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Open Access Publications from the University of California

Scholarly Works (14 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2017)

The hippocampus plays an important role in memory. Hippocampal subfield CA1 serves as the primary output of the hippocampus to neocortex and thus is important for supporting hippocampal function. Based on this role, a lesion targeting the entire CA1 region should block hippocampal output to neocortex and disrupt hippocampus-dependent memory as severely as a large hippocampal lesion. However, some findings contradict this idea, demonstrating more severe impairments following DG or CA3 lesions than after CA1 lesions. This could be explained by (i) information leaving the hippocampus through descending CA3 projections, or (ii) the incompleteness of existing CA1 lesions, which separately target only dorsal or ventral CA1. Overall, it remains unclear if CA1 output to neocortex is required to support memory.

We resolve this issue with a novel lesion that targets the entire dorsoventral CA1 axis. First, we tested the effect of the lesion on retrograde memory and found that complete CA1 lesions caused severe impairments in the watermaze, context fear conditioning, and trace fear conditioning tasks (similar to previous findings with large hippocampal lesions). We next tested the effect of the CA1 lesion and large hippocampal lesions on anterograde memory. Both lesions impaired performance in the watermaze task and delayed match-to-position (DMP). However, when rats were given prior DMP training, CA1 lesions no longer impaired watermaze performance, and when rats were given prior watermaze training, CA1 lesions no longer impaired DMP performance. In contrast, rats with hippocampal lesions were impaired in both tasks regardless of prior training.

These studies demonstrate that CA1 output to neocortex is normally needed to support memory, but prior experience can ameliorate anterograde memory impairments caused by the loss of CA1 output. Because prior experience only benefited rats with CA1 lesions, we suggest that descending CA3 efferents may be able to support some forms of memory. However, we also consider that CA1 sparing or a reduction in remote lesion effects might also account for the superior CA1 performance. Additionally, we suggest that the concept of the schema may be particularly important for understanding the beneficial effect of prior experience.

    Cover page: Characterizing the Effect of a Novel CA1 Lesion on Memory in Rats
    • Thesis
    • Peer Reviewed
    UC San Diego Electronic Theses and Dissertations (2016)

    The hippocampus- the aptly named seahorse-shaped structure located in the medial temporal lobe of the human brain- has been central to the study of memory for over fifty years. Over this time period, memory research in humans and rodents has focused on the hippocampus’ role in memory differently, with the human work focused on declarative memories for events and facts while rodent work has emphasized the spatial nature of memories. While these two views are not necessarily incompatible, there are still many open questions as to why the rodent hippocampus appears to rely upon spatial aspects of memory far more than its human counterpart.

    This dissertation was designed to bridge these two traditions using a spatial navigation task, path integration, which was first described in both humans and animals by Charles Darwin. We approached this first by studying whether working memory could support path integration. Working memory is independent of the hippocampus; however, its capacity is limited by the amount and complexity of information needed for recall. If the paths the subjects needed to recall were short and simple, presumably working memory could support them. Indeed, we found that patients with hippocampal damage were able to path integrate as well as normal subjects. However, rats with hippocampal damage were impaired relative to controls regardless of path complexity.

    This finding may reflect the limited capacity of rodent working memory; it may not be possible for rodents to path integrate without using long-term memory. Rats with lesions of the hippocampus and the medial prefrontal cortex (the region commonly associated with working memory) were tested on a variety of spatial and nonspatial memory tasks. We concluded that the hippocampus is needed for spatial memory in rodents not because it is dedicated to spatial processing, but because spatial tasks inherently exceed the capacity of rodent working memory.

    These studies, in addition to a third study on extrahippocampal regions involved in the path integration, help to connect the declarative and spatial memory views of the hippocampus and provide a cross-species interpretation of how the brain helps us remember.

      Cover page: Spatial Navigation and Memory: The Role of the Hippocampus and Neocortical Structures
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2018)
      Prior experience has been shown to improve learning in both humans and animals, but it is unclear what aspects of recent experience are necessary to produce beneficial effects. Here, we examined the capacity of rats with complete hippocampal lesions, restricted CA1 lesions, or sham surgeries to benefit from prior experience. Animals were tested in two different spatial tasks in the watermaze, the conventional watermaze task and delayed match-to-position. The two lesions impaired performance in both tasks when rats had no prior experience. However, when given prior training with one task, CA1 lesions had no effect on performance in the other task. In contrast, rats with hippocampal lesions did not benefit from prior training. The findings show that prior experience can benefit learning even when the previously learned task and a new task are quite different. The concept of schema may be useful for understanding the benefits of prior experience.
        Cover page: The beneficial effect of prior experience on the acquisition of spatial memory in rats with CA1, but not large hippocampal lesions: a possible role for schema formation
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2019)
        Prior knowledge about the probabilistic structure of visual environments is necessary to resolve ambiguous information about objects in the world. Expectations based on stimulus regularities exert a powerful influence on human perception and decision making by improving the efficiency of information processing. Another type of prior knowledge, termed top-down attention, can also improve perceptual performance by facilitating the selective processing of relevant over irrelevant information. While much is known about attention, the mechanisms that support expectations about statistical regularities are not well-understood. The hippocampus has been implicated as a key structure involved in or perhaps necessary for the learning of statistical regularities, consistent with its role in various kinds of learning and memory. Here, we tested this hypothesis using a motion discrimination task in which we manipulated the most likely direction of motion, the degree of attention afforded to the relevant stimulus, and the amount of available sensory evidence. We tested memory-impaired patients with bilateral damage to the hippocampus and compared their performance with controls. Despite a modest slowing in response initiation across all task conditions, patients performed similar to controls. Like controls, patients exhibited a tendency to respond faster and more accurately when the motion direction was more probable, the stimulus was better attended, and more sensory evidence was available. Together, these findings demonstrate a robust, hippocampus-independent capacity for learning statistical regularities in the sensory environment in order to improve information processing.
          Cover page: Preserved capacity for learning statistical regularities and directing selective attention after hippocampal lesions
          • Thesis
          • Peer Reviewed
          UC San Diego Electronic Theses and Dissertations (2016)

          The hippocampus and related medial temporal lobe (MTL) structures are known to be important for declarative memory. Yet, their precise role remains unclear. In three studies, we sought to characterize the role of the hippocampus in encoding, remembering, and imagining. The first study assessed the role of the hippocampus in encoding and remembering memories for words encountered in a laboratory setting. The second study assessed the role of the hippocampus in encoding and remembering real- world events. The third study assessed the role of the hippocampus in remembering natural autobiographical memories and imagining future episodes. We conclude that the hippocampus plays a broad role in declarative memory, functioning to encode information whenever the capacity of working memory is surpassed.

            Cover page: Encoding, Remembering, Imagining, and Medial Temporal Lobe Function
            • Article
            • Peer Reviewed
            UC San Diego Previously Published Works (2018)
            When individuals select the recently studied (and familiar) item in a multiple-choice memory test, they direct a greater proportion of viewing time toward the to-be-selected item when their choice is correct than when their choice is incorrect. Thus, for both correct and incorrect choices, individuals indicate that the chosen item is old, but viewing time nevertheless distinguishes between old and new items. What kind of memory supports this preferential viewing effect? We recorded eye movements while participants made three-alternative, forced-choice recognition memory judgments for scenes. In experiment 1 (n = 30), the magnitude of the preferential viewing effect was strongly correlated with measures of conscious, declarative memory: recognition accuracy as well as the difference in confidence ratings and in response times for correct and incorrect choices. In four analyses that minimized the contribution of declarative memory in order to detect a possible contribution from other processes, the preferential viewing effect was absent. In experiment 2, five memory-impaired patients with medial temporal lobe lesions exhibited a diminished preferential viewing effect. These patients also exhibited poor recognition accuracy and reduced differences in confidence ratings and response times for correct and incorrect choices. We propose that the preferential viewing effect is a phenomenon of conscious, declarative memory and is dependent on the medial temporal lobe. The findings support the link between medial temporal lobe function and declarative memory. When the effects of experience depend on the medial temporal lobe, the effects reflect conscious memory.
              Cover page: Eye movements support the link between conscious memory and medial temporal lobe function
              • Article
              • Peer Reviewed
              Proceedings of the Annual Meeting of the Cognitive Science Society, Volume 6 (1984)
                Cover page: Multiple Learning Mechanisms: Psychological, Neurophysological, and Neurobiological Evidence
                • Article
                • Peer Reviewed
                Proceedings of the Annual Meeting of the Cognitive Science Society, Volume 12 (1990)
                  Cover page: Symposium: What is Cognitive Neuroscience?
                  • Article
                  • Peer Reviewed
                  UC San Diego Previously Published Works (2020)
                  We report neuropsychological and neuropathological findings for a patient (A.B.), who developed memory impairment after a cardiac arrest at age 39. A.B. was a clinical psychologist who, although unable to return to work, was an active participant in our neuropsychological studies for 24 y. He exhibited a moderately severe and circumscribed impairment in the formation of long-term, declarative memory (anterograde amnesia), together with temporally graded retrograde amnesia covering ∼5 y prior to the cardiac arrest. More remote memory for both facts and autobiographical events was intact. His neuropathology was extensive and involved the medial temporal lobe, the diencephalon, cerebral cortex, basal ganglia, and cerebellum. In the hippocampal formation, there was substantial cell loss in the CA1 and CA3 fields, the hilus of the dentate gyrus (with sparing of granule cells), and the entorhinal cortex. There was also cell loss in the CA2 field, but some remnants remained. The amygdala demonstrated substantial neuronal loss, particularly in its deep nuclei. In the thalamus, there was damage and atrophy of the anterior nuclear complex, the mediodorsal nucleus, and the pulvinar. There was also loss of cells in the medial and lateral mammillary nuclei in the hypothalamus. We suggest that the neuropathology resulted from two separate factors: the initial cardiac arrest (and respiratory distress) and the recurrent seizures that followed, which led to additional damage characteristic of temporal lobe epilepsy.
                    Cover page: Neuropsychological and neuropathological observations of a long-studied case of memory impairment
                    • Article
                    • Peer Reviewed
                    UC San Diego Previously Published Works (2018)
                    Neurocomputational models have long posited that episodic memories in the human hippocampus are represented by sparse, stimulus-specific neural codes. A concomitant proposal is that when sparse-distributed neural assemblies become active, they suppress the activity of competing neurons (neural sharpening). We investigated episodic memory coding in the hippocampus and amygdala by measuring single-neuron responses from 20 epilepsy patients (12 female) undergoing intracranial monitoring while they completed a continuous recognition memory task. In the left hippocampus, the distribution of single-neuron activity indicated that only a small fraction of neurons exhibited strong responding to a given repeated word and that each repeated word elicited strong responding in a different small fraction of neurons. This finding reflects sparse distributed coding. The remaining large fraction of neurons exhibited a concurrent reduction in firing rates relative to novel words. The observed pattern accords with longstanding predictions that have previously received scant support from single-cell recordings from human hippocampus.
                      Cover page: Coding of episodic memory in the human hippocampus.
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