ABSTRACT

Evoking high quality visual perception in a blind person, via direct microstimulation of the brain, poses great difficulties. One major obstacle has been that electrical stimulation of the brain typically affects neuronal populations that are mutually suppressive, which subverts proper neuronal signaling. The visual system has two antagonistic information channels that encode either the perception of lightness, in ON cells, or darkness, in OFF cells. Inappropriate coactivation of these two channels results in nullification of contrast, and deprived visual perception. It follows that high-quality prosthetic stimulation systems must avoid unwanted coactivation of mutually suppressive neurons, just as the natural visual system does. This is a challenge because the antagonistic neurons typically lie within microns of each other in the brain. The project aims at transformative advances in viral transfection and imaging methodology, computational theory, and cortical prosthetic neuroengineering design for the purpose of restoring vision by genetically modifying neurons in the brain and then stimulating them with light, a method called optogenetics. The expected results and methodology will form the scientific basis to build a breakthrough neuroprosthetic, with transformative potential to further brain research in sensory, motor, and cognitive parts of the cortex and to advance human medicine. To promote the development and availability of derived products to the public, the team will disseminate the discoveries to general audiences through public lectures and publications in popular science magazines. The investigators will supervise trainees from underrepresented groups, including postdoctoral fellows, graduate students, undergraduates, and high school students. The investigators are faculty mentors for The Children's Aid Society (CAS) Workforce Development Department Summer Youth Employment Program (SYEP), which provides summer research opportunities to disadvantaged and minority youth in NYC to inspire them to pursue STEM careers.

Recent research has shown that, for any given retinal position, the ON and OFF cell inputs to the brain's visual cortex are purely excitatory, concentrate in a specific layer, and are laid out in a pattern that can be targeted with light from outside the brain. First, the team will modify these neurons genetically, to turn them into a novel type of photoreceptor, embedded within the brain. The team will then target light stimulation to the identified ON and OFF cells, determining the precise balance of activation to either channel to generate high-quality prosthetic vision based on a video camera's signal. This technology can then be used to bypass the eye to stimulate the brain from the camera. The project aims to develop the computational model to drive an optogenetic brain stimulation system that will optimally activate neural responses in the primary visual cortex. By comparing the neuronal responses of sighted nonhuman primates viewing natural visual stimuli to prosthetic responses in the same neurons, the work will optimize stimulation patterns that evoke naturalistic visual perception. The balanced targeting of appropriate ON and OFF inputs at each position in visual space is expected to achieve maximal contrast perception at the highest attainable acuity, with full stereoscopic binocular vision. The team's computational model of spatiotemporal visual inputs into the cortex will also account for the effects of eye movements on early visual responses, a novel approach to visual prosthetics tested here for the first time.

This project is funded by Integrative Strategies for Understanding Neural and Cognitive Systems (NSF-NCS), a multidisciplinary program jointly supported by the Directorates for Computer and Information Science and Engineering (CISE), Education and Human Resources (EHR), Engineering (ENG), and Social, Behavioral, and Economic Sciences (SBE).

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