Cortico-Hippocampal Circuit Dynamics in Humans

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PROJECT SUMMARY: The ability to learning rapidly is one of the defining features of human cognition. Despite its importance, the circuit mechanism that governs rapid learning in humans is unknown. It has been proposed that prior-knowledge or a “mental schema” facilitates rapid learning via prefrontal-hippocampal network interactions to improve acquisition of novel associative memory. There is, however, limited empirical evidence supporting this model of learning. Moreover, comparisons of circuit dynamics underlying rapid learning have not been conducted between humans and nonhuman primates. The proposal bridges systems neuroscience across primate species and addresses three fundamental knowledge gaps: 1) Circuit dynamics between the prefrontal cortex and hippocampus that support associative and categorical learning, 2) The influence sleep overnight on memory retention, 3) Commonalities and differences in neural activity and circuit dynamics between human and nonhuman primates during learning. To establish cross-species comparisons, we will conducts a set of experiments in humans tightly linked to the nonhuman primate projects to elucidate the circuit mechanisms of cortical-hippocampal interactions during rapid schema-based and categorical learning. The pre-surgical evaluation of patients with epilepsy provides a unique and potent opportunity to study these brain networks directly. Specially, we will use large-scale high-density intracranial electrodes to record neural signals from prefrontal cortex and hippocampus while patients perform associative and categorical learning. We will also leverage the unique ability to record single neurons in the human hippocampus and medial prefrontal regions to directly compare neural activity across species. Our studies will greatly advance the neurobiology of learning and memory, for which impairments form core clinical features of diverse neurological disorders such as Alzheimer's disease, autism, major depression, and epilepsy. Understanding the neural mechanisms of rapid learning will provide critical framework to develop circuit specific intervention in people with disordered memory.