Memory functions six to nine months after electroconvulsive therapy. 1975.
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Depressive Disorder↗
Biomedical subjects
L R Squire
Publications and source records attributed to L R Squire.
Memory, memory impairment, and the medial temporal lobe.
The cognitive and neuroanatomical work described here should be viewed as a first step in analyzing how the brain has organized its memory functions, which can open the door to more detailed neurobiological analysis. With respect to declarative memory, it should soon be possible to study representations directly in neocortex with the technique of single-cell recording, to observe directly the development of neuronal plasticity important for declarative memory, and to determine how the medial temporal lobe interacts with neocortex during learning, consolidation, and retrieval. In this regard, the paradigms developed by Miyashita and his colleagues appear to hold particular promise (Sakai and Miyashita 1991; Higuchi and Miyashita 1996). With respect to nondeclarative memory, it is now possible to identify particular brain systems that are essential for particular kinds of memory. An important next step will be to determine whether these systems are essential for the acquisition, storage, or expression of memory, and to identify exactly where the synaptic changes occur that support each kind of memory.
Animals↗
Learning about categories in the absence of memory.
A fundamental question about memory and cognition concerns how information is acquired about categories and concepts as the result of encounters with specific instances. We describe a profoundly amnesic patient (E.P.) who cannot learn and remember specific instances--i.e., he has no detectable declarative memory. Yet after inspecting a series of 40 training stimuli, he was normal at classifying novel stimuli according to whether they did or did not belong to the same category as the training stimuli. In contrast, he was unable to recognize a single stimulus after it was presented 40 times in succession. These findings demonstrate that the ability to classify novel items, after experience with other items in the same category, is a separate and parallel memory function of the brain, independent of the limbic and diencephalic structures essential for remembering individual stimulus items (declarative memory). Category-level knowledge can be acquired implicitly by cumulating information from multiple training examples in the absence of detectable conscious memory for the examples themselves.
Aged↗
The deferred imitation task as a nonverbal measure of declarative memory.
We tested amnesic patients, patients with frontal lobe lesions, and control subjects with the deferred imitation task, a nonverbal test used to demonstrate memory abilities in human infants. On day 1, subjects were given sets of objects to obtain a baseline measure of their spontaneous performance of target actions. Then different event sequences were modeled with the object sets. On day 2, the objects were given to the subjects again, first without any instructions to imitate the sequences, and then with explicit instructions to imitate the actions exactly as they had been modeled. Control subjects and frontal lobe patients reproduced the events under both uninstructed and instructed conditions. In contrast, performance by the amnesic patients did not significantly differ from that of a second control group who had the same opportunities to handle the objects but were not shown the modeled actions. These findings suggest that deferred imitation is dependent on the brain structures essential for declarative memory that are damaged in amnesia, and they support the view that infants who imitate actions after long delays have an early capacity for long-term declarative memory.
Aged↗
Retrograde amnesia and memory consolidation: a neurobiological perspective.
The fact that information acquired before the onset of amnesia can be lost (retrograde amnesia) has fascinated psychologists, biologists, and clinicians for over 100 years. Studies of retrograde amnesia have led to the concept of memory consolidation, whereby medial temporal lobe structures direct the gradual establishment of memory representations in neocortex. Recent theoretical accounts have inspired a simple neural network model that produces behavior consistent with experimental data and makes these ideas about memory consolidation more concrete. Recent physiological and anatomical findings provide important information about how memory consolidation might actually occur.
Amnesia, Retrograde↗
Remembering and knowing: two different expressions of declarative memory.
Amnesic patients and a control group were given a recognition test 10 min after studying words. For each recognized word, participants indicated whether they remembered it (R) or whether simply they knew that the word was presented but had no recollections about it (K). The patients were impaired for both R and K responses, performing like a control group tested after 1 week. Another control group was tested both 10 min and 1 week after study. The proportion of words initially eliciting an R response and later eliciting a K response exceeded the proportion of K responses that shifted to R responses. These data are accounted for if items initially eliciting R responses can also elicit K responses. We conclude that the R-K distinction does not reflect the operation of explicit and implicit memory but reflects instead a distinction within declarative memory. Thus, K responses depend on brain structures damaged in amnesia; R responses depend on these same structures and also on the frontal lobes for contextual information.
Aged↗
On the acquisition of new declarative knowledge in amnesia.
In 2 experiments, the acquisition of new declarative knowledge was examined in amnesic patients and in 7 groups of controls, with a study-only procedure that delayed testing until the conclusion of training. The study-only procedure was compared with a standard procedure in which study and test trials alternated (study-test). The amnesic patients acquired new factual (declarative) knowledge at an abnormally slow rate, learning more with the study-only procedure than with the study-test procedure. Controls exhibited the opposite pattern. The advantage of the study-only procedure for amnesic patients was related to the presence of frontal lobe dysfunction. The 2 groups exhibited a similar ability to use their knowledge flexibly, suggesting that the information acquired by amnesic patients was based on their residual capacity for declarative memory. In addition, the capacity for factual learning in amnesia was proportional to the capacity to recollect specific events in the learning session.
Aged↗
Transient memory impairment in monkeys with bilateral lesions of the entorhinal cortex.
Performance on five behavioral tasks was assessed post-operatively in Macaca fascicularis monkeys prepared with bilateral lesions of the entorhinal cortex (E group). Three of the tasks were also readministered 9-14 months after surgery. Initial learning of the delayed nonmatching-to-sample (DNMS) task was impaired in the E animals relative to unoperated control monkeys. On the delay portion of DNMS, the performance of E animals was nearly at control levels at short delays (up to 60 sec) but was impaired at 10 min and 40 min retention intervals. On the retest of DNMS, the E animals performed normally at all retention intervals. The E animals were unimpaired on the four other memory tasks. Neuroanatomical studies revealed a significant transverse expansion of the terminal field of the perirhinal cortical projection in the CA1 region of the hippocampus. Compared to unlesioned, anatomical control monkeys, the transverse length of the perirhinal terminal field in CA1 increased approximately 70% in the E monkeys. Although this was a striking morphological alteration, it is not known whether the sprouting of this projection influenced the behavioral recovery. The results of these studies suggest that the entorhinal cortex may normally participate in the learning and performance of tasks that are dependent on the medial temporal lobe memory system. However, recovery of normal DNMS performance demonstrates that the entorhinal cortex is not, by itself, essential for learning and performance of such tasks.
Animals↗
Damage limited to the hippocampal region produces long-lasting memory impairment in monkeys.
Research in humans and monkeys has demonstrated a system of anatomically related structures in the medial temporal lobe that is important for memory function. This system is comprised of the hippocampal region (i.e., the dentate gyrus, hippocampus proper and subicular complex) and the entorhinal, perirhinal, and parahippocampal cortices. While the hippocampal region has long been thought to be important in memory, there are few systematic studies in primates of the effects on memory of damage limited to the hippocampal region. We have used magnetic resonance imaging techniques, together with a stereotaxic approach, to produce bilateral lesions limited to the hippocampal region (the H lesion). Damage to the adjacent perirhinal, entorhinal, and parahippocampal cortex was minimal. Monkeys with the H lesion exhibited significant and long-lasting impairment on the delayed non-matching to sample task. At the same time, on this and other amnesia-sensitive tasks, monkeys with the H lesion performed better overall than monkeys with lesions of the hippocampal region that also included damage to the adjacent entorhinal and parahippocampal cortices (the H+ lesion). These findings show that, first, the hippocampal region itself is essential for normal memory function; and second, the adjacent entorhinal and parahippocampal cortices, either alone or in combination, are also an essential component of the medial temporal lobe memory system.
Animals↗
Functional anatomical studies of explicit and implicit memory retrieval tasks.
Across three experiments, PET scans were obtained while subjects performed different word-stem completion and FIXATION control tasks designed to study the functional anatomy of memory retrieval. During each of three different word-stem completion scans, word-stem cues were visually presented in uppercase letters. The RECALL task required explicit retrieval of study words presented prior to the PET scan. The PRIMING task addressed the implicit effects of the prior study words without requiring intentional recall. The BASELINE task encouraged retrieval of information from a general knowledge store. Across experiments, the similarity between study words and word stems was manipulated by presenting prescan study words in either uppercase letters identical to the stems, in lowercase letters, or auditorily. The PRIMING task was not studied with auditory presentation. Many activations were consistent across experiments. The BASELINE task activated several regions in response to the reading and verbal-response demands of the task (visual, motor, and premotor cortices, cerebellum), as well as a left prefrontal region. The RECALL task additionally activated regions in anterior right prefrontal cortex. Bilateral occipitotemporal regions showed blood flow reductions during the PRIMING task as compared to the BASELINE task. Activation in the right hippocampal/parahippocampal region was observed only in one experiment, and no experiment showed activation in the left medial temporal lobe. These experiments suggest that areas of frontal cortex play a role in explicit recall and that an effect of priming may be to require less activation of perceptual regions for the processing of recently presented information.
Adult↗
Memory consolidation and the medial temporal lobe: a simple network model.
Some forms of memory have been shown to depend on a system of medial temporal lobe structures that includes the hippocampus and the adjacent cortical areas (entorhinal, perirhinal, and parahippocampal cortex). The role of this system is only temporary, however, as indicated by the fact that, after damage to the medial temporal lobe, recent memories are impaired but very remote memories are intact. Here we review the evidence that the medial temporal lobe memory system is involved in a process of consolidation: memories are initially dependent on this system but gradually become established in other areas of the brain. We then review some of the ideas that have been proposed about the phenomenon of consolidation and suggest a synthesis of these views. Finally, we describe a simple neural network model that captures some key features of consolidation.
Animals↗
The animal model of human amnesia: long-term memory impaired and short-term memory intact.
Normal monkeys and monkeys with lesions of the hippocampal formation and adjacent cortex (the H+ lesion) were trained on the delayed nonmatching to sample (DNMS) task with a delay of 0.5 s between the sample and the choice. The animals with H+ lesions learned the task normally at this short delay and also exhibited the same pattern of response latencies as normal monkeys. This finding contrasts with previous observations that initial learning of the DNMS task with delays of 8-10 s is impaired after H+ lesions. The absence of an impairment at a delay of 0.5 s indicates that the H+ lesion does not affect short-term memory. In contrast, when monkeys with H+ lesions were tested at longer delays (> 30 s), an impairment was observed. This selective impairment occurred when the delays were presented sequentially (from 0.5 s to 10 min) and also when delays were presented in a mixed order (1 s, 1 min, and 10 min). The data indicate that the H+ lesion produces a selective impairment in long-term memory, in the absence of a detectable deficit in short-term memory or perception. Accordingly, the findings confirm the long-standing idea, based primarily on studies of humans, that short-term memory is independent of medial temporal lobe function. The findings thereby establish an important parallel between memory impairment in monkeys and humans and provide additional support for the validity of the animal model of human amnesia in the monkey.
Amnesia↗
Severity of memory impairment in monkeys as a function of locus and extent of damage within the medial temporal lobe memory system.
During the past decade, work with monkeys has helped identify the structures in the medial temporal lobe that are important for memory: the hippocampal region (including the hippocampus proper, the dentate gyrus, and the subicular complex) and adjacent cortical areas that are anatomically linked to the hippocampus, i.e., the entorhinal, perirhinal, and parahippocampal cortices. One idea that has emerged from this work is that the severity of memory impairment might increase as more components of the medial temporal lobe are damaged. We have evaluated this idea directly by examining behavioral data from 30 monkeys (ten normal monkeys and 20 monkeys with bilateral lesions involving structures within the medial temporal lobe) that have completed testing on our standard memory battery during the last 10 years. The main finding was that the severity of memory impairment depended on the locus and extent of damage to the medial temporal lobe. Specifically, damage limited to the hippocampal region produced a mild memory impairment. More severe memory impairment was produced when the damage was increased to include the adjacent entorhinal and parahippocampal cortices (the H+ lesion). Finally, memory impairment was even more severe when the H+ lesion was extended forward to include the anterior entorhinal cortex and the perirhinal cortex (H++ lesion). Taken together, these findings suggest that, whereas damage to the hippocampal region produces measurable memory impairment, a substantial part of the severe memory impairment produced by large medial temporal lobe lesions in humans and monkeys can be attributed to damage to entorhinal, perirhinal, and parahippocampal cortices adjacent to the hippocampal region.
Animals↗
The information acquired during artificial grammar learning.
In an artificial grammar learning task, amnesic patients classified test items as well as normal subjects did. Item similarity did not affect grammaticality judgments when similar and nonsimilar test items were balanced for the frequency with which bigrams and trigrams (chunks) that appeared in the training set also appeared in the test items. Amnesic patients performed like normal subjects. The results suggest that concrete information about letter chunks can influence gramaticality judgments and that this information is acquired implicitly. The similarity of whole test items to training items does not appear to affect grammaticality judgments.
Aged↗
Memory and forgetting: long-term and gradual changes in memory storage.
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Alcohol Amnestic Disorder↗
The learning of categories: parallel brain systems for item memory and category knowledge.
A fundamental question about cognition concerns how knowledge about a category is acquired through encounters with examples of the category. Amnesic patients and control subjects performed similarly at classifying novel patterns according to whether they belonged to the same category as a set of training patterns. In contrast, the amnesic patients were impaired at recognizing which dot patterns had been presented for training. Category learning appears to be independent of declarative (explicit) memory for training instances and independent of the brain structures essential for declarative memory that are damaged in amnesia. Knowledge about categories can be acquired implicitly by cumulating information from multiple examples.
Aged↗
P300 from amnesic patients with bilateral hippocampal lesions.
P3(00) event-related brain potentials (ERPs) were recorded using auditory and visual stimuli from 5 amnesic patients with confirmed (n = 4) or suspected (n = 1) bilateral damage to the hippocampal formation without skull defects. Four normal control subjects were matched to each amnesic patient with respect to age, sex, education, and IQ subtest scores (n = 20 total controls). All 5 amnesic patients exhibited ERPs, and no reliable differences in P3 amplitude or latency could be detected between the patients and the control subjects in either modality. The findings indicate that the hippocampal formation does not contribute significantly to the scalp-recorded P3 from auditory and visual target stimuli, a conclusion also supported by additional recent findings from studies of patients with extensive bilateral medial temporal lobe damage studies. The significance of the P3 component for cognitive processing is discussed.
Acoustic Stimulation↗
The hippocampus and spatial memory.
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Animals↗