Project Grant R21MH137588

A NOVEL TECHNIQUE FOR SELECTIVE MANIPULATION OF PREFRONTAL COMPUTATIONS IN ECONOMIC CHOICE - SUMMARY MANIPULATING NEURAL ACTIVITY TO SHOW CAUSALITY IS AN ESSENTIAL APPROACH IN NEUROSCIENCE, BUT MANIPULATING PRIMATE PREFRONTAL CORTEX (PFC) PRESENTS UNIQUE CHALLENGES NOT ADDRESSED BY CURRENT OR NASCENT TECHNIQUES. IN PARTICULAR, THE PRIMATE PFC OFTEN ENCODES INFORMATION WITH SPATIALLY DISTRIBUTED AND MIXED ACTIVITY PATTERNS. CURRENT APPROACHES FOR PRIMATES CANNOT TARGET THESE PATTERNS, AND THEREFORE CANNOT SELECTIVELY MODIFY THE INFORMATION THAT THE PFC ENCODES. TO OVERCOME THIS BARRIER WE PROPOSE A NOVEL APPROACH USING MULTI-CHANNEL, LOW-CURRENT ELECTRICAL STIMULATION GUIDED BY A STATE-SPACE THEORETICAL FRAMEWORK; THIS METHOD AIMS TO MODULATE THE SUBSPACE (SPATIALLY DISTRIBUTED PATTERNS OF NEURAL ACTIVITY) THAT ENCODES A SPECIFIC TASK VARIABLE, WITH MINIMAL EFFECTS ON OTHER SUBSPACES. TO VALIDATE AND REFINE THIS METHOD, WE USE OUR RECENTLY DEVELOPED PRIMATE ECONOMIC DECISION PARADIGM (LUPKIN & MCGINTY, 2023, ELIFE), AND EXPLOIT THE KNOWN RELATIONSHIP BETWEEN CHOICE BEHAVIOR AND ECONOMIC VALUE SIGNALS IN THE ORBITOFRONTAL CORTEX (OFC, MCGINTY & LUPKIN, 2023, NAT. NEURO). IN AIM 1 WE WILL ATTEMPT TO SELECTIVELY MODIFY THE SUBJECTIVE VALUE OF A DECISION OFFER ENCODED IN OFC, AND OBSERVE THE EFFECTS ON CHOICE. THE METHOD USES DENSE MULTI-CHANNEL ARRAYS (32 OR 64 CHANNELS, 50MM CONTACT SPACING) THAT CAN BOTH RECORD AND ELECTRICALLY STIMULATE INDEPENDENTLY AT EACH ELECTRODE (