Understanding the Nature, Extent, and Brain Dynamics of Deficient Pattern Separation

Recent research suggests that the specificity and precision in long-term declarative memory depend on pattern separation. Subfields within the mammalian hippocampus have been shown to mediate this neurobiological process, particularly the dentate gyrus (DG). This subfield interacts with other parts of the medial temporal lobe and neocortex to differentiate highly similar details belonging to separate, yet overlapping, events into discrete episodes at encoding. In humans, the brain-behavior correlates of pattern separation have been explored in modified associative memory tests, which tax the mnemonic discrimination of previously learned images of everyday objects from visually similar lures. Older individuals with reduced hippocampal volumes and patients with hippocampal lesions are impaired relative to controls on these tests. Based on this evidence, researchers have concluded that visual mnemonic discrimination tests are functionally sensitive to the process of hippocampal pattern separation. This assertion may be premature. Despite the preponderance of studies of visual pattern separation over the past 15 years, little is known about whether hippocampal pattern separation works 1) in other modalities or cognitive domains; 2) through interacting with prior knowledge or pre-experimentally novel information, and 3) in concert with activities of perceptual categorization. The present research addresses these issues. In Study 1, I examine whether presumed deficits in pattern separation apply to perception as they do to memory and are evident, even within vision, for stimuli such as faces, which presumably do not crucially depend on the hippocampus. In Study 2, I pursue whether pattern separation extends to modalities other than vision, notably audition. In Study 3, I aim to quantify the impact of prior knowledge on pattern separation and whether discrimination of abstract inputs can be measured at encoding and retrieval. Three groups of participants were tested throughout these studies: young adults, middle-older adults, and older adults. In addition, a rare individual with focal hippocampal lesions to his DG helped to contextualize hippocampal involvement in Studies 1 and 2. The research I conducted on memory and perception combines novel behavioral paradigms and electrophysiological (EEG) techniques sensitive to the temporal dynamics involved in oddity detection to understand better the nature, extent, and brain dynamics of deficient pattern separation. The data analyzed allowed me to make inferences about the nature, scope, and brain dynamics of pattern separation in younger, middle-older, and older adults and in a hippocampal patient. The research addresses unanswered questions about pattern separation and the role of the hippocampus in learning and memory across other processing domains, modalities and involving different types of stimuli. As our population ages, so will the number of individuals who will suffer age-related cognitive impairment. One of the most common among them is a decline or loss of episodic memory, characterized by an inability to recall past personal experiences in detail, specificity, and precision. Similar losses of detail, specificity, and accuracy are observed in perception. Knowledge gained from this research helps to inform the development of tools for clinical assessment and intervention.

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