Project Summary – Restoring Sight to the Blind: Neural Imaging with Retinal Prostheses Retinal prostheses restore sight to the blind by electrically stimulating still viable cells in the retina. These devices consist of a microstimulator array attached to the retina that is driven by video input from a glasses-mounted camera. Retinal prostheses have been shown to restore basic visual functions such as the recognition of shapes and rudimentary navigation. However, patients show significant variability in visual skills, and currently fall short of expected visual capabilities. The postdoctoral research proposed in this study focuses on explaining these patient limitations by investigating the sensory reorganization that occurs during blindness. Neural reorganization during blindness enables auditory and tactile tasks to be processed in visual brain regions. This type of reorganization in brain sensory regions was shown to be a key limiting factor in the use of the cochlear implant for artificial audition. In Aims 1 and 2 of this proposal, Dr. Noelle Stiles will evaluate blindness- induced cortical reorganization and adaptation with neural imaging in retinal prosthesis patients, which in turn could allow for better selection of patients for visual restoration. Dr. Stiles’ postdoctoral work is also focused on investigating the interaction of artificial vision with the natural senses, such as audition. Her research has already shown that artificial vision influences auditory localization in ways similar to natural vision’s influence on audition. In Aim 3, she will expand this research to determine whether enhanced auditory and tactile perception developed during blindness are retained or reduced following the restoration of vision. This project will provide a more complete understanding of blind brain reorganization and the effects of artificial vision. Aim 1 will be completed during the K99 phase (pilot data collection is complete). Aims 2 and 3 will continue through the K99 and R00 phases, allowing for fellow training and data piloting. The proposed research is designed to prepare Dr. Stiles for successful transition to a tenure- track faculty position. She will receive training in structural neural imaging data collection, processing, and visualization from Prof. Yonggang Shi. She will also be trained in ophthalmological retinal imaging by her principal mentor Prof. Vivek R. Patel at USC, and in biomedical engineering by her co-mentor Prof. James D. Weiland at the University of Michigan. All of these fields are critical to the study of visual prostheses. She will be mentored by an advisory committee including Profs. Mark S. Humayun, Arthur W. Toga, and Yonggang Shi. Both USC and Michigan have retinal prosthesis implantation and behavioral testing programs involving clinicians, engineers, and visual neuroscientists, in addition to state of the art neuroimaging facilities, making them ideal locations for this research.

Project Narrative Retinal prostheses restore limited visual perception to the blind by stimulating still viable cells in the eye with an implanted device, particularly for patients with Retinitis Pigmentosa (RP) and potentially Age-Related Macular Degeneration (AMD). We will investigate whether the sensory reorganization that occurs during blindness limits the restoration of vision with intraocular retinal prostheses, which may have implications for emerging alternative approaches such as stem cells and gene therapy as well. This study will advance the understanding of how the brain adapts to vision loss and subsequent vision restoration, which are key to improving patient selection, therapeutic choice, and visual rehabilitation outcomes.