Abstract In this proposal, we will develop next-generation flexible micro-electrocortigraphic (ECoG) and penetrating electrode arrays using active electronics in complementary metal-oxide-semiconductor (CMOS) technology. Active electronics enable amplification and multiplexing directly at each electrode, eliminating the need for implanted electrodes to be individually wired to remote electronics and greatly increasing the number and density of electrodes that can be recorded and stimulated. The flexibility of our arrays allows them to conform to the irregular geometry of the brain, yielding higher fidelity signals and reduces damage to the brain when used in penetrating configurations. Integrated wireless data and power enables completely tether-free implants. Together, these innovations enable us to take high resolution measurements over large areas of the brain while being less invasive, a substantial improvement over the current state-of-the-art. In surface recording structures, we will demonstrate electrode arrays of up to 65,536 electrodes and amplifiers, spaced just 25.4m apart, where each electrode can be simultaneously sampled at 20 ksps, enabling a cellular-resolution brain interface across a 64 mm brain area. Each electrode can also be independently stimulated, or stimulated with patterns of activation, mimicking more natural excitation patterns. In penetrating arrays, we will demonstrate fully integrated, flexible penetrating neural probes with up to 512 electrodes per shank. The probe ?head? containing active electronics will fold over the outer surface of the cortex, at the point of the probe?s insertion, positioning its inductor for a near-field link through the skull. This link will be powered wirelessly with near-field radio-frequency data telemetry, eliminating the need to run wired interconnections through the skull. Integration with wireless interfaces will permit sealing chronically- implantable probes subcutaneously and in a manner in which the entire probe floats on the brain. The developed technologies will be rigorously tested in vitro and in vivo. This project will make high density electrode arrays based on manufacturable flexible CMOS technology available for the broader neuroscience community, enabling studies of large-scale recording and modulation in the nervous system. The innovations generated through this work have the potential to revolutionize our ability to understand the brain, and will improve epilepsy surgery outcomes as well as advance the performance of motor and auditory prosthetics. This project leverages a successful, long-term collaboration between clinicians, engineers, material scientists and neuroscientists at Duke University, Columbia University, New York University and the University of Illinois at Urbana-Champaign, to translate active, flexible electronics technology into next generation implantable neurological devices.