Different events usually contain similar elements that can contribute to interference during memory encoding and retrieval. The hippocampus (HPC), a structure that is critically involved in some forms of memory, has been hypothesized to reduce interference between memories with overlapping content, thus facilitating correct recall. Pattern separation is one hypothetical process whereby input ambiguity is reduced. Here we test the hypothesis that the HPC and/or dentate gyrus (DG) are important for pattern separation by measuring performance by rats with damage in tasks that require discrimination between visual stimuli that share systematically varying numbers of common elements. Rats with HPC damage were slower to resolve discriminations with minimal degrees of overlap. Lesions of the DG did not affect the ability of rats to deal with overlap, suggesting a dissociation between the HPC and DG. Our results provide partial support for the idea that the HPC contributes to the pattern separation process. / ix, 84 leaves : ill. ; 29 cm.

This thesis investigates the role of the hippocampus in object memory. Currently, the role of the hippocampus in object recognition is unclear, with some studies demonstrating a delay-dependent impairment after hippocampal damage, others showing no impairment. The present thesis used the novel object recognition task and its variants to investigate various types of object memory in hippocampal lesion rats. In the first study, impairments were observed in discriminating object order and associating objects with contexts, while no impairment was observed in novel object recognition. In the second study, it was found that encountering another object shortly prior to or after encountering a target object impairs the recognition of the target object. In a control procedure, encountering a novel context either shortly before or after encountering the target object did not impair object recognition. In sum, in the absence of the hippocampus, object memory becomes vulnerable to interference, rendering rats unable to discern memories of multiple objects. The present thesis concludes that the hippocampus discriminates multiple objects via pattern separation. A stimulus-response model relating the role of the hippocampus to object memory is proposed. / vii, 150 leaves : ill. ; 29 cm. --

The hippocampus and non-hippocampal long-term memory systems each have the capacity to learn and express contextual fear memory. How these systems interact during learning and remembering revolves around hippocampal mediated interference, where the hippocampus dominates for both the acquisition and expression of long-term memory. Hippocampal interference during learning can be overcome by modifying learning parameters such that learning is distributed across multiple independent sessions. The standard view of the role of the hippocampus in long-term memory retrieval is that it is temporally limited, where recently acquired memory is dependent on hippocampal function though as a memory ages, dependency is transferred to other memory systems by a process called systems consolidation. Distributed training demonstrates that learning parameters create a memory that is resistant to hippocampal damage. We find little evidence to support temporally based systems consolidation, and present data that supports the view that if the hippocampus is initially involved in learning a memory, it will always be necessary for accurate retrieval of that memory. A critical assessment of the rat literature revealed that initial memory strength, and/or lesion techniques might be responsible for the few studies that report temporally graded retrograde amnesia using contextual fear conditioning. Our experiments designed to directly test these possibilities resulted in flat gradients, providing further evidence that the hippocampus plays a permanent role in long-term memory retrieval. We propose and assess alternatives to the standard model and conclude that a dual store model is most parsimonious within the presented experiments and related literature. Interactions of the hippocampus and non-hippocampal systems take place at the time of learning and remembering, and are persistent over time. / xvi, 161 leaves : ill. (some col.) ; 29 cm

Memory is critical to our everyday lives, allowing us to attach meaning to our experiences of the world. However, a number of neurocognitive disorders can result in the loss of this fundamental function. The development of effective treatments for loss of episodic memory depends on a detailed understanding of the neural signals that support memory and a thorough characterization of how brain stimulation may be targeted to modulate memory-related patterns of brain activity. In this dissertation, I approach these questions with a series of three studies to examine the effects of direct electrical brain stimulation, the role of large-scale patterns of brain activity in memory, and how stimulation can be used to modulate these signals. In my first study, I characterize changes in neuronal activity across the brain that resulted from delivering stimulation at a range of frequencies, amplitudes, and locations. To do this, I developed an analysis framework and applied it to a large-scale dataset of direct human brain recordings from electrodes implanted in neurosurgical epilepsy patients while intracranial stimulation was delivered. With these analyses, I found that stimulation most often had an inhibitory effect; however, high-frequency stimulation delivered near white-matter tracts was most likely to excite neuronal activity. In my second study, I investigated the functional role of brain oscillations that moved across the cortex during memory tasks. I found that traveling waves of low-frequency oscillations that moved anteriorly across the cortex most often supported successful memory encoding. Additionally, the timing, or phase, of brain oscillations propagating across specific areas of the cortex predicted efficient memory retrieval. In my last study, having determined that the direction of traveling waves is important for memory processes, I then investigated how different types of stimulation changed the direction of traveling waves of low-frequency oscillations. By analyzing intracranial recordings during a stimulation mapping procedure, I found that stimulation at high frequencies oriented in line with the direction of wave propagation was most effective in changing the propagation direction of traveling waves. Additionally, I tested how changes traveling wave direction from stimulation affected patients’ memory performance during an episodic memory task. For patients where stimulation changed the propagation direction of their waves from anterior to posterior directions, stimulation also impaired their memory, and when stimulation had the opposite effect on direction, it enhanced their memory. This provides the first preliminary causal evidence that stimulation can be targeted to modulate specific features of large-scale patterns of brain oscillations— the direction of traveling waves— and, in turn, affect memory performance. Broadly, this body of work shows that direct electrical stimulation of the brain applied with specific parameters holds the potential to modulate neural activity related to memory. This work expands our current understanding of the functional role of brain oscillations by showing that specific features of traveling waves across the cortex are key signals linked to human behavior. These findings provide both a basic understanding of how neural oscillations support human behavior as well as a foundation for designing stimulation protocols to precisely target desired changes in neural activity with the potential to improve diagnostic and therapeutic applications.

The world is a complex and dynamic place. The incredibly dense and constantly changing information stream with which our senses are bombarded must be decomposed, taken in, and processed by any organism hoping to make enough sense of this world in order to survive to the next moment. For complex behaviors, and in particular a great many of those that we often feel define us as a human species, this dense sensory stream must not just be processed, but the important features of the environment must be further distilled and structured into representations that can then be stored long-term to guide future behavior through the joint processes of Learning and Memory. The primary goal of this thesis is to further our understanding of the neurobiological bases - at the subcellular, circuit, and network level - of learning and memory. The hippocampus, one of the most studied systems in the brain by far, is thought to play a central role in learning and memory. Principal cells in the hippocampus become tuned to environmental features, forming persistent representations of an animal’s environment, but the precise mechanisms by which these representations are formed, used, and maintained remain unresolved. By employing a variety of experimental techniques including in vivo two-photon calcium imaging, extracellular electrophysiology, optogenetics, and chemogenetics in awake, behaving mice, we attempted to characterize the subcellular and circuit determinants of place field representations and to connect them to these cells’ role in spatial learning and memory.

Memory serves an integral function in every aspect of human life. Losing that function can be adevastating consequence of disease, dementia, and trauma. In order to develop treatments or prophylactics for memory disorders we must identify the neural basis of memory. Animal research has made prominent strides studying the neural correlates of memory by examining the more easily observable and manipulable neural correlates of spatial context, since the brain regions necessary for declarative memory intersect profoundly with those needed for spatial navigation. My research has two main goals. My first two studies, in Chapters 2 and 3, translate animal research relating the neural correlates of space to memory processes, and go beyond animal work to explore how internal features of experience such as goal states influence these conjunctive representations of space and memory. In Chapter 4, I expand my scope to examine how another internal feature, emotional context, affects the same brain regions on a network level to influence memory representations in the human brain. To perform these studies I recorded directly from the human brain in epilepsy patients performing a variety of memory tasks. First, I measured single-neuron activity as subjects navigated a virtual environment, encountering various objects at unique locations. As subjects moved through the environments, they were instructed to recall the locations of specific objects they encountered—I identified neurons in the human entorhinal cortex, called “memory-trace cells”, which selectively activated near the object-location that people were instructed to retrieve from memory. This is the first evidence that neurons in the brain can be tuned to the spatial context of an event for memory, and demonstrated a direct link between memory retrieval and the spatial tuning properties of neurons. For my second study, I examined whether spatially-tuned neurons in the MTL discharge at intervals organized by theta (2–10 Hz) oscillations (which represent network level brain-activity). I identified a particular pattern that is prominent in rodents, called “phase precession”, during which spatially-tuned neurons spike slightly faster than the network oscillation, and which is theorized to hold great value throughout the brain for learning and memory. In addition to discovering this pattern for spatial sequences, I discovered that phase precession was also present during more abstract features of experience, like the specific goal a person was seeking. These findings suggest that principles of network-level brain activity for organizing spatial navigation may extend to humans, and to broader forms of cognition and memory. Finally, I examined the role of the amygdala in memory encoding during a verbal episodic memory task, finding that the emotional context of a word influenced the probability of its subsequent recall. By measuring the prevalence and coordination of brain oscillations in the amygdala-hippocampal circuit, I found that gamma oscillations (30–120 Hz) increased in both regions as a function of word arousal and encoding success, and connectivity within the amygdala-hippocampal circuit also showed significant theta-gamma coupling as a function of memory and high arousal. Furthermore, direct 50 Hz stimulation impaired memory for high arousal words. These findings suggest a causal relationship between gamma oscillations in the amygdala-hippocampal circuit for memory as a function of emotional context during encoding. My work generalizes important neuronal principles from animal studies to humans (such as spatially-tuned neurons and phase precession), but also extends those findings more deeply to memory, and to internal/subjective aspects of memory that are difficult to directly measure in animals. Overall this work represents an important step towards understanding how the human brain enables declarative memory.

The objective of this research effort was to identify opportunities and demonstrate methods to reduce aircraft crew member cognitive workload (CWL) by reducing short-term memory (STM) demand. Two experiments qualitatively and quantitatively compared memory loading as a function of stimulus class. Experiment 1 employed a dual-task paradigm where the primary task was compensatory tracking used to load STM and the secondary task was item recognition using the Sternberg paradigm. Experiment 2 employed a singletask paradigm using a modified version of the Sternberg task. Digits, letters, colors, words, and geometrical shapes were tested as memory-set (MSET) items in the Sternberg task. Recognition latency and error rate served as objective measures of STM performance while the Subjective Workload Assessment Technique (SWAT) was employed as a Subjective second measure. Root Mean Square error was used to gauge tracking performance. Analyses of the experiments' results revealed that recognition latency and SWAT ratings Statistically varied as functions of stimulus class, MSET size, and the interaction between stimulus class and MSET size. Error rate was not statistically different across stimulus class or MSET size. Post-hoc analyses found SWAT to be a more sensitive STM measurement instrument than recognition latency or error rate. No statistically significant degree of secondary task intrusion on the tracking task was found. In addition to the commonly used classes of digits and letters, this research demonstrated that colors, words, and geometrical shapes could also be utilized as MSET items in short-term memory workload investigations. This research has, more importantly, provided further support for the vital link between STM demand and perceived workload. The main conclusion of this research is that stimulus class optimization can be a feasible method for reducing STM demand. Differences in processing rate among stimulus classes are large enough to impact visual display design. For many context-specific applications, it should be possible to determine the most efficient stimulus class in which to portray the needed information. The findings of this research are especially applicable in situations of elevated STM demand (e.g., aviation systems operations). In general, however, the results provide helpful information for visual display designers. / Ph. D.

This thesis investigates a test method to detect the presence of Variable Retention Time (VRT) bits in manufactured DRAM. The VRT bits retention time is modeled as a 2-state random telegraph process that includes miscorrelation between test and use. The VRT defect is particularly sensitive to test and use conditions. A new test method is proposed to screen the VRT bits by simulating the use conditions during manufacturing test. Evaluation of the proposed test method required a bit-level VRT model to be parameterized as a function of temperature and voltage conditions. The complete 2-state VRT bit model combines models for the time-in-state and for the retention-time including miscorrelation. A copula is used to model the eect of miscorrelation between test and use. The proposed VRT test algorithm runtime is estimated as a function of VRT test coverage, test temperature and test voltage.

There are numerous clinical and experimental accounts of retrograde and anterograde amnesia resulting from damage to the hippocampus (HPC). Several theories on the HPC hold that only certain types of recent memories should be affected by HPC damage. These theories do not accurately predict the circumstances within which memories are vulnerable to HPC damage. Here I show the HPC plays a role in the formation and storage of a wider range of memories than is posited in contemporary theories. I will demonstrate that an important factor in elciting retrograde amnesia is the number of similar learning episodes. Exposure to multiple problems in the same task context leads to retorgrade amnesia that is not observed when only one problem is learned under otherwise identical parameters. When multiple discriminations are learned, the output of the HPC blocks recall from and future use of the extra-HPC memory system. / x, 78 leaves : ill. ; 29 cm.

Establishing appropriate animal models for the study of human memory is paramount to the development of memory disorder treatments. Damage to the hippocampus, a medial temporal lobe brain structure, has been implicated in the memory loss associated with Alzheimer’s disease and other dementias. In humans, the role of the hippocampus is largely defined; yet, its role in rodents is much less clear due to conflicting findings. To investigate these discrepancies, an extensive review of the rodent literature was conducted, with a focus on studies that used the Novel Object Recognition (NOR) paradigm for testing. The total amount of time the objects were explored during training and the delay imposed between training and testing seemed to determine hippocampal recruitment in rodents. Male C57BL/6J mice were implanted with bilateral dorsal CA1 guide cannulae to allow for the inactivation of the hippocampus at discrete time points in the task. The results suggest that the rodent hippocampus is crucial to the encoding, consolidation and retrieval of object memory. Next, it was determined that there is a delay-dependent involvement of the hippocampus in object memory, implying that other structures may be supporting the memory prior to the recruitment of hippocampus. In addition, when the context memory and object memory could be further dissociated, by altering the task design, the results imply a necessary role for the hippocampus in the object memory, irrespective of context. Also, making the task more perceptually demanding, by requiring the mice to perform a two-dimensional to three-dimensional association between stimuli, engaged the hippocampus. Then, in the traditional NOR task, long and short training exploration times were imposed to determine brain region activity for weak and strong object memory. The inactivation and immunohistochemistry findings imply weak object memory is perirhinal cortex dependent, while strong object memory is hippocampal-dependent. Taken together, the findings suggest that mice, like humans, process object memory on a continuum from weak to strong, recruiting the hippocampus conditionally for strong familiarity. Confirming this functional similarity between the rodent and human object memory systems could be beneficial for future studies investigating memory disorders. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2016. / FAU Electronic Theses and Dissertations Collection