Time, space, and rhythm across neurons in the human medial temporal lobe and prefrontal cortex

Despite their limitations, single- and multi-neuron recordings in humans have incredible potential to reveal how cellular and circuit-level responses give rise to the regional activity patterns found in functional MRI and electroencephalography studies, among other, more widely available techniques in cognitive neuroscience. This research also provides a necessary bridge to discoveries made in animal models, where recent technological advancements have accelerated our understanding of the biological mechanisms that underlie cognition. How- ever, fundamental questions remain about how closely these findings translate to humans. The goal of this dissertation is to further the understanding of how activity patterns at the level of neurons facilitate the complicated processes of human memory. We describe our research on individual neuron correlates of time and place, which together provide a scaffold for organizing events in memory. In a novel experiment involving timed navigation through a virtual environment, we find that neurons in the medial temporal lobe (MTL) and medial prefrontal cortex continually represent time when place is held constant, while neural codes for time and place emerge in parallel when subjects navigate for fixed durations. In a second study, we ask how the timing of neural firing is coordinated across space in the hippocampal-dependent memory system. Combining data from multiple experiments to gather a large sample of neuronal recordings, we find that the answer is partly one of rhythm. Specifically, we show that sporadic bouts of theta frequency (2-10Hz) oscillations in the hippocampus synchronize the timing of neuronal firing not only within the hippocampus, but in connected MTL regions. Collectively, these studies provide answers to long-held questions in memory neuroscience, while opening exciting new avenues for continued research.