Spinal cord pattern generators for locomotion

Abstract

It is generally accepted that locomotion in mammals, including humans, is based on the activity of neuronal circuits within the spinal cord (the central pattern generator, CPG). Afferent information from the periphery (i.e. the limbs) influences the central pattern and, conversely, the CPG selects appropriate afferent information according to the external requirement. Both the CPG and the reflexes that mediate afferent input to the spinal cord are under the control of the brainstem. There is increasing evidence that in central motor diseases, a defective utilization of afferent input, in combination with secondary compensatory processes, is involved in typical movement disorders, such as spasticity and Parkinson's disease. Recent studies indicate a plastic behavior of the spinal neuronal circuits following a central motor lesion. This has implications for any rehabilitative therapy that should be directed to take advantage of the plasticity of the central nervous system. The significance of this research is in a better understanding of the pathophysiology underlying movement disorders and the consequences for an appropriate treatment.

Introduction

Locomotion in mammals is largely dependent upon the central pattern generator (CPG); that is to say, neuronal circuits (networks of interneurons) within the spinal cord. The CPG is defined as a neural circuit that can produce self-sustained patterns of behavior, independent of sensory input (Grillner, 1986). The understanding of basic principles of CPG function is based on research in invertebrates and primitive fish like the lamprey (Grillner et al., 2001; for reviews, see Grillner, 1981, Grillner, 1985; Marder, 1998). There is nothing comparable to mammals, especially human beings, where our understanding is only based on indirect evidence.

According to observations made during the last years, bipedal and quadrupedal locomotion share some common spinal neuronal control mechanisms. As in quadrupeds, long projecting propriospinal neurons couple the cervical and lumbar enlargements in humans (Nathan et al., 1996). Furthermore, the co-ordination of limb movements during walking is similar in human infants (Yang et al., 1998, Pang and Yang, 2000) and adults (Dietz, 1992, Dietz, 1997) as described for quadrupeds (Grillner, 1981, Grillner, 1986). Nevertheless, there are also distinct differences because the upper limbs in primates have become specialised to perform skilled hand movements. The evolution of upright stance and gait, in association with a differentiation of hand movements, represent a basic requirement for human cultural development (Herder, 1785).

Pattern generation is basically innate. In humans, step-like movements are present at birth; they are spontaneously initiated or triggered by peripheral stimuli. A central origin of these movements is implied, as an electromyographic (EMG) burst preceding the actual mechanical events (Forssberg, 1986). Infant stepping also occurs in unencephalic children (Forssberg, 1986), which suggests that a spinal mechanism coordinates these movements. Central programming can be influenced by sensory input (Brooks, 1979). This again is illustrated by infant-stepping. Although rhythmic alternating leg movements are coordinated by a CPG, the infant is unable to maintain body equilibrium. These children lack an integration of the appropriate afferent input into the programmed leg muscle electromyographic (EMG) pattern, which is needed to achieve modulation and adaptation to the actual needs.

Afferent information influences the central (spinal) pattern and, conversely, the CPG selects the appropriate afferent information according to the external requirements (Grillner, 1986, McCrea, 2001; Van de Crommert et al., 1998). Both the spinal locomotor center and the reflexes that mediate afferent input to the spinal cord are under the control of the brainstem (Jankowska and Lundberg, 1981). In addition, there is a cortico-spinal control of locomotion in humans (Capaday et al., 1999, Schubert et al., 1996) and in the cat (Drew, 1996, Leblond et al., 2001). Voluntary commands have to interact with the spinal locomotor generator in order to change, for example, the direction of gait (Bosco and Poppele, 2001; for review, see Dietz, 1997). In fact, cortico-spinal input during human locomotion is phase-linked (Schubert et al., 1997), similar to that seen in the cat (Drew, 1996). This enables the subject to voluntarily circumvent obstacles without losing postural stability.

For most other rhythmic elementary motor behavior, such as hopping or swimming, CPGs have also been assumed to exist (Grillner, 1986). Any disturbance of the finely coordinated interaction between afferent input and the pattern generation following a central lesion, such as stroke or spinal cord injury (SCI), leads to a movement disorder.

This review deals with the behavior of central pattern generation as the basis of locomotion. It will focus on the neuronal control of walking in humans and the plasticity within this system. Novel rehabilitation strategies use this plasticity after a spinal or supraspinal lesion to improve locomotor function. Only important relationships to observations made in animals will be discussed.