PROJECT SUMMARY Facial paralysis from stroke or other neurological disorders often causes loss of the eye-blink reflex, leading to pain and visual disability. Eyelid dysfunction leaves the eye chronically exposed, which is not only painful, but is fundamentally incompatible with functional vision. Further, because eyelid movement plays a critical role in facial expression and human communication, loss of natural eyelid motion can also have negative social and cultural implications. Unfortunately, current surgical management strategies have major limitations in both functionality and appearance. In theory, dynamic natural blink restoration via a facial neuroprosthesis would be an ideal solution; unfortunately, this ideal has proven elusive, due in large part to a lack of knowledge regarding the neurophysiological mechanisms that enable eyelid function. There is a critical need for neuroprostheses that reproduce functionally complete and aesthetically natural eye closure, blink, and other behaviors. In response to this need, our long-term goal is to advance a novel class of neuroprostheses that are informed by a deep understanding of the fundamental neuromechanics of the muscle that controls the eyelid. To achieve our long- term goal, we will first carry out fundamental neuroscientific studies to establish the currently-unknown mechanisms that link segmental muscle activation to eyelid motion and function. The innovation of this work lies in our ability to measure intramuscular activation and three-dimensional eyelid kinematics with unprecedented precision and resolution. This sets our work apart from all other prior research into eyelid function, and will allow us to develop the first predictive dynamic neuromuscular model of the eyelid. In the present work, our objective is to study the neurophysiology of how activation sequences and intensities produce blink and other eyelid behaviors under both healthy and pathological activation. We will accomplish this by first studying eyelid function in persons without paralysis during a range of eyelid behaviors, including spontaneous blink, reflexive blink, and forced closure. As the participants perform these behaviors, we will record high-resolution intramuscular EMG from multiple points within and around the eyelid, while simultaneously tracking the three-dimensional motion of several points along the eyelid margin in high definition. We will use these data to implement a mechanistic neuromuscular model of the eyelid musculature, which can then inform where and when stimulation from future neuroprostheses should be delivered. We will then repeat these experiments in a group of persons with partial facial paralysis, to study the mechanisms by which eyelid function can be compromised. Upon completion of this work, we expect to have established the mechanistic basis for model-informed facial neuroprostheses that restore natural blink. These results are expected to provide the foundation for development an...