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Integrated memory for objects, places, and temporal order: evidence for episodic-like memory in mice.

Human episodic memory refers to the recollection of an unique past experience in terms of what happened, and where and when it happened. Factoring out the issue of conscious recollection, episodic memory, even at the behavioral level, has been difficult to demonstrate in non-human mammals. Although, it was previously shown that rodents can associate what and when or what and where information given on unique trials, it proved to be difficult to demonstrate memory for what, where, and when simultaneously in mammals, without using extensive training procedures, which might induce semantic rather than episodic memory recall. Towards the goal of an animal model of human episodic memory we designed an three-trial object exploration task in which different versions of the novelty-preference paradigm were combined to subsume (a) object recognition memory, (b) the memory for locations in which objects were explored, and (c) the temporal order memory for object presented at distinct time points. We found that mice spent more time exploring two "old familiar" objects relative to two "recent familiar" objects, reflecting memory for what and when and concomitantly directed more exploration at a spatially displaced "old familiar" object relative to a stationary "old familiar" object, reflecting memory for what and where. These results suggest that during a single test trial the mice were able to (a) recognize previously explored objects, (b) remember the location in which particular objects were previously encountered, and (c) to discriminate the relative recency in which different objects were presented. According to the currently discussed behavioral criteria for episodic-like memory in animals, our results suggest that mice are capable to form such higher order memories.

Analysis of Variance↗

Subjective memory complaints: a review of patient self-assessment of memory after electroconvulsive therapy.

Interest in patients' subjective complaints about the adverse cognitive effects of electroconvulsive therapy (ECT) spans several decades. This article reviews the major areas that have been examined in relation to patients' subjective assessment of memory function: 1) technical aspects in the administration of ECT; 2) objective tests of cognitive function; and 3) clinical state. For the most part, subjective assessments of memory following ECT have relied on a single instrument, the Squire Subjective Memory Questionnaire (SSMQ). While older reports of the impact of the technical aspects of ECT on subjective memory assessment following ECT suggest a detectable negative influence with certain forms of treatment, most recent studies indicate that subjective memory improves following ECT. This shift in findings may be due to the change in practice from sine wave to brief-pulse ECT. While the impact of ECT on objective tests of memory is clear and reproducible, the relationship of objective findings to subjective memory assessment appears to be weak. Instead, subjective reports of cognitive function are strongly influenced by mood state. Current batteries of objective tests of memory may not include components that are most affected in reports about subjective memory. In addition, the literature mainly reports group effects, and sample sizes have been small. We lack data on the number of individuals who believe ECT has had a markedly negative effect on memory functioning, and on the characteristics of memory function in this subgroup of patients who complain of severe impairment. Furthermore, there is a paucity of information relating patient characteristics to subjective memory outcomes with ECT.

Amnesia↗

Detection of changes in material-specific memory following temporal lobectomy using the Wechsler Memory Scale-Revised.

To determine the utility of the Wechsler Memory Scale-Revised (WMS-R) in measuring material-specific memory changes, within-subject comparisons of the Verbal-Visual Memory Index discrepancy and discrepancy scores using short-term and delayed Logical Memory and Visual Reproduction subtests from the WMS-R were studied prior to and following temporal lobectomy among 30 patients with left temporal lobectomy, 30 with right temporal lobectomy, and 50 epileptic, non-surgical controls. The groups were matched on age, sex, handedness, age at seizure onset, duration of epilepsy, and presurgical Verbal and Performance IQ; the right temporal group had a higher mean educational level (p <.05). All surgical patients were left hemisphere dominant for speech; those who had persistent postoperative seizures were excluded from study. On retesting, left temporal lobectomy was associated with a marked change in short-term and delayed memory discrepancy scores primarily due to a drop in verbal memory. Right temporal lobectomy was not associated with a drop in visual memory, suggesting that the WMS-R appears to reflect decrements in material-specific memory following left but not right temporal lobectomy. The nonsurgical controls showed increases in both short-term and delayed memory discrepancy scores due to increases in short-term and delayed verbal memory. Relative to these controls, the absence of comparable increases in verbal memory among the right temporal patients suggests that right temporal lobectomy may be associated with risk to verbal memory.

Journal Article↗

Spatial memory following prenatal alcohol exposure: more than a material specific memory deficit.

Spatial memory deficits have been reported following prenatal alcohol exposure and animal studies have demonstrated hippocampal vulnerability to alcohol. This study examined spatial memory in children diagnosed with fetal alcohol syndrome (FAS) or fetal alcohol effects (FAE) and matched controls. Spatial memory was examined with location recall measures. Since visual perceptual skills and nonspecific memory impairment could impact spatial memory, tasks assessing perception and verbal memory were administered. Analyses revealed group differences on perceptual and verbal and spatial memory tasks. There was no significant difference in spatial memory once perceptual and verbal memory task performance was taken into account, suggesting that differences in spatial memory were not solely attributable to a material specific memory deficit.

Adolescent↗

Application of new WAIS-III/WMS-III discrepancy scores for evaluating memory functioning: relationship between intellectual and memory ability.

Analysis of the discrepancy between memory and intellectual ability has received some support as a means for evaluating memory impairment. Recently, comprehensive base rate tables for General Ability Index (GAI) minus memory discrepancy scores (i.e., GAI-memory) were developed using the WAIS-III/WMS-III standardization sample (Lange, Chelune, & Tulsky, in press). The purpose of this study was to evaluate the clinical utility of GAI-memory discrepancy scores to identify memory impairment in 34 patients with Alzheimer's type dementia (DAT) versus a sample of 34 demographically matched healthy participants. On average, patients with DAT obtained significantly lower scores on all WAIS-III and WMS-III indexes and had larger GAI-memory discrepancy scores. Clinical outcome analyses revealed that GAI-memory scores were useful at identifying memory impairment in patients with DAT versus matched healthy participants. However, GAI-memory discrepancy scores failed to provide unique interpretive information beyond that which is gained from the memory indexes alone. Implications and future research directions are discussed.

Aged↗

Content memory and temporal memory for actions in survivors of traumatic brain injury.

Memory for performed actions, a rehearsal-independent form of memory, was compared to verbal memory in 30 survivors of traumatic brain injury (TBI) and 30 demographically matched controls. Subjects were tested on recognition and recall memory for the content of recently performed actions in the laboratory, as well as the ability to reconstruct the temporal order in which the actions were performed. Each subject performed actions under incidental and intentional memory instructions. Half of the subjects performed 12 actions, the other half 24 actions, with an equal number of usual and unusual actions in each list. Verbal memory was assessed with paired-associate and temporal order tests. Although recall was more proficient overall for the control compared to the brain-injured subjects on both content and temporal memory for actions, memory for actions was better than verbal memory in both groups. Both groups performed better overall on the short compared to the long list of actions and recalled unusual actions better than usual actions. The rehearsal-independent nature of action memory was supported, with no advantage for the intentional instruction. It is proposed that a retrieval deficit may be in part responsible for deficits in memory for actions following TBI. However, preserved ability to benefit from the abundant contextual cues available through motor actions may account for the better recall of actions compared to words.

Adolescent↗

Distinguishing short-term memory from working memory.

The aim of the present research was to determine whether short-term memory and working memory could be distinguished. In two studies, 7- to 13-year-olds (N = 155, N = 132) were administered tasks thought to assess short-term memory as well as tasks thought to assess working memory. Both exploratory and confirmatory factor analyses distinguished short-term memory tasks from working memory tasks. In addition, performance on working memory tasks was related to word decoding skill but performance on short-term memory tasks was not. Finally, performance on both short-term memory and working memory tasks were associated with age-related increases in processing speed. Results are discussed in relation to models of short-term and working memory.

Adolescent↗

A dissociation in infants' memory for stimulus size: evidence for the early development of multiple memory systems.

Adults' memory performance on recognition (explicit memory) tests is sensitive to stimulus size, but their performance on priming (implicit memory) tests is not. This memory dissociation is taken as evidence for two, functionally distinct memory systems. Young infants, however, are thought to possess only a single representational system that supports implicit memory; the system that supports explicit memory is thought not to mature before 8-9 months of age. In two experiments with 54 infants, we asked if 3-month-olds exhibit a memory dissociation for stimulus size on recognition and priming tests. All infants learned to move a mobile displaying +s of a given size. In Experiment 1, infants recognized +s in the original size but not 33% smaller or larger. In Experiment 2, +s were effective memory primes in a reactivation task, irrespective of size. The finding that young infants exhibit a memory dissociation for stimulus size adds to growing evidence that two memory systems are functional from early in development.

Association Learning↗

Transfer of memory cells into antigen-pretreated hosts. II. Influence of localized antigen on the migration of specific memory B cells.

Following i.v. injection, 2,4,6-trinitrophenol (TNP)-primed memory cells localized in recipient lymph nodes draining a footpad injection of TNP-hemocyanin (TNP-KLH) in greater numbers than in contralateral nodes draining a p-azobenzenearsonate-coupled KLH injection. Such hapten-specific, unilateral memory B cell localization was still observed in immunosuppressed mice when antigen injections were given as long as 4 days prior to the memory cell transfer. The memory cells could be challenged to form plaque-forming cells by footpad injections of TNP-labeled Brucella abortus at 5 days, but not one day, after cell transfer. The present studies further clarify some parameters of this adoptive memory, as a model for the study of persistent local memory. Measures that promoted the unilateral lymph node retention of 125I-labeled antigen also facilitated unilateral accumulation of TNP-specific memory cells. Such measures included pretreatment of the recipients with cyclophosphamide, rather than gamma irradiation, injection of anti-carrier antibody the day before antigen, or use of small doses of preformed immune complexes instead of antigen alone. In general, a high ratio of lymph node-to-spleen and lymph node-to-blood concentration of antigen in recipients appeared crucial for unilateral localization of memory B cells. Splenectomy of recipients prior to cell transfer enhanced the difference in plaque-forming cell responses between draining and contralateral nodes, but decreased their difference when performed 1 day after cell transfer, suggesting that the spleen may have served as a trap for memory cells. I.v. injection of antigen at the time of B cell transfer also interfered with unilateral localization. The results demonstrate that in the presence of persisting depots of antigen within lymph nodes (and absence of significant amounts of antigen elsewhere), memory B cells can be retained locally without activation into antibody-secreting cells. This mechanism may, therefore, by responsible for the phenomenon of local, humoral, immunological memory.

Animals↗

Developmental D-methamphetamine treatment selectively induces spatial navigation impairments in reference memory in the Morris water maze while sparing working memory.

In previous studies, we have shown that P11-20 treatment with D-methamphetamine (MA) (10 mg/kg x 4/day at 2-h intervals) induces impairments in spatial learning and memory in the Morris water maze after the offspring reach adulthood. Using a split-litter, multiple dose, design (0, 5, 10, and 15 mg/kg MA administered s.c. 4/day at 2-h intervals), the spatial learning effect was further explored with a multiple shifted platform (reversal), reference memory-based procedure and a working memory procedure. Prior to spatial learning, animals were first tested for swimming ability (in a straight swimming channel), sequential learning (in the Cincinnati multiple-T water maze), and proximal cue learning (in the Morris water maze). Rats were then assessed in the hidden platform, reference memory-based spatial version of the Morris maze for acquisition and on five subsequent phases in which the platform was moved to new locations. After the reference memory-based, fixed platform position learning phases, animals were tested in the trial-dependent, matching-to-sample, working memory version of the Morris maze. No group differences were found in straight channel, sequential maze, or cued Morris maze performance. By contrast, all MA groups were impaired in spatial learning during acquisition, multiple shift, and shifted with a reduced platform phases of reference memory-based learning. In addition, MA animals were impaired on memory (probe) trials during the acquisition and shifted with a reduced platform phases of learning. No effects on trial-dependent, matching-to-sample, working memory were found. The findings demonstrate that neonatal treatment with MA induces a selective impairment of reference memory-based spatial learning while sparing sequential, cued, and working memory-based learning.

Animals↗

The effects of acute hypoglycaemia on memory acquisition and recall and prospective memory in type 1 diabetes.

AIMS/HYPOTHESIS: Global memory performance is impaired during acute hypoglycaemia. This study assessed whether moderate hypoglycaemia disrupts learning and recall in isolation, and utilised a novel test of prospective memory which may better reflect the role of memory in daily life than conventional tests. SUBJECTS AND METHODS: Thirty-six subjects with type 1 diabetes participated, 20 with normal hypoglycaemia awareness (NHA) and 16 with impaired hypoglycaemia awareness (IHA). Each underwent a hypoglycaemic clamp with target blood glucose 2.5 mmol/l. Prior to hypoglycaemia, subjects attempted to memorise instructions for a prospective memory task, and recall was assessed during hypoglycaemia. Subjects then completed the learning and immediate recall stages of three conventional memory tasks (word recall, story recall, visual recall) during hypoglycaemia. Euglycaemia was restored and delayed memory for the conventional tasks was tested. The same procedures were completed in euglycaemic control studies (blood glucose 4.5 mmol/l). RESULTS: Hypoglycaemia impaired performance significantly on the prospective memory task (p = 0.004). Hypoglycaemia also significantly impaired both immediate and delayed recall for the word and story recall tasks (p < 0.01 in each case). There was no significant deterioration of performance on the visual memory task. The effect of hypoglycaemia did not differ significantly between subjects with NHA and IHA. CONCLUSIONS/INTERPRETATION: Impaired performance on the prospective memory task during hypoglycaemia demonstrates that recall is disrupted by hypoglycaemia. Impaired performance on the conventional memory tasks demonstrates that learning is also disrupted by hypoglycaemia. Results of the prospective memory task support the relevance of these findings to the everyday lives of people with diabetes.

Acute Disease↗

Episodic-like memory in mice: simultaneous assessment of object, place and temporal order memory.

Episodic memory refers to the conscious recollection of a unique past experience in terms of "what" happened and "where" and "when" it happened. Since deficits in episodic memory are found in a number of neuropsychiatric diseases, such as Alzheimer's disease, for which several pharmacological, lesion and genetic animal models are available, there is a need for animal models of episodic-like memory, which can be used to devise appropriate treatments. However, even when the problem of conscious recollection in animals is factored out, episodic memory has been difficult to demonstrate in nonhuman mammals because it has not yet been possible to demonstrate an integrated memory for "what",-"where"-and-"when". We designed a three-trial "what",-"where"-and-"when" object exploration task in which different versions of the novelty preference paradigm were combined to subsume (a) object recognition memory, (b) the memory for locations in which objects were explored and (c) the temporal order memory for objects presented at distinct time points. Our results suggest that mice are able to (a) recognize previously explored objects, (b) remember the location in which particular objects were previously encountered and (c) discriminate the relative recency in which different objects were presented. We suggest that our protocol providing the simultaneous assessment of object memory for "what",-"where"-and-"when" in mice might be useful in the search for the neural substrates of episodic memory, the screening for promnestic drugs and the behavioral phenotyping of genetic models of neuropsychiatric diseases affecting episodic memory.

Animals↗

The relationship between working memory and episodic memory disorders in transient global amnesia.

In a previous study, we investigated the relationship between the disorders of both episodic memory and working memory in the acute phase of transient global amnesia (TGA). Since executive functions were spared, another dysfunction may be responsible for the binding and maintenance of multimodal informations and contribute to the encoding disorders observed in some patients [Quinette, P., Guillery, B., Desgranges, B., de la Sayette, V., Viader, F., & Eustache, F. (2003). Working memory and executive functions in transient global amnesia. Brain, 126, 1917-1934.]. The aim of this present study was to assess the functions of binding and maintenance of multimodal information during TGA and explore their involvement in episodic memory disorders. We therefore conducted a more thorough investigation of working memory in 16 new patients during the acute phase of TGA using two tasks designed to assess the binding process and both dimensions of the maintenance, namely the active storage and the memory load ability. We also investigated the nature of the episodic memory impairment in distinguishing between the performance of patients with preferential encoding deficits and those of patients with preferential storage disorders on the episodic memory task. This distinction was closely related to the severity of amnesia, i.e. an encoding disorder was observed rather in the early phase of TGA. The results showed that while the functions of binding and maintenance of multimodal information were intact in patients with storage disorders, they were impaired in the case of encoding deficits. These results are interpreted in the recent framework of episodic buffer proposed by Baddeley [Baddeley, A. D. (2000). The episodic buffer: A new component of working memory? Trends in Cognitive Sciences, 4, 417-423] that represents an interface between working memory and episodic memory.

Aged↗

Verbal memory outcome in patients with normal preoperative verbal memory and left mesial temporal sclerosis.

PURPOSE: Previous studies have shown that structural integrity (i.e., presence/absence of mesial temporal sclerosis (MTS)) of the left mesial temporal lobe is associated with verbal memory outcome following left anterior temporal lobectomy (ATL). However, the functional integrity of the left temporal lobe, as exemplified by preoperative verbal memory performance, has also been associated with verbal memory outcome following surgery. We investigated the risk of verbal memory loss in patients with known structural abnormality (i.e., left mesial temporal sclerosis by MRI) and normal preoperative verbal memory performance who undergo left ATL. METHODS: Seventeen patients with left temporal lobe epilepsy, MRI-based exclusive left MTS, and normal preoperative verbal memory were identified. Normal verbal memory was defined as performance on both Acquisition (learning across trials 1-5) and Retrieval (long delayed free recall) portions of the California Verbal Learning Test (CVLT) above a T score of 40 (>16%ile). Postoperative verbal memory outcome was established by incorporating standardized regression-based (SRB) change scores. RESULTS: Postoperative declines across both CVLT Retrieval T scores and Acquisition T scores (average 20% and average 15% declines from baseline scores, respectively) were measured for the group. The average CVLT Retrieval SRB change score was -2.5, and the average CVLT Acquisition SRB change score was -1.0. A larger proportion of patients demonstrated postoperative declines on Retrieval scores than Acquisition scores (64.7% vs 17.6%, respectively). CONCLUSIONS: Even in the presence of left MTS, patients exhibiting normal presurgical verbal memory are at risk for verbal memory declines following ATL. These results suggest that the functional integrity of the left mesial temporal lobe may play an important role in the verbal memory outcome in this patient group.

Adolescent↗

Lateral ventricle injection of the protein synthesis inhibitor anisomycin impairs long-term memory in a spatial memory task.

Although protein synthesis inhibition has been shown to affect long-term memory in a wide variety of animal species, cases have been reported in which protein synthesis inhibition failed to affect memory consolidation [S. Wittstock, R. Menzel, Color learning and memory in honey bees are not affected by protein synthesis inhibition, Behav. Neural Biol., 62 (1994) 224-229.]. Most findings argue that the critical time for protein synthesis is during or immediately after training. However, other reports show a second time window, hours after training, where protein synthesis inhibition can cause amnesia [F.M. Freeman, S.P.R. Rose, A.B. Scholey, Two time windows of anisomycin-induced amnesia for passive avoidance training in the day-old chick, Neurobiol. Learn. Mem., 63 (1995) 291-295.][G. Grecksch, H. Matthies, Two sensitive periods for the amnesic effect of anisomycin, Pharmacol. Biochem. Behav., 12 (1980) 663-665.]. In this study, we addressed two questions: (1) Is protein synthesis essential for spatial memory? and (2) At what injection time window(s) will protein synthesis inhibition cause spatial memory amnesia? We report that bilateral intraventricular microinjection of anisomycin (Ani) impairs consolidation of long-term memory, in the hippocampal-dependent Morris water maze spatial memory task. Memory was impaired in a dose-dependent manner without affecting short-term memory. Spatial memory was affected only if Ani was injected 20 min before performing the task and not in any other time window before or after the behavioral test. The inhibition did not affect pre-existing memories or the capability to memorize once the effect of the inhibition diminished.

Animals↗

Memory, amnesia, and the issue of recovered memory: neurobiological aspects.

The main thesis of this article is that the debate about the credibility of "recovered memories"--reports by adults of recovered memories of childhood sexual abuse and trauma that were allegedly repressed for many years--can be usefully informed by considering the biological and behavioral facts and ideas about how memory works. Accordingly, the first section of this review describes current facts and ideas about the neurobiology and neuropsychology of memory and amnesia, including what parts of the brain are important for memory, distinctions between different memory systems in the brain, and the phenomena of infantile amnesia and source amnesia. The second section takes into account the information about the biological and behavioral bases of memory and addresses two questions about memory that have become a focus of debate in the recovered memory controversy, that is, whether memories for traumatic events change over time, and whether memories can be created for traumatic events that did not actually happen.

Adult↗

Spatial memory, recognition memory, and the hippocampus.

There is wide agreement that spatial memory is dependent on the integrity of the hippocampus, but the importance of the hippocampus for nonspatial tasks, including tasks of object recognition memory is not as clear. We examined the relationship between hippocampal lesion size and both spatial memory and object recognition memory in rats. Spatial memory was impaired after bilateral dorsal hippocampal lesions that encompassed 30-50% total volume, and as lesion size increased from 50% to approximately 100% of total hippocampal volume, performance was similarly impaired. In contrast, object recognition was intact after dorsal hippocampal lesions that damaged 50-75% of total hippocampal volume and was impaired only after larger lesions that encompassed 75-100% of hippocampal volume. Last, ventral hippocampal lesions that encompassed approximately 50% of total hippocampal volume impaired spatial memory but did not affect object recognition memory. These findings show that the hippocampus is important for both spatial memory and recognition memory. However, spatial memory performance requires more hippocampal tissue than does recognition memory.

Animals↗

Memory self-awareness and memory self-monitoring following severe closed-head injury.

OBJECTIVE: To examine the accuracy of memory self-awareness and memory self-monitoring abilities in participants with severe closed-head injury (CHI). DESIGN AND METHODS: A performance-prediction paradigm was used to evaluate meta-memory abilities in 31 participants with severe CHI (>1 year post-injury) and 31 controls. To assess memory self-awareness, before completing story recall, visual reproduction and list learning memory tasks, participants predicted the amount of information they would remember for each task. Memory self-monitoring was evaluated by examining participants' ability to increase the accuracy of their predictions following experience with each memory task. RESULTS: Although participants with CHI exhibited poorer recall than controls, they were equally aware of how differing task demands influence recall. They also successfully modified their predictions following task exposure. CONCLUSIONS: Meta-memory was better preserved than actual memory performance. It may be possible to build on meta-memory skills to help patients with CHI more consistently use strategies that aid memory performance.

Adult↗