Brain-computer interfaces (BCI) can assist paralyzed individuals and amputees by translating their neural activity into movements of a BCI plant, such as a computer cursor or prosthetic limb. For many years, the field sought offline decoders that could best map neural activity to arm movements. It has become increasingly recognized that designing an effective online, closed-loop decoder is quite a different challenge. A key difference is that, in a closed-loop setting, the subject receives sensory feedback about the state of the BCI plant and can compensate for errors by generating new neural activity patterns. To engineer clinically-viable, closed-loop BCI systems, many fundamental questions about the neural underpinnings of their performance must be answered. Can subjects generate arbitrary neural activity patterns to compensate for errors? Do subjects form an internal model of the BCI plant to achieve proficient control in the presence of noisy, delayed feedback? Do subjects exploit the redundancy inherent in the mapping from neural activity to BCI plant kinematics to maximize control accuracy? A critical roadblock for answering these questions is the lack of an appropriate statistical framework to rigorously analyze closed-loop BCI data on a timestep-by-timestep basis. We propose to develop such a framework inspired by control theory, in close conjunction with novel closed-loop BCI experiments. We will train non-human primates to perform dextrous control of a BCI cursor using neural activity recorded in primary motor cortex with chronic, multi-electrode arrays. We will test the hypothesis that BCI learning depends on constraints imposed by the underlying neural circuitry. In parallel, we will develop and validate algorithms to explain the observed, high-dimensional neural activity at each timestep by accounting for the sensory feedback, subject's internal model of the BCI cursor, and behavioral task goals. We will then leverage the developed algorithms to investigate whether subjects can exploit neural redundancy during BCI control. Broader Impact: We envision five areas of broader impact. First, BCI systems promise to dramatically improve the quality of life for disabled patients. Clinical trials are ongoing, so opportunities exist to translate our research directly and in the near term into clinical practice. Second, our understanding of the neural basis for arm movement control is still incomplete, in large part because the system is so complex. BCIs provide a simplified motor control system, where a well-defined relationship exists between neural activity and movement. As such, BCIs provide a novel experimental testbed to investigate the neural mechanisms of motor control and learning. Third, the statistical framework we develop may be applicable to the study of feedback control systems in other domains. Fourth, with the advent of large-scale neural recordings, systems neuroscience is becoming a far more quantitative field. The next generation of researchers must be well-versed in computational and biological principles. We believe that our collaboration provides an excellent dual-training environment for our students and postdocs. Fifth, our research discoveries can directly feed into our classroom teaching. Yu teaches Neural Signal Processing at CMU and Batista teaches Control Theory in Neuroscience at Pitt;both are annual, graduate-level courses. Intellectual Merit: In the last decade, several groups have demonstrated compelling proof-of- concept laboratory demonstrations of closed-loop BCI control. For clinical translation, one of the major challenges is to improve the performance and robustness of BCI systems. To make this leap, we believe that it is critical to rigorously study existing systems to understand i) why some BCI decoders work better than others, ii) to what extent we can depend on the subjects'ability to learn, and iii) the neural strategies adopted by the subjects for proficient control. There is a long-overdue need for a general statistical framework for dissecting closed-loop BCI data, which we propose to develop. Discoveries enabled by the developed methods will help us and others in the field to design high-performance, clinically-viable BCI systems that allow the subject to quickly reach and maintain a high level of proficiency.

Public Health Relevance

To bring proof-of concept laboratory demonstrafions of BCI systems to widespread clinical use, it is crifical to improve their performance and robustness. Discoveries stemming from the proposed work will help us and others in the field to design clinically-viable BCI systems that allow the subject to quickly reach and maintain a high level of proficiency.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-IFCN-B (50))
Program Officer
Shinowara, Nancy
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Carnegie-Mellon University
Engineering (All Types)
Schools of Engineering
United States
Zip Code
Hennig, Jay A; Golub, Matthew D; Lund, Peter J et al. (2018) Constraints on neural redundancy. Elife 7:
Snyder, Adam C; Yu, Byron M; Smith, Matthew A (2018) Distinct population codes for attention in the absence and presence of visual stimulation. Nat Commun 9:4382
Golub, Matthew D; Sadtler, Patrick T; Oby, Emily R et al. (2018) Learning by neural reassociation. Nat Neurosci 21:607-616
Oby, Emily R; Perel, Sagi; Sadtler, Patrick T et al. (2016) Extracellular voltage threshold settings can be tuned for optimal encoding of movement and stimulus parameters. J Neural Eng 13:036009
Degenhart, Alan D; Eles, James; Dum, Richard et al. (2016) Histological evaluation of a chronically-implanted electrocorticographic electrode grid in a non-human primate. J Neural Eng 13:046019
Golub, Matthew D; Chase, Steven M; Batista, Aaron P et al. (2016) Brain-computer interfaces for dissecting cognitive processes underlying sensorimotor control. Curr Opin Neurobiol 37:53-58
Golub, Matthew D; Yu, Byron M; Chase, Steven M (2015) Internal models for interpreting neural population activity during sensorimotor control. Elife 4:
Perel, Sagi; Sadtler, Patrick T; Oby, Emily R et al. (2015) Single-unit activity, threshold crossings, and local field potentials in motor cortex differentially encode reach kinematics. J Neurophysiol 114:1500-12
Lakshmanan, Karthik C; Sadtler, Patrick T; Tyler-Kabara, Elizabeth C et al. (2015) Extracting Low-Dimensional Latent Structure from Time Series in the Presence of Delays. Neural Comput 27:1825-56
Sadtler, P T; Ryu, S I; Tyler-Kabara, E C et al. (2015) Brain-computer interface control along instructed paths. J Neural Eng 12:016015

Showing the most recent 10 out of 21 publications