Brainstem Circuits for Locomotion

Locomotion is a universal motor behavior that is expressed as the output of many integrated brain functions. Locomotion is organized at several levels of the nervous system, with brainstem circuits acting as the gate between brain areas regulating innate, emotional, or motivational locomotion and executive spinal circuits. Here we review recent advances on brainstem circuits involved in controlling locomotion. We describe how delineated command circuits govern the start, speed, stop, and steering of locomotion. We also discuss how these pathways interface between executive circuits in the spinal cord and diverse brain areas important for context-specific selection of locomotion. A recurrent theme is the need to establish a functional connectome to and from brainstem command circuits. Finally, we point to unresolved issues concerning the integrated function of locomotor control. Expected final online publication date for the Annual Review of Neuroscience, Volume 45 is July 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Mobile Electroencephalography for Studying Neural Control of Human Locomotion

Walking or running in real-world environments requires dynamic multisensory processing within the brain. Studying supraspinal neural pathways during human locomotion provides opportunities to better understand complex neural circuity that may become compromised due to aging, neurological disorder, or disease. Knowledge gained from studies examining human electrical brain dynamics during gait can also lay foundations for developing locomotor neurotechnologies for rehabilitation or human performance. Technical barriers have largely prohibited neuroimaging during gait, but the portability and precise temporal resolution of non-invasive electroencephalography (EEG) have expanded human neuromotor research into increasingly dynamic tasks. In this narrative mini-review, we provide a (1) brief introduction and overview of modern neuroimaging technologies and then identify considerations for (2) mobile EEG hardware, (3) and data processing, (4) including technical challenges and possible solutions. Finally, we summarize (5) knowledge gained from human locomotor control studies that have used mobile EEG, and (6) discuss future directions for real-world neuroimaging research.

Brain Correlates of Persistent Postural-Perceptual Dizziness: A Review of Neuroimaging Studies

Persistent postural-perceptual dizziness (PPPD), defined in 2017, is a vestibular disorder characterized by chronic dizziness that is exacerbated by upright posture and exposure to complex visual stimuli. This review focused on recent neuroimaging studies that explored the pathophysiological mechanisms underlying PPPD and three conditions that predated it. The emerging picture is that local activity and functional connectivity in multimodal vestibular cortical areas are decreased in PPPD, which is potentially related to structural abnormalities (e.g., reductions in cortical folding and grey-matter volume). Additionally, connectivity between the prefrontal cortex, which regulates attentional and emotional responses, and primary visual and motor regions appears to be increased in PPPD. These results complement physiological and psychological data identifying hypervigilant postural control and visual dependence in patients with PPPD, supporting the hypothesis that PPPD arises from shifts in interactions among visuo-vestibular, sensorimotor, and emotional networks that overweigh visual over vestibular inputs and increase the effects of anxiety-related mechanisms on locomotor control and spatial orientation.

Modelling spinal locomotor circuits for movements in developing zebrafish

Many spinal circuits dedicated to locomotor control have been identified in the developing zebrafish. How these circuits operate together to generate the various swimming movements during development remains to be clarified. In this study, we iteratively built models of developing zebrafish spinal circuits coupled to simplified musculoskeletal models that reproduce coiling and swimming movements. The neurons of the models were based upon morphologically or genetically identified populations in the developing zebrafish spinal cord. We simulated intact spinal circuits as well as circuits with silenced neurons or altered synaptic transmission to better understand the role of specific spinal neurons. Analysis of firing patterns and phase relationships helped identify possible mechanisms underlying the locomotor movements of developing zebrafish. Notably, our simulations demonstrated how the site and the operation of rhythm generation could transition between coiling and swimming. The simulations also underlined the importance of contralateral excitation to multiple tail beats. They allowed us to estimate the sensitivity of spinal locomotor networks to motor command amplitude, synaptic weights, length of ascending and descending axons, and firing behaviour. These models will serve as valuable tools to test and further understand the operation of spinal circuits for locomotion.

Tardigrades exhibit robust interlimb coordination across walking speeds and terrains

Tardigrades must negotiate heterogeneous, fluctuating environments and accordingly utilize locomotive strategies capable of dealing with variable terrain. We analyze the kinematics and interleg coordination of freely walking tardigrades (species: Hypsibius exemplaris). We find that tardigrade walking replicates several key features of walking in insects despite disparities in size, skeleton, and habitat. To test the effect of environmental changes on tardigrade locomotor control circuits we measure kinematics and interleg coordination during walking on two substrates of different stiffnesses. We find that the phase offset between contralateral leg pairs is flexible, while ipsilateral coordination is preserved across environmental conditions. This mirrors similar results in insects and crustaceans. We propose that these functional similarities in walking coordination between tardigrades and arthropods is either due to a generalized locomotor control circuit common to panarthropods or to independent convergence onto an optimal strategy for robust multilegged control in small animals with simple circuitry. Our results highlight the value of tardigrades as a comparative system toward understanding the mechanisms—neural and/or mechanical—underlying coordination in panarthropod locomotion.

Environment Classification for Robotic Leg Prostheses and Exoskeletons using Deep Convolutional Neural Networks

Robotic leg prostheses and exoskeletons can provide powered locomotor assistance to older adults and/or persons with physical disabilities. However, the current locomotion mode recognition systems being developed for intelligent high-level control and decision-making use mechanical, inertial, and/or neuromuscular data, which inherently have limited prediction horizons (i.e., analogous to walking blindfolded). Inspired by the human vision-locomotor control system, we designed and evaluated an advanced environment classification system that uses computer vision and deep learning to forward predict the oncoming walking environments prior to physical interaction, therein allowing for more accurate and robust locomotion mode transitions. In this study, we first reviewed the development of the ExoNet database – the largest and most diverse open-source dataset of wearable camera images of indoor and outdoor real-world walking environments, which were annotated using a hierarchical labelling architecture. We then trained and tested over a dozen state-of-the-art deep convolutional neural networks (CNNs) on the ExoNet database for large-scale image classification of the walking environments, including: EfficientNetB0, InceptionV3, MobileNet, MobileNetV2, VGG16, VGG19, Xception, ResNet50, ResNet101, ResNet152, DenseNet121, DenseNet169, and DenseNet201. Lastly, we quantitatively compared the benchmarked CNN architectures and their environment classification predictions using an operational metric called NetScore, which balances the image classification accuracy with the computational and memory storage requirements (i.e., important for onboard real-time inference). Although we designed this environment classification system to support the development of next-generation environment-adaptive locomotor control systems for robotic prostheses and exoskeletons, applications could extend to humanoids, autonomous legged robots, powered wheelchairs, and assistive devices for persons with visual impairments.

Developing Proprioceptive Countermeasures to Mitigate Postural and Locomotor Control Deficits After Long-Duration Spaceflight

Astronauts experience post-flight disturbances in postural and locomotor control due to sensorimotor adaptations during spaceflight. These alterations may have adverse consequences if a rapid egress is required after landing. Although current exercise protocols can effectively mitigate cardiovascular and muscular deconditioning, the benefits to post-flight sensorimotor dysfunction are limited. Furthermore, some exercise capabilities like treadmill running are currently not feasible on exploration spaceflight vehicles. Thus, new in-flight operational countermeasures are needed to mitigate postural and locomotor control deficits after exploration missions. Data from spaceflight and from analog studies collectively suggest that body unloading decreases the utilization of proprioceptive input, and this adaptation strongly contributes to balance dysfunction after spaceflight. For example, on return to Earth, an astronaut’s vestibular input may be compromised by adaptation to microgravity, but their proprioceptive input is compromised by body unloading. Since proprioceptive and tactile input are important for maintaining postural control, keeping these systems tuned to respond to upright balance challenges during flight may improve functional task performance after flight through dynamic reweighting of sensory input. Novel approaches are needed to compensate for the challenges of balance training in microgravity and must be tested in a body unloading environment such as head down bed rest. Here, we review insights from the literature and provide observations from our laboratory that could inform the development of an in-flight proprioceptive countermeasure.

An intracortical neuroprosthesis immediately alleviates walking deficits and improves recovery of leg control after spinal cord injury

Most rehabilitation interventions after spinal cord injury (SCI) only target the sublesional spinal networks, peripheral nerves, and muscles. However, mammalian locomotion is not a mere act of rhythmic pattern generation. Recovery of cortical control is essential for voluntary movement and modulation of gait. We developed an intracortical neuroprosthetic intervention to SCI, with the goal to condition cortical locomotor control. Neurostimulation delivered in phase coherence with ongoing locomotion immediately alleviated primary SCI deficits, such as leg dragging, in rats with incomplete SCI. Cortical neurostimulation achieved high fidelity and markedly proportional online control of leg trajectories in both healthy and SCI rats. Long-term neuroprosthetic training lastingly improved cortical control of locomotion, whereas short training held transient improvements. We performed longitudinal awake cortical motor mapping, unveiling that recovery of cortico-spinal transmission tightly parallels return of locomotor function in rats. These results advocate directly targeting the motor cortex in clinical neuroprosthetic approaches.

Tardigrades exhibit robust inter-limb coordination across walking speeds

Tardigrades must negotiate heterogeneous, fluctuating environments, and accordingly utilize locomotive strategies capable of dealing with variable terrain. We analyze the kinematics and inter-leg coordination of freely walking tardigrades (species: Hypsibius dujardini). We find that tardigrade walking replicates several key features of walking in insects despite disparities in size, skeleton, and habitat. To test the effect of environmental changes on tardigrade locomotor control circuits, we measure kinematics and inter-leg coordination during walking on two substrates of different stiffnesses. We find that the phase offset between contralateral leg pairs is flexible, while ipsilateral coordination is preserved across environmental conditions. This mirrors similar results in insects and crustaceans. We propose that these functional similarities in walking co-ordination between tardigrades and arthropods is either due to a generalized locomotor control circuit common to panarthropods, or to independent convergence onto an optimal strategy for robust multi-legged control in small animals with simple circuitry. Our results highlight the value of tardigrades as a comparative system towards understanding the mechanisms – neural and/or mechanical – underlying coordination in panarthropod locomotion.