PubMed HealthSearch

Biomedical subjects

L R Squire

Publications and source records attributed to L R Squire.

At least 19 recordsLinked to original sources

Impairment of long-term memory and sparing of short-term memory in monkeys with medial temporal lobe lesions: a response to Ringo.

During the last decade, an animal model of human amnesia was developed in the monkey. Studies using this model have identified structures in the medial temporal lobe that are essential for forming long-term memory (i.e. the hippocampus and the entorhinal, perirhinal and parahippocampal cortices). Recently, an important aspect of these studies was questioned by Ringo (Behav. Brain Res., 42 (1991) 123-134). He suggested that the data from the delayed non-matching-to-sample task, which has been extensively used in these studies, have been analyzed in a potentially misleading way. He reanalyzed the data from several laboratories by transforming percent correct data to a discriminability (d') measure based on signal detection theory. In monkeys with lesions, performance appeared to be equivalently impaired at short and long retention delays. He concluded that the data do not support the idea that medial temporal lobe damage produces an impairment in long-term memory, but not short-term memory. However, most of the studies he analyzed were not designed to address the distinction between short-term and long-term memory. We show here that, in studies designed to compare short-term and long-term memory directly, medial temporal lobe lesions impair long-term memory while leaving short-term memory intact. This result is obtained whether the data are analyzed using a percent correct measure, the d' measure, or an arcsine transform.

Animals

Activation of the hippocampus in normal humans: a functional anatomical study of memory.

We studied regional cerebral blood flow using the H2(15)O method while normal subjects performed four similar tasks involving three-letter word beginnings (stems). Prior to each task, subjects studied a list of words. Local blood flow was then monitored during a 40-sec period while subjects (i) silently viewed word stems, (ii) completed stems to form the first words to come to mind, but the stems were not the beginnings of any study words (baseline), (iii) completed stems and half of them could form study words (priming), or (iv) tried to recall study words, and half of the stems could form these words (memory). There were three major findings. (i) The memory task engaged the right hippocampal region when the memory task was compared to either the baseline or the priming condition. The right hemispheric locus suggests that performance is driven by the visual characteristics of the words rather than by semantic or phonetic analysis. (ii) In the priming-minus-baseline comparison, there was reduction in blood flow in the right posterior cortex. (iii) Right prefrontal cortex was activated in the memory-minus-baseline condition. The results provide evidence for selective activation of the human hippocampal region in association with memory function. The results also lead to a suggestion about the neural basis of repetition priming: following presentation of a stimulus, less neural activity is required to process the same stimulus.

Adult

Intact verbal and nonverbal short-term memory following damage to the human hippocampus.

Short-term memory was assessed in two groups of amnesic patients. Six patients had confirmed or suspected damage to the hippocampal formation, and six patients had diencephalic damage as a result of alcoholic Korsakoff's syndrome. Verbal short-term memory was evaluated with seven separate administrations of the standard digit span test in order to obtain a precise measure of short-term memory. Nonverbal short-term memory was evaluated with four tests that assessed apprehension, retention, and the ability to manipulate nonverbal material--all within the span of immediate memory. One of these four tests assessed short-term memory for spatial location. Patients with damage to the hippocampal formation had a digit span equivalent to that of control subjects and also performed normally on the four tests of nonverbal short-term memory. The patients with Korsakoff's syndrome had a marginally low digit span and performed poorly on three of the four nonverbal tasks, a finding consistent with the deficits in attention and visuospatial processing previously described for this patient group. These deficits are likely due to the frontal lobe atrophy typically associated with Korsakoff's syndrome, rather than to diencephalic damage. The results support the view that short-term (immediate) memory, including short-term spatial memory, is independent of the hippocampus.

Aged

Componential analysis of problem-solving ability: performance of patients with frontal lobe damage and amnesic patients on a new sorting test.

A new sorting task designed to isolate and measure specific components of problem-solving ability was administered to four subject groups: patients with focal frontal lobe lesions, patients with both frontal dysfunction and amnesia (Korsakoff's syndrome), patients with circumscribed (non-Korsakoff) amnesia, and normal control subjects. The patients with circumscribed (non-Korsakoff) amnesia, and normal control subjects. The patients with frontal lobe lesions and patients with Korsakoff's syndrome were impaired on eight of the nine components of the task. The findings run counter to theories of a single or primary impairment in patients with frontal lobe dysfunction. Rather, the results suggest that a wide spectrum of deficits in abstract thinking, cognitive flexibility, and use of knowledge to regulate behavior contributes to the problem-solving impairment of these patients. Although the (non-Korsakoff) amnesic patients performed similarly to normal subjects on most measures, a finer analysis suggested that successful performance on this complex sorting task, in addition to being strongly dependent upon frontal lobe function, is mildly dependent upon memory function.

Alcohol Amnestic Disorder

Influence of prior events on cognitive judgments in amnesia.

Amnesic patients and control Ss read the names of famous and nonfamous persons. Subsequently, both groups were more likely to designate a name as famous if it had been encountered previously. The facilitatory effect of prior presentation was similar for amnesic patients and control Ss and similar for famous and nonfamous names. For amnesic patients, the effect occurred despite severely impaired recognition memory for the names. In a 2nd experiment, recombining the first and last names that had been presented together did not diminish the facilitatory effect of prior presentation, which indicates that the effect does not depend on forming an association between first and last names. The results show that nondeclarative (implicit) memory can support the acquisition of information that is specific (e.g., names of persons) and that has no preexisting representation (e.g., nonfamous names).

Aged

Form-specific visual priming in the right cerebral hemisphere.

Results of 4 experiments indicate that both within-modality and case-specific visual priming for words are greater when test stimuli are presented initially to the right cerebral hemisphere (RH). In contrast, neither within-modality nor case-specific explicit memory for words is greater when stimuli are presented initially to the RH. Priming is measured using word-stem completion, and explicit memory is measured using word-stem cued recall. In both cases, Ss first rate how much they like words, and then word stems are presented briefly to the RH (in the left visual field) or to the left hemisphere (in the right visual field). Results suggest that at least 2 separate systems encode the visual representations that produce priming. The system that is more effective in the RH is better at representing form-specific information, whereas another system that is not more effective in the RH does not distinguish among distinct instances of word forms.

Adult

Intact and long-lasting repetition priming in amnesia.

In 2 experiments, we evaluated the ability of amnesic patients to exhibit long-lasting perceptual priming after a single exposure to pictures. Ss named pictures as quickly as possible on a single occasion, and later named the same pictures mixed with new pictures. In Experiment 1, amnesic patients exhibited fully intact priming effects lasting at least 7 days. In Experiment 2, the priming effect for both groups was shown to depend on both highly specific visual information and on less visual, more conceptual information. In contrast, recognition memory was severely impaired in the patients, as assessed by both accuracy and response time. The results provide the first report of a long-lasting priming effect in amnesic patients, based on a single encounter, which occurs as strongly in the patients as in normal Ss. Together with other recent findings, the results suggest that long-lasting priming and recognition memory depend on separate brain systems.

Adult

On the relationship between recall and recognition memory.

The relationship between recall and recognition has been a central topic for the study of memory. A test of alternative views about recall and recognition was arranged by studying amnesic patients. In amnesia, damage has occurred to a brain system important for declarative (conscious) memory, but skill learning, priming, and other forms of nonconscious memory are intact. Recall and recognition were found to be proportionately impaired in amnesic patients, and confidence ratings for the recognition judgments were commensurate with the level of impaired performance. The results are contrary to views that either recognition memory or associated confidence judgments are ordinarily supported significantly by nonconscious memory. The results favor the view that recall and recognition are related functions of declarative memory and equivalently dependent on the brain system damaged in amnesia.

Aged

Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans.

This article considers the role of the hippocampus in memory function. A central thesis is that work with rats, monkeys, and humans--which has sometimes seemed to proceed independently in 3 separate literatures--is now largely in agreement about the function of the hippocampus and related structures. A biological perspective is presented, which proposes multiple memory systems with different functions and distinct anatomical organizations. The hippocampus (together with anatomically related structures) is essential for a specific kind of memory, here termed declarative memory (similar terms include explicit and relational). Declarative memory is contrasted with a heterogeneous collection of nondeclarative (implicit) memory abilities that do not require the hippocampus (skills and habits, simple conditioning, and the phenomenon of priming). The hippocampus is needed temporarily to bind together distributed sites in neocortex that together represent a whole memory.

Animals

Nonverbal priming in amnesia.

In this experiment, we examined whether a group of well-characterized amnesic patients would exhibit normal priming for novel nonverbal materials after a single exposure. Both amnesic patients and normal control subjects studied line figures and were then given a priming test in which they were asked to reproduce both old (studied) and new (unstudied) figures after a brief exposure. The measure of priming was the number of old patterns drawn correctly relative to the number of new patterns drawn correctly. Both subject groups reproduced more old patterns than new patterns, and the effect was similar in the two groups. In contrast, amnesic patients were significantly impaired on a recognition memory test for the items that had been presented. This study contributes to recent evidence that implicit memory can support the rapid acquisition of novel verbal and nonverbal information. Perceptual priming for such material is independent of the structures damaged in amnesia.

Aged

Equivalent forgetting rates in long-term memory for diencephalic and medial temporal lobe amnesia.

Amnesia can result from damage to either the midline diencephalon or the medial temporal lobe. An important related question has been whether these two forms of amnesia result in similar or different kinds of memory impairment. Earlier studies raised the possibility that differences might exist in the rate of forgetting within long-term memory, specifically, that the forgetting rate is normal in diencephalic amnesia but abnormally rapid in medial temporal lobe amnesia. In the present study, forgetting was studied in five amnesic patients with damage to the medial temporal lobe, six amnesic patients with damage to the diencephalon, and 10 normal subjects. One hundred twenty pictures were presented to the control subjects for 1 sec each and to the amnesic patients for 8 sec each. Retention was then tested after 10 min, 2 hr, and 30-32 hr using four different procedures for testing recognition memory. The different exposure times for the pictures succeeded in matching the performance scores of both groups of amnesic patients and the control subjects at the 10 min retention interval. Both groups of amnesic patients also performed similarly to control subjects at retention delays of 2 hr and 30-32 hr. In addition, performance was nearly identical, regardless whether recognition memory was assessed by asking subjects to select the new items or the old items. The findings emphasize the similarities between medial temporal lobe and diencephalic amnesia.

Aged

Enduring memory impairment in monkeys after ischemic damage to the hippocampus.

Patient RB became amnesic following an episode of global ischemia that resulted in a bilateral lesion of the CA1 field of the hippocampus. This finding suggested that damage restricted to the hippocampus is sufficient to produce clinically significant memory impairment. To evaluate further the effect of ischemic brain damage on memory, we have developed an animal model of cerebral ischemia in the monkey. Monkeys were subjected to 15 min of reversible ischemia, using a noninvasive technique involving carotid occlusion and pharmacologically induced hypotension. These monkeys sustained significant loss of pyramidal cells in the CA1 and CA2 fields of the hippocampus, as well as loss of somatostatin-immunoreactive cells in the hilar region of the dentate gyrus. Cell loss occurred bilaterally throughout the rostrocaudal extent of the hippocampus but was greater in the caudal portion. Except for patchy loss of cerebellar Purkinje cells, significant damage was not detected in areas outside the hippocampus, including adjacent cortical regions, that is, entorhinal, perirhinal, and parahippocampal cortex, and other regions that have been implicated in memory function. On behavioral tests, the ischemic monkeys exhibited significant and enduring memory impairment. On the delayed nonmatching to sample task, the ischemic monkeys were as impaired as monkeys with lesions of the hippocampal formation and adjacent parahippocampal cortex (the H+ lesion). On two other memory tasks, the ischemic monkeys were less impaired than monkeys with the H+ lesion. In neuropathological evaluations, it has always been difficult to rule out the possibility that significant areas of neuronal dysfunction have gone undetected. The finding that ischemic lesions produced overall less memory impairment than H+ lesions indicates that the ischemic monkeys (and by extension, patient RB) are unlikely to have widespread neuronal dysfunction affecting memory that was undetected by histological examination. These results provide additional evidence that the hippocampus is a focal site of pathological change in cerebral ischemia, and that damage limited to the hippocampus is sufficient to impair memory.

Amnesia

The medial temporal lobe memory system.

Studies of human amnesia and studies of an animal model of human amnesia in the monkey have identified the anatomical components of the brain system for memory in the medial temporal lobe and have illuminated its function. This neural system consists of the hippocampus and adjacent, anatomically related cortex, including entorhinal, perirhinal, and parahippocampal cortices. These structures, presumably by virtue of their widespread and reciprocal connections with neocortex, are essential for establishing long-term memory for facts and events (declarative memory). The medial temporal lobe memory system is needed to bind together the distributed storage sites in neocortex that represent a whole memory. However, the role of this system is only temporary. As time passes after learning, memory stored in neocortex gradually becomes independent of medial temporal lobe structures.

Amnesia

Independence of memory functions and emotional behavior: separate contributions of the hippocampal formation and the amygdala.

Structures and connections in the medial temporal lobe of humans and nonhuman primates have long been recognized as important for normal memory and emotional behavior. The present study investigated memory and emotional behavior in normal monkeys and six groups of monkeys with lesions of the medial temporal lobe. Two groups had damage to the hippocampal formation (or adjacent perirhinal and parahippocampal cortex) but not the amygdaloid complex; two groups had either partial or complete damage to the amygdaloid complex but not the hippocampal formation; and two groups had damage to both the hippocampal formation and the amygdaloid complex. Memory was evaluated with three tasks sensitive to human amnesia: (1) delayed nonmatching to sample; (2) retention of object discriminations; and (3) concurrent discrimination learning. Emotional behavior was assessed by measuring the responsiveness of monkeys to 12 different stimulus situations. Damage to the hippocampal formation or anatomically related cortex impaired memory but did not affect emotional behavior. Partial or complete damage to the amygdaloid complex affected emotional behavior but not memory. These findings show that memory impairment and abnormal emotional behavior are anatomically dissociable and independent effects of damage to the medial temporal lobe.

Amygdala

Equivalent impairment of spatial and nonspatial memory following damage to the human hippocampus.

The hippocampus has sometimes been proposed to function as a cognitive map, a memory system that stores information about allocentric space. Work with experimental animals and memory-impaired patients has raised difficulties with this view by showing that the hippocampus is not performing an exclusively spatial function. However, the possibility has remained that the hippocampus plays a special role in spatial memory or a disproportionately large role in spatial memory compared to other kinds of memory. This study compared spatial and nonspatial memory in amnesic patients with lesions of the hippocampal formation or diencephalon. Subjects studied an array of 16 toy objects and were subsequently tested for object recall, object recognition, and memory for the location of the objects. Control subjects were tested after long retention intervals in order to equate their object memory performance with that of the patients. The main finding was that, when the performance of amnesic patients on the object memory tests was matched to the object memory performance of control subjects, spatial memory performance of the amnesic patients also matched the spatial memory performance of the control subjects. The results were the same for the two groups of patients. These findings suggest that the hippocampus is not especially involved in spatial memory. Spatial memory is simply one instance of a broader category of memory that requires the hippocampus. While cognitive mapping in its most abstract sense may describe hippocampal function, our results support alternative formulation, suggesting that the hippocampus is necessary for the rapid acquisition of relational, configural, or declarative (as opposed to purely spatial) information.

Adult

Stereotaxic lesions of the hippocampus in monkeys: determination of surgical coordinates and analysis of lesions using magnetic resonance imaging.

A technique is described for producing accurate stereotaxic lesions of the hippocampus in monkeys. This technique overcomes the problem that the size and shape of the brain can vary considerably from monkey to monkey. Magnetic resonance imaging (MRI) is used to create an individual brain atlas for each monkey. The atlas is then used to derive coordinates for making stereotaxic radio frequency lesions of the hippocampus. There are two key features of this procedure. First, a specially-designed, acrylic, stereotaxic headholder was constructed that could be used safely with the MR magnet. Second, small glass beads, anchored to the skull of the monkey, served as common landmarks from which lesion coordinates were determined in the MR images and then again in neurosurgery. MRI techniques are also described for determining the extent of tissue damage postoperatively. This technique could also prove useful in other areas of neuroscience research that depend on accurate stereotaxic placement of electrodes (e.g., electrophysiological studies and neuroanatomic tracing studies).

Animals

Normal acquisition of novel verbal information in amnesia.

Amnesic patients (n = 9) and normal subjects (n = 12) read lists of unique words, repeated words, unique nonwords, and repeated nonwords as quickly as possible. In the first experiment both groups of subjects read the lists of repeated items faster than the lists of unique items and improved at the same rate within each list. In the second experiment, subjects read four new lists of items and then reread the same four lists after a 10-min delay. The results replicated the findings from the first experiment and demonstrated in addition that the facilitated reading speed persisted across the delay. These results show that the acquisition of novel verbal information can be supported by nondeclarative (implicit) memory. It is suggested that facilitated reading speed for words and nonwords reflects changes in early-stage perceptual systems and that these changes occur independently of the brain structures damaged in amnesia.

Aged