walking one can assume that parts of the muscle activation patterns are not centrally generated but are reflexly induced, e.g. through stretch reflexes 2, 3, 4, 5, 116.
The term CPG refers to a functional network, which could consist of neurons located in different parts of the CNS. This network generates the rhythm and shapes the pattern of the motor bursts of motoneurons 1, 6. For the cat it is assumed that there is at least one such CPG for each limb and that these CPGs are located in the spinal cord.
It is generally thought that the commands for initiation and termination of these rhythm generators are coming from supraspinal levels. After gait initiation, afferents deliver movement-related information to spinal and supraspinal levels. Some of this feedback acts directly on the CPG to aid the phase transitions during the step cycle thus providing the possible induction of variations to meet the environmental demands. On the other hand, afferent feedback is more directly connected to motor neurones through various reflex pathways and these pathways themselves are largely under the control of the CPG. In this way it is ensured that reflex activations of given muscles occurs only at the appropriate times in the step cycle (phase-dependent modulation [111]).
This very general model for locomotion, as described above briefly, is mainly based on data obtained from experimental animals. The extrapolation of the `animal'-model of locomotion to humans finds its basis in the implicit assumption that no fundamental differences exist between the neural networks of humans and other vertebrates. In the present review it will be shown that there are indeed striking similarities between cat and human with respect to the neural control of locomotion.
This is not to say that there are no important differences as well. The basic pattern may be similar but amplitudes and functions of bursts of activity may differ. For example, the cats hip extensors are propulsion muscles during stance whereas in humans they are dominant for balance control of the upper body (pelvis to head). In humans the plantarflexors are by far the dominant propulsion muscles but in cats they may be less important. The paraspinal muscles in humans are balance control muscles but in cats they are not. During swing the similarities for hip and knee muscles are quite good.
The practical implication of the similarity in neural control between cat an human is that novel approaches towards the restoration of locomotor abilities in spinal cord injured (SCI) patients can be based on findings in cats (see Part 2 of this review). Furthermore, the possible demonstration of a CPG in humans opens the way to entirely new approaches for experiments on humans. In particular, attention will be given to some very recent data, obtained both on SCI patients and intact humans, which strongly support the view that there exists a human CPG for locomotion. The results of experiments on cats, which have given rise to the present existing models of locomotion, will be used as a guide and will be compared with results obtained on humans.
Section snippets
Evidence for CPG in cat
Gait in intact animals relies on the activation and appropriate coordination of a large variety of muscles in a given phase-dependent pattern. This pattern is to a large extent stereotypic and, once developed, very difficult to change. For example, experiments in newts have shown that transplantations of flexors and extensors, or the implantation of inverted supernumary limbs do not alter the pattern, even if this pattern is entirely contra productive [7]. Similar experiments with
CPG in primates, including man
In contrast to the abundance of data in animals leading to the general assumption of a CPG underlying the central control of locomotion, there is very little known about spinal networks acting like CPGs in primates in general and in humans in particular. Hence, in the context of human locomotion, the important question arises: is there a CPG in primates?
In non-human primates, several attempts have been made to find evidence for the existence of a CPG for locomotion. Phillipson (1905) reported
Supraspinal activation of CPG
After transection of their spinal cord, most cats are not able to generate locomotor movements. This suggests that commands for the initiation of locomotor activity must be given at some level in the CNS above the lesion. By varying the level of transection of the neural axis, it was shown that the regions for initiation of locomotion are located in the brain stem, at supraspinal level (reviewed most recently by Rossignol (1996) [75]and Whelan (1996) [97]). In paralysed decerebrated cat,
Conclusions
In the cat, there is good evidence for a spinal rhythm generating system, which most researchers in this field refer to as a locomotor CPG. This rhythm generating structure normally receives supraspinal and afferent input, yet in its absence it can still generate a pattern which often closely mimics the one seen in normal locomotion.
In contrast to the abundance of data in cats leading to the general assumption of a CPG underlying the central control of locomotion, there is relatively little
Acknowledgements
We would like to thank B Bussel for providing us with some very valuable references and for general guidance, DA Winter and V Dietz for helpful discussions and comments, T Mulder for providing the Weiss references and for support, B Van Wezel and S Donker for reading this paper and for providing critical remarks. This work was supported by a grant from Nato (twinning grant 910574) to JD and from STW and Sint Maartenskliniek to HC.
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