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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37NS012542-37
Application #
8081057
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Ludwig, Kip A
Project Start
1978-09-30
Project End
2013-05-31
Budget Start
2011-06-01
Budget End
2012-05-31
Support Year
37
Fiscal Year
2011
Total Cost
$631,048
Indirect Cost
Name
University of Washington
Department
Physiology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Lajoie, Guillaume; Krouchev, Nedialko I; Kalaska, John F et al. (2017) Correlation-based model of artificially induced plasticity in motor cortex by a bidirectional brain-computer interface. PLoS Comput Biol 13:e1005343
Eaton, Ryan W; Libey, Tyler; Fetz, Eberhard E (2017) Operant conditioning of neural activity in freely behaving monkeys with intracranial reinforcement. J Neurophysiol 117:1112-1125
Seeman, Stephanie C; Mogen, Brian J; Fetz, Eberhard E et al. (2017) Paired Stimulation for Spike-Timing-Dependent Plasticity in Primate Sensorimotor Cortex. J Neurosci 37:1935-1949
Weaver, Kurt E; Wander, Jeremiah D; Ko, Andrew L et al. (2016) Directional patterns of cross frequency phase and amplitude coupling within the resting state mimic patterns of fMRI functional connectivity. Neuroimage 128:238-251
Nishimura, Yukio; Perlmutter, Steve I; Eaton, Ryan W et al. (2013) Spike-timing-dependent plasticity in primate corticospinal connections induced during free behavior. Neuron 80:1301-9
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
Lucas, Timothy H; Fetz, Eberhard E (2013) Myo-cortical crossed feedback reorganizes primate motor cortex output. J Neurosci 33:5261-74
Fetz, Eberhard E (2013) Volitional control of cortical oscillations and synchrony. Neuron 77:216-8
Richardson, Andrew G; Fetz, Eberhard E (2012) Brain state-dependence of electrically evoked potentials monitored with head-mounted electronics. IEEE Trans Neural Syst Rehabil Eng 20:756-61
Seki, Kazuhiko; Fetz, Eberhard E (2012) Gating of sensory input at spinal and cortical levels during preparation and execution of voluntary movement. J Neurosci 32:890-902

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