We will investigate the neural mechanisms controlling voluntary hand and arm movement in primates. The functional roles of neurons in primary motor cortex and spinal cord will be directly compared. The activity of premotor (PreM) cells (identified by correlational linkages to forelimb motoneurons) and multiple muscles will be documented during multidirectional wrist movements and grip. This repertoire of movements will activate muscles in different synergistic combinations and test the degree to which PreM cells and non-PreM cells are organized in terms of muscles and movement parameters. Spinal interneurons will be identified by their synaptic inputs from different forelimb muscles and from functionally identified cortical sites. The results should reveal significant differences between motor cortex cells and spinal interneurons. We will further investigate the involvement of spinal cord interneurons in preparation and execution of voluntary movements in a two-dimensional instructed delay task. We will also investigate the movements of arm and hand evoked by electrical stimulation of spinal cord sites;the modulations of these responses during an instructed delay task will reveal the interaction of intraspinally evoked responses with preparation and execution of voluntary movements. To obtain information important for the use of neural activity to control brain-computer interfaces [BCI] we will systematically investigate the volitional control of identified neurons in different cortical areas using biofeedback training. The correlated responses in other cortical cells and muscles will be documented to determine the extent and variability of correlated activity. A novel chronically implanted recurrent BCI will be used to investigate the consequences of directly linking cortical cell activity to stimuli delivered in motor cortex, spinal cord and muscles. .An implanted computer chip will allow long-term monitoring of cell and muscle activity during unrestrained behavior and will test the monkeys'adaptation to continuous operation of recurrent circuits. The recurrent BCI will be used to test the feasibility of directly controlling functional electrical stimulation of muscles with activity of motor cortex cells. These studies of the primate motor system will provide unique information essential to understanding and effectively treating clinical motor disorders, like cerebral palsy, stroke and spinal cord injury. Results with the implanted recurrent BCI will have significant consequences for development of prosthetic applications.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Method to Extend Research in Time (MERIT) Award (R37)
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Sensorimotor Integration Study Section (SMI)
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Ludwig, Kip A
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University of Washington
Schools of Medicine
United States
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Zanos, Stavros; Rembado, Irene; Chen, Daofen et al. (2018) Phase-Locked Stimulation during Cortical Beta Oscillations Produces Bidirectional Synaptic Plasticity in Awake Monkeys. Curr Biol 28:2515-2526.e4
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Nishimura, Yukio; Perlmutter, Steve I; Fetz, Eberhard E (2013) Restoration of upper limb movement via artificial corticospinal and musculospinal connections in a monkey with spinal cord injury. Front Neural Circuits 7:57
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