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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↗

The real relationship between short-term memory and working memory.

Storage-oriented memory span tasks with no explicit concurrent processing are usually referred as short-term memory (STM) tasks, whereas tasks involving storage plus concurrent processing requirements are designated as working memory (WM) tasks. The present study explores a question that remains unsolved: Do STM and WM tasks clearly tap distinguishable theoretical constructs? For that purpose, a large sample of 403 participants was tested through 12 diverse memory span tasks. Half of those tasks are widely accepted as measures of STM, whereas the other half measure WM. The results show that STM and WM share largely overlapping underlying capacity limitations, suggesting that all memory span tasks tap essentially the same construct. Some implications are discussed.

Adult↗

Pre-operative verbal memory fMRI predicts post-operative memory decline after left temporal lobe resection.

Functional MRI (fMRI) of cognitive tasks depends on technology widely available in the clinical sphere, but has yet to show a role in the investigation of patients. We report here the first demonstration of a clinically valuable role for cognitive fMRI. Temporal lobe epilepsy (TLE) is commonly caused by hippocampal sclerosis and is frequently resistant to drug treatment. Surgical resection of the left hippocampus in this setting can cure seizures, but may produce significant verbal memory decline, which is hard to predict. We report 10 right-handed TLE patients with left hippocampal sclerosis who underwent left hippocampal resection. We compared currently used data for the prediction of post-operative verbal memory decline in such patients with a novel fMRI assessment of verbal memory encoding. Multiple regression analyses showed that fMRI provided the strongest independent predictor of memory outcome after surgery. At the individual subject level, the fMRI data had high positive predictive value for memory decline.

Adult↗

Memory encoding in Alzheimer's disease: an fMRI study of explicit and implicit memory.

Alzheimer's disease is the most common cause of dementia in older adults. Although the cognitive deficits and pathologic hallmarks of Alzheimer's disease have been well characterized, few functional imaging studies have examined the functional competency of specific brain regions and their relationship to specific behavioural memory deficits in Alzheimer's disease. We used functional MRI (fMRI) to examine seven early stage Alzheimer's disease patients and seven healthy age-matched neurologically normal control subjects during intentional encoding of scenes. Subjects viewed blocks of novel scenes, repeated scenes or baseline. Data were analysed using whole-brain statistical parametric mapping and region of interest approaches. The Alzheimer's disease group demonstrated impaired explicit recognition memory, but intact implicit memory (repetition priming), for the scenes. Alzheimer's disease patients demonstrated a graded deficit in activation for novel versus repeated scenes along the ventral visual stream, with most impaired activation changes in the mesial temporal lobe (MTL) and fusiform regions, most preserved activations in primary visual cortex and variably affected activations in secondary visual areas. Group-level correlations with behavioural measures of explicit memory were found in MTL, lingual and fusiform areas, whereas correlations with priming were found in lateral occipital, parietal and frontal areas. Together, these fMRI findings indicate a dissociation in Alzheimer's disease between impaired explicit memory encoding in MTL and fusiform regions and intact implicit encoding in earlier-stage occipital cortex.

Aged↗

Animal models of declining memory in the aged: short-term and spatial memory in the aged rat.

Short-term and spatial memory were studied in Fischer 344 rats ranging in age from 6 to 26 months of age. Spatial memory, as measured by performance in an 8-armed radial maze, declined gradually with age. In contrast, short-term memory, as measured by retention of previous choices in the spatial maze over short intervals and performance on a modified form of Konorski's discriminated delayed response task, did not decline differentially as a function of age. These findings may be comparable to those obtained in the aged human, who also show marked deficits in spatial memory and little change in primary memory under appropriate test conditions.

Aging↗

Long-term memory is the representational basis for semantic verbal short-term memory.

The present study supports activation models of verbal short-term memory that include a semantic contribution to the retention process. Event-related brain potentials were used to probe the level of activation of semantic representations of a series of words in a delay interval following their presentation. The levels of activation were compared in two tasks: (1) a short-term memory task that involved a semantic judgment in the recall phase following the delay interval, and (2) a nonmemory control task. The level of semantic activation during the delay interval was higher in the short-term memory task, indicating that enhanced activation of semantic representations is involved in the short-term storage of verbal information. This result implies that activated long-term memory provides a representational basis for semantic verbal short-term memory, and hence supports theories that postulate that short- and long-term stores are not separate.

Adult↗

B cell memory to thymus-independent antigens type 1 and type 2: the role of lipopolysaccharide in B memory induction.

Several studies have indicated that thymus-independent (TI) antigens, unlike their thymus-dependent (TD) counterparts, are poor at generating memory antibody responses (Immunol. Today 1981. 3:217). In contrast to this view, the present report shows that the TI type 1 (TI-1) antigen, 2,4,6-trinitrophenyl-lipopolysaccharide (TNP-LPS), elicits good secondary responses in rats. These secondary antibody responses are not only greater in magnitude than the primary responses, but display a different pattern of Ig classes with more IgG and IgA antibodies produced. In transfer experiments between congenic strains of rats which differ in their kappa light chain Ig allotype, it is shown that this memory is attributable to persistent B cell clones. The TI-2 antigen, 2,4-dinitrophenyl-hydroxyethyl starch (DNP-HES), given alone did not elicit B cell memory. However, when DNP-HES is presented to the immune system in association with LPS, the pattern of the anti-DNP response is similar to that elicited by TNP-LPS. The capacity to generate TI memory is associated with the appearance of hapten-specific B cells in the marginal zones of the spleen. Hapten-binding cells were induced in the marginal zones following immunization with TNP-LPS, but not by DNP-HES. However, concurrent immunization with DNP-HES and LPS which were not covalently linked was found to induce DNP-binding cells in the marginal zone. There is complete correlation between the appearance of hapten-binding memory B cells in the marginal zone and the capacity of these antigens to induce secondary responses.

Animals↗

Validation of a memory inventory for the assessment of awareness of memory deficits in Alzheimer's disease in Chinese elderly.

BACKGROUND: This paper describes the development and validation of the Memory Inventory for Chinese (MIC), for measuring the awareness of memory deficits in the Chinese population with Alzheimer's disease (AD). METHODS: A combination of qualitative and quantitative approaches was adopted. The MIC was developed with focus group discussion and pilot testing. It has a patient and a caregiver version. A consecutive series of 79 new out-patients with the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorder Association (NINCDS-ADRDA) criteria of probable and possible AD and 20 non-demented elderly subjects were recruited. RESULTS: A high internal consistency was found, with Cronbach alpha of 0.89 for the patient version and 0.90 for the caregiver version of MIC. The inter-rater reliability was satisfactory. For validity assessment, the caregiver score of the MIC correlated significantly with cognitive score of the subject as assessed by the Mini-Mental State Examination (rp = -0.37; p < 0.01). The Memory Deficit Awareness Score, calculated by subtracting the patient score from the caregiver score, correlated significantly with clinician ratings of awareness of memory impairment (rs = -0.67; p < 0.01). CONCLUSIONS: The MIC appears to be a culturally appropriate and valid instrument for the measurement of awareness of memory deficits in Chinese patients with AD. Potential applications of the MIC should be further explored in other subtypes of dementia and in prospective studies.

Aged↗

Mechanisms of memory disturbance during stages of memory acquisition and fixation.

Using the conditioned response of passive avoidance in experiments on rats, we investigated the character of amnesias caused by scopolamine and ketamine. By varying the time intervals between training and testing and the time of injection of pharmacological agents, we show that blockade of M-cholinoreactive systems of the brain during injection of scopolamine has no effect upon memory acquisition but does disrupt the process of memory fixation, i.e., the transfer to long-term memory. At the same time, ketamine, a blocker of the ionic channels of the nicotinic receptor, disturbs the process of memory acquisition. Memory recall (reproduction) is impaired under the influence of both agents, but is impaired to a greater degree by ketamine. Piracetam, believed to be a universal anti-amnesic agent, attenuates the disturbance of fixation caused by scopolamine only; it does not attenuate ketamine amnesia.

Animals↗

Dynamic memory networks: dissecting molecular mechanisms underlying associative memory in the temporal domain.

The molecular mechanisms underlying the induction and maintenance of memory are highly dynamic and comprise distinct phases covering a time window from seconds to even a lifetime. Neuronal networks, which contribute to these processes, have been extensively characterized on various levels of analysis, and imaging techniques allow monitoring of both gross brain activity as well as functional changes in defined brain areas during the time course of memory formation. New techniques developed in honeybees and fruit flies even allow for manipulation of neuronal networks and molecular cascades in a short temporal domain while a living animal under observation acquires new associative memories. These advantages make honeybees and flies ideal organisms to study transient molecular events underlying dynamic memory processing in vivo. In this review we will focus on the temporal features of molecular processes in learning and memory formation, summarize recent knowledge and present an outlook on future developments.

Animals↗

Hallucinating the past: a case of spontaneous and involuntary recall of long-term memories: perspectives on the hemispheric organization of visual memory.

This paper presents the unique case of a patient who developed palinopsias and formed visual hallucinations, representing spontaneous recall of memories from a discrete 10-year time period. The visual phenomena began shortly after the initiation of prophylactic whole-brain radiation therapy, following the removal of a metastatic adenocarcinoma in the region of the right cuneus. The most striking feature of this patient's hallucinations is the composition: memories from a discrete 10-year time period from about 30 years ago. This case provides further evidence to support the theory of a contralateral and hemispheric organization of visual memory. We propose that visual memory traces formed nearly three decades ago were spontaneously recalled in the form of hallucinations and palinopsias. It is noteworthy that the region of the brain most affected by the tumor and subsequent radiation therapy is postulated to permit perception of mental imagery. To our knowledge, no other case involving hallucination of 30-year-old memories has been reported.

Adenocarcinoma↗

The effect of visual similarity on short-term memory for spatial location: implications for the capacity of visual short-term memory.

Evidence from the recency effect suggests that visual short-term memory is limited to preserving information about a single pattern. Three experiments explored the capacity of visual short-term memory using a task which involved presenting a series of patterns in a random spatio-temporal sequence and probing memory for the spatial location of one of them. Experiment 1 used sequences of quasi-random block patterns which were either visually similar or dissimilar. Serial position curves showed a single-item recency effect. However, there was also a deleterious effect of visual similarity for the earlier patterns, indicating that visual short-term memory was supporting their retention. Experiment 2 showed that performance was unaffected by articulatory suppression, confirming that phonological coding is not an important factor in the localisation task. Experiment 3 switched to letter stimuli and, because of the known tendency for this type of stimulus to be phonologically recoded, required articulatory suppression. Letters were shown in a customised form in sequences which were either visually similar or visually dissimilar. The results replicated experiment 1 in showing restricted recency combined with an effect of visual similarity extending across earlier list items. When the same letters were shown in standard form, the recency effect remained but the similarity effect disappeared, ruling out possible interpretations in terms of semantic as well as phonological coding. It is concluded that the recency effect gives a misleading indication of the capacity of visual short-term memory. The visual similarity effect suggests that it is capable of supporting the retention of several patterns.

Adult↗

Scopolamine degrades spatial working memory but spares spatial reference memory: dissimilarity of anticholinergic effect and restriction of distal visual cues.

The influence of the centrally active anticholinergic, scopolamine hydrobromide, on working and reference memory was studied in rats tested in a 12-arm radial maze. Both 0.25 and 0.5 mg/kg doses of the drug increased the number of working memory (WM) errors but had no effect on reference memory (RM) errors. A lower dose (0.125 mg/kg) was ineffective, as was the peripherally active anticholinergic, scopolamine methylbromide (0.5 mg/kg). Some of the behavioral effects of anticholinergics on spatial memory are mimicked by blindness or eliminating distal visual cues. If distal visual cues were more important for maintaining accurate WM than for RM, the selective effect of scopolamine on WM could be easily explained. But surrounding the maze with a curtain to eliminate extramaze cues increased RM errors without significantly increasing WM errors. Thus, the selective effect of anticholinergies on spatial memory in the radial maze is qualitatively different from the effect of restricting distal visual cues and must arise from some other action of the drug.

Animals↗

Control of memory CD4 T cell activation: MHC class II molecules on APCs and CD4 ligation inhibit memory but not naive CD4 T cells.

Memory or antigen-experienced CD4 T cells differ from naive CD4 T cells both phenotypically by cell surface marker expression, and functionally by their dissimilar pattern of cytokine secretion and activation requirements through their T cell receptor (TCR). We show here that activation of memory CD4 T cells (CD45RBlo subset), but not naive CD4 T cells (CD45RBhi subset), is inhibited by MHC class II molecules on antigen-presenting cells and by CD4 ligation. We propose that the selective negative signal in memory cells is a direct result of the differences in signaling via CD4 and CD3, exemplified in the disparate pattern of tyrosine-phosphorylated proteins visible after activation of the two subsets. In vivo, this inhibitory signal may serve to prevent irrelevant interactions between memory CD4 T cells and bystander MHC class II+ cells, and may also be responsible for the defective functioning of memory CD4 T cells in AIDS.

Animals↗

Human implicit memory for irrelevant dimension values is similar to rats' incidental memory in simultaneous discrimination tasks.

Participants completed a category-learning task in which they needed to discover which of three stimulus dimensions (shape, color or size) was relevant. After meeting a learning criterion (nine of 10 consecutive correct responses), participants continued making categorization choices and response latencies associated with these trials were examined. In both Experiments 1 and 2, people responded reliably faster when correct responses matched the previous responses with respect to irrelevant dimension values. Thus, they demonstrated a form of incidental short-term memory analogous to that we previously reported in studies of rats. In Experiment 2, participants' explicit memory for irrelevant dimension values was assessed after category learning was complete. The results indicated that people were unaware of the irrelevant dimension values encountered on trials preceding surprise probe trials. This indicates that memory for the irrelevant dimension values was implicit (i.e. unconscious). The findings are discussed with respect to both human and non-human studies of hippocampus-independent memory and implicit memory.

Animals↗

Sensitivity of human EEG alpha band desynchronization to different working memory components and increasing levels of memory load.

Event-related alpha band desynchronization is frequently used to analyze spatiotemporal cortical activation patterns during the performance of cognitive tasks. In the present paper the sensitivity of alpha band desynchronization to increasing levels of cognitive load and to different cognitive working memory components is investigated. A 27-channel electroencephalogram of 62 participants while solving (a) a short-term memory and (b) a working memory task (dual task), each with five levels of memory load, was analyzed. We found (a) a linearly increasing desynchronization in the upper alpha band with ascending cognitive load, and (b) evidence of the involvement of distinguishable cognitive components (storage and controlled attention) in the memory tasks.

Alpha Rhythm↗

Autobiographical memory specificity, psychopathology, depressed mood and the use of the Autobiographical Memory Test: a meta-analysis.

Reviewing the literature on autobiographical memory overgenerality, as measured by a cueing task like the Autobiographical Memory Test (AMT), gives a diffuse view of the moderating role of depression. This meta-analysis is an attempt to investigate the role of depression in the specificity of autobiographical memory, while accounting for the role of patient and task variables as possible moderators. Meta-analytic techniques are used to synthesize data from 14 studies on the recall of specific autobiographical memories in psychiatric and non-psychiatric samples. The results confirm the relationship between overgenerality and depression. The psychiatric patients are less specific than their non-clinical controls. It is not possible to establish that this result is solely due to a (co-morbid) diagnosis of depression. Self-reported depressed mood is also related to an impairment of autobiographical memory specificity. The way of presenting cues, audio taping responses and the maximum available amount of time to respond, are moderators of AMT performance.

Autobiographies as Topic↗

Recognition memory and memory for order in script-based stories following frontal lobe excisions.

Memory for stories was investigated in 25 patients with frontal lobe excisions and 25 control subjects. The subjects were presented with three different story types that either conformed to a well-known script, contained the same elements as a script but in a randomised order, or described a novel event. Subjects were asked to perform a test of recognition memory and memory for order on words presented in each story. The frontal lobe patients were unimpaired on the recognition memory test for salient words taken from each story. However, an impairment was observed in the frontal patients when they were asked to order the words taken from the novel story only. This deficit was no longer seen when the subjects were required to order sentences describing the key events in the story. These findings help to elucidate the role of the frontal lobes in memory for order information.

Adult↗