Mechanisms of localized neuronal excitation with diamond Wireless Axon and electrical microstimulation - Project Summary: This BRG R01 (PAR-22-242) application, a competing renewal of a previous PAR-16-242 submission, aims to significantly enhance the spatial and temporal resolution of intracortical microstimulation— a crucial element in basic neuroscience research and human neuroprosthetics. Current challenges with penetrating electrical stimulation arrays, tethered to the skull, include chronic issues such as mechanical mismatch, neural degeneration, infection risks, mechanical trauma-induced failure, electrode position shifts, axonal activation preference, and increased electrical impedances from glial scarring. These challenges compromise the effectiveness of electrical stimulation, making longevity a formidable issue, with compensatory increases in electrical current posing risks of permanent tissue damage. This proposal introduces an innovative strategy that utilizes advanced biocompatible materials to develop ultra-small, untethered Diamond Wireless Axon electrodes for electrically excitable tissue stimulation compared to conventional and novel electrical stimulation parameters. The project aims to uncouple the mechanical constraints inherent in traditional microstimulation technology, enhancing the spatial selectivity of activated neurons for stable, long-term electrical stimulation. The guiding hypothesis posits that decoupling the mechanical tether will improve tissue integration. The project aims to enhance spatial selectivity and longevity by decoupling mechanical constraints in traditional microstimulation technology. The study investigates electrical (faradaic/pseudocapacitive) and photovoltaic (capacitive) stimulation parameters, focusing on improving electrode-neuron signal coupling and enhancing stimulation selectivity for neuronal somas. The project will establish the foundation for Diamond Wireless Axon electrodes, considering varying boron doping, micro (MCD) and nanometer (NCD) diamond sizes, and diverse packaging. Benchtop experiments will measure photovoltaic and photothermal properties, identifying safety limits. Wireless Axon stimulation will be quantified, and strategies explored to insulate conductive boron-doped diamond, anticipating superior biocompatibility. This comprehensive project addresses both mechanical and stimulatory aspects, aiming to develop advanced neural probes for long-term, high-quality, and selective neural stimulation. Outcomes could lead to paradigm shifts in neuroscience and clinical neuroprosthetics, offering the capability to activate specific neurons with precision. Anticipated impacts include new paradigms for enduring neural interfaces and longitudinal probing of neural circuits, benefiting both the research community and clinical scientists.