The rapid formation of new memories and the recall of old memories to inform decisions is essential for human cognition, but the underlying neural mechanisms remain poorly understood. We utilize the opportunity to record in-vivo from human single neurons simultaneously in multiple brain areas in patients undergoing treatment for drug resistant epilepsy to study the underlying mechanisms. Supported by the BRAIN initiative, we formed a consortium among four institutions (Cedars-Sinai/Caltech, Johns Hopkins, U Toronto, and Children’s/Harvard) to maximize to use of these rare and precious opportunities for science. 

We are developing a circuit-level understanding of human memory by utilizing invasive in-vivo recordings together with behavior, focal electrical stimulation, and computational modeling. In this talk, I will provide a scientific overview that motivates the hypothesis we are exploring in this ongoing work.  I will describe a putative circuit for human recognition memory composed of cells in the medial temporal lobe (MTL), and the medial frontal cortex (MFC). In the MTL, this putative circuit is composed of two functional cell types, visually-and memory selective neurons, whose interaction is mediated by theta oscillations. Visually-selective neurons are tuned to high-level concepts, are sensitive to attention, and their activity forms attractors through persistent activity over several seconds while stimuli are held in working memory. Memory-selective neurons, on the other hand, signal whether a stimulus is novel or familiar, a property that changes after a single learning trial. In the MFC, on the other hand, memory-based choice cells represent a putative readout of memories to support memory-based recognition and confidence decisions. Together, these results begin to provide a circuit-level understanding of human memory at a level of detail that is needed for the development of new treatments for memory disorders.