Project Grant 2339748

CAREER: MULTIMODAL BIOELECTRONICS FOR CLOSED-LOOP MAPPING AND MODULATION OF NEURAL DYNAMICS AT MULTIPLE SCALES -NEUROLOGICAL DISORDERS ARE AMONG THE MOST COMMON CAUSES OF DISABILITY AND DEATH IN THE UNITED STATES AND WORLDWIDE. DESPITE THE SIGNIFICANT ECONOMIC AND SOCIETAL BURDEN, OUR CURRENT UNDERSTANDING OF NEUROLOGICAL DISORDERS IS LIMITED BY THE LACK OF TOOLS TO INVESTIGATE, CONTROL, AND RESTORE BRAIN FUNCTION WITH THE REQUIRED SPATIAL AND TEMPORAL PRECISION. THIS CAREER PROJECT WILL DEVELOP AN INNOVATIVE TECHNOLOGY TO MONITOR AND CONTROL THE ELECTRICAL, CHEMICAL, AND OPTICAL ACTIVITY OF INTACT NEURAL CIRCUITS WITH UNPRECEDENTED PRECISION. BY INTEGRATING NOVEL MATERIALS, DESIGNS, FABRICATION, AND TESTING METHODS, THIS MULTIMODAL NEURAL INTERFACE WILL HELP UNVEILING THE FUNDAMENTAL PROCESSES UNDERLYING BRAIN DISORDERS, AS WELL AS TESTING TARGETED STIMULATION AND PHARMACOLOGICAL INTERVENTIONS. THE KNOWLEDGE AND METHODOLOGICAL ADVANCES GENERATED IN THIS PROJECT WILL ALSO ENABLE THE DEVELOPMENT OF NEW NEUROPROSTHETIC AND NEUROMODULATION DEVICES WITH LONG-TERM STABILITY, SAFETY, AND FUNCTIONALITY. THE RESEARCH OBJECTIVES OF THIS PROJECT ARE INTEGRATED WITH EDUCATIONAL AND OUTREACH ACTIVITIES INCLUDING ESTABLISHING A TEACHING AND RESEARCH CURRICULUM IN BIOELECTRONICS FOR UNDERGRADUATE STUDENTS; OUTREACH, TRAINING, AND HANDS-ON EXPERIENCES IN ENGINEERING RESEARCH FOR K-12 STUDENTS FROM DISADVANTAGED LOCAL COMMUNITIES. THE BRAIN FUNCTION RELIES ON THE PERFECTLY ORCHESTRATED INTERPLAY BETWEEN NEUROTRANSMISSION AND ELECTROPHYSIOLOGICAL ACTIVITY. UNDERSTANDING THE DYNAMICS GOVERNING NEUROTRANSMITTER RELEASE/UPTAKE AND ELECTROPHYSIOLOGY IS CRITICAL TO REVEAL THE FUNDAMENTAL MECHANISMS BEHIND FUNCTION, BEHAVIOR, AND NEUROLOGICAL DISORDERS, AND TO INFORM THE DESIGN OF EFFECTIVE THERAPEUTIC INTERVENTIONS. HOWEVER, THERE IS A CRITICAL KNOWLEDGE GAP IN OUR UNDERSTANDING OF BRAIN FUNCTION AND DISEASE, WHICH RESULTS FROM THE LACK OF BIOELECTRONIC TECHNOLOGIES AND MATERIALS FOR SAFELY AND EFFECTIVELY INTERFACING WITH NEURAL CIRCUITS ACROSS MODALITIES AND SCALES. TO GOAL OF THIS CAREER PROJECT IS TO DEVELOP NOVEL MULTIMODAL DEVICES FOR SIMULTANEOUS ELECTROPHYSIOLOGY, NEUROCHEMISTRY, AND OPTICAL MAPPING OF NEURONAL CIRCUITS IN VIVO AND AT MULTIPLE SCALES. TO ACHIEVE THIS GOAL THE INVESTIGATOR WILL ADOPT A MULTIDISCIPLINARY APPROACH COMBINING NOVEL BIOELECTRONIC MATERIALS AND FABRICATION METHODS WITH CUSTOM WIRELESS CONTROLLERS AND SURGICAL PREPARATIONS FOR IN VIVO CLOSED-LOOP RECORDING, IMAGING, AND CONTROL OF NEURAL ACTIVITY. THE RESEARCH ACTIVITIES OF THE PROJECT ARE ORGANIZED IN THREE MAIN OBJECTIVES: 1) DESIGN, FABRICATION, AND CHARACTERIZATION OF A MULTIMODAL NEURAL INTERFACE BASED ON NANOSCALE SOFT CONDUCTORS AND CUSTOM FABRICATION PROCESSES; 2) ESTABLISH IN VIVO SAFETY AND LONG-TERM FUNCTIONALITY OF THE MULTIMODAL DEVICES; 3) INVESTIGATE AND CONTROL THE DYNAMICS OF NEURAL CIRCUITS IN VIVO WITH MULTIMODAL MAPPING AND RESPONSIVE STIMULATION. THIS PROJECT BUILDS ON THE INVESTIGATOR EXPERTISE AND MULTIDISCIPLINARY RESEARCH PROGRAM ON ENGINEERED MATERIALS AND BIOELECTRONICS FOR BASIC AND TRANSLATIONAL NEUROSCIENCE. BY DEVELOPING A NOVEL TOOL TO MAP AND MODULATING NEURAL CIRCUITS ACROSS MULTIPLE DOMAINS AND SCALES SIMULTANEOUSLY, THIS PROJECT WILL ADDRESS THE FUNDAMENTAL FUNCTIONALITY AND STABILITY CHALLENGES IN IMPLANTABLE INTERFACES. FURTHERMORE, IT WILL ESTABLISH A PLATFORM FOR BIOMARKER DISCOVERY AND TESTING OF NOVEL THERAPIES FOR NEUROLOGICAL DISORDERS. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.