Biomedical subjects

L R Squire

Publications and source records attributed to L R Squire.

At least 19 recordsLinked to original sources

PubMed2005

On the contribution of perceptual fluency and priming to recognition memory.

Repetition priming has been shown to be independent of recognition memory. Thus, the severely amnesic patient E.P. has demonstrated intact stem completion priming and perceptual identification priming, despite at-chance performance on recognition memory tasks. It has also been shown that perceptual fluency can influence feelings of familiarity, in the sense that items perceived more quickly tend to be identified as familiar. If studied items are identified more fluently, due to perceptual priming, and fluency leads to familiarity, why do severely amnesic patients perform no better than chance on recognition memory tasks? One possibility is that severely amnesic patients do not exhibit normal fluency. Another possibility is that fluency is not a sufficiently strong cue for familiarity. In two experiments, 2 severely amnesic patients, 3 moderately amnesic patients, and 8 controls saw words slowly clearing from a mask. The participants identified each word as quickly as possible and then made a recognition (old/new) judgment. All the participants exhibited fluency, in that old responses were associated with shorter identification times than new responses were. In addition, for the severely amnesic patients, priming was intact, and recognition memory performance was at chance. We next calculated how much priming and fluency should elevate the probability of accurate recognition. The tendency to identify studied words rapidly (.6) and the tendency to label these rapidly identified words old (.6) would result in 36% of the studied words being labeled old. Other studied words were identified slowly (.4) but were still labeled old (.4), resulting in an additional 16% of studied words labeled old. Thus, the presence of fluency increases the probability of accurate recognition judgments to only 52% (chance = 50%). This finding explains why amnesic patients can exhibit both priming and fluency yet still perform at chance on recognition tests.

Adult↗

PubMed2004

The anatomy of semantic knowledge: medial vs. lateral temporal lobe.

Semantic knowledge (e.g., long-established knowledge about objects, facts, and word meanings) is known to be severely impaired by damage to the anterolateral temporal lobe. For example, patients with semantic dementia have prominent atrophy in anterolateral temporal cortex and also have significant damage within the medial aspect of the temporal lobe. However, there is uncertainty about the contribution of medial temporal lobe damage, including perirhinal cortex damage, to impaired semantic knowledge. Drawing largely on published material from multiple sources, we compared the performance of severely amnesic patients with large medial temporal lobe lesions and patients with semantic dementia on nine tests of semantic knowledge and two tests of new learning ability. On the tests of semantic knowledge, the amnesic patients performed markedly better than the patients with semantic dementia. By contrast, on the tests of new learning, the patients with semantic dementia performed markedly better than the amnesic patients. We conclude that medial temporal lobe damage impairs the formation of declarative memory, and that semantic knowledge is impaired to the extent that damage extends laterally in the temporal lobe. Reports that the extent of atrophy in perirhinal cortex correlated with the severity of impaired semantic knowledge may be understood by supposing that the extent of damage in many temporal lobe areas is intercorrelated in this progressive disease, and that the extent of atrophy in perirhinal cortex is a proxy for the overall severity of dementia.

Aged↗

PubMed2004

Intact conceptual priming in the absence of declarative memory.

Priming is an unconscious (nondeclarative) form of memory whereby identification or production of an item is improved by an earlier encounter. It has been proposed that declarative memory and priming might be related-for example, that conceptual priming results in more fluent processing, thereby providing a basis for familiarity judgments. In two experiments, we assessed conceptual priming and recognition memory across a 5-min interval in 5 memory-impaired patients. All patients exhibited fully intact priming in tests of both free association (study tent; at test, provide an association to canvas) and category verification (study lemon; at test, decide: Is lemon a type of fruit?). Yet the 2 most severely amnesic patients performed at chance on matched tests of recognition memory. These findings count against the notion that conceptual priming provides feelings of familiarity that can support accurate recognition judgments. We suggest that priming is inaccessible to conscious awareness and does not influence declarative memory.

Cognition↗

PubMed2001

When zero is not zero: the problem of ambiguous baseline conditions in fMRI.

By using blocked and rapid event-related functional MRI studies of memory, we explored the implications of using rest periods as a baseline condition in functional MRI studies. Activity in the medial temporal lobe (as well as in other brain regions) was substantially higher during rest than during several alternative baseline conditions. The effect of this elevated activity during rest was to reduce, eliminate, or even reverse the sign of the activity during task conditions relevant to memory functions. The results demonstrate that periods of rest are associated with significant cognitive activity and, therefore, provide a nonoptimal baseline for memory tasks. These results were observed not only when relatively long blocks of rest were used (experiment 1), but also when rest consisted of the short null trials typically used in rapid event-related designs (experiment 2). The findings have important implications for the design and interpretation of a wide range of fMRI studies of cognition.

Adult↗

PubMed2001

Neuronal representations of stimulus associations develop in the temporal lobe during learning.

Visual stimuli that are frequently seen together become associated in long-term memory, such that the sight of one stimulus readily brings to mind the thought or image of the other. It has been hypothesized that acquisition of such long-term associative memories proceeds via the strengthening of connections between neurons representing the associated stimuli, such that a neuron initially responding only to one stimulus of an associated pair eventually comes to respond to both. Consistent with this hypothesis, studies have demonstrated that individual neurons in the primate inferior temporal cortex tend to exhibit similar responses to pairs of visual stimuli that have become behaviorally associated. In the present study, we investigated the role of these areas in the formation of conditional visual associations by monitoring the responses of individual neurons during the learning of new stimulus pairs. We found that many neurons in both area TE and perirhinal cortex came to elicit more similar neuronal responses to paired stimuli as learning proceeded. Moreover, these neuronal response changes were learning-dependent and proceeded with an average time course that paralleled learning. This experience-dependent plasticity of sensory representations in the cerebral cortex may underlie the learning of associations between objects.

Animals↗

PubMed2001

Retrograde amnesia.

In humans, the phenomenon of temporally graded retrograde amnesia has been described in the clinic and the laboratory for more than 100 years. In the 1990s, retrograde amnesia began to be studied prospectively in experimental animals. We identified 13 published studies in which animals were given equivalent training at two or more separate times before damage to the fornix or hippocampal formation. Eleven of these studies found temporally graded retrograde amnesia, with the extent of amnesia ranging from several days to a month or two. We consider these studies and also suggest why temporally graded retrograde amnesia has sometimes not been observed. Although the evidence in favor of temporally graded retrograde amnesia is substantial, the inference from this work, that memory is reorganized as time passes, is rather vague and depends on mechanisms yet to be identified. It is therefore encouraging that many opportunities exist for moving beyond purely descriptive studies to studies that involve treatments or manipulations directed toward yielding information about mechanisms.

Amnesia, Retrograde↗

PubMed2001

Relationship between magnitude of damage to the hippocampus and impaired recognition memory in monkeys.

Two recent meta-analyses, drawing on data from many of the same studies with monkeys, reached different conclusions about the relationship between hippocampal damage and recognition memory performance. Both studies found evidence of recognition memory impairment following hippocampal damage. However, Zola et al. (J Neurosci 2000;20:451-463) found no significant correlation between extent of hippocampal damage and recognition memory performance, whereas Baxter and Murray (Hippocampus 2001;11:61-71) concluded that the extent of hippocampal damage in monkeys was inversely correlated with impaired performance. Here, we first consider the requirements for carrying out a valid meta-analysis, and point out that the analysis carried out by Baxter and Murray (Hippocampus 2001;11:61-71) is invalid on simple statistical grounds. We then adopt the appropriate statistical procedures (multiple regression analyses rather than simple correlational analysis) to assess the relationship between extent of hippocampal damage and recognition performance across different studies. None of these analyses, including a reanalysis of the data of Baxter and Murray (Hippocampus 2001;11:61-71), revealed a significant inverse relationship between lesion size and behavioral impairment. Most of the variance was explained by differences between the studies that contributed to the meta-analysis, not by lesion size itself. Indeed, analysis of covariance indicated that there were differences among the studies beyond lesion size that significantly affected performance. Finally, we consider what relationship might hold between lesion size and memory performance in the monkey.

Animals↗

PubMed2001

Rats with lesions of the hippocampus are impaired on the delayed nonmatching-to-sample task.

Rats with ibotenic acid lesions of the hippocampus (H-IBO) were trained on the trial-unique delayed nonmatching-to-sample task (DNMS) using a short delay of 4 s. The H-IBO group learned the nonmatching rule as quickly as control animals. However, performance was impaired on the DNMS task when the delay between the sample and choice phase was increased to 1 or 2 min. The use of 4-s delay (probe) trials indicated that the H-IBO animals retained the nonmatching-to-sample rule throughout testing. In a second experiment, using the same groups of rats, extended training at the 1-min delay did not ameliorate the deficit produced by H-IBO lesions. The finding of impaired recognition memory in rats after hippocampal lesions is consistent with findings from humans and monkeys. Several methodological issues are considered that have complicated the interpretation of earlier studies of recognition memory in rats following hippocampal lesions. The capacity for recognition memory in humans, monkeys, and rodents is discussed as a straightforward example of hippocampus-dependent (declarative) memory.

Animals↗

PubMed2001

Perceptual learning, awareness, and the hippocampus.

Declarative memory depends on the hippocampus and related medial temporal lobe and diencephalic structures. Declarative memory has usually been found to be available to conscious recollection. A recent study (Chun and Phelps, Nat Neurosci 1999;2:844-847) found that damage to the medial temporal lobe (including the hippocampus) impaired performance on a perceptual learning task, yet the learning was accomplished in the absence of memory for the stimuli. This finding raised the possibility that some hippocampus-dependent tasks may be inaccessible to awareness and may be performed without evoking conscious memory processes. Using the same task, we show that when damage is confined largely to the hippocampal formation, perceptual learning is intact. Thus, the available data suggest that damage limited to the hippocampal formation does not impair nonconscious (nondeclarative) memory. Further, the data do not contradict the idea that hippocampus dependent memory is accessible to conscious recollection. Finally, perceptual learning was impaired in patients, with extensive damage to the medial temporal lobe and with additional variable damage to lateral temporal cortex.

Aged↗

PubMed2001

Trace and delay eyeblink conditioning: contrasting phenomena of declarative and nondeclarative memory.

We tested the proposal that trace and delay eyeblink conditioning aref fundamentally different kinds of learning. Strings of one, two, three, or four trials with the conditioned stimulus (CS) alone and strings of one, two, three, or four trials with paired presentations of both the CS and the unconditioned stimulus (US) occurred in such a way that the probability of a US was independent of string length. Before each trial, participants predicted the likelihood of the US on the next trial. During both delay (n = 20) and trace (n = 18) conditioning, participants exhibited high expectation of the US following strings of CS-alone trials and low expectation of the US following strings of CS-US trials--a phenomenon known as the gambler's fallacy. During delay conditioning, conditioned responses (CRs) were not influenced by expectancy but by the associative strength of the CS and US. Thus, CR probability was high following a string of CS-US trials and low following a string of CS-alone trials. The results for trace conditioning were opposite. CR probability was high when expectancy of the US was high and low when expectancy of the US was low: The results show that trace and delay eyeblink conditioning are fundamentally different phenomena. We consider how the findings can be understood in terms of the declarative and nondeclarative memory systems that support eyeblink classical conditioning.

Adolescent↗

PubMed2001

Impaired perception of facial emotions following bilateral damage to the anterior temporal lobe.

Two patients (E.P. and G.T.) were previously described with damage to amygdala and anterior temporal cortex (S.B. Hamann et al., 1996). Both rated emotions in facial expressions normally (the rating task) when the data analysis followed a method that had revealed an impairment in the well-studied patient S.M. The present study reports findings for a 3rd patient (G.P.) with the rating task and reexamines the data for E.P. and G.T. All 3 patients were also given a labeling task in which they selected, from a list of 6 words, which word they thought best described the emotion expressed by a face. All 3 patients were unmistakably impaired on both tasks. However, the impairment exhibited by these patients is different from S.M.'s impairment. The difference may depend on the etiology (congenital vs. adult-onset lesion) or the site of the damage (relatively selective amygdala damage vs. damage to amygdala as well as anterior temporal cortex).

Aged↗

PubMed2000

Impaired recognition memory in rats after damage to the hippocampus.

Rats with radio-frequency or ibotenic acid lesions of the hippocampus and rats with radio-frequency lesions of the fornix were tested on the visual paired comparison task (VPC), a test of recognition memory. Memory was assessed at five different delay intervals ranging from 10 sec to 24 hr. All operated groups performed normally at the shorter delays (10 sec and 1 min). Across longer delays, the two groups with hippocampal damage were impaired. Rats with fornix lesions performed well on the VPC task but were impaired on a spatial task (spontaneous alternation). The results show that the hippocampus is essential for normal recognition memory. Moreover, fornix lesions need not mimic the effects of direct damage to hippocampal tissue. The findings are discussed in the context of the contribution of the hippocampus to recognition memory.

Animals↗

PubMed2000

Neuroscience: breaking down scientific barriers to the study of brain and mind.

In this month's essay, Eric R. Kandel and Larry R. Squire chronicle how brain research has migrated from the peripheries of biology and psychology to assume a central position within those disciplines. The multidiscipline of neuroscience that emerged from this process now ranges from genes to cognition, from molecules to minds.

Animals↗

PubMed2000

The visual paired-comparison task as a measure of declarative memory.

Performance on the visual paired-comparison task depends on the integrity of the hippocampal formation in humans, monkeys, and, for an analogous task, in rats. The present study sought additional evidence in healthy volunteers concerning the nature of this task. We found that performance on the visual paired-comparison task was predictive of subsequent recognition memory performance whereas perceptual priming was unrelated to subsequent recognition memory performance. The results are consistent with the data from lesions and suggest that performance on the visual paired-comparison task measures a form of declarative memory.

Humans↗

PubMed2000

Functional magnetic resonance imaging (fMRI) activity in the hippocampal region during recognition memory.

Neuroimaging studies have often failed to observe activity in the hippocampal region during memory retrieval. Recently, two functional magnetic resonance imaging studies reported activity in the hippocampal region associated with recollective success. In both, participants studied pictures of objects and were given a recognition memory test with words that either did or did not name the studied objects. The recognition test was therefore cross-modal or associative in nature. These findings raise the question of what circumstances are required to observe activity in the hippocampal region during memory retrieval. Here, we report that robust hippocampal activity for targets relative to foils occurred during retrieval in a recognition memory task when single words were used at both study and test, as well as when pictures of single nameable objects were used at both study and test. The hippocampal region is involved not just in overtly associative tasks but more broadly in the recollection of recently occurring facts and events.

Adolescent↗

PubMed2000

Profound amnesia after damage to the medial temporal lobe: A neuroanatomical and neuropsychological profile of patient E. P.

E. P. became profoundly amnesic in 1992 after viral encephalitis, which damaged his medial temporal lobe bilaterally. Because of the rarity of such patients, we have performed a detailed neuroanatomical analysis of E. P.'s lesion using magnetic resonance imaging, and we have assessed his cognitive abilities with a wide range of neuropsychological tests. Finally, we have compared and contrasted the findings for E. P. with the noted amnesic patient H.M, whose surgical lesion is strikingly similar to E. P.'s lesion.

Aged↗

PubMed2000

Contrasting effects on discrimination learning after hippocampal lesions and conjoint hippocampal-caudate lesions in monkeys.

Eighteen monkeys with lesions of the hippocampal region (the hippocampus proper, the dentate gyrus, and the subiculum) made by an ischemic procedure, radio frequency, or ibotenic acid were tested on a simple, two-choice object discrimination learning task that has been shown to be sensitive to large lesions of the medial temporal lobe. The monkeys were also tested on two other discrimination tasks (pattern discrimination and eight-pair concurrent discrimination) that can be learned normally by monkeys with large medial temporal lobe lesions. All of the lesion groups were impaired at learning the simple object discrimination task. Seven of the monkeys who had sustained damage to the hippocampal region also sustained damage to the tail of the caudate nucleus. These seven monkeys, but not the other 11 monkeys with hippocampal lesions, were impaired on pattern discrimination and concurrent discrimination learning. The results suggest that the hippocampal region is important for learning easy, two-choice discriminations, whereas the caudate nucleus is necessary for the normal learning of more difficult, gradually acquired discrimination tasks. The findings support the distinction between declarative memory, which depends on the hippocampus and related medial temporal lobe structures, and habit learning, which depends on the caudate nucleus.

Animals↗

PubMed2000

Impaired recognition memory in monkeys after damage limited to the hippocampal region.

Monkeys with lesions limited to the hippocampal region (the hippocampus proper, the dentate gyrus, and the subiculum) were impaired on two tasks of recognition memory: delayed nonmatching to sample and the visual paired-comparison task. Recognition memory was impaired in five different groups of monkeys, whether the lesions were made by an ischemic procedure, by radio frequency, or by ibotenic acid. The finding that the hippocampal region is essential for normal recognition memory performance is considered in the context of current ideas about the role of the hippocampus in declarative memory.

Animals↗