A general concern in functional electrical stimulation (FES) is the changes in the extracellular microenvironment that accompany long-term electrical stimulation that can give rise to reversible and irreversible tissue damage and to neural dysfunction. In this program we will fabricate and evaluate a novel series of electrochemical biosensors for monitoring the chemical microenvironment during acute and chronic neural stimulation. These biosensors will employ electrochemical detection of the reaction products of analyte-specific enzymes incorporated in a hydrous oxide electrode matrix. They will be fabricated directly onto elements of electrode arrays currently employed in neural stimulation. These new tools will be valuable in neural prosthesis research for determining chemical imbalances which occur. Ultimately they will provide means of feedback control of artificial neural stimulation as long-lived, permanent additions to chronically implanted FES arrays. Phase I will demonstrate the feasibility of determining cerebrospinal fluid components (glucose, lactate, choline, glutamate, acetylcholine and urea) and demonstration of one or more sensors on an existing intracortical electrode array. Phase II will entail developing a wider range of improved biosensors for additional CSF components, design of optimal stimulation/biosensor microfabricated arrays, and in vivo studies of local extracellular chemistry during neural stimulation using the new microsensors.