Larry Squire

Larry Squire
University of California, San Diego | UCSD · Department of Psychiatry

About

166
Publications
28,363
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24,454
Citations
Citations since 2017
17 Research Items
7080 Citations
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201720182019202020212022202302004006008001,0001,200
201720182019202020212022202302004006008001,0001,200

Publications

Publications (166)
Article
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Significance Episodic memories represent the “what,” “when,” and “where” of specific episodes. In epilepsy patients, we detected single-unit activity reflecting episodic memory only in the hippocampus. This neural signal is sparsely coded and pattern-separated, consistent with predictions from neurocomputational models. We also detected single-unit...
Preprint
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Some studies of the neural representation of memory in the human hippocampus have identified memory signals reflecting the categorical status of test items (novel vs. repeated). Others have identified pattern-separated, episodic memory signals reflecting recognition of particular test items. Here, we report that both kinds of memory signals can be...
Article
Full-text available
Significance Studies of memory have established a distinction between ordinary recollection of the past (declarative memory), which depends on medial temporal lobe (MTL) structures and other (nondeclarative) forms of memory that are expressed through performance and depend on other brain systems. One phenomenon that has eluded classification is one...
Article
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Significance The most useful information about the anatomy of human memory comes from postmortem neurohistological analysis of patients who have been well-studied during life. Because of practical difficulties, this has rarely been accomplished. Here, we describe neuropsychological and neuropathological findings for a memory-impaired patient whom w...
Article
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Encoding activity in the medial temporal lobe, presumably evoked by the presentation of stimuli (postonset activity), is known to predict subsequent memory. However, several independent lines of research suggest that preonset activity also affects subsequent memory. We investigated the role of preonset and postonset single-unit and multiunit activi...
Article
Significance The hippocampus is important for many kinds of learning and memory. We explored the role of the hippocampus in the learning of statistical regularities. We administered a motion discrimination task where expectation about stimulus regularities, the degree of attention afforded to the relevant stimulus, and the amount of available senso...
Article
To explore whether the hippocampus might be important for certain spatial operations in addition to its well-known role in memory, we administered two tasks in which participants judged whether objects embedded in scenes or whether scenes themselves could exist in 3-D space. Patients with damage limited to the hippocampus performed as well as contr...
Article
Significance When memory-impaired patients with medial temporal lobe (MTL) damage recollected the events of a guided walk, their memory was not only impoverished and lacking in detail but was also characterized by peculiarities in language use. However, as time passed after learning (up to 2.6 years), the recollections of healthy volunteers came to...
Article
Significance Knowledge (or awareness) of what has been learned has been described as a key feature of hippocampus-dependent memory or as unhelpful for understanding hippocampal function. We recorded eye movements while memory-impaired patients with hippocampal lesions and controls viewed familiar scenes or familiar scenes that had been altered. Con...
Article
The hippocampus has long been recognized as important for the formation of long-term memory. Recent work has suggested that the hippocampus might also be important for certain kinds of spatial operations, as in constructing scenes, shifting perspective, or perceiving the geometry of scenes and their boundaries. We explored this proposal using a tas...
Article
We tested the proposal that medial temporal lobe (MTL) structures support not just memory but also high-level object perception. In one task, participants decided whether a line drawing could represent an object in three-dimensional space and, in another task, they saw the components of an object and decided what object could be formed if the compo...
Article
Significance Memory consists of conscious and unconscious systems with different brain substrates. Eye movements are affected by past experience, but it is often unclear what kind of memory is involved. We examined the preferential viewing effect, whereby in multiple-choice tests of recognition memory, more viewing is directed toward an item that i...
Article
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...
Article
Significance Neurocomputational models hold that episodic memories are represented by sparse, stimulus-specific neural codes. In tests of episodic memory, single-unit recording studies of the human hippocampus have found neurons that operate as general novelty detectors or general familiarity detectors. Here, we investigated whether neurons can be...
Article
Hippocampal lesions often produce temporally graded retrograde amnesia (TGRA), whereby recent memory is impaired more than remote memory. This finding has provided support for the process of systems consolidation. However, temporally graded memory impairment has not been observed with the watermaze task, and the findings have been inconsistent with...
Article
Significance We investigated the role of the medial temporal lobe (MTL) in topographical memory. Participants studied a scene depicting four hills of different shapes and sizes and made a choice among four test images. MTL patients were impaired in a Rotation condition where the correct choice depicted the study scene from a shifted perspective. An...
Article
Eye movements can reflect memory. For example, participants make fewer fixations and sample fewer regions when viewing old versus new scenes (the repetition effect). It is unclear whether the repetition effect requires that participants have knowledge (awareness) of the old-new status of the scenes or if it can occur independent of knowledge about...
Article
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Significance The hippocampus has been linked to both memory and spatial cognition, but these ideas are not entirely compatible. We administered navigation tasks in which participants transformed map coordinates into geographical coordinates to follow paths indicated on maps. Patients with limited hippocampal lesions performed normally. A patient wi...
Article
Full-text available
Significance We explored the role of the medial temporal lobe (MTL) in remembering recent events. Patients with MTL damage and healthy controls were taken on a walk during which 11 planned events occurred. Patients remembered fewer details about the events than controls. Nevertheless, the details made reference to particular places and events from...
Article
Full-text available
Significance We explored the role of the medial temporal lobe (MTL) in autobiographical remembering and future imagining. Patients with MTL damage and controls produced narratives in four time periods (past and future). Findings showed that anterograde amnesia (forgetfulness) can interfere with narrative construction. Under conditions that minimize...
Article
In earlier work, patients with hippocampal damage successfully path integrated, apparently by maintaining spatial information in working memory. In contrast, rats with hippocampal damage were unable to path integrate, even when the paths were simple and working memory might have been expected to support performance. We considered two ways to unders...
Chapter
Memory is a large topic, growing out of the fundamental fact that the experiences we have can modify the nervous system such that our mental life and our behaviour can be different than they were in the past. The study of memory ranges widely — from cellular and molecular questions about the nature of synaptic change to questions about what memory...
Article
A major development in understanding the structure and organization of memory was the identification of the medial temporal lobe memory system as one of the brain systems that support memory. Work on this topic began in the 1950s with the study of the noted amnesic patient H.M. and culminated in studies of an animal model of human memory impairment...
Article
Recent studies have asked whether activity in the medial temporal lobe (MTL) and the neocortex can distinguish true memory from false memory. A frequent complication has been that the confidence associated with correct memory judgments (true memory) is typically higher than the confidence associated with incorrect memory judgments (false memory). A...
Article
Full-text available
Conscious memory for a new experience is initially dependent on information stored in both the hippocampus and neocortex. Systems consolidation is the process by which the hippocampus guides the reorganization of the information stored in the neocortex such that it eventually becomes independent of the hippocampus. Early evidence for systems consol...
Article
Full-text available
Significance It has been suggested that the primary role of the hippocampus is to construct spatial scenes and further that memory impairments following hippocampal damage may be attributed to spatial processing demands in memory tasks. Two types of tasks have contributed evidence to this perspective: boundary extension and scene imagination. Bound...
Article
Full-text available
The idea that memory is not a single mental faculty has a long and interesting history but became a topic of experimental and biologic inquiry only in the mid-20th century. It is now clear that there are different kinds of memory, which are supported by different brain systems. One major distinction can be drawn between working memory and long-term...
Article
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Structures in the medial temporal lobe, including the hippocampus and perirhinal cortex, are known to be essential for the formation of long-term memory. Recent animal and human studies have investigated whether perirhinal cortex might also be important for visual perception. In our study, using a simultaneous oddity discrimination task, rats with...
Article
Full-text available
Significance The ability to form episodic memories in rapid succession depends on the hippocampus, but how do hippocampal neurons represent such memories? Most neurocomputational models envision a sparse distributed coding scheme in which individual neurons each participate in the coding of a few memories, and each memory is coded by a small fracti...
Article
Significance Hippocampal damage has been thought to impair memory for all domains of material (sounds, objects, words, odors). We investigated face recognition memory in patients with hippocampal lesions or large medial temporal lobe lesions. Recognition of novel faces was unequivocally intact in hippocampal patients but only at a short retention i...
Article
Full-text available
Significance Declarative memory for rapidly learned, novel associations is thought to depend on structures in the medial temporal lobe (MTL). A recent study suggested that rapidly learned associations can nevertheless be supported by structures outside the MTL when a promising, incidental encoding procedure termed “fast mapping” (FM) is used. In tw...
Article
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For more than a decade, the high threshold dual process (HTDP) model has served as a guide for studying the functional neuroanatomy of recognition memory. The HTDP model's utility has been that it provides quantitative estimates of recollection and familiarity, two processes thought to support recognition ability. Important support for the model ha...
Article
Full-text available
We tested proposals that medial temporal lobe (MTL) structures support not just memory but certain kinds of visual perception as well. Patients with hippocampal lesions or larger MTL lesions attempted to identify the unique object among twin pairs of objects that had a high degree of feature overlap. Patients were markedly impaired under the more d...
Article
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In four experiments, we explored the capacity for spatial mental imagery in patients with hippocampal lesions, using tasks that minimized the role of learning and memory. On all four tasks, patients with hippocampal lesions performed as well as controls. Nonetheless, in separate tests, the patients were impaired at remembering the materials that ha...
Article
The study of anterograde and retrograde amnesia (AA and RA) in the laboratory and the clinic has provided important information about the structure and organization of memory. The severity of AA is usually correlated with the severity of RA. Nevertheless, variations in the expression of AA and RA have been reported, which presumably reflect variati...
Article
We begin by describing an historical scientific debate in which the fundamental idea that species are related by evolutionary descent was challenged. The challenge was based on supposed neuroanatomical differences between humans and other primates with respect to a structure known then as the hippocampus minor. The debate took place in the early 18...
Article
Significance Patient E.P. developed profound amnesia from encephalitis and then was studied for 14 years before his death in 2008. He had no capacity for acquiring new knowledge about facts and events and had retrograde amnesia covering several decades. This report presents detailed neurohistological findings for this case and relates these finding...
Article
Full-text available
Declarative memory is thought to rely on two processes: recollection and familiarity. Recollection involves remembering specific details about the episode in which an item was encountered, and familiarity involves simply knowing that an item was presented even when no information can be recalled about the episode itself. There has been debate wheth...
Article
Full-text available
The hippocampus and other medial temporal lobe structures have been linked to both memory and spatial cognition, but it has been unclear how these ideas are connected. We carried out parallel studies of path integration in patients with medial temporal lobe lesions and rats with hippocampal lesions. Subjects entered a circular arena without vision,...
Article
In this chapter, the developments that led to the establishment of an animal model of amnesia are summarized, and recent work with nonhuman primates is reviewed that addresses the specific role in memory of the hippocampal region itself (the hippocampus proper, the dentate gyrus, and the subicular complex). (PsycINFO Database Record (c) 2012 APA, a...
Article
Full-text available
We evaluated recent proposals that structures in the medial temporal lobe (MTL)--in particular, perirhinal cortex--support not just memory but certain kinds of perceptual abilities as well. Specifically, it has been suggested that the perirhinal cortex supports the perceptual abilities needed to accomplish visual discrimination performance when the...
Article
Full-text available
Patients with medial temporal lobe (MTL) damage are sometimes impaired at remembering visual information across delays as short as a few seconds. Such impairments could reflect either impaired visual working memory capacity or impaired long-term memory (because attention has been diverted or because working memory capacity has been exceeded). Using...
Article
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Early studies of memory-impaired patients with medial temporal lobe (MTL) damage led to the view that the hippocampus and related MTL structures are involved in the formation of long-term memory and that immediate memory and working memory are independent of these structures. This traditional idea has recently been revisited. Impaired performance i...
Article
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Recognition memory is thought to consist of two component processes--recollection and familiarity. It has been suggested that the hippocampus supports recollection, while adjacent cortex supports familiarity. However, the qualitative experiences of recollection and familiarity are typically confounded with a quantitative difference in memory streng...
Article
Full-text available
Human neuroimaging studies of recognition memory have often been interpreted to mean that the hippocampus supports recollection but not familiarity. This interpretation is complicated by the fact that recollection-based decisions are typically associated with stronger memories than familiarity-based decisions. Some studies of source memory controll...
Article
Montaldi and Mayes [1] write that the distinction between recollection and familiarity is critical for understanding medial temporal lobe function. They begin by suggesting that the hippocampus has a role in pattern completion. We agree. However, they link pattern completion to recollection, which overlooks the possibility that familiarity might al...
Article
Guidelines for submitting commentsPolicy: Comments that contribute to the discussion of the article will be posted within approximately three business days. We do not accept anonymous comments. Please include your email address; the address will not be displayed in the posted comment. Cell Press Editors will screen the comments to ensure that they...
Article
Full-text available
Recognition memory is thought to consist of two components: recollection and familiarity. Whereas it is widely agreed that the hippocampus supports recollection (remembering the episode in which an item was learned), there is uncertainty about whether it also supports familiarity (simply knowing that an item was encountered but without remembering...
Article
Neuroimaging and lesion studies have seemed to converge on the idea that the hippocampus selectively supports recollection. However, these studies usually involve a comparison between strong recollection-based memories and weak familiarity-based memories. Studies that avoid confounding memory strength with recollection and familiarity almost always...
Article
Full-text available
Patients with hippocampal damage are sometimes impaired at remembering information across delays as short as a few seconds. How are these impairments to be understood? One possibility is that retention of some kinds of information is critically dependent on the hippocampus, regardless of the retention interval and regardless of whether the task dep...
Article
We developed a behavioral paradigm for the rat that made it possible to separate the evaluation of memory functions from the evaluation of perceptual functions. Animals were given extensive training on an automated two-choice discrimination task and then maintained their memory performance at a high level while interpolated probe trials tested visu...
Article
The role of the hippocampus in recollecting past events and imagining future events is of some theoretical interest, but experimental work on this issue is difficult because it depends on analysis of spoken narrative and the availability of appropriate patients. Because lateral temporal and frontal damage can markedly impair the ability to produce...
Article
Full-text available
Findings from functional MRI (fMRI) studies of recognition memory and the medial temporal lobe often suggest qualitative differences in the contribution of the hippocampus and perirhinal cortex. This interpretation is complicated by the fact that most of the methods intended to demonstrate qualitative differences also separate strong memories from...
Article
Full-text available
We evaluated recent proposals that the hippocampus supports certain kinds of visual discrimination performance, for example, when spatial processing is required and the stimuli have a high degree of feature overlap. Patients with circumscribed hippocampal lesions tried to discriminate between images of similar faces or images of similar scenes. In...
Article
The ability to recognize a previously encountered stimulus is dependent on the structures of the medial temporal lobe and is thought to be supported by two processes, recollection and familiarity. A focus of research in recent years concerns the extent to which these two processes depend on the hippocampus and on the other structures of the medial...
Article
Full-text available
It has been suggested that the hippocampus selectively supports recollection and that adjacent cortex in the medial temporal lobe can support familiarity. Alternatively, it has been suggested that the hippocampus supports both recollection and familiarity. We tested these suggestions by assessing the performance of patients with hippocampal lesions...
Article
Memories are initially stored in a labile state and are subject to modification by a variety of treatments, including disruption of hippocampal function. We infused a sodium channel blocker (or CNQX) to inactivate the rat dorsal hippocampus reversibly for 1 week following training on a task of spatial memory (the water maze). Previous work with con...
Article
Many recent studies have investigated how the structures of the medial temporal lobe (MTL) support recollection and familiarity, which are two processes widely thought to support recognition memory. The behavioral methods that are used to isolate recollection and familiarity in neuroimaging and lesion studies typically assume that recollection is a...
Article
Full-text available
Working memory has traditionally been viewed as independent of the hippocampus and related medial temporal lobe structures. Yet memory-impaired patients with medial temporal lobe damage are sometimes impaired at remembering relational information (e.g., an object and its location) across delays as short as a few seconds. This observation has raised...
Article
It has been proposed that a core network of brain regions, including the hippocampus, supports both past remembering and future imagining. We investigated the importance of the hippocampus for these functions. Five patients with bilateral hippocampal damage and one patient with large medial temporal lobe lesions were tested for their ability to rec...
Article
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Two recent studies described conditions under which recognition memory performance appeared to be driven by nondeclarative memory. Specifically, participants successfully discriminated old images from highly similar new images even when no conscious memory for the images could be retrieved. Paradoxically, recognition performance was better when ima...
Article
Since an automobile accident in 2005, patient FL has reported difficulty retaining information from one day to the next. During the course of any given day, she describes her memory as normal. However, memory for each day disappears during a night of sleep. She reports good memory for events that occurred before the accident. Although this pattern...
Article
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Work with patient H.M., beginning in the 1950s, established key principles about the organization of memory that inspired decades of experimental work. Since H.M., the study of human memory and its disorders has continued to yield new insights and to improve understanding of the structure and organization of memory. Here we review this work with em...
Article
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In rodents, the novel object recognition task (NOR) has become a benchmark task for assessing recognition memory. Yet, despite its widespread use, a consensus has not developed about which brain structures are important for task performance. We assessed both the anterograde and retrograde effects of hippocampal lesions on performance in the NOR tas...
Article
The medial temporal lobe includes a system of anatomically connected structures that are essential for declarative memory (conscious memory for facts and events). A prominent form of declarative memory is recognition memory (the ability to identify a recently encountered item as familiar). Recognition memory has been frequently assessed in humans a...
Chapter
Amnesia refers to difficulty in acquiring new declarative (conscious) knowledge and in remembering the recent past. This condition results from bilateral damage to the medial temporal lobe or diencephalic midline. Memory impairment can occur as a well-circumscribed disorder against a background of otherwise intact intellectual and cognitive functio...
Article
Full-text available
Recognition memory is thought to depend on two distinct processes: recollection and familiarity. There is debate as to whether damage to the hippocampus selectively impairs recollection or whether it impairs both recollection and familiarity. If hippocampal damage selectively impairs recollection but leaves familiarity intact, then patients with ci...
Article
During the past two centuries, the study of learning and memory has been central to three disciplines: first philosophy, then psychology, and now biology. Biological inquiry began in earnest during the latter part of the 20th century, as technological advances made it feasible to move beyond
Chapter
The fourth edition of the work that defines the field of cognitive neuroscience, offering completely new material. Each edition of this classic reference has proved to be a benchmark in the developing field of cognitive neuroscience. The fourth edition of The Cognitive Neurosciences continues to chart new directions in the study of the biologic und...
Article
We collected fMRI data and confidence ratings as participants performed a recognition memory task that intermixed recently studied words and new (non-studied) words. We first replicated a typical finding from such studies; namely, increasing activity in medial temporal lobe structures with increasing confidence in the old/new decision. Because ther...
Article
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We measured brain activity using event-related fMRI as participants recalled answers to 160 questions about news events that had occurred during the past 30 years. Guided by earlier findings from patients with damage limited to the hippocampus who were given the same test material, we looked for regions that exhibited gradually decreasing activity...
Article
Full-text available
fMRI studies of recognition memory have often been interpreted to mean that the hippocampus selectively subserves recollection and that adjacent regions selectively subserve familiarity. Yet, many of these studies have confounded recollection and familiarity with strong and weak memories. In a source memory experiment, we compared correct source ju...
Article
Full-text available
New granule cells are born throughout life in the dentate gyrus of the hippocampal formation. Given the fundamental role of the hippocampus in processes underlying certain forms of learning and memory, it has been speculated that newborn granule cells contribute to cognition. However, previous strategies aiming to causally link newborn neurons with...
Article
The hippocampus and adjacent medial temporal lobe structures support declarative memory. This chapter addresses two issues of recent interest concerning the function of medial temporal lobe structures. The first issue concerns the proposal that the structures of the medial temporal lobe support visual perception in addition to memory, which challen...
Article
Full-text available
We investigated the relationship between experience-dependent eye movements, hippocampus-dependent memory, and aware memory. We measured eye movements in young adults, older adults, and memory-impaired patients with damage to the medial temporal lobe as they viewed 120 novel scenes and 120 previously viewed scenes. Participants indicated if each sc...
Article
Full-text available
Functional magnetic resonance imaging studies of recognition memory have often been interpreted to mean that the hippocampus supports recollection and that the adjacent perirhinal cortex supports familiarity. Other work points out that these studies have confounded recollection and familiarity with strong and weak memories. In a source memory study...