Volitional Control of the Nonhuman Primate Lower Limbs - SUMMARY The ability to modify ongoing gait with precise, voluntary adjustments is what allows animals to navigate complex terrains and to execute skilled actions during ongoing pursuits. However, how the nervous system generates the signals to precisely control the lower limbs while simultaneously maintaining ongoing locomotion is still poorly understood. While there is some consensus in the role of spinal cord (SC) central pattern generators (CPGs) in the maintenance of locomotion, little is known about the role of primary motor cortex (M1), especially in the case of volitional adjustments to ongoing locomotion movements. Our own work suggests that M 1 plays at least a dual role in both the monitoring and the adjustment of the hindlimbs during locomotor adjustments, expressed in different subspaces (manifolds) of its neuronal spiking activity. We hypothesize that the emergence of these distinct neural subspaces plays a critical role in the dynamic sensorimotor cortical control of locomotion. Specifically, the emergence of distinct low-dimensional subspaces allows M1 to track sensed ongoing locomotion states, which are primarily driven by spinal-cord CPGs, and to generate occasional descending motor commands to drive volitional adjustments without destructive interference. Besides the basic neuroscience relevance, fully understanding the role of M1 in modulating locomotion is essential for the development of new mobility therapies, including brain-machine interfaces (BMls), for restoring walking and volitional leg control in people with paralysis. We have recently developed a new experimental paradigm to test these hypotheses in nonhuman primates. It enables wireless recordings from microelectrode arrays implanted in multiple sensorimotor cortical areas during natural locomotion and navigation around obstacles visually cued on a treadmill and other spaces. In addition to M 1, we plan to simultaneously record primary sensorimotor cortex (S1) and lower limb electromyography (EMG), while actively probing M1-S1-SC interactions via cortical and spinal electrical stimulation. There are 3 specific aims. AIM 1: To test the hypothesis that information streams necessary for the control of ongoing locomotion and volitional adjustments are coordinated in motor cortex activity via the emergence of distinct neural subspaces. AIM 2: To test the hypothesis that specific subspaces emerge to coordinate the bidirectional interactions between M 1 and S 1 during sensorimotor control of ongoing locomotion and volitional adjustments. Finally, we have previously shown that neural decoders trained on ongoing locomotion do not generalize to the decoding of volitional adjustments, thus motivating AIM 3: To develop adaptive BM I neural decoding approaches for locomotion under distinct regimes of sensorimotor cortical control. PUBLIC/HEALTH/RELEVANCE: This research's long-term goal is the restoration of movement in people with paralysis. The project will advance the understanding of sensorimotor control of locomotion and lead to better BM Is for restoring walking ability in humans with spinal cord injury due to partial damage of ascending and descending pathways.
