It is increasingly clear that olfactory perception is impaired in a wide variety of neurological and neuropsychiatric disorders. However, this growing clinical appreciation for the human sense of smell is offset by a poor scientific understanding at the physiological level. Indeed, much of our basic knowledge about the human olfactory system is inferred from studies in rodents and insects, but whether the cortical computations established in animals are relevant for humans is largely unknown. The major aim of this research project is to elucidate the spatiotemporal mechanisms of odor processing in the human olfactory system. In collaboration with the Comprehensive Epilepsy Center and Functional Neurosurgery teams at Northwestern, we will record odor-evoked patterns of electroencephalographic (EEG) activity directly from the human brain in patients with medically intractable seizures. The highly accurate placement of high-density invasive electrodes around the medial temporal and orbital frontal lobes during standard surgical exploration offers a unique window into the functional anatomy of the olfactory system with unparalleled temporal and spatial resolution. Studies are designed to compare odor-evoked oscillatory activity profiles in the olfactory bulb, olfactory (piriform) cortex, and orbitofrontal cortex, and to understand how these different brain regions interact to support olfactory categorical perception and coding. Work proposed here will yield a more comprehensive basic research understanding of human olfaction, particularly with regard to its temporal dynamics, and will provide a direct link to non human animal studies. From a clinical translational perspective, this project may help in diagnosis and prediction of functional outcome in epilepsy patients, and open up new avenues for monitoring disease onset and progression in other neurological disorders involving the sense of smell.