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Emotional Memory Processing and Pattern Separation in Medial Temporal Lobe

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Remembering a salient experience and discriminating between similar events are two cognitive abilities that are critical for human adaptation and survival. They depend on optimal functioning of neurobiological mechanisms underlying episodic memory processing. Enhanced memory for emotional stimuli requires more pronounced memory encoding of emotional, relative to neutral stimuli. Discrimination between two different events depends on a neural computation of pattern separation. However, the exact neural mechanisms underlying memory encoding and pattern separation are still unclear.In the present thesis, I applied an emotional memory encoding and discrimination task in human participants and examined the neural dynamics in the medial temporal lobe, known as a critical brain structure for memory processing. Local field potentials were recorded in the amygdala, hippocampus and peri-hippocampal regions, including entorhinal, parahippocampal and perirhinal cortex, from drug-resistant epilepsy patients undergoing pre-surgical monitoring. First, I examined the role of hippocampal awake sharp-wave ripples (aSWRs) on emotional memory encoding, finding increased aSWRs after encoding of emotional, compared to neutral stimuli. The aSWRs were accompanied by memory reinstatement in the amygdala-hippocampal network. Additionally, the cross-structure joint-reinstatement during aSWR events was predictive of later memory performance. Next, I investigated the neural mechanisms of pattern separation during memory discrimination. Stimulus-specific neural representation in the hippocampus predicted memory discrimination. Moreover, I designed a machine learning algorithm to decode the neural state, and found that the neural trajectory of dentate gyrus/Cornu Ammonis3 (DG/CA3) visited more unexplored state and predicted successful pattern separation. Finally, continuously increasing dimensionality predicts correct discrimination, suggesting code expansion as a mechanism implementing the pattern separation in the DG/CA3 region. Overall, these results suggest a putative mechanism for encoding and discriminating for emotional experience.

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This item is under embargo until June 22, 2023.