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L R Squire

Publications and source records attributed to L R Squire.

At least 37 records · Page 2Linked to original sources

Awareness predicts the magnitude of single-cue trace eyeblink conditioning.

Studies of differential eyeblink conditioning (CS+ and CS-) have demonstrated that successful conditioning requires awareness of the stimulus contingencies and that delay conditioning does not. Two experiments were carried out to determine whether awareness is also important for single-cue trace eyeblink conditioning. In experiment 1, participants who performed a secondary, attention-demanding task emitted significantly fewer conditioned eyeblink responses than participants who watched a silent movie during the conditioning session. In experiment 2, participants who became aware of the stimulus contingencies early in the conditioning session emitted significantly more conditioned responses during the remainder of the session than participants who became aware later in the session or who never became aware. These results indicate that awareness is important for single-cue trace eyeblink conditioning, just as it is for differential trace conditioning. The relationship between awareness and trace eyeblink conditioning is discussed in the light of these and other recent findings.

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fMRI activity in the medial temporal lobe during recognition memory as a function of study-test interval.

The phenomenon of temporally graded retrograde amnesia (loss of information acquired before the onset of amnesia) suggests that the hippocampus, and possibly other medial temporal lobe (MTL) structures, have a time-limited role in memory. In three experiments, we made a first attempt to use fMRI to assess activity in the hippocampal region (the CA fields of the hippocampus, the dentate gyrus, and the subiculum) and the adjacent parahippocampal gyrus (parahippocampal, entorhinal, and perirhinal cortices) during recognition memory testing as a function of study-test interval. Experiment 1 (n = 5) demonstrated activity in the hippocampal region and parahippocampal gyrus for targets relative to foils during recognition memory performance following a single study-test delay of about one-half hour. In Experiment 2, 15 participants studied line drawings at each of three different times prior to scanning: one-half hour, 1 day, and 1 week. fMRI data were then collected during recognition memory testing, using targets from all three delays and foils. While an overall effect of targets vs. foils was found in both the hippocampal region and the parahippocampal gyrus, there was no effect of study-test interval on target activity. In Experiment 3 (n = 13), behavioral performance (reaction time and accuracy) was equated across the three delays. Again, no effect of study-test interval was observed. It is possible that the time span sampled in our study (one-half hour to 1 week) was too short to observe changes in activity. Alternatively, activity in the MTL during memory testing may occur even when these structures are not necessary for retrieval.

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Detection and explanation of sentence ambiguity are unaffected by hippocampal lesions but are impaired by larger temporal lobe lesions.

We address the recent suggestion that the "hippocampal system" is important for understanding ambiguities in language (MacKay et al., J Cogn Neurosci 1998;10:377-394). Seven amnesic patients and 11 controls first decided whether a sentence was ambiguous and then tried to explain the ambiguity. Three amnesic patients with damage limited to the hippocampal formation and one amnesic patient with primarily diencephalic damage performed like the controls in all respects. Thus, the ability to comprehend ambiguity is independent of the hippocampal formation. By contrast, three patients with larger temporal lobe lesions, which extended beyond the medial temporal lobe, were impaired to about the same degree as the noted amnesic patient H.M. (as reported by Lackner, Neuropsychologia 1974;12:199-207; MacKay et al., J Cogn Neurosci 1998;10:377-394). Patient H.M., like our 3 impaired patients, has some damage outside the medial temporal lobe. However, patient H.M. also had additional difficulties on these and other language tests that the patients with larger temporal lobe lesions did not exhibit. Accordingly, it is possible that H.M.'s impairment has a different basis.

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Recognition memory and familiarity judgments in severe amnesia: no evidence for a contribution of repetition priming.

The amnesic patient E.P. has demonstrated normal levels of repetition priming and at-chance recognition performance (S. B. Hamann & L. R. Squire, 1997), suggesting that the sense of familiarity used to make a recognition memory judgment is not based on the same mechanism responsible for repetition priming. However, the recognition tests previously used may have discouraged the use of familiarity and encouraged reliance on episodic memory. This issue was addressed in 5 experiments with E.P., 3 other amnesic patients with hippocampal damage, and 8 healthy controls. In Experiments 1-3, which were designed to discourage the use of episodic memory, the amnesic patients were impaired and E.P. performed at chance. In Experiments 4 and 5A, a stem-completion priming task was combined with a recognition memory task on each trial. E.P.'s priming was intact, yet his recognition memory performance was at chance. This suggests that although recognition memory judgments may be made on the basis of familiarity, repetition priming is not the source of this feeling of familiarity.

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Memory distortions develop over time: recollections of the O.J. Simpson trial verdict after 15 and 32 months.

Fifteen or 32 months after the verdict was announced in the O.J. Simpson murder trial, we asked college students about how they had heard the news, and we compared their responses with what they had told us 3 days after the verdict. Our study is the first to have assessed recollective accuracy at two different intervals more than 1 year after a noted public event. The quality of the recollections after 32 months was strikingly different from the quality of the recollections after 15 months. After 15 months, 50% of the recollections were highly accurate, and only 11% contained major errors or distortions. After 32 months, only 29% of the recollections were highly accurate, and more than 40% contained major distortions. Retention interval appears to be an important factor determining the frequency of memory distortions, and differences in the retention interval across studies may account for some of the contradictions in the flashbulb-memory literature. Metamemory errors and source memory difficulties are a likely basis of poor memory performance after long retention intervals. The results highlight the marked qualitative changes in recollections that can occur between 1 and 3 years after information has been acquired.

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Impaired verbal category learning in amnesia.

Amnesic patients and controls listened to verbal descriptions of imaginary animals and then classified novel descriptions according to whether they belonged to the studied category. Controls performed well, but the amnesic patients did not acquire categorical knowledge. These findings contrast with previous demonstrations of intact category learning by amnesic patients for dot patterns, artificial grammars, and cartoon animals. It appears that category knowledge can be acquired implicitly when training exemplars are presented visually and when the similarities among items can be readily perceived. Verbal category learning requires the extraction and retention of meaning from training exemplars that are separated in time and may make demands on declarative memory that are beyond the capacity of amnesic patients.

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Memory for places learned long ago is intact after hippocampal damage.

The hippocampus is part of a system of structures in the medial temporal lobe that are essential for memory. One influential view of hippocampal function emphasizes its role in the acquisition and retrieval of spatial knowledge. By this view, the hippocampus constructs and stores spatial maps and is therefore essential for learning and remembering places, including those learned about long ago. We tested a profoundly amnesic patient (E.P.), who has virtually complete bilateral damage to the hippocampus and extensive damage to adjacent structures in the medial temporal lobe. We asked him to recall the spatial layout of the region where he grew up, from which he moved away more than 50 years ago. E.P. performed as well as or better than age-matched control subjects who grew up in the same region and also moved away. In contrast, E.P. has no knowledge of his current neighbourhood, to which he moved after he became amnesic. Our results show that the medial temporal lobe is not the permanent repository of spatial maps, and support the view that the hippocampus and other structures in the medial temporal lobe are essential for the formation of long-term declarative memories, both spatial and non-spatial, but not for the retrieval of very remote memories, either spatial or non-spatial.

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Impaired recognition memory on the Doors and People Test after damage limited to the hippocampal region.

There have been conflicting reports about the importance of the hippocampal region for recognition memory. Vargha-Khadem et al. (1997) described three patients who became amnesic early in life as a result of damage apparently limited to the hippocampal region. One of these patients (Jon) performed normally on the recognition portion of the Doors and People Test but was severely impaired in recall. To compare adult-onset amnesia directly with these early-onset cases, we tested six amnesic patients on the Doors and People Test. Three of the patients have damage thought to be limited to the hippocampal region. All six patients were markedly impaired on both the recall and recognition portions of the test. To account for the difference between our adult-onset cases and the early-onset case (Jon), we suggest that some compensation for Jon's injury occurred during development, either due to functional reorganization of cortex adjacent to the hippocampus or as the result of learned strategies.

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Impaired transverse patterning in human amnesia is a special case of impaired memory for two-choice discrimination tasks.

Three amnesic patients with damage limited to the hippocampal formation, a severely amnesic patient with extensive medial temporal lobe damage, and 9 controls were tested on the transverse patterning problem (A + B-, B + C-, and C + A-) and also on 2 control problems. One of the control problems was matched to the transverse patterning problem with respect to the number of pairwise decisions that were required. The 2nd control problem was matched to the transverse patterning problem with respect to the number of trials needed by controls to learn the task. The amnesic patients were impaired at solving both the transverse patterning problem and the control problems. The findings suggest that impaired learning of the transverse patterning problem by amnesic patients derives from their general impairment in declarative memory, which affects performance on most 2-choice discrimination tasks.

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Intact learning of artificial grammars and intact category learning by patients with Parkinson's disease.

Patients with Parkinson's disease (PD) have been shown to be impaired on some nondeclarative memory tasks that require cognitive skill learning (perceptual-motor sequence learning, probabilistic classification). To determine what other skill-based tasks are impaired, 13 patients with PD were tested on artificial grammar learning, artificial grammar learning with transfer to novel lettersets, and prototype learning. Patients with PD performed similarly to controls on all 3 tests. The intact learning exhibited by PD patients on these tests suggests that nondeclarative cognitive skill learning is not a single entity supported by the neostriatum. If learning the regularities among visual stimuli is the principal feature of artificial grammar learning and prototype learning, then these forms of skill learning may be examples of perceptual learning, and they may occur in early visual cortical processing areas.

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Learning about categories that are defined by object-like stimuli despite impaired declarative memory.

Exposure to members of a category facilitates later categorization of similar but novel instances of the category. Past studies have suggested that category knowledge can be acquired implicitly and independently of declarative memory. However, these studies have relied on dot pattern stimuli that, unlike most real-world objects, are difficult to verbalize and cannot be broken into component features. It is therefore unclear how relevant such studies are to an understanding of everyday categorization. In the present studies, category learning in amnesic patients was tested with stimuli that both exhibit discrete features and are easy to describe (namely, cartoon animals). Amnesic patients were as competent as healthy volunteers in learning to categorize these animals, despite their impairment in recalling the animals' features. The results suggest that the implicit acquisition of category knowledge is a common process in everyday experience, and that it can occur whenever individuals encounter a large group of related items.

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Relaxing decision criteria does not improve recognition memory in amnesic patients.

An important question about the organization of memory is whether information available in non-declarative memory can contribute to performance on tasks of declarative memory. Dorfman, Kihlstrom, Cork, and Misiaszek (1995) described a circumstance in which the phenomenon of priming might benefit recognition memory performance. They reported that patients receiving electroconvulsive therapy improved their recognition performance when they were encouraged to relax their criteria for endorsing test items as familiar. It was suggested that priming improved recognition by making information available about the familiarity of test items. In three experiments, we sought unsuccessfully to reproduce this phenomenon in amnesic patients. In Experiment 3, we reproduced the methods and procedure used by Dorfman et al. but still found no evidence for improved recognition memory following the manipulation of decision criteria. Although negative findings have their own limitations, our findings suggest that the phenomenon reported by Dorfman et al. does not generalize well. Our results agree with several recent findings that suggest that priming is independent of recognition memory and does not contribute to recognition memory scores.

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Retrograde amnesia for facts and events: findings from four new cases.

Two patients with presumed hippocampal formation lesions and two patients with more extensive temporal lobe damage, all of whom became amnesic in a known year, were given tests of anterograde and retrograde memory function. The two patients with hippocampal formation lesions had moderately severe anterograde amnesia and limited retrograde amnesia for facts and events that affected, at most, the decade preceding the onset of amnesia. Content analysis could not distinguish the autobiographical recollections of the patients from the recollections of control subjects. The two patients with more extensive temporal lobe damage had severe anterograde amnesia and extensive retrograde memory loss for both facts and events. The results suggest that whether retrograde amnesia is temporally limited or very extensive depends on whether the damage is restricted to the hippocampal formation or also involves additional temporal cortex.

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Classical conditioning and brain systems: the role of awareness.

Classical conditioning of the eye-blink response, perhaps the best studied example of associative learning in vertebrates, is relatively automatic and reflexive, and with the standard procedure (simple delay conditioning), it is intact in animals with hippocampal lesions. In delay conditioning, a tone [the conditioned stimulus (CS)] is presented just before an air puff to the eye [the unconditioned stimulus (US)]. The US is then presented, and the two stimuli coterminate. In trace conditioning, a variant of the standard paradigm, a short interval (500 to 1000 ms) is interposed between the offset of the CS and the onset of the US. Animals with hippocampal lesions fail to acquire trace conditioning. Amnesic patients with damage to the hippocampal formation and normal volunteers were tested on two versions of delay conditioning and two versions of trace conditioning and then assessed for the extent to which they became aware of the temporal relationship between the CS and the US. Amnesic patients acquired delay conditioning at a normal rate but failed to acquire trace conditioning. For normal volunteers, awareness was unrelated to successful delay conditioning but was a prerequisite for successful trace conditioning. Trace conditioning is hippocampus dependent because, as in other tasks of declarative memory, conscious knowledge must be acquired across the training session. Trace conditioning may provide a means for studying awareness in nonhuman animals, in the context of current ideas about multiple memory systems and the function of the hippocampus.

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Cortical areas supporting category learning identified using functional MRI.

Functional MRI was used to identify cortical areas involved in category learning by prototype abstraction. Participants studied 40 dot patterns that were distortions of an underlying prototype and then, while functional MRI data were collected, made yes-no category judgments about new dot patterns. The dot patterns alternated between ones mostly requiring a "yes" response and ones mostly requiring a "no" response. Activity in four cortical areas correlated with the category judgment task. A sizeable posterior occipital cortical area (BA 17/18) exhibited significantly less activity during processing of the categorical patterns than during processing of noncategorical patterns. Significant increases in activity during processing the categorical patterns were observed in left and right anterior frontal cortex (BA 10) and right inferior lateral frontal cortex (BA 44/47). Decreases in activation of visual cortex when categorical patterns were being evaluated suggest that these patterns could be processed in a more rapid or less effortful manner after the prototype had been learned. Increases in prefrontal activity associated with processing categorical patterns could be related to any of several processes involved in retrieving information about the learned exemplars.

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Episodic memory, semantic memory, and amnesia.

Episodic memory and semantic memory are two types of declarative memory. There have been two principal views about how this distinction might be reflected in the organization of memory functions in the brain. One view, that episodic memory and semantic memory are both dependent on the integrity of medial temporal lobe and midline diencephalic structures, predicts that amnesic patients with medial temporal lobe/diencephalic damage should be proportionately impaired in both episodic and semantic memory. An alternative view is that the capacity for semantic memory is spared, or partially spared, in amnesia relative to episodic memory ability. This article reviews two kinds of relevant data: 1) case studies where amnesia has occurred early in childhood, before much of an individual's semantic knowledge has been acquired, and 2) experimental studies with amnesic patients of fact and event learning, remembering and knowing, and remote memory. The data provide no compelling support for the view that episodic and semantic memory are affected differently in medial temporal lobe/diencephalic amnesia. However, episodic and semantic memory may be dissociable in those amnesic patients who additionally have severe frontal lobe damage.

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The human perirhinal cortex and recognition memory.

The importance of the perirhinal cortex for visual recognition memory performance is undisputed. However, it has not been clear whether its contribution to performance is mainly perceptual, or mainly mnemonic, or whether the perirhinal cortex contributes to both perception and memory. We determined the effects of medial temporal lobe damage that includes complete damage to the perirhinal cortex in two amnesic patients by assessing recognition memory for complex visual stimuli across delays from 0 to 40 s. These patients, as well as six other amnesic patients with damage limited to the hippocampal formation or diencephalic structures, exhibited intact recognition memory at delays of 0-2 s and a delay-dependent memory impairment at delays of 6 s and longer. Additionally, the patients with damage to the perirhinal cortex performed worse than the other amnesic patients at delays of 25 s and longer. The findings suggest that the perirhinal cortex is not important for visual perception or immediate memory. In this respect, the findings for perirhinal cortex resemble the findings for other medial temporal lobe structures, including the hippocampus.

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