Cognitive neuroscience and the study of memory.
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Animals↗
Biomedical subjects
L R Squire
Publications and source records attributed to L R Squire.
A reexamination of the concurrent discrimination learning task: the importance of anterior inferotemporal cortex, area TE.
For 30 years, the concurrent discrimination learning task has figured prominently in studies used to determine the effects of medial temporal lobe damage in monkeys. However, the findings from these studies have been contradictory. We explored the contribution to concurrent discrimination performance of inadvertent damage to area TE by reexamining the behavioral data and histological material from monkeys with medial temporal lobe lesions previously tested in our laboratory. The amount of inadvertent damage to area TE was more predictive of impaired performance on the concurrent discrimination learning task than was the amount of damage to any medial temporal lobe structure, including the perirhinal cortex. These findings resolve earlier inconsistent findings regarding the concurrent discrimination learning task by demonstrating that performance on this task depends on area TE and not on perirhinal cortex or other medial temporal lobe structures.
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Encapsulation of implicit and explicit memory in sequence learning.
Contrasts between implicit and explicit knowledge in the serial reaction time (SJRT) paradigm have been challenged because they have depended on a single dissociation; intact implicit knowledge in the absence of corresponding explicit knowledge. In the SRT task, subjects respond with a corresponding keypress to a cue that appears in one of four locations. The cue follows a repeating sequence of locations, and subjects can exhibit knowledge of the repeating sequence through increasingly rapid performance (an implicit test) or by being able to recognize the sequence (an explicit test). In our study, amnesic patients were given extensive SRT training. Their implicit and explicit test performance was compared to the performance of control subjects who memorized the training sequence. Compared with control subjects, amnesic patients exhibited superior performance on the implicit task and impaired performance on the explicit task. This crossover interaction suggests that implicit and explicit knowledge of the embedded sequence are separate and encapsulated and that they presumably depend on different brain systems.
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Amnesia, memory and brain systems.
Bilateral damage to either the medial temporal lobe or the diencephalic midline causes an amnesic syndrome, i.e. a global impairment in the ability to acquire new memories regardless of sensory modality, and a loss of some memories, especially recent ones, from the period before amnesia began. The memory deficit can occur against a background of intact intellectual and perceptual functions. Two themes have been prominent in recent work. First, the amnesic syndrome is narrower than once believed in the sense that a number of learning and memory abilities are preserved (e.g. skill and habit learning, simple forms of conditioning and the phenomenon of priming). Second, the brain system damaged in amnesia has only a temporary role in memory. As time passes after learning, memory is reorganized and consolidated within neocortex, such that eventually medial temporal lobe and diencephalic structures are not needed for storage or retrieval.
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Transient global amnesia and functional retrograde amnesia: contrasting examples of episodic memory loss.
We studied 11 patients with transient global amnesia (TGA) and ten patients with functional retrograde amnesia (FRA). Patients with TGA had a uniform clinical picture: a severe, relatively isolated amnesic syndrome that started suddenly, persisted for 4-12 h, and then gradually improved to essentially normal over the next 12-24 h. During the episode, the patients had severe anterograde amnesia for verbal and non-verbal material and retrograde amnesia that typically covered at least two decades. Thirty hours to 42 days after the episode, the patients had recovered completely and performed normally on tests of anterograde and retrograde amnesia. By contrast, patients with FRA had a sudden onset of memory problems that were characterized by severe retrograde amnesia without associated anterograde amnesia and with a clinical presentation that otherwise varied considerably. The episodes persisted from several weeks to more than two years, and some of the patients had not recovered at the time of our last contact with them. The uniform clinical picture of TGA and the variable clinical picture of FRA presumably reflect their respective neurologic ('organic') and psychogenic ('non-organic') aetiologies.
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Impaired recognition memory in patients with lesions limited to the hippocampal formation.
A recent literature survey of results from a widely used recognition memory test raised questions about the extent to which recognition memory impairment ordinarily occurs in human amnesia and, in particular, whether recognition memory is impaired at all after damage limited to the hippocampal region (J. P. Aggleton & C. Shaw, 1996). Experiment 1 examined the performance of 6 amnesic patients on 11 to 25 different recognition memory tests. Three patients had bilateral lesions limited primarily to the hippocampus (G.D.) or the hippocampal formation (W.H. and L.M.), as determined by postmortem, neurohistological analysis (N. Rempel-Clower, S. M. Zola, L. R. Squire, & D. G. Amaral, 1996). All 6 patients exhibited unequivocally impaired recognition memory. In Experiment 2, the 3 patients still available for study were each markedly impaired on a test of object recognition similar to the kind used to test recognition memory in nonhuman primates. Recognition memory impairment is a robust feature of human amnesia, even when damage is limited primarily to the hippocampus.
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Intact perceptual memory in the absence of conscious memory.
Declarative memory enables conscious recollection of the past and has been proposed to be distinct from priming, a perceptual form of memory that operates nonconsciously and improves the ability to detect or identify recently presented stimuli. Yet, it has been difficult to obtain unambiguous evidence for the independence of declarative memory and priming. The authors report the first demonstration, using matched tests, of fully intact perceptual memory (priming) in a profoundly amnesic patient (E.P.), despite at-chance recognition memory. The priming and recognition tests included tests that were matched with respect to test materials, length of the study and test lists, and the kind of cues available at test. Priming appears to reflect neural changes within perceptual processing systems that occur before information reaches the brain systems that transform visual perception into conscious visual memory.
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When amnesic patients perform well on recognition memory tests.
Extended exposure to study material can markedly improve subsequent recognition memory performance in amnesic patients, even the densely amnesic patient H.M. To understand this phenomenon, the severely amnesic patient E.P., 3 other amnesic patients, and controls studied pictorial material and then were given either a yes-no (Experiment 1) or a 2-alternative, forced-choice (Experiment 2) recognition test. The amnesic patients and controls benefited substantially from extended exposure, but patient E.P. consistently performed at chance. Furthermore, confidence ratings corresponded to recognition accuracy. The results do not support the idea that the benefit of extended study time is due to some kind of familiarity process made available through nondeclarative memory. It is likely that amnesic patients benefit from extended study time to the extent that they have residual capacity for declarative memory.
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Emotional perception and memory in amnesia.
The authors examined whether perception of emotional stimuli is normal in amnesia and whether emotional arousal has the same enhancing effect on memory in amnesic patients as it has in healthy controls. Forty standardized color pictures were presented while participants rated each picture according to emotional intensity (arousal) and pleasantness (valence). An immediate free-recall test was given for the pictures, followed by a yes-no recognition test. Arousal and valence ratings were highly similar among the amnesic patients and controls. Emotional arousal (regardless of valence) enhanced both recall and recognition of the pictures, and this enhancement was proportional for amnesic patients and controls. Results suggest that emotional perception and the enhancing effect of emotional arousal on memory are intact in amnesia.
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Structure and function of declarative and nondeclarative memory systems.
This article reviews recent studies of memory systems in humans and nonhuman primates. Three major conclusions from recent work are that (i) the capacity for nondeclarative (nonconscious) learning can now be studied in a broad array of tasks that assess classification learning, perceptuomotor skill learning, artificial grammar learning, and prototype abstraction; (ii) cortical areas adjacent to the hippocampal formation, including entorhinal, perirhinal, and parahippocampal cortices, are an essential part of the medial temporal lobe memory system that supports declarative (conscious) memory; and (iii) in humans, bilateral damage limited to the hippocampal formation is nevertheless sufficient to produce severe anterograde amnesia and temporally graded retrograde amnesia covering as much as 25 years.
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A neostriatal habit learning system in humans.
Amnesic patients and nondemented patients with Parkinson's disease were given a probabilistic classification task in which they learned which of two outcomes would occur on each trial, given the particular combination of cues that appeared. Amnesic patients exhibited normal learning of the task but had severely impaired declarative memory for the training episode. In contrast, patients with Parkinson's disease failed to learn the probabilistic classification task, despite having intact memory for the training episode. This double dissociation shows that the limbic-diencephalic regions damaged in amnesia and the neostriatum damaged in Parkinson's disease support separate and parallel learning systems. In humans, the neostriatum (caudate nucleus and putamen) is essential for the gradual, incremental learning of associations that is characteristic of habit learning. The neostriatum is important not just for motor behavior and motor learning but also for acquiring nonmotor dispositions and tendencies that depend on new associations.
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Three cases of enduring memory impairment after bilateral damage limited to the hippocampal formation.
Patient RB (Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus, S. Zola-Morgan, L. R. Squire, and D. G. Amaral, 1986, J Neurosci 6:2950-2967) was the first reported case of human amnesia in which detailed neuropsychological analyses and detailed postmortem neuropathological analyses demonstrated that damage limited to the hippocampal formation was sufficient to produce anterograde memory impairment. Neuropsychological and postmortem neuropathological findings are described here for three additional amnesic patients with bilateral damage limited to the hippocampal formation. Findings from these patients, taken together with the findings from patient RB and other amnesic patients, make three important points about memory. (1) Bilateral damage limited primarily to the CA1 region of the hippocampal formation is sufficient to produce moderately severe anterograde memory impairment. (2) Bilateral damage beyond, the CA1 region, but still limited to the hippocampal formation, can produce more severe anterograde memory impairment. (3) Extensive, temporally graded retrograde amnesia covering 15 years or more can occur after damage limited to the hippocampal formation. Findings from studies with experimental animals are consistent with the findings from amnesic patients. The present results substantiate the idea that severity of memory impairment is dependent on locus and extent of damage within the hippocampal formation and that damage to the hippocampal formation can cause temporally graded retrograde amnesia.
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Ischemic brain damage and memory impairment: a commentary.
Studies in humans and monkeys have identified structures in the medial temporal lobe essential for memory (the hippocampal region, i.e., the dentate gyrus, the hippocampus, and the subicular complex, and the adjacent perirhinal, entorhinal, and parahippocampal cortices). Additional work has revealed that for both species, damage limited to the hippocampal region produces less severe memory impairment than damage that includes additional structures within the medial temporal lobe. This work has been based on both neurosurgical lesions and on lesions produced by global ischemia or anoxia. An important issue about ischemic damage is whether the damage identifiable in histopathological examination provides an accurate estimate of direct neural damage or whether additional direct damage might be present that is sufficient to disrupt neuronal function in areas important for memory and sufficient to impair behavioral performance, but not sufficient to progress to cell death and to be detectable in conventional histopathology. This commentary explores the issue of ischemic damage and memory impairment. Although few studies have addressed this issue directly, the currently available data from global ischemia in rats, monkeys, and humans are consistent with the hypothesis that the detectable neuronal damage is responsible for the severity of the observed behavioral impairment. Yet it is also true that this hypothesis has not been the target of very much systematic work. We encourage additional experimental work, especially in rats, that could further illuminate how to evaluate the behavioral effects of ischemic lesions.
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Artificial grammar learning depends on implicit acquisition of both abstract and exemplar-specific information.
The contributions of exemplar-specific and abstract knowledge to artificial grammar learning were examined in amnesic patients and controls. In Experiment 1, grammatical rule adherence and chunk strength exerted separate effects on grammaticality judgments. Amnesic patients exhibited intact classification performance, demonstrating the same pattern of results as controls. In Experiment 2, amnesic patients exhibited impaired declarative memory for chunks. In Experiment 3, both amnesic patients and controls exhibited transfer when tested with a letter set different than the one used for training, although performance was better when the same letter sets were used at training and test. The results suggest that individuals learn both abstract information about training items and exemplar-specific information about chunk strength and that both types of learning occur independently of declarative memory.
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Level-of-processing effects in word-completion priming: a neuropsychological study.
Recent reviews (A.S. Brown & D.B. Mitchell, 1994; B. Challis & D.R. Brodbeck, 1992) concluded that level-of-processing (LOP) manipulations affect priming in perceptual tasks, contrary to earlier suggestions that such tasks are insensitive to LOP. In 3 experiments with amnesic patients and control subjects, the authors examined the effect of LOP manipulations on priming in word-stem and word-fragment completion and on recognition memory. Amnesic patients exhibited reduced or near-zero LOP effects in word-completion priming compared with control subjects. LOP affected recognition memory for both amnesic patients and control subjects, confirming that the LOP manipulation affected explicit memory. When the effect of explicit retrieval on control performance was reduced by using a low-level encoding task, priming was the same for amnesic patients and control subjects. The authors suggest that LOP effects in word-completion priming tasks reflect the influence of explicit retrieval, which can be used usefully by control subjects but much less so by amnesic patients.
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Dissociable properties of memory systems: differences in the flexibility of declarative and nondeclarative knowledge.
Amnesic patients (n = 8), who have severely impaired declarative memory, learned a probabilistic classification task at the same rate as normal subjects (n = 16) but subsequently were impaired on transfer tests that required flexible use of their task knowledge. A second group of controls (n = 20) rated the questions on the transfer tests according to whether the questions simply reinstated the training conditions or required flexible use of task knowledge. The amnesic patients tended to be impaired on the same items that were rated as requiring indirect or flexible use of knowledge. Thus, control subjects acquired declarative knowledge about the task that could be applied flexibly to the transfer tests. The nondeclarative memory available to amnesic patients was relatively inflexible and available only in conditions that reinstantiated the conditions of training. These findings show that declarative memory has different operating characteristics than nondeclarative memory.
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