Possibilities for examining the neural control of gait in humans with fNIRS

Although the existence of a central pattern generator system modulated by sensory information has become broadly accepted in the control of gait, many findings indicate that the cortex also plays a role of primary importance in human walking (Miyai et al., 2001; Gwin et al., 2011; Petersen et al., 2012). Examining the neural control of gait in humans requires recording cortical activity during gait. Direct evidence for cortical involvement in human locomotion comes from neuroimaging studies using position emission tomography (la Fougère et al., 2010), electroencephalography (EEG, Gwin et al., 2011) and functional near-infrared spectroscopy (fNIRS, Miyai et al., 2001) methods. Among possible neuroimaging methods, fNIRS is ideally suited to perform brain imaging during walking as it represents several advantages over other methods (Perrey, 2008). In this opinion article, we concentrate on the possibilities of examining the neural control of gait in humans with fNIRS method. Until now this versatile neuroimaging technique has been used rarely while the subject is moving in neuroscientific research and clinical setting (e.g., Holtzer et al., 2011). While clinical gait evaluation belongs to the neurological examination, very little research on gait with fNIRS measurement from a neurological perspective has been done. Because fNIRS is still at its infancy, it suffers from the lack of standards for a well understanding of signals obtained and signal-processing method. Based on a quick review of recent studies using fNIRS modality for studying gait in humans, this paper aims to address the sensitivity and pitfalls of fNIRS to activation over multiple cortical areas involved in gait control in humans. Traditional neuroimaging has focused on detecting brain activity in response to a task. However, due to the lack of flexibility of most imaging techniques (e.g., functional magnetic resonance imaging or fMRI), little is known about brain activity during everyday motor tasks and when a patient undergoes gait training. Like fMRI, fNIRS is a non-invasive imaging technique for measuring local variations of hemoglobin concentration changes related to neuronal activity by the phenomenon of neurovascular coupling. By measuring absorption properties of hemoglobin at two or more wavelengths, fNIRS exploits the changes of the wavelength-dependent extinction spectra of the oxygenated (O2Hb) and deoxygenated (HHb) form. Although some pitfalls are to consider using fNIRS during gait (i.e., low spatial resolution, inter-subject variability of the hemodynamic response, positioning of the optodes and systemic interference), the advantages of fNIRS, such as non-invasiveness, highly portable make it a promising method for studying the cortical activation patterns associated with whole-body tasks by wearable multichannel fNIRS system (Piper et al., 2014). In healthy people, the first study using multichannel fNIRS demonstrated significantly increased levels of O2Hb in bilateral supplementary motor area (SMA) and primary motor (M1) and somatosensory (S1) cortical regions during treadmill walking (with arm swing) at 1 km/h (Miyai et al., 2001). Walking at 3 and 4 km/h induced evoked hemodynamic responses from the bilateral primary sensorimotor areas (SM1, Suzuki et al., 2004). Running at 9 km/h led to additional oxygenation changes in premotor cortex (PMC) and especially in prefrontal cortex (PFC). While clear SMA and PFC activation changes are also well documented (Holtzer et al., 2011; Koenraadt et al., 2014), changes in speed had little effect on M1 or S1 activity (Suzuki et al., 2004). fNIRS studies have shown that SMA is playing a role in the period prior to the start of gait (Mihara et al., 2007) and for the more difficult task (such as backward walking at 1.6 km/h in Kurz et al., 2012). Although coordinated movement during walking appear relatively effortless, motor commands are important because of the added need for control of stability (Yang and Gorassini, 2006), especially during backward walking (Kurz et al., 2012). Preliminary data from Mazerie et al. (2012) showed that varied terrains (downhill and uphill) activated differently the cortical motor networks (including SM1, SMA, and PFC) than steady-speed treadmill walking due to larger contribution from sensory afferents in walking control and a higher degree of movement difficulty. Besides investigating cortical patterns related to different walking speed and terrain, a verbal cue while walking leads profoundly to different PFC and PMC activation patterns than walking without a verbal cue (Suzuki et al., 2008). This indicates that anticipated adaptations of gait to changes of treadmill speed readily affect regional activations in PFC, SMA, PMC, and SMC. Altogether, an involvement of M1 remains controversial during normal gait in humans (Miyai