Search PubMed⌕ Search

Biomedical subjects

Larry R Squire

Publications and source records attributed to Larry R Squire.

At least 37 records · Page 2Linked to original sources

Acquisition of differential delay eyeblink classical conditioning is independent of awareness.

There has been debate about whether differential delay eyeblink conditioning can be acquired without awareness of the stimulus contingencies. In 4 experiments, the authors reexamined this question. Older participants were tested with a tone and white noise (Experiment 1) or with 2 tones (Experiment 2). In addition, younger participants were tested with 2 tones (Experiment 3) or with 2 tones plus the parameters from an earlier study that had reported a relationship between conditioning and awareness (Experiment 4). Participants who were designated aware of the stimulus contingencies and participants who were designated unaware exhibited equivalent levels of differential eyeblink conditioning. Awareness of stimulus contingencies is not required for differential delay eyeblink conditioning when simple conditioned stimuli are used.

Adult↗

Impaired odor recognition memory in patients with hippocampal lesions.

In humans, impaired recognition memory following lesions thought to be limited to the hippocampal region has been demonstrated for a wide variety of tasks. However, the importance of the human hippocampus for olfactory recognition memory has scarcely been explored. We evaluated the ability of memory-impaired patients with damage thought to be limited to the hippocampal region to recognize a list of odors. The patients were significantly impaired after a retention delay of 1 h. Olfactory sensitivity was intact. This finding is in agreement with earlier reports that rats with hippocampal lesions exhibited memory impairment on an odor delayed nonmatching to sample task (after 30 min and 1 h) and that patients with damage thought to be limited to the hippocampal region were impaired on an odor span memory task. Olfactory recognition memory, similar to recognition memory in other sensory modalities, depends on the integrity of the hippocampal region.

Adult↗

Spatial memory, recognition memory, and the hippocampus.

There is wide agreement that spatial memory is dependent on the integrity of the hippocampus, but the importance of the hippocampus for nonspatial tasks, including tasks of object recognition memory is not as clear. We examined the relationship between hippocampal lesion size and both spatial memory and object recognition memory in rats. Spatial memory was impaired after bilateral dorsal hippocampal lesions that encompassed 30-50% total volume, and as lesion size increased from 50% to approximately 100% of total hippocampal volume, performance was similarly impaired. In contrast, object recognition was intact after dorsal hippocampal lesions that damaged 50-75% of total hippocampal volume and was impaired only after larger lesions that encompassed 75-100% of hippocampal volume. Last, ventral hippocampal lesions that encompassed approximately 50% of total hippocampal volume impaired spatial memory but did not affect object recognition memory. These findings show that the hippocampus is important for both spatial memory and recognition memory. However, spatial memory performance requires more hippocampal tissue than does recognition memory.

Animals↗

Memory systems of the brain: a brief history and current perspective.

The idea that memory is composed of distinct systems has a long history but became a topic of experimental inquiry only after the middle of the 20th century. Beginning about 1980, evidence from normal subjects, amnesic patients, and experimental animals converged on the view that a fundamental distinction could be drawn between a kind of memory that is accessible to conscious recollection and another kind that is not. Subsequent work shifted thinking beyond dichotomies to a view, grounded in biology, that memory is composed of multiple separate systems supported, for example, by the hippocampus and related structures, the amygdala, the neostriatum, and the cerebellum. This article traces the development of these ideas and provides a current perspective on how these brain systems operate to support behavior.

Animals↗

The importance of awareness for eyeblink conditioning is conditional: theoretical comment on Bellebaum and Daum (2004).

Eyeblink conditioning entails a variety of paradigms that differ in terms of the brain systems that support conditioning and the importance of awareness. In this issue, C. Bellebaum and I. Daum (2004) that reports that conditional discrimination learning depends on awareness. Their findings, along with other recent work, suggest a framework whereby the temporal features of the conditioning paradigm are critical in determining the ability of the cerebellum to support conditioning and, as a result, the role of awareness in conditioning.

Awareness↗

The medial temporal lobe.

The medial temporal lobe includes a system of anatomically related structures that are essential for declarative memory (conscious memory for facts and events). The system consists of the hippocampal region (CA fields, dentate gyrus, and subicular complex) and the adjacent perirhinal, entorhinal, and parahippocampal cortices. Here, we review findings from humans, monkeys, and rodents that illuminate the function of these structures. Our analysis draws on studies of human memory impairment and animal models of memory impairment, as well as neurophysiological and neuroimaging data, to show that this system (a) is principally concerned with memory, (b) operates with neocortex to establish and maintain long-term memory, and (c) ultimately, through a process of consolidation, becomes independent of long-term memory, though questions remain about the role of perirhinal and parahippocampal cortices in this process and about spatial memory in rodents. Data from neurophysiology, neuroimaging, and neuroanatomy point to a division of labor within the medial temporal lobe. However, the available data do not support simple dichotomies between the functions of the hippocampus and the adjacent medial temporal cortex, such as associative versus nonassociative memory, episodic versus semantic memory, and recollection versus familiarity.

Animals↗

Recall and recognition are equally impaired in patients with selective hippocampal damage.

In two recent studies, the hypothesis that recall is more severely impaired than recognition in patients with damage thought to be limited to the hippocampus was tested. Yonelinas et al. (2002) reported findings that appeared to support this hypothesis, whereas Manns, Hopkins, Reed, Kitchener, and Squire (2003) found that recall and recognition were equally impaired. An analysis of the individual subject data from the two studies revealed that the apparent disagreement stemmed from the inclusion of a single outlying recognition score for 1 of the 55 control subjects in Yonelinas et al. (2002). When that outlier was excluded, the studies were in agreement that recognition and recall are substantially and similarly impaired in these patients. Yonelinas et al. (2002) also analyzed remember/know judgments and ROC data in an effort to show that recollection is selectively impaired in patients, but these analyses also raise problems.

Brain Damage, Chronic↗

Semantic memory and the human hippocampus.

It has been unclear whether the hippocampus is uniquely important for episodic memory (memory for events that are specific to time and place) or whether the hippocampus is also important for learning and remembering facts (semantic memory). In two studies, we assessed the capacity for semantic memory in patients with bilateral damage thought to be restricted primarily to the hippocampal region who developed memory impairment at a known time. Since the onset of their memory impairment, the patients have acquired less factual knowledge than controls. The patients also exhibit temporally limited retrograde amnesia for factual information from the several years preceding the onset of memory impairment. Remote memory for factual knowledge (from 11-30 years before amnesia) is intact. The results show that the hippocampal region supports semantic memory as well as episodic memory and that its role in the acquisition and storage of semantic knowledge is time limited.

Adult↗

Successful recollection of remote autobiographical memories by amnesic patients with medial temporal lobe lesions.

Current views about the organization of human memory make strikingly different predictions about the integrity of remote autobiographical memory following damage to the medial temporal lobe. We have carried out a detailed analysis of narrative content in memory-impaired patients for whom neuropsychological and neuroanatomical information is available. All eight patients were able to recall detailed memories from their early lives. The recollections of the patients and the recollections of 25 matched controls contained the same number of details (+/-5%) and were also similar by several other measures. The results support the view that autobiographical memories eventually become independent of the medial temporal lobe as time passes after learning. A number of other considerations suggest that the neocortex ultimately supports the capacity for recollecting remote autobiographical memory.

Adult↗

Recognition memory and the human hippocampus.

The capacity for declarative memory depends on the hippocampal region and adjacent cortex within the medial temporal lobe. One of the most widely studied examples of declarative memory is the capacity to recognize recently encountered material as familiar, but uncertainty remains about whether intact recognition memory depends on the hippocampal region itself and, if so, what the nature of the hippocampal contribution might be. Seven patients with bilateral damage thought to be limited primarily to the hippocampal region were impaired on three standard tests of recognition memory. In addition, the patients were impaired to a similar extent at Remembering and Knowing, measures of the two processes thought to support recognition performance: the ability to remember the learning episode (episodic recollection) and the capacity for judging items as familiar (familiarity).

Adult↗

Hippocampal damage equally impairs memory for single items and memory for conjunctions.

In a prior study of continuous recognition performance, data were reported in support of the hypothesis that the hippocampus is not needed to remember the individual components of a stimulus but is important for remembering associations between its components (Kroll et al. 1996. J Mem Lang 35:176-196). Patients with left hippocampal damage were able to endorse recently encountered words and to reject novel words, as well as disyllabic words in which one of the syllables had been previously encountered. However, they failed to reject words in which both syllables had been encountered independently in different words. We present data from five experiments designed to examine this finding in more detail. In each experiment, five patients with bilateral hippocampal damage and eight controls were tested using the same protocol as Kroll et al. (1996). On each trial, a two-component stimulus was presented. Stimuli could be entirely novel, novel with one previously encountered (repeated) component, novel but with both components repeated, or a true repetition. The first experiment was a direct replication using the same disyllabic words as Kroll et al. (1996). The second experiment used pseudo-words, constructed of two monosyllabic words (e.g., jambark). The third experiment used the same pairs of monosyllabic words, but presented separately on the screen to encourage participants to treat each component independently. The fourth experiment used pairs of objects, and the fifth experiment used face-house pairs. In all five experiments, patients with hippocampal damage exhibited impaired recognition memory. The impairment extended across all trial types with no evidence that hippocampal damage selectively (or disproportionately) impaired the associative or conjunctive component of memory. We discuss our findings in the light of the work by Kroll et al. (1996) and other recent neuropsychological, electrophysiological, and neuroimaging studies of hippocampal function and single-item and associative memory.

Adult↗

Medial temporal lobe amnesia: Gradual acquisition of factual information by nondeclarative memory.

Most amnesic patients with damage to the medial temporal lobe retain some capacity to learn new information about facts and events. In many cases, the learning appears to depend on a residual ability to acquire conscious (declarative) knowledge. We have studied the capacity for semantic (fact) learning in the profoundly amnesic patient E.P., who has extensive damage limited primarily to the medial temporal lobe. E.P. was presented with factual information (novel three-word sentences) during 24 study sessions across 12 weeks. E.P. performed much more poorly than controls but demonstrated unmistakable improvement across the sessions, achieving after 12 weeks a score of 18.8% correct on a cued-recall test and 64.6% correct on a two-alternative, forced-choice test. Unlike controls, E.P.'s learning was not accompanied by conscious knowledge about which answers were correct. He assigned the same confidence ratings to his correct answers as his incorrect answers. Moreover, on the forced-choice test his response times were identical for correct and incorrect responses. Furthermore, unlike controls, he could not respond correctly when the second word in each sentence was replaced by a synonym. Thus, what E.P. learned was rigidly organized, unavailable as conscious knowledge, and in all respects exhibited the characteristics of nondeclarative memory. Thus, factual information, which is ordinarily learned as declarative (conscious) knowledge and with the participation of the medial temporal lobe, can be acquired as nondeclarative memory, albeit very gradually and in a form that is outside of awareness and that is not represented as factual knowledge. We suggest that E.P.'s learning depended on a process akin to perceptual learning and occurred directly within neocortex.

Aged↗

Anterograde amnesia and temporally graded retrograde amnesia for a nonspatial memory task after lesions of hippocampus and subiculum.

We studied the importance of the hippocampus and subiculum for anterograde and retrograde memory in the rat using social transmission of food preference, a nonspatial memory task. Experiment 1 asked how long an acquired food preference could be remembered. In experiment 2, we determined the anterograde amnesic effects of large lesions of the hippocampus that included the subiculum. In experiment 3, large lesions of the hippocampus that included the subiculum were made 1, 10, or 30 d after learning to determine the nature and extent of retrograde amnesia. Normal rats exhibited memory of the acquired food preference for at least 3 months after learning. Hippocampal lesions that included the subiculum produced marked anterograde amnesia and a 1-30 d temporally graded retrograde amnesia. The results show the importance of the hippocampus and related structures for nonspatial memory and also demonstrate the temporary role of these structures in long-term memory.

Amnesia, Anterograde↗

Semantic knowledge in patient H.M. and other patients with bilateral medial and lateral temporal lobe lesions.

We investigated the effects of damage to the medial temporal lobe (MTL) and anterolateral temporal cortex on semantic knowledge. We studied eight male controls, two patients with lesions limited to the hippocampal formation, three postencephalitic patients with extensive MTL lesions and variable damage to the lateral temporal cortex, and patient H.M. (whose lesion is limited mostly to the MTL, but who also has minimal damage to the anterolateral cortex). On 13 tests of semantic memory, patients with lesions limited to the hippocampal formation performed similarly to controls. Postencephalitic patients were mildly to moderately impaired on most tests. Patient H.M.'s performance was impaired on only a few tests and was less severely impaired overall than the three postencephalitic patients. A ranking of test scores showed a direct relationship between impairment and the extent of damage to lateral temporal cortex. These findings, and related findings from other studies, point to the importance of anterolateral temporal cortex for semantic knowledge. Patient H.M. performed uniquely in certain respects. For example, when providing definitions of objects, he made many grammatical errors. In contrast, the other patients with large MTL lesions made no more errors than those made by controls. Considering that H.M.'s lesion, both medially and laterally, is less extensive than the lesions in these other patients, it appears unlikely that his shortcomings in language production are related to his temporal lobe lesion.

Aged↗

Standard delay eyeblink classical conditioning is independent of awareness.

P. F. Lovibond and D. R. Shanks (2002) suggested that all forms of classical conditioning depend on awareness of the stimulus contingencies. This article considers the available data for eyeblink classical conditioning, including data from 2 studies (R. E. Clark, J. R. Manns, & L. R. Squire, 2001; J. R. Manns, R. E. Clark, & L. R. Squire, 2001) that were completed too recently to have been considered in their review. In addition, in response to questions raised by P. F. Lovibond and D. R. Shanks, 2 new analyses of data are presented from studies published previously. The available data from humans and experimental animals provide strong evidence that delay eyeblink classical conditioning (but not trace eyeblink classical conditioning) can be acquired and retained independently of the forebrain and independently of awareness. This conclusion applies to standard conditioning paradigms; for example, to single-cue delay conditioning when a tone is used as the conditioned stimulus (CS) and to differential delay conditioning when the positive and negative conditioned stimuli (CS+ and CS-) are a tone and white noise.

Aged↗

Reversible hippocampal lesions disrupt water maze performance during both recent and remote memory tests.

Conventional lesion methods have shown that damage to the rodent hippocampus can impair previously acquired spatial memory in tasks such as the water maze. In contrast, work with reversible lesion methods using a different spatial task has found remote memory to be spared. To determine whether the finding of spared remote spatial memory depends on the lesion method, we reversibly inactivated the hippocampus with lidocaine either immediately (0-DAY) or 1 mo (30-DAY) after training in a water maze. For both the 0-DAY and 30-DAY retention tests, rats that received lidocaine infusions exhibited impaired performance. In addition, when the 0-DAY group was retested 2 d later, (when the drug was no longer active), the effect was reversed. That is, rats that had previously received lidocaine performed as well as control rats did. These findings indicate that the rodent hippocampus is important for both recent and remote spatial memory, as assessed in the water maze. What determines whether remote spatial memory is preserved or impaired following disruption of hippocampal function appears to be the type of task used to assess spatial memory, not the method used to disrupt the hippocampus.

Anesthetics, Local↗