fMRI studies of remote spatial memory in an amnesic person.
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Amnesia, Retrograde↗
Biomedical subjects
G Winocur
Publications and source records attributed to G Winocur.
Brain interleukin-1 is involved in spatial memory and passive avoidance conditioning.
Within the brain, the inflammatory cytokine interleukin-1 (IL-1) mediates illness-associated neural, neuroendocrine, and behavioral responses; however, its role in normal neurobehavioral processes is not clear. To examine the role of IL-1 signaling in memory, we infused Long-Evans rats intracerebroventricularly with IL-1beta (10 ng/rat), IL-1 receptor antagonist (IL-1ra, 100 microg/rat), or saline immediately following a learning task and tested memory functioning 1-8 days later. In the Morris water maze (MWM), IL-1ra caused memory impairment in the hippocampus-dependent, spatial version, whereas IL-1beta had no effect. Neither IL-1beta nor IL-1ra influenced the hippocampus-independent, nonspatial version of the MWM. In the passive avoidance response, which also depends on hippocampal functioning, IL-1ra caused memory impairment, and IL-1beta caused memory improvement. These results suggest that IL-1 signaling within the hippocampus plays a critical role in learning and memory processes.
Animals↗
New views on old memories: re-evaluating the role of the hippocampal complex.
Evidence of temporally graded retrograde amnesia (RA) following hippocampal damage has fuelled the long-standing belief that memory undergoes a consolidation process, whereby memories are progressively modified in neocortical regions until they are independent of the hippocampal (HPC) complex. Support for this position derives from both the animal and human RA literature, although the results are not consistent. Specifically, consolidation theory does not account for loss of episodic (detail) information in humans and context-dependent information in animals, which often extend back for much of the life span. We discuss an alternative approach, the Multiple Trace Theory, which suggests that the HPC complex contributes to the retrieval of recent and remote episodic and context-dependent memories. According to this view, such memory traces are represented as spatially distributed interactions between the HPC and neocortex that persist for as long as those memories exist. On the other hand, semantic, or context-free, memories can become independent of the HPC as consolidation theory predicts. In support of this view, we report recent accounts of relatively flat RA gradients in autobiographical and spatial detail loss in patients and animal models with extensive bilateral HPC lesions. By comparison, temporally graded RA was observed in tests of semantic and context-free memory. We also report neuroimaging studies in which hippocampal activity, elicited during recollection of autobiographical memories, did not distinguish recent from remote episodes. Our discussion suggests ways to reconcile discrepancies in the literature and guide predictions of the occurrence of flat versus temporally limited gradients of remote episodic and semantic memory loss following lesions to HPC.
Amnesia, Retrograde↗
Anterograde and retrograde amnesia in rats with large hippocampal lesions.
A test of socially acquired food preferences was used to study the effects of large lesions to the hippocampal formation (HPC) on anterograde and retrograde memory in rats. In the anterograde test, rats with HPC lesions normally acquired the food preference but showed a faster rate of forgetting than control groups. When the food preference was acquired preoperatively, HPC groups exhibited a temporally graded retrograde amnesia in which memory was impaired when the preference was acquired within 2 days of surgery but not at longer delays. The results support the traditional theory that the HPC contributes to the consolidation of newly acquired information into a durable memory trace that is represented in other brain areas. Consistent with this view, the results indicate that, once a memory trace is consolidated, the HPC does not participate in its storage or retrieval. The possibility is considered that extrahippocampal areas in the medial temporal lobe are needed to maintain a memory trace throughout its existence.
Amnesia, Anterograde↗
Learning and memory in S100-beta transgenic mice: an analysis of impaired and preserved function.
S100-beta, a calcium-binding astrocytic protein from chromosome 21, has been implicated in CNS function generally and the hippocampus in particular. Elevated levels of S100-beta have been observed reliably in the brains of patients with Alzheimer's Disease and Down Syndrome. Groups of transgenic mice, carrying multiple S100-beta gene copies, and nontransgenic controls were administered a series of behavioral tests (delayed spatial and nonspatial non-matching-to-sample, radial arm maze, socially acquired food preference) that assessed a wide range of cognitive functions. Consistent with the widespread presence of S100-beta throughout the brain, transgenic mice exhibited learning or memory impairment on all tasks. The dementia-like cognitive profile of S100-beta mice represents a promising model for studying comparable cognitive deficits associated with neurodegenerative diseases.
Animals↗
Glucose treatment reduces memory deficits in young adult rats fed high-fat diets.
Feeding rats high-fat diets for 3 months produces a widespread cognitive deficit that affects performance on a wide range of learning and memory tasks. The present study tested the hypothesis that this effect is related to a fat-induced impairment in glucose metabolism. Following 3 months of dietary intervention (20% by weight fat diets, composed primarily of either beef tallow or soybean oil versus standard laboratory chow), male Long-Evans rats were tested on a variable interval delayed alternation (VIDA) task that measures learning and memory functions that differentially involve specific brain regions. Relative to rats fed chow, rats consuming the high-fat diets were impaired on all aspects of VIDA performance. Following baseline testing, rats were maintained on their respective diets and the effect of glucose administration (100 mg/kg BW; i.p.) was examined. For the next 6 days, animals alternately received injections of saline or glucose 30 min prior to VIDA testing. Glucose treatment improved performance, with the effect being most pronounced at the longer intertrial intervals where task performance is sensitive to hippocampal impairment. Importantly, the beneficial effect of glucose were confined to those animals consuming the high-fat diets and were not observed in rats fed chow. These results demonstrate that glucose administration can overcome those deficits associated with hippocampal function in rats fed high-fat diets and are consistent with the hypothesis that high-fat diets, in part, mediate their effect through the development of insulin resistance and glucose intolerance.
Age Factors↗
Dietary protein, carbohydrate, and fat enhance memory performance in the healthy elderly.
BACKGROUND: Dietary carbohydrates can improve memory. Whether these effects are related to elevations in blood glucose or to energy ingestion is unknown. OBJECTIVES: Our objectives were to determine 1) the influence of isoenergetic protein-, carbohydrate-, and fat-containing drinks on cognitive performance and 2) whether the time period after ingestion affects cognition. DESIGN: After fasting overnight, 11 men and 11 women aged 61-79 y consumed either a 300-mL drink containing 774 kJ as pure protein (whey), carbohydrate (glucose), or fat (safflower oil) or a nonenergy placebo on 4 separate mornings. Cognitive tests were administered 15 and 60 min after ingestion of the drinks. Plasma glucose and serum insulin concentrations were measured. RESULTS: Only the carbohydrate drink increased blood glucose (P < 0.0001). Compared with the placebo, all 3 macronutrients improved delayed paragraph recall (PR) (P < 0.001) and improved or tended to improve immediate PR (P < 0.04) 15 min after ingestion. Beneficial effects on other cognitive tests were confined to one or more of the macronutrients: carbohydrate improved Trail Making Test (Trails) performance at 60 min (P = 0.02) and tended to improve Trails at 15 min (P = 0.04) and PR at 60 min in men, carbohydrate and fat improved or tended to improve performance on Trails at 15 and 60 min in subjects with poor baseline scores (r > -0.41, P < 0.03), fat tended to improve attention at 60 min (P < 0.05), and protein reduced the rate of forgetting on the PR at 15 min (P = 0.002). CONCLUSIONS: Energy intake from protein, carbohydrate, or fat can enhance memory independently of elevations in blood glucose. Each macronutrient may also exert unique effects on cognition.
Aged↗
Cognitive rehabilitation in clinical neuropsychology.
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Brain Injuries↗
Episodic encoding and recognition of pictures and words: role of the human medial temporal lobes.
In the present PET study, we examined brain activity related to processing of pictures and printed words in episodic memory. Our goal was to determine how the perceptual format of objects (verbal versus pictorial) is reflected in the neural organization of episodic memory for common objects. We investigated this issue in relation to encoding and recognition with a particular focus on medial temporal-lobe (MTL) structures. At encoding, participants saw pictures of objects or their written names and were asked to make semantic judgments. At recognition, participants made yes-no recognition judgments in four different conditions. In two conditions, target items were pictures of objects; these objects had originally been encoded either in picture or in word format. In two other conditions, target items were words; they also denoted objects originally encoded either as pictures or as words. Our data show that right MTL structures are differentially involved in picture processing during encoding and recognition. A posterior MTL region showed higher activation in response to the presentation of pictures than of words across all conditions. During encoding, this region may be involved in setting up a representation of the perceptual information that comprises the picture. At recognition, it may play a role in guiding retrieval processes based on the perceptual input, i.e. the retrieval cue. Another more anterior right MTL region was found to be differentially involved in recognition of objects that had been encoded as pictures, irrespective of whether the retrieval cue provided was pictorial or verbal in nature; this region may be involved in accessing stored pictorial representations. Our results suggest that left MTL structures contribute to picture processing only during encoding. Some regions in the left MTL showed an involvement in semantic encoding that was picture specific; others showed a task-specific involvement across pictures and words. Together, our results provide evidence that the involvement of some but not all MTL regions in episodic encoding and recognition is format specific.
Adult↗
Event-related potentials during conscious and automatic memory retrieval.
The effects of study-test lags of between 0 and 32 items on conscious (C) and automatic (A) memory processes in a running word-completion task were investigated with event-related potentials (ERPs). The process dissociation procedure (PDP) can distinguish between C and A contributions to memory by comparing performance when subjects respond with either an old item (inclusion) or a new item (exclusion). C can be estimated by subtracting the probability of an intrusion of an old item during the exclusion task (due to A without C) from the probability of correctly producing an old item during the inclusion task (due to C and/or A). The behavioral results showed that C was stronger when the test item followed the studied word in the next trial or after a lag of one stimulus. The strength of A did not vary with lag. The ERP waveforms contained a broad parietal positive wave between 300 and 800 ms. This parietal wave distinguished between correctly recalled old and new words. The early portion of this old-new effect was significantly affected by lag. Subtracting waveforms to obtain a measure of C revealed an effect in the later portion of this wave, lateralized over the left hemisphere. A sustained frontal negativity occurred during all recordings and was larger during conscious retrieval. There was no consistent ERP effect related to automatic memory retrieval.
Adult↗
Cross-cultural differences in memory: the role of culture-based stereotypes about aging.
The extent to which cultural stereotypes about aging contribute to age differences in memory performance is investigated by comparing younger and older Anglophone Canadians to demographically matched Chinese Canadians, who tend to hold more positive views of aging. Four memory tests were administered. In contrast to B. Levy and E. Langer's (1994) findings, younger adults in both cultural groups outperformed their older comparison group on all memory tests. For 2 tests, which made use of visual stimuli resembling ideographic characters in written Chinese, the older Chinese Canadians approached, but did not reach, the performance achieved by their younger counterparts, as well as outperformed the older Anglophone Canadians. However, on the other two tests, which assess memory for complex figures and abstract designs, no differences were observed between the older Chinese and Anglophone Canadians. Path analysis results suggest that this pattern of findings is not easily attributed to a wholly culturally based account of age differences in memory performance.
Adult↗
Cognitive performance is associated with glucose regulation in healthy elderly persons and can be enhanced with glucose and dietary carbohydrates.
BACKGROUND: A glucose drink has been shown to improve memory in persons with poor glucose regulation and poor cognition. OBJECTIVE: The objective of this study was to determine 1) whether an association between cognition and glucose regulation is apparent in healthy seniors and 2) the effects of dietary carbohydrates on cognition. DESIGN: After an overnight fast, 10 men and 10 women (aged 60-82 y) consumed 50 g carbohydrate as glucose, potatoes, or barley or a placebo on 4 separate mornings. Cognitive tests were administered 15, 60, and 105 min after ingestion of the carbohydrate. Plasma glucose and serum insulin were measured. RESULTS: In a multiple regression analysis, poor baseline (placebo) verbal declarative memory (immediate and 20-min delayed paragraph recall and word list recall) and visuomotor task performance were predicted by poor beta cell function, high incremental area under the glucose curve, low insulin resistance, and low body mass index. The difference in plasma glucose after food consumption [glucose > potatoes > barley > placebo (P: < 0.03)] did not predict performance. Although overall performance did not differ with consumption of the different test foods, baseline score and beta cell function correlated with improvements in immediate and delayed paragraph recall for all 3 carbohydrates (compared with placebo); the poorer the baseline memory or beta cell function, the greater the improvement (correlation between beta cell function and improvement in delayed paragraph recall: r > -0.50, P: < 0.03). Poor beta cell function correlated with improvement for all carbohydrates in visuomotor task performance but not on an attention task. CONCLUSIONS: Glucose regulation was associated with cognitive performance in elderly subjects with normal glucose tolerance. Dietary carbohydrates (potatoes and barley) enhanced cognition in subjects with poor memories or beta cell function independently of plasma glucose.
Aged↗
Anterograde and retrograde amnesia after lesions to frontal cortex in rats.
A socially acquired food-preference test was used to assess effects of lesions to the frontal cortex on anterograde and retrograde memory in rats. In Experiment 1, there was no effect of lesion when rats were administered a two-choice test in which the target food was to be selected in the presence of a single distractor. In Experiment 2, a three-choice memory test was administered in which the target food was presented along with two equally palatable alternatives. In the latter test, lesioned groups displayed anterograde amnesia that increased with the length of the interval between postoperative acquisition and test, and a severe retrograde amnesia that extended equally over the entire range of intervals between preoperative acquisition and test. This outcome, which contrasted with the pattern of memory loss previously observed in rats with hippocampal lesions on this test, was interpreted as evidence for the strategic role of the frontal lobes in directing response selection and retrieval processes in memory.
Amnesia, Anterograde↗
The effects of high fat diets and environmental influences on cognitive performance in rats.
As part of a continuing investigation of the relationship between dietary factors and cognitive function, the present study examined the combined effects of environmental influences and high-fat diets on learning and memory. Following 3 months of dietary (20% by weight fat diets, composed primarily of either beef tallow or soybean oil versus standard laboratory chow) and environmental treatments (standard, enriched or impoverished), subjects were tested on a variable interval delayed alternation (VIDA) task which measures learning and memory functions that differentially involve specific brain regions. The results confirmed the negative effects of high fat diets, relative to chow, on all aspects of VIDA performance and showed that environmental enrichment overcame deficits associated with dietary fat. Housing rats fed high-fat diets in an impoverished environment did not further exacerbate cognitive deficits observed in such rats living under standard conditions. By comparison, chow-fed rats exhibited no benefit associated with the enriched environment on any aspect of task performance, and only a transitory learning impairment when housed in an impoverished environment. The results show that high fat diets and environmental conditions influence cognitive function and that these two factors interact with one another to produce different profiles of benefits and impairments.
Animals↗
Aging and time-of-day effects on cognition in rats.
This study used an animal model to investigate the importance of the time at which testing occurs for age differences in learning and memory. Groups of old and young rats were entrained to a 12-hr light-dark schedule and administered tests of delayed alternation and inhibitory avoidance conditioning at the beginning or end of their high-activity cycle. Apart from normal age differences in test performance, the behavioral results demonstrated that old but not young rats were affected by the time of testing. In both tasks, old rats tested late in the activity cycle performed significantly worse than did old rats tested early in the cycle, under conditions that challenged memory processes that are known to involve the hippocampus. The results indicate that circadian disruption in old age can adversely affect memory and related cognitive function, with important implications for inhibitory control.
Age Factors↗
Source memory and divided attention: reciprocal costs to primary and secondary tasks.
Source memory, in comparison with item memory, is more sensitive to frontal lesions and may require more strategic processing. Divided attention was used to restrict attentional resources and strategic processing on memory tasks. Participants encoded and retrieved items (i.e., words) and source (i.e., voice or spatial location) while concurrently performing a finger-tapping (FT) or visual reaction-time (VRT) task. Memory accuracy costs under divided attention were greater for retrieval of source than item and were greater with VRT than FT. Similarly, costs to the secondary task were greater when concurrently retrieving source as opposed to item and were greater for VRT than FT. Effects were stronger when spatial location was used as the source task. Findings support the idea that processing source information requires more attentional resources and effort than processing item information. Furthermore, concurrent performance of VRT produced greater interference with a task that was more dependent on intact frontal functioning and better simulated the performance of patients with frontal dysfunction.
Adult↗
Networks of domain-specific and general regions involved in episodic memory for spatial location and object identity.
Positron emission tomography (PET) was used to investigate human episodic memory for spatial location and object identity. We measured regional cerebral bloodflow (rCBF) while subjects engaged in perceptual matching of the location or the identity of line drawings of objects. Perceptual matching also involved incidental encoding of the presented information. Subsequently, rCBF was measured when subjects retrieved the location or the identity of these objects from memory. Using the multivariate partial least squares image analysis, we identified three patterns of activity across the brain that allowed us to distinguish structures that are differentially involved in processing spatial location and object identity from structures that are differentially involved in encoding and retrieval but operate across both domains. Domain-specificity was evident by increased rCBF during the processing of spatial location in the right middle occipital gyrus, supramarginal gyrus, and superior temporal sulcus, and by increased rCBF during the processing of object identity in portions of bilateral lingual and fusiform gyri. There was a nearly complete overlap between domain-specific dorsal and ventral extrastriate cortex activations during perceptual matching and memory retrieval. Evidence of domain-specificity was also found in the prefrontal cortex and the left hippocampus, but the effect interacted with encoding and retrieval. Domain-general structures included bilateral superior temporal cortex regions, which were preferentially activated during encoding, and portions of bilateral middle and inferior frontal gyri, which were preferentially activated during retrieval. Together, our data suggest that encoding and retrieval in episodic memory depend on the interplay between domain-specific structures, most of which are involved in memory as well as perception, and domain-general structures, some of which operate more at encoding and others more at retrieval.
Adult↗
Clustering and switching on verbal fluency: the effects of focal frontal- and temporal-lobe lesions.
We examined the hypothesis that, on verbal fluency, clustering (i.e. generating words within subcategories) is related to temporal-lobe functioning, whereas switching (i.e. shifting between subcategories) is related to frontal-lobe functioning. Tests of phonemic and semantic fluency were administered to 53 patients with focal frontal-lobe lesions (FL), 23 patients with unilateral temporal-lobe lesions (TL) and 55 matched controls. Performance by FL patients was consistent with our hypothesis: in comparison to controls, patients with left-dorsolateral or superior-medial frontal lesions switched less frequently and produced normal cluster sizes on both phonemic and semantic fluency. Performance by TL patients was not consistent across fluency tasks and provided partial support for our hypothesis. On phonemic fluency, TL patients were unimpaired on both switching and clustering. On semantic fluency, TL patients were impaired on switching in comparison to controls and left TL patients produced smaller clusters than right TL patients. The best indices for discriminating the patient groups, therefore, were phonemic-fluency switching (impaired only with frontal lesions) and semantic-fluency clustering (impaired only with temporal-lobe lesions).
Adult↗