Browsing by Subject "Memory, Episodic"
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Item Flexibility of Functional Neuronal Assemblies Supports Human Memory(2021-05-01T05:00:00.000Z) Umbach, Gray Steven; Lega, Bradley C.; Pfeiffer, Brad E.; Rugg, Michael D.BACKGROUND: Assemblies, groups of neurons that fire together on short timescales, could provide the fundamental building block of cognition but have eluded observation in human recordings. OBJECTIVE: Leveraging a large single unit dataset obtained from human epilepsy patients, we observe neuronal assemblies and relate their composition and dynamics to human memory for the first time. METHODS: We enrolled human epilepsy patients implanted with electrodes capable of recording both large-scale brain oscillations as well as the spiking activity of single neurons. Using established methods, we identified groups of neurons that consistently fire within 25 ms of each other across recording. We extracted several features of these assemblies, such as the order of neuron firing within the identified groups, the relationship of assembly activity to underlying gamma oscillations (40 Hz), and the dynamics of neuron membership in assemblies across recording. RESULTS: We find that assemblies are comprised of sequences of neurons phase-locked to underlying gamma oscillations, and that both the consistency of these sequences and their reactivation rate correlates with successful memory. Further, we find that the relative contribution of each neuron to the assembly drifts across recording. The magnitude of drift predicts memory performance and varies along the hippocampal longitudinal axis. CONCLUSION: Our data provide human validation to the hypothesized relevance of transiently co-active neurons to memory. This work has important implications for the continuing efforts to develop brain computer interface devices that rescue cognitive deficits and for elucidating the fundamental mechanisms by which the brain constructs thought.Item Molecular Underpinnings of Human Brain Evolution and Cognition at Cellular Resolution(December 2023) Caglayan, Emre; Chahrour, Maria; Hon, Gary C.; Madabhushi, Ram; Sun, Lu O.; Konopka, GenevieveMolecular and functional characterization of the human brain is challenging due to its experimental inaccessibility. Most of our understanding about human brain function relies on the assumption that biological processes uncovered in model organisms are conserved in humans. Comparisons of the humanii brain with non-human primate brains offer to both uncover the novelties in human brain evolution and better evaluate the insights obtained from model organisms about human brain function. To achieve this, highthroughput sequencing methods on post-mortem brain tissues provide a rewarding readout to understand human brain evolution at the molecular level. In addition to their use in comparative studies, these technologies were also utilized with a hope to understand molecular underpinnings of measurable human brain activity metrics. During my dissertation, I read relevant literature extensively (Chapter 1) and sought to understand human-specific epigenomic and transcriptomic changes at cellular resolution in the cortical brain (Chapter 2). Additionally, after in-depth analysis of many human brain single-nuclei RNA-seq datasets, I found a pervasive ambient RNA contamination problem, and devised in silico solutions to tackle this problem. My efforts improved the analytical approach in the field as well as in my research (Chapter 3). I have also been involved in efforts to identify transcriptomic correlates of brain activity in human subjects (Chapters 4-5). After detailing these efforts, I discuss the implications of these findings, weigh their impact on our understanding of human brain function and offer ideas for further research (Chapter 6).