Project Summary The long-term goal of our research is to investigate mechanisms to restore and optimize facial movement in cases of facial paralysis. The specific goal of the proposed research is to develop and study the long-term feasibility of a functional electrical stimulation (FES) paradigm to restore dynamic symmetrical facial motion in a rodent model of unilateral facial palsy (UFP). We will utilize conductive polymer electrode arrays to detect normal rodent facial muscle EMG activity on one side of the face, and nerve cuff electrodes to evoke contralateral-side corresponding muscle activity. We will couple the two systems via an implantable signal acquisition and generation platform, and anticipate that digital signal processing can be applied to trigger near- simultaneous and symmetric facial movement in rodents with UFP. We will begin by establishing the relationship between EMG activity and normal rodent facial movement, and the relationship between neural stimulation and evoked facial movements, under the hypothesis that there exists a mathematical model that links electrical and functional data. We will then construct a control algorithm for online processing of EMG input signals to drive FES, to examine the hypothesis that it is possible to subjugate the movements on one side of the face to normal movements on the opposite side. Importantly, we will also introduce proximal neural blockade on the subjugated side in order to prevent undesired physiologic activation of the facial musculature, to mimic clinically relevant scenarios for the application of these devices. Finally, we plan to implement the FES paradigm using a novel implantable neuroprosthetic device powered through inductive coupling, and demonstrate that neither the device, the presence of electrodes, nor the application of electrical stimulation induces neuropathy or myopathy in the long term. Knowledge gained from this research would be of immediate impact to the implementation of an analogous system in humans suffering from UFP, and provide significant impetus for the re-establishment of motor-neuron input to preserve native facial musculature following severe facial nerve injury. Furthermore, the novel approach proposed here could be applied to other clinical scenarios – such as functional muscle and nerve transfers – where poor control and undesirable physiologic activation of a muscle occurs.