The fundamental objective of the BRAIN Initiative is to understand how dynamic activity in distributed neural circuits mediates human cognitive behavior. The non-human primate (NHP) is a key animal model in this effort, due to the close similarities of its brain to that of humans and its ability to perform complex cognitive tasks. However, developing and testing novel hypotheses for how neural circuit activity in NHPs mediates cognitive function is severely constrained by several technical limitations. We propose to design, build, and test a “next generation” cranially-mounted prosthetic appliance that can be configured for individual monkeys and tailored to provide optimal recording coverage for virtually any experimental plan. The appliance will be designed using anatomical reconstructions of the brain and skull from high resolution MRI scans. Appliances will incorporate an integrated head holder system, mount accurately and easily onto the cranial surface, be MRI-compatible, and include hermetically sealed access ports that enable semi-chronic implantation (and easy removal) of multiple modular devices for large-scale electrophysiology and neural circuit manipulation. In specific aim 1, we will design, build, and bench test an MRI-compatible appliance that can be custom fit to the cranium of an individual monkey. In specific aim 2, we will conduct an in vivo test of the performance of the cranial appliance in two NHPs to evaluate its overall feasibility for future use. The outcome of this research has the potential to transform the way large-scale electrophysiological studies are conducted in NHPs. By alleviating the difficulties in measuring and manipulating large-scale neural circuits, this approach will enable more researchers to greatly expand their scope of inquiry, leading to rapid progress in understanding cognitive brain function.
Public Health Relevance Statement: This project aims to develop state-of-the-art technology for the recording and manipulation of neuronal activity throughout large-scale networks in the brain of behaving non-human primates. If the objectives are achieved, the proposed research will lead to major technological advances for studying the neural mechanisms of cognition and aid in the diagnosis and treatment of cognitive and psychiatric disorders in humans. !
Project Terms: Anatomy; Animal Model; Area; base; Behavior; biomaterial compatibility; bone; Brain; BRAIN initiative; Brain region; Cephalic; Chronic; Cognition; Cognition Disorders; Cognitive; cognitive function; cognitive task; Complex; cost; Craniotomy; cranium; Custom; design; Devices; Diagnosis; Electrophysiology (science); Excision; Failure; Finite Element Analysis; flexibility; Future; Generations; Head; Human; Implant; implantation; in vivo; Individual; Infection; Location; Magnetic Resonance Imaging; Measures; Mediating; Mental disorders; Methods; microstimulation; Modeling; Monkeys; MRI Scans; neural circuit; neural prosthesis; neuromechanism; Neurons; next generation; nonhuman primate; novel; Operative Surgical Procedures; optogenetics; Outcomes Research; Performance; performance tests; Pharmacology; Phase; Plasticizers; Printing; Procedures; Prosthesis; prototype; reconstruction; relating to nervous system; Research; Research Personnel; Resolution; sample fixation; seal; Silicon; Site; Stress Tests; Structure; Surface; System; Technology; Testing; virtual
