Our overarching goal is to establish an animal model of freely moving humans. We choose to do so in order to directly measure the context-dependency of motor cortical activity and, ultimately, other activity reliant upon free movement such as social interaction among animals. Achieving this major technological challenge requires a complete system that includes (Specific Aim 1) wireless transmission of neural data from electrode arrays chronically implanted in monkeys, (Specific Aim 2) computer-vision algorithms to automatically extract body and limb orientation during free movement, and (Specific Aim 3) new mathematical and computational models to represent and extract information from high-dimensional neural and behavioral activity. This technology will enable an animal model of freely moving humans that will advance the development of cortical neural prostheses by providing models of the context-dependant nature of motor cortical control. Unlike traditional laboratory environments used to study animal movement, human amputees and tetraplegics operate in a variety of contexts that involve their movement in the world. Understanding the motor control of complex movement in these natural settings is absolutely critical for future advances in cortically- controlled prostheses. Given our overarching goal, our hypothesis is that motor cortical activity (e.g., directional tuning curves, absolute firing rates, correlations among units, etc.) will be different in important ways when rhesus monkeys perform the same reaching arm movements in an un-constrained context (e.g., not sitting quietly, not head restrained, not in dark and quiet room, etc.) as in a traditional, highly constrained context. Our three Specific Aims will put in place the electronic, computational and mathematical technology necessary to address this hypothesis, and also to make such studies of free behavior in rhesus monkeys possible. The innovative integration of neural engineering, neuroscience, computer vision, mathematics and neural modeling will provide new tools to enable the unprecedented study of motor control during natural, unconstrained behavior.

Public Health Relevance

The proposed research project is directly relevant to both basic neuroscience studies of higher brain function and to neural prosthesis research aimed at, ultimately, helping patients with motor disorders. We will conduct neurophysiological and behavioral experiments with rhesus monkeys in two different contexts - in home cage and in rig - to investigate the context dependence of motor cortical activity. With this knowledge, we will then design context independent models of the neural-behavioral relationship which we, and other researchers, could then use in neural prosthetic experiments while monkeys freely move around their less- constrained home cages.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS066311-02
Application #
7883275
Study Section
Special Emphasis Panel (ZMH1-ERB-L (05))
Program Officer
Chen, Daofen
Project Start
2009-07-01
Project End
2013-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
2
Fiscal Year
2010
Total Cost
$303,756
Indirect Cost
Name
Stanford University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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Kao, Jonathan C; Nuyujukian, Paul; Ryu, Stephen I et al. (2017) A High-Performance Neural Prosthesis Incorporating Discrete State Selection With Hidden Markov Models. IEEE Trans Biomed Eng 64:935-945
Willett, Francis R; Murphy, Brian A; Memberg, William D et al. (2017) Signal-independent noise in intracortical brain-computer interfaces causes movement time properties inconsistent with Fitts' law. J Neural Eng 14:026010
Pandarinath, Chethan; Nuyujukian, Paul; Blabe, Christine H et al. (2017) High performance communication by people with paralysis using an intracortical brain-computer interface. Elife 6:
Willett, Francis R; Pandarinath, Chethan; Jarosiewicz, Beata et al. (2017) Feedback control policies employed by people using intracortical brain-computer interfaces. J Neural Eng 14:016001
Nuyujukian, Paul; Fan, Joline M; Kao, Jonathan C et al. (2015) A high-performance keyboard neural prosthesis enabled by task optimization. IEEE Trans Biomed Eng 62:21-29
Pandarinath, Chethan; Gilja, Vikash; Blabe, Christine H et al. (2015) Neural population dynamics in human motor cortex during movements in people with ALS. Elife 4:e07436
Gilja, Vikash; Pandarinath, Chethan; Blabe, Christine H et al. (2015) Clinical translation of a high-performance neural prosthesis. Nat Med 21:1142-5
Blabe, Christine H; Gilja, Vikash; Chestek, Cindy A et al. (2015) Assessment of brain-machine interfaces from the perspective of people with paralysis. J Neural Eng 12:043002
Jarosiewicz, Beata; Sarma, Anish A; Bacher, Daniel et al. (2015) Virtual typing by people with tetraplegia using a self-calibrating intracortical brain-computer interface. Sci Transl Med 7:313ra179

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