Walking is a common yet complex activity. Accumulating evidence suggests that walking is not fully autonomous, and instead, relies upon considerable cognitive input and its underlying cortical structures. We now know that the brain is organized into distinct functional networks comprised of spatially separated, yet functionally connected regions. However, it remains unclear whether and how these functional brain networks are involved in the control of walking. Besides, walking has distinct features such as gait speed and gait variability. Is it possible that these features are controlled by distinct functional brain networks? If so, in what way? In this study, we start to answer some of these questions by using a neuroimaging technique that evaluates connectivity between brain regions that share functional properties; namely, resting-state functional magnetic resonance imaging (rs-fMRI).

Twelve older adults with relatively slow walking speed and mild-to-moderate cognitive impairment, yet without overt neurological disease, completed a gait assessment and a rs-fMRI visit. Preferred gait speed (m/s) and gait variability (%, coefficient of variation of stride time) were evaluated. Functional connectivity within and between seven known functional brain networks was estimated and compared to gait outcomes. We discovered that gait speed and variability were linked to distinct networks (see Figure). Specifically, gait speed was correlated with the strength of functional connectivity within the fronto-parietal network, suggesting that this gait feature depends upon the integrity of communication within brain regions linked to executive functions. Gait variability, on the other hand, correlated with the degree to which spontaneous brain activity within the dorsal attention network and the default network were anti-correlated. This suggests that one’s gait variability, or steadiness of walking, may depend upon the capacity of the brain to dissociate the neural activity of these two networks—a capacity that has been closely linked to sustained attention.

This small study demonstrated for the first time that clinically-meaningful gait features are linked to the functional integrity of distinct brain networks. Future studies are warranted to 1) examine these relationships in other populations such as Alzheimer’s disease or related dementias, and 2) determine if gait speed and variability can be differentially targeted by non-invasive brain stimulation. These results, while preliminary, also suggest that clinicians should treat gait speed and variability as distinct features of locomotor control that are controlled by cognitive functions.

Figure. Gait speed (A, C) and gait variability (B, D) are linked to distinct functional brain networks in functionally-limited older adults. In particular, gait speed is significantly linked to functional connectivity within the frontoparietal network (A, upper left, shown in red). Gait variability is significantly linked to functional connectivity between the dorsal attention network and the default network (D, lower right, shown in red).

Publication

Lo O, Halko MA, Zhou J, Harrison R, Lipsitz LA, Manor B (2017). Gait speed and gait variability are associated with different functional brain networks. Frontiers in Aging Neuroscience, 9:390. https://www.frontiersin.org/articles/10.3389/fnagi.2017.00390/full

About the Author

In humans, gait initiation is particularly challenging for motor and postural control. While standing on only two legs, we have to move our whole body forward and pass from a (relatively) stable (double leg stance) to an (very!) unstable position (single leg stance). This process is associated with anticipatory postural adjustments (APAs). The neural substrates for generating these APAs and initiating a step are not fully known. By applying repetitive transcranial magnetic stimulation (rTMS), we can manipulate APAs. Previous research showed that rTMS applied above the supplementary motor area provokes a shortening of the APA duration of the first step with no change in APA amplitude and rTMS applied over the cerebellum affects spatial characteristics of walking during locomotor adaptation. This study extends this research further by looking at the effects of supplementary motor area and cerebellar stimulation on the generation of APAs and gait initiation.

We selectively disrupted the supplementary motor area and cerebellum with continuous theta burst rTMS (cTBS, 600 stimuli, three-pulse bursts at 50 Hz, repeated every 200 ms continuously for 40 s-5 Hz) and evaluated the effects of the stimulation on the APAs and execution phases of gait initiation. We recorded biomechanical parameters of gait initiation and EMG activity of the lower leg muscles in 22 healthy volunteers. Our volunteers were instructed to walk at their usual self-paced speed for 10 trials before and after rTMS. They performed separate sessions in a randomised order for rTMS over the supplementary motor area, cerebellum and sham stimulation (to either supplementary motor area or cerebellum), the sessions being separated at least 7 days. We found that functional inhibition of the supplementary motor area led to a shortened APA phase duration with advanced and increased muscle activity. During execution, it also advanced muscle co-activation and decreased the duration of stance soleus activity. Functional inhibition of the cerebellum on the other hand did not influence the APA phase duration and amplitude. During execution, it did increase muscle co-activation and decreased execution duration with increased swing soleus muscle duration and activity. Neither SMA nor cerebellar functional inhibition provoked significant changes in the step length and velocity or postural control during gait execution (i.e. double stance duration and braking index).

The results support distinct roles for the supplementary motor area and the lateral posterior cerebellum in human gait initiation. The supplementary motor area is important for the timing and amplitude of the preparatory phase of the gait initiation, and the posterior cerebellum contributes to the inter- and intra-limb muscle coordination, and probably coupling between the APAs and the execution phases. This study enhances our understanding of how the cortico-pontine-cerebello-thalamo-cortical pathway contributes to the preparation and the execution of the first step in humans.

Figure – Effects of cTBS SMA and sham stimulation on gait initiation in an individual subject. Note that after SMA stimulation (left panel) the duration of the anticipatory postural adjustments phase (delay between t0 and FC) decreased with an advanced TA muscle activity. Such is not the case after sham stimulation (right panel).

Publication

Richard A, Van Hamme A, Drevelle X, Golmard JL, Meunier S, Welter ML. Contribution of the supplementary motor area and the cerebellum to the anticipatory postural adjustments and execution phases of human gait initiation. Neuroscience. 2017 Sep 1;358:181-189. doi: 10.1016/j.neuroscience.2017.06.047. Epub 2017 Jul 1. PMID: 28673716 (http://www.sciencedirect.com/science/article/pii/S0306452217304529?via%3Dihub)

About the Author

Both animals and humans can change their gait speed over a wide range to suit the situation. The coordinated locomotor muscle activity among various speeds is mainly generated by the spinal central pattern generators (CPGs). Recent animal studies have demonstrated the following two characteristics of the speed control mechanisms of the spinal CPGs: (i) rostral spinal segment activation is essential to achieving high-speed locomotion; and (ii) different spinal neural modules are sequentially activated with increasing speed. To examine whether similar control mechanisms exist in the spinal cord of humans, we estimated spinal neural activity during varied-speed locomotion from surface electromyographic (EMG) signals.

We recorded EMG activity from 14 lower leg muscles during a range of speeds (from very slow walking [0.3 m/s] to fast running [4.3 m/s]). We estimated spinal neural activity by mapping the EMG activations onto the estimated location in the spinal cord based on innervation relationships between muscles and spinal segments (Fig. 1A-2). We then broke down the spinal activities into fundamental units of the activity generated by each locomotor module (i.e., muscle synergy) (Fig. 1A-3). We found that the reconstructed spinal activity patterns were divided into the following three patterns depending on the locomotion speed: slow walking, fast walking and running (Fig.1B, the first column). During these three activation patterns, the activity in rostral segments was more increased than that in caudal segments as speed increased. Additionally, the different spinal activation patterns were generated by distinct combinations of locomotor modules (Fig.1B, second and subsequent columns). Most modules newly recruited in fast walking and running were activated by the upper lumbar segments.

Figure 1. (A) Procedures of reconstruction of spinal activity patterns from surface EMG signals. (B) Reconstructed spinal activity patterns (the first column) are divided into several locomotor modules (second and subsequent columns from the left) at slow walking, fast walking and running. The locomotor modules were obtained by non-negative matrix factorization method. Muscle weighting component (top bars) and its corresponding temporal pattern component (the same color waveform) for each locomotor module is also shown in the figure.

To summarize the results, we found the following spinal activation patterns regarding speed control of human locomotion: (i) spinal activity in the rostral segments increased compared with the caudal segments with increasing locomotion speed; and (ii) the different spinal activation patterns recruited distinct combinations of locomotor modules. These results are consistent with the speed control characteristics of vertebrate CPGs. This commonality supports a hypothesis that basic locomotor neural circuits are highly conserved among in humans, mammals, and birds over vertebrate evolution. Our results provide fascinating insight into not only human locomotor control but also the evolution of vertebrate locomotion.

Publication

Yokoyama H, Ogawa T, Shinya M, Kawashima N, Nakazawa K (2017). Speed dependency in α-motoneuron activity and locomotor modules in human locomotion: indirect evidence for phylogenetically conserved spinal circuits. Proc Roy Soc B. 284(1851), 20170290. doi: 10.1098/rspb.2017.0290.
Link: http://dx.doi.org/10.1098/rspb.2017.0290

About the Author

Multiple sclerosis (MS) is characterized by central nervous system white matter lesions that affect people’s ability to move independently. Further, people with MS often report significant asymmetries in muscle strength and function in the left versus the right leg. These are often associated with increased postural sway (i.e. worse balance) and less symmetrical stepping patterns during walking (i.e. worse walking). It is no surprise that such lower limb asymmetries are frequently associated with poorer balance control, falls, and reduced quality of life. Currently there is limited understanding as to why these limb asymmetries exist in MS and which areas within the central nervous system contribute to these mobility-limiting issues. It is also unknown whether improving these lower limb asymmetries may concomitantly improve balance and mobility during activities of daily living.

To address these questions, participants stood on a platform and tried to maintain their balance while the  platform continually slid forward and backward at a fixed frequency of differing amplitudes. We measured their ability to anticipate changes in direction (i.e. temporal performance) and their ability to control the amplitude of sway (i.e. spatial performance) with repeated exposures to this moving platform. To understand the neural underpinnings of postural motor learning, we correlated the acquisition and retention of practice-related improvements in postural control to brain white matter microstructural integrity acquired via diffusion weighted magnetic resonance images using a tract-based spatial statistical approach. Despite having worse postural control than control participants, those with MS exhibited improvements in temporal performance (over one day of practice) and retention (ability to maintain improvements 24 hours later) in a similar manner as control participants. Improvements in temporal performance were directly correlated to microstructural integrity of white matter tracts in the corpus callosum, posterior parieto-sensorimotor fibers and the brainstem in people with MS. Within the corpus callosum, fibers connecting the primary motor cortices (red fibers in Figure 1)were most strongly correlated to temporal improvements in postural control, in contrast to those connecting pre-supplementary or supplementary motor areas (yellow and orange fibers in Figure 1).

For movements that require precise coordination between the two sides of the body (e.g. walking, postural control of balance, typing) a delicate balance of excitation and inhibition is required between the right and left sensorimotor cortices. This interhemispheric communication is principally accomplished through the corpus callosum. Reduced quality of the corpus callosum is common in people with MS and has been directly related to poorer communication between the two sides of the brain and upper extremity motor performance. We suggest that impairments in gait and balance control are also, at least in part, a result of reduced structure and altered communication between the two sides of the brain in people with MS. However, our understanding of how changes in communication between the two sides of the brain contribute to lower limb asymmetries and the resultant declines in mobility for those with MS remains incomplete.

Figure 1 – Interhemispheric white matter fiber tracts connecting the right and left pre-supplementary motor areas (yellow), supplementary motor areas (orange), and primary motor cortices (red).

Copyright:

The ISPGR blog applied Creative Commons Attribution-ShareAlike 4.0 International (CC BY-SA 4.0) license to figure and text of the article.

https://creativecommons.org/licenses/by-sa/4.0/

Publication:

Daniel S. Peterson, Geetanjali Gera, Fay B. Horak, Brett W. Fling. Corpus Callosum Structural Integrity Is Associated With Postural Control Improvement in Persons With Multiple Sclerosis Who Have Minimal Disability. Neurorehabilitation and Neural Repair, Vol 31, Issue 4, pp. 343 – 353

http://journals.sagepub.com/doi/abs/10.1177/1545968316680487

About the Author

Falls are increasingly prevalent with advancing age and the consequences are often devastating, resulting in loss of independence, institutionalization and premature mortality. Evidence supports impairments in cognitive functions, specifically executive functions, as major contributors to falls. Worse performance on dual-task assessments that involve executive functions, such as walking while performing an attention demanding task, predict falls in non-demented older adults. The prefrontal cortex (PFC), a key structure for performing executive functions, also plays a vital role in control of cognition and mobility, indicating its important role in fall risk. Although the PFC is recognized as a potentially important contributor to falls, conventional neuroimaging techniques cannot image the brain during motion, leaving a gap in the understanding of underlying neural processes that might predict fall risk, and necessitated the use of newer approaches that can be used to study people while they walk, such as the functional Near Infrared Spectroscopy (fNIRS).

The primary goal of the study was to determine whether brain activity in the PFC measured during walking predicts falls in high-functioning older adults. We selected a high-functioning group of community-dwelling older adults enrolled in a prospective aging study at Albert Einstein College of Medicine to evaluate early brain activation changes that predict falls. Task-related changes in oxygen levels in the PFC were measured using fNIRS during single-task conditions (normal pace walking and standing while reciting alternate letters of the alphabet), and a dual-task condition (walking while reciting alternate letters of the alphabet). Over the 50-month study period 71 of the 166 participants reported 116 falls. People who had increases in brain activity levels during the dual-task condition were 32 percent more likely to fall. Brain activity levels during both the cognitive or motor single task conditions did not predict fall risk.

These findings provide evidence that brain activity patterns during cognitively demanding assessments predict falls in older adults and may not be elicited by more simple tasks. From a clinical perspective, these findings suggest that there may be changes in brain activity before visible signs of clinical dysfunction and physical symptoms manifest in high-functioning people who are at risk of falls. In the future, a brain scan assessment such as fNIRS might be used to help predict falls in older adults. Clinicians may be able to use this information to recommend behavioral and lifestyle modifications or treatments for their patients that may reduce the risk of future falls.

Figure 1. Participant completing fNIRS assessment.

Publication:

Verghese J, Wang C, Ayers E, Izzetoglu M, Holtzer R. Brain activation in high-functioning older adults and falls Prospective cohort study. Neurology. 2017 Jan 10;88(2):191-7. http://www.neurology.org/content/88/2/191

About the Author

When standing or walking, we often perform additional cognitive tasks such as talking, reading or listening to a friend.  This “dual tasking” is critical to the completion of activities of daily living.  Dual-tasking often results in reduced performance in one or both tasks, especially in older adults. The observation that dual tasking comes at a “cost” to performance means that the involved tasks use shared brain networks. Strategies designed to increase brain network excitability and/or efficiency thus hold great promise to improve dual task capacity across the lifespan. Transcranial direct current stimulation (tDCS) is one safe and non-invasive method that uses low-level electrical currents to temporarily change brain excitability. The purpose of this experiment was to determine the immediate effects of tDCS on dual task balance performance in older adults.

Thirty-seven adults aged 60-85 years completed two laboratory visits separated by one week.  They received 20-minutes of tDCS during each visit. On one visit, they received tDCS designed to increase the excitability of the left dorsolateral prefrontal cortex—a region closely linked to cognition and motor control.  On the other visit, they received “sham,” (i.e. placebo) stimulation.  Participants and study personnel were blinded to tDCS condition.  Before and after each tDCS session, participants completed a dual task paradigm comprising trials of standing and walking both with and without performance of a mental arithmetic task.  The Figure below illustrates the effects of tDCS on single- and dual-task standing postural sway in a selected participant.  Results indicated that real tDCS reduced the dual task cost to both standing postural sway area and walking speed compared to sham stimulation. It also effectively mitigated the cost of walking on performance within the serial subtraction task. Intriguingly, tDCS did not alter standing, walking, or serial-subtraction performance within single task conditions. The reduction in dual task costs was instead spurred by significantly improved performance in each outcome specifically within dual task conditions.

This study demonstrated for the first time that dual tasking performance can be enhanced by modulating prefrontal brain excitability using non-invasive electrical brain stimulation. These results suggest that following just 20 minutes of stimulation, older adults may be able to more safely stand and walk while completing additional, unrelated cognitive tasks.  These results also suggest that the cost of dual tasking is not a fixed, obligatory consequence of aging, and identify tDCS as a novel approach to preserving dual tasking and balance into old age.

Publication

Manor B, Zhou J, Jor’dan A, Zhang J, Fang J, Pascual-Leone A. (2016). Reduction of dual-task costs by noninvasive modulation of prefrontal activity in healthy elders. Journal of Cognitive Neuroscience. Doi: 10.1162/jocn_a_00897.
https://www.ncbi.nlm.nih.gov/pubmed/26488591

About the Author