Real versus imagined locomotion: A [¹⁸F]-FDG PET-fMRI comparison

Abstract

The cortical, cerebellar and brainstem BOLD-signal changes have been identified with fMRI in humans during mental imagery of walking. In this study the whole brain activation and deactivation pattern during real locomotion was investigated by [¹⁸F]-FDG-PET and compared to BOLD-signal changes during imagined locomotion in the same subjects using fMRI. Sixteen healthy subjects were scanned at locomotion and rest with [¹⁸F]-FDG-PET. In the locomotion paradigm subjects walked at constant velocity for 10 min. Then [¹⁸F]-FDG was injected intravenously while subjects continued walking for another 10 min. For comparison fMRI was performed in the same subjects during imagined walking. During real and imagined locomotion a basic locomotion network including activations in the frontal cortex, cerebellum, pontomesencephalic tegmentum, parahippocampal, fusiform and occipital gyri, and deactivations in the multisensory vestibular cortices (esp. superior temporal gyrus, inferior parietal lobule) was shown. As a difference, the primary motor and somatosensory cortices were activated during real locomotion as distinct to the supplementary motor cortex and basal ganglia during imagined locomotion. Activations of the brainstem locomotor centers were more prominent in imagined locomotion. In conclusion, basic activation and deactivation patterns of real locomotion correspond to that of imagined locomotion. The differences may be due to distinct patterns of locomotion tested. Contrary to constant velocity real locomotion (10 min) in [¹⁸F]-FDG-PET, mental imagery of locomotion over repeated 20-s periods includes gait initiation and velocity changes. Real steady-state locomotion seems to use a direct pathway via the primary motor cortex, whereas imagined modulatory locomotion an indirect pathway via a supplementary motor cortex and basal ganglia loop.

Introduction

Erect locomotion in humans is a complex sensorimotor task requiring the dynamic interaction between spinal locomotor pattern generators and hierarchically organized supraspinal locomotion centers in the brainstem, cerebellum, and cortex. This cerebral network is believed to modulate locomotion (e.g., gait initiation, termination, velocity, direction, and spatial orientation) and to control balance and gait by integration of multisensory information (Rossignol et al., 2006). Our knowledge about the hierarchical network of supraspinal locomotion centers is derived from basic science studies mainly performed in the cat (Mori et al., 2001, Shik and Orlovsky, 1976). The most important regions are the cerebellar locomotor region (CLR), the mesencephalic locomotor region (MLR), and the subthalamic locomotor region (SLR).

In recent years functional imaging was also used to investigate human locomotion. The cortical processing of locomotion was shown by means of single-photon-emission-computed-tomography (SPECT) (Fukuyama et al., 1997, Greenstein et al., 1995), positron-emission-tomography (PET) (Ishii et al., 1995, Malouin et al., 2003, Tashiro et al., 2001), and functional magnetic resonance imaging (fMRI) (Jahn et al., 2008b, Jahn et al., 2004, Wang et al., 2008). SPECT studies of the regional cerebral blood-flow (rCBF) during walking reported brain activations in different cortical and subcortical regions known to be related to motor activity (Fukuyama et al., 1997, Greenstein et al., 1995). Only two higher resolution PET studies used [¹⁸F]-fluoro-desoxy-glucose ([¹⁸F]-FDG) to investigate the human locomotion, one after running (Tashiro et al., 2001) and one during walking on a treadmill (Ishii et al., 1995). In the latter, activation was mostly observed in the cerebellum.

More recent studies used mental imagery of locomotion and standing to investigate rCBF changes with PET (Malouin et al., 2003) and blood oxygen level-dependent (BOLD) signal alterations with fMRI (Jahn et al., 2008b, Jahn et al., 2004), because active locomotion cannot be performed in MRI or PET scanners.

In summary, a supraspinal locomotor network in humans was identified which includes the frontal cortex, basal ganglia, brainstem tegmentum and cerebellum. This network is remarkably similar to the feline locomotor network (Jahn et al., 2008a, Jahn et al., 2008b).

Despite the existing functional imaging studies on locomotion, the locomotor network of the entire brain has so far not been investigated during real locomotion. Furthermore, although the imagery of movements has been suggested to correspond well to real sensorimotor activations (Deiber et al., 1998, Lacourse et al., 2005, Porro and Cavazzuti, 1996, Stippich et al., 2002), mental imagery of locomotion in fMRI has not been directly compared to real human locomotion. Therefore, in the present study we propose a new approach for investigating brain activation during real steady-state locomotion using [¹⁸F]-FDG PET and qualitatively compare our findings with BOLD response in fMRI during imagined locomotion in the same group of subjects. This is essential for future studies especially on patients with cerebral gait disorders.