Ph.D. Dissertation Abstract

The Cortical-Hippocampal Interplay during Episodic Memory Retrieval in Humans

One of the most remarkable functions of the human brain is the ability to recall a personal experience from the past and reenact it vividly in our mind, in a way that allows us to reflect upon the memory and derive from it relevant information that can guide our future behavior. My doctoral research explored the neuronal mechanisms that enable this core cognitive function in the human brain. Using rare electrophysiological recordings obtained in neurosurgical patients we investigated and characterized the complex bidirectional interactions that occur between the hippocampus and the cerebral cortex during retrieval of conscious, reportable memories.

Our results are twofold. First, we show that 1-2 seconds before the onset of individual recollections, the hippocampus elicits transient electrical oscillations known as Sharp Wave Ripples (SWRs). These oscillatory events, extensively studied in animal models, reflect massive synchronization events during which millions of pyramidal neurons in the hippocampus output pathway fire simultaneously. Our results demonstrate that SWR events are selective to memory contents and play a major role in coordinating the reactivation of hippocampal-neocortical memory representations during retrieval. We show a tight coupling between SWR events and visual cortex activation, and reveal a massive peri-ripple activation of the Default Mode Network. Second, we show that the cortex employs a flexible, goal-directed "baseline shift" mechanism that imposes predefined boundaries on spontaneous recollections. Specifically, we demonstrate that when free recall is limited to a particular category, the average neuronal activity level in cortical sites representing the targeted category is steadily and significantly enhanced throughout the free recall period. This steady-state enhancement likely introduces a category-specific bias in the cortical input to the hippocampus, facilitating the reactivation of memory traces belonging to the relevant category.

Altogether, the results place hippocampal SWRs firmly as a central mechanism in the retrieval of declarative memory. They demonstrate a key role for SWRs in coordinating the hippocampus-cortical dialogue during recollection and point to a flexible "baseline shift" mechanism that can account for the remarkable ease and precision by which we can constrain this dialogue to support retrieval goals.