Chapter 4.20 - Supraspinal locomotor control in quadrupeds and humans

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Abstract:

Locomotion in humans and other vertebrates is based on spinal pattern generators, which are regulated by supraspinal control. Most of our knowledge about the hierarchical network of supraspinal locomotion centres derives from animal experiments, mainly in the cat. Here we summarize evidence that the supraspinal network of quadrupeds is conserved in humans despite their transition to bipedalism. By use of mental imagery of locomotion in fMRI we found (1), locomotion modulates sensory systems and is itself modulated by sensory signals. During automated locomotion in healthy subjects cortical sensory inhibition occurs in vestibular and somatosensory areas; this inhibition is cancelled in the congenitally blind; (2), we delineated separate and distinct areas in the brainstem and cerebellum which are remarkably similar to the feline locomotor network. The activations found here include homologues to the pacemakers for gait initiation and speed regulation in the interfastigial cerebellum and bilateral midbrain tegmentum (cerebellar and mesencephalic locomotor regions), their descending target regions in the pontine reticular formation, and the rhythm generators in the cerebellar vermis and paravermal cerebellar cortex. This conservation of the basic organization of supraspinal locomotor control during vertebrate phylogeny opens new perspectives for both, the diagnosis and treatment of common gait disorders. It is conceivable that electrical stimulation of locomotor brain stem centres may initiate and improve gait in selected patients suffering from Parkinson's disease or progressive supranuclear palsy.

Introduction

Quadrupeds and bipedal humans actively explore their environment by locomotion. Most of our knowledge about the sensorimotor control of posture and gait has been gained from different preparations of the intact, decorticate, and decerebrate cat. In all vertebrates this coordination is provided by “central pattern generators” (CPGs), segmentally organized groups of interneurons in the spinal cord (Grillner, 1981, Grillner, 2006). The CPGs are controlled by descending input from specific locomotor command regions in the brainstem and cerebellum. Several distinct regions that initiate and modulate spinal stepping have been identified by electrical or chemical stimulation in the cat (Shik and Orlovsky, 1976; Armstrong, 1988; Mori et al., 2001; Fig. 1B). Proceeding rostrocaudally, the most important regions are the subthalamic locomotor region (SLR) in the lateral hypothalamic area, the mesencephalic locomotor region (MLR), corresponding to the cuneiform and pedunculopontine nuclei in the dorsal midbrain, the cerebellar locomotor region (CLR) located close to the fastigial nuclei in the cerebellar midline, and the pontine locomotor region in the pontomedullary reticular formation (PMRF). The locomotor regions in the cat have been associated with different functions in the network for supraspinal locomotor control (Armstrong, 1988; Whelan, 1996; Mori et al., 2001; Grillner, 2006). For simplification we can assume that the SLR and MLR initiate locomotion when disinhibited from tonic basal ganglia control. The CLR receives rhythmic input from the vermis and paravermal cerebellar cortex to control speed. The CLR output converges with descending MLR projections in the PMRF, where locomotor signals are transmitted to the spinal cord CPGs.

There are several lines of evidence that the organization of supraspinal locomotor control in humans was conserved during their transition from quadrupedal to bipedal locomotion. First, electrophysiological studies have demonstrated that the quadrupedal interlimb coordination remains conserved during bipedal walking (Dietz et al., 2001; Wannier et al., 2001; Dietz, 2002; Balter and Zehr, 2007). Second, anecdotal reports on single patients with vascular midbrain lesions support the view that the MLR also mediates gait initiation in humans (Masdeu et al., 1994; Hathout and Bhidayasiri, 2005). Third, a few brain activation studies have identified homologues to cat locomotor regions during actual and imagined gait (Hanakawa et al., 1999; Jahn et al., 2008, Jahn et al., 2004). Surprisingly, the clinical implications of these centres for common central disorders of gait and posture like Parkinson's disease, progressive supranuclear palsy (PSP), and cerebellar ataxia have so far been largely ignored. Postmortem histological studies, however, revealed that Parkinson's disease and PSP are associated with reduced cell counts in the pedunculopontine nucleus (Zweig et al., 1989; Pahapill and Lozano, 2000). Moreover, stimulation of this area with low frequency electrical stimulation improved the gait of patients with advanced Parkinson's disease (Plaha and Gill, 2005, Stefani et al., 2007).

The locomotor network in all mammals is modulated by cortical control and sensory feedback on multiple levels. This feedback originates from muscles and skin afferents as well as from the visual and vestibular senses. It modulates transmission in locomotor pathways in a state- and phase-dependent manner (Rossignol et al., 2006). Besides modulating the phases of the gait cycle, certain aspects of sensory control seem to be in general suppressed during locomotion to prevent adverse interactions with an optimized sensorimotor pattern. In humans, it was shown that the H-reflex excitability is lower during locomotion (Capaday et al., 1986). Changes in the gain of reflexes were explained by a task-dependent increase of tonic presynaptic inhibition in group Ia afferents (Dietz, 1992; Faist et al., 1996). For the vestibular system it was shown in the cat that locomotion decreased the responses of neurons in the lateral vestibular nucleus to tilt stimulation (Orlovsky, 1972). In humans, galvanic vestibular stimulation was used to demonstrate reduced vestibular control during running compared to walking by measuring gait deviations (Jahn et al., 2000). Further, slow phase velocity of spontaneous nystagmus in patients with acute unilateral vestibular failure decreases during locomotion (Jahn et al., 2002). Functional magnetic resonance imaging (fMRI) data show reduced activity of multisensory cortical areas during walking and even more so during running (Jahn et al., 2003).

Here we present an overview of human supraspinal control of locomotion. Drawing on additional analyses of data from a series of experiments using mental imagery of locomotion in fMRI, we correlate the locations and functions of locomotor regions in the human brainstem and cerebellum with those of the cat. These experiments focused on (1) the demonstration of brainstem and cerebellar locomotor regions in humans (Jahn et al., 2008); (2) the investigation of task-dependent suppression of cortical sensory control during locomotion (Jahn et al., 2003, Jahn et al., 2004); and (3) the changes of multisensory supraspinal control in the congenitally blind (Deutschländer et al., 2008).

Section snippets

Methods

A total of 45 subjects were examined during three different studies using mental imagery of locomotion in fMRI in sighted healthy adults (n=38, Jahn et al., 2004, Jahn et al., 2008) and congenitally blind subjects (n=7, Deutschländer et al., 2008). Subjects were trained to perform (eyes open) and then to imagine (eyes closed) these four conditions: lying (rest condition), standing, walking, and running. The experimental procedure is described in detail in Jahn et al. (2008). Functional imaging

Results

Mental imagery of locomotion in fMRI caused BOLD-signal increases in frontal and precentral gyri with left hemispheric dominance, bilaterally in the precuneus, the parahippocampal gyrus, the thalamus, and basal ganglia. A large cluster of activation was found in the brainstem and cerebellum, including the anterior vermis and paravermal cerebellar cortices, and extending bilaterally to the midbrain tegmentum and pontine reticular formation (n=26, Table 1).

The infratentorial activations are shown

Discussion

The fMRI data presented here strongly support the assumption that the organization of supraspinal locomotor control was conserved during vertebrate phylogeny, despite the transition from quadrupedal to bipedal human locomotion.

Acknowledgements

We thank Judy Benson for copy-editing the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft (JA 1087/1-1).

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