This career development proposal aims at providing the investigator, Dr. Truccolo, with the required experimental expertise for an independent research career in sensorimotor neurophysiology. Dr. Truccolo's goal is to integrate his background in statistical and computational modeling with active experimental work in neurophysiology to investigate the function of interacting cortical networks. The training program is designed to further the understanding of the role of fronto-parietal sensorimotor loops in the online control of voluntary movements. Specifically, the proposed research will test several experimental predictions of a computational model whose hypotheses are: 1) that primary motor cortex (M1) corrects for visual and mechanical perturbations of reaching movements, based on a motor error computed in parietal cortex (5d); and 2) that when visual feedback about the arm is unavailable, 5d uses a forward model prediction of the hand position, derived from proprioceptive feedback and motor commands received from M1, in order to compute the motor error. Unique intracortical recording technology using two 10X10 electrode-arrays will record the activities of cell ensembles and local field potentials (LFPs) in M1 and 5d as monkeys correct for transient visual and mechanical perturbations of reaching movements. A 2-link robot arm will be employed to deliver mechanical perturbations. Statistical methods recently developed by the investigator will be used to test for the existence of predicted sensory, motor and error signals as well as for predicted interactions between M1 and 5d during corrective movements. The training program will be conducted under the mentorship of Dr. Donoghue in the Department of Neuroscience at Brown University. The mentor and the environment are ideally suited: Brown is a well-known center for neuro-technology and systems neuroscience, and Dr. Donoghue is a leading expert in sensorimotor systems, multielectrode neurophysiology, and neural prostheses. In addition to training in experimental neurophysiology, activities will include training in translational neuroscience involving an ongoing clinical trial of cortical neuroprosthetic devices. The proposed program will form the basis for a research career whose long term goals include: 1) shedding new light on the mechanisms underlying movement disorders arising from pathologies of fronto-parietal networks, and 2) the design of cortical neuroprosthetic devices that incorporate sensory feedback in the online closed-loop control of robotic limbs.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Scientist Development Award - Research & Training (K01)
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NST-2 Subcommittee (NST)
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Chen, Daofen
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Brown University
Schools of Medicine
United States
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Heitmann, Stewart; Rule, Michael; Truccolo, Wilson et al. (2017) Optogenetic Stimulation Shifts the Excitability of Cerebral Cortex from Type I to Type II: Oscillation Onset and Wave Propagation. PLoS Comput Biol 13:e1005349
Aghagolzadeh, Mehdi; Truccolo, Wilson (2016) Inference and Decoding of Motor Cortex Low-Dimensional Dynamics via Latent State-Space Models. IEEE Trans Neural Syst Rehabil Eng 24:272-82
Lu, Yao; Truccolo, Wilson; Wagner, Fabien B et al. (2015) Optogenetically induced spatiotemporal gamma oscillations and neuronal spiking activity in primate motor cortex. J Neurophysiol 113:3574-87
Wagner, Fabien B; Truccolo, Wilson; Wang, Jing et al. (2015) Spatiotemporal dynamics of optogenetically induced and spontaneous seizure transitions in primary generalized epilepsy. J Neurophysiol 113:2321-41
Harrison, Matthew T; Amarasingham, Asohan; Truccolo, Wilson (2015) Spatiotemporal conditional inference and hypothesis tests for neural ensemble spiking precision. Neural Comput 27:104-50
Milekovic, Tomislav; Truccolo, Wilson; GrĂ¼n, Sonja et al. (2015) Local field potentials in primate motor cortex encode grasp kinetic parameters. Neuroimage 114:338-55
Park, Yun S; Hochberg, Leigh R; Eskandar, Emad N et al. (2014) Early detection of human focal seizures based on cortical multiunit activity. Conf Proc IEEE Eng Med Biol Soc 2014:5796-9
Aghagolzadeh, Mehdi; Truccolo, Wilson (2014) Latent state-space models for neural decoding. Conf Proc IEEE Eng Med Biol Soc 2014:3033-6
Truccolo, Wilson; Ahmed, Omar J; Harrison, Matthew T et al. (2014) Neuronal ensemble synchrony during human focal seizures. J Neurosci 34:9927-44
Menzer, David L; Rao, Naveen G; Bondy, Adrian et al. (2014) Population interactions between parietal and primary motor cortices during reach. J Neurophysiol 112:2959-84

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