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PubMed2001

Parieto-frontal interactions in visual-object and visual-spatial working memory: evidence from transcranial magnetic stimulation.

This study aimed to investigate whether transcranial magnetic stimulation (TMS) can induce selective working memory (WM) deficits of visual-object versus visual-spatial information in normal humans. Thirty-five healthy subjects performed two computerized visual n-back tasks, in which they were required to memorize spatial locations or abstract patterns. In a first series of experiments, unilateral or bilateral TMS was delivered on posterior parietal and middle temporal regions of both hemispheres after various delays during the WM task. Bilateral temporal TMS increased reaction times (RTs) in the visual-object, whereas bilateral parietal TMS selectively increased RTs in the visual-spatial WM task. These effects were evident at a delay of 300 ms. Response accuracy was not affected by bilateral or unilateral TMS of either cortical region. In a second group of experiments, bilateral TMS was applied over the superior frontal gyrus (SFG) or the dorsolateral prefrontal cortex (DLPFC). TMS of the SFG selectively increased RTs in the visual-spatial WM task, whereas TMS of the DLPFC interfered with both WM tasks, in terms of both accuracy and RTs. These effects were evident when TMS was applied after a delay of 600 ms, but not one of 300 ms. These findings confirm the segregation of WM buffers for object and spatial information in the posterior cortical regions. In the frontal cortex, the DLPFC appears to be necessary for WM computations regardless of the stimulus material.

Adult↗
PubMedDate not supplied

Age differences in entropy: primary versus secondary memory.

We report a spatial-memory scanning experiment that was used to measure age differences in entropy. A target grid consisting of four adjacent letters followed by the presentation of a single probe letter was presented on each trial. Half of the trials presented the probe stimulus in the same spatial position was the target letter (i.e., the probe letter was always a member of the positive set), and half of the trials transposed the target letter one, two, or three spaces of the right or left of the original target display position (i.e., different trials). The experiment involved blocks of primary-memory and secondary-memory tasks. Reaction-time and error-rate data, as well as entropy analyses and the fitting of an entropy model (based on Allen, Kaufman, Smith, and Propper, in press) to the empirical data indicated that older adults showed higher entropy levels than young adults. These results are interpreted in a "computational temperature" framework in which older adults' higher computational temperatures result in less efficient spatial, episodic memory functioning.

Adolescent↗
PubMed1998

The APOE epsilon4 allele is associated with decline on delayed recall performance in community-dwelling older adults.

OBJECTIVE: This study investigated whether the Apolipoprotein (APOE) epsilon4 allele was associated with cognitive decline in community-dwelling older adults. DESIGN: Longitudinal cognitive performance of older adults with the epsilon3/epsilon4 genotype was compared with that of older adults with the epsilon3/epsilon3 genotype. SETTING: Aging Clinical Research Center, Stanford University. PARTICIPANTS: One hundred community-dwelling older adults were recruited from a pool of 531 individuals who had participated in a memory training study 4 to 5 years earlier. These individuals were concerned about their memory functioning and were recruited through newspaper advertisements and contacts with local senior centers. The 100 individuals who agreed to participate in the follow-up investigation were between 59 and 95 years of age. MEASUREMENTS: At both baseline and follow-up, subjects were administered a battery of seven cognitive tests that examined verbal and spatial memory, attention, speed-of-processing, and language abilities. APOE genotype was determined at follow-up. RESULTS: Individuals with the epsilon3/epsilon4 APOE genotype were significantly younger than individuals with the APOE epsilon3/epsilon3 genotype. No significant differences were observed between the two groups on measures of attention, speed-of-processing, vocabulary, immediate verbal memory, and immediate spatial memory. However, those older adults with the epsilon3/epsilon4 genotype exhibited significantly greater decline in performance on delayed recall of verbal material than did those with the epsilon3/epsilon3 APOE genotype. CONCLUSION: These findings are consistent with previous studies, which suggest that the APOE epsilon4 allele predicts decline on measures of delayed recall.

Adult↗
PubMed1997

Neurosteroids: deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus.

Pregnenolone sulfate (PREG S) is synthesized in the nervous system and is a major neurosteroid in the rat brain. Its concentrations were measured in the hippocampus and other brain areas of single adult and aged (22-24 month-old) male Sprague-Dawley rats. Significantly lower levels were found in aged rats, although the values were widely scattered and reached, in about half the animals, the same range as those of young ones. The spatial memory performances of aged rats were investigated in two different spatial memory tasks, the Morris water maze and Y-maze. Performances in both tests were significantly correlated and, accompanied by appropriate controls, likely evaluated genuine memory function. Importantly, individual hippocampal PREG S and distance to reach the platform in the water maze were linked by a significant correlation, i.e., those rats with lower memory deficit had the highest PREG S levels, whereas no relationship was found with the PREG S content in other brain areas (amygdala, prefrontal cortex, parietal cortex, striatum). Moreover, the memory deficit of cognitively impaired aged rats was transiently corrected after either intraperitoneal or bilateral intrahippocampal injection of PREG S. PREG S is both a gamma-aminobutyric acid antagonist and a positive allosteric modulator at the N-methyl-D-aspartate receptor, and may reinforce neurotransmitter system(s) that decline with age. Indeed, intracerebroventricular injection of PREG S was shown to stimulate acetylcholine release in the adult rat hippocampus. In conclusion, it is proposed that the hippocampal content of PREG S plays a physiological role in preserving and/or enhancing cognitive abilities in old animals, possibly via an interaction with central cholinergic systems. Thus, neurosteroids should be further studied in the context of prevention and/or treatment of age-related memory disorders.

Aging↗
PubMed1997

Serotonin and acetylcholine are crucial to maintain hippocampal synapses and memory acquisition in rats.

Treatment with serotonin and acetylcholine depletors reduced the number of synapses in the rat hippocampus. Animals that received the drug treatment lost a substantial number of synapses and showed an apparent impairment in memory acquisition. Although the animals were behaviorally impaired following the treatment, spatial memory was nonetheless eventually attained despite the disappearance of long-term potentiation. These data suggest that synapses in the hippocampus that are normally maintained by serotonin and acetylcholine are crucial for normal acquisition of spatial memory. The number of synapses maintained by biogenic amines may be a basic mechanism for neurobehavioral plasticity.

Acetylcholine↗
PubMed1990

Post-ictal recognition memory predicts laterality of temporal lobe seizure focus: comparison with post-operative data.

Standardized verbal and visuo-spatial memory recognition were obtained on 15 patients with unilateral temporal lobe epilepsy (TLE), using a reference group of 43 (12 males, 31 females) subjects with no previous history of neurological disease. Inter-ictal measures on these two tasks failed to differentiate between those patients with left vs right seizure foci. When eight of these patients were tested post-ictally (within 1 hr of seizure), seven showed the expected selective memory impairment when compared to inter-ictal performance. Left TLE patients showed a relative lowering of verbal memory, whereas patients with right TLE showed a relative visuo-spatial memory impairment. A similar result was also found in the patients when a comparison between pre-operative (inter-ictal) and post-operative performance was made, thereby further substantiating the validity of the tasks. This significant association between side of seizure focus and selective impairment of post-ictal memory performance provides evidence of a more direct method of neuropsychological diagnosis in TLE patients prior to surgery.

Adolescent↗
PubMed1999

Estrogen and NMDA receptor antagonism: effects upon reference and working memory.

Since both estrogen and NMDA receptor antagonists act on the hippocampus CA1 region and behaviorally affect hippocampal memory tasks, we examined how estrogen depletion (ovariectomy) and NMDA receptor antagonism interact upon spatial memory of the mouse. After ovariectomy or sham operation, mice were given a 2-week recovery before behavioral tests began under the influence of vehicle or (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP 2, 5 and 10 mg/kg) intraperitoneal injections. CPP is a competitive, full NMDA receptor antagonist. Spatial reference memory was tested by the water maze, spatial working memory was tested by the radial arm maze, while overall locomotive activity was monitored by the Y-maze. Results from the water maze and the Y-maze did not show any spatial reference memory or activity differences between sham-operated and ovariectomized mice. The radial arm maze, however, highlighted some working memory differences between intact and ovariectomized mice. CPP treatment impaired dose dependently--the performance of ovariectomy and sham-operated mice equally on both water maze and radial arm maze, while the drug had no effect on Y-maze performance. These results suggest that short term estrogen deprivation has no effect upon spatial-reference memory, while it impairs spatial working memory. This effect is probably not mediated by NMDA receptors.

Animals↗
PubMed1994

Memory for spatial location as a function of temporal lag in rats: role of hippocampus and medial prefrontal cortex.

Rats with medial prefrontal cortex, hippocampus, or cortical control lesions were tested on an eight-arm radial maze task, in order to examine memory for the temporal order of spatial locations as a function of temporal lag. During the study phase of each trial, rats were allowed to visit each of eight arms once in an order that was randomly selected for that trial. The test phase required the rats to choose which of two arms occurred earlier in the sequence of arms visited during the study phase. The arms selected as test arms varied according to temporal lag (0-6) or the number of arms that occurred between the two test arms in the study phase. The control rats performed at chance at a temporal lag of zero, but their performance was above chance for the remaining lags, improving after the temporal lag exceeded zero. The hippocampal-lesioned rats showed a marked deficit, performing at chance for all lags, with some savings for those items occurring at the end of the list. The medial prefrontal cortex-lesioned rats showed a less severe deficit. The results of these data support the notion that both the hippocampus and the medial prefrontal cortex play significant roles in memory for the temporal order of spatial locations.

Animals↗
PubMed2000

Hippocampal mossy fibers and swimming navigation learning in two vole species occupying different habitats.

We showed previously for mice that size differences of the infrapyramidal hippocampal mossy fiber projection (IIP-MF) correlate with spatial learning abilities. In order to clarify the role of the IIP-MF in a natural environment, we studied the bank vole (Clethrionomys glareolus), adapted to a wide range of different habitats, and the root vole (Microtus oeconomus), living in homogenous grassland habitats with small home ranges. Morphometry on Timm-stained horizontal brain sections of six C. glareolus and six M. oeconomus revealed that the size of the entire mossy fiber projection was 42% larger in C. glareolus than M. oeconomus. C. glareolus had also an IIP-MF projection about 230% larger than that of the root vole. A sample of captured animals was then transferred to the laboratory (C. glareolus, n = 23; M. oeconomus, n = 15) and underwent testing for swimming navigation according to a standardized protocol used to assess water maze learning in about 2,000 normal and transgenic mice. Both species learned faster than laboratory mice. Overall escape times showed no differences, but path length was significantly reduced in C. glareolus, which also showed superior performance in a variety of scores assessing spatial search patterns. On the other hand, M. oeconomus showed faster swimming speed, and strong thigmotaxis combined with circular swimming. M. oeconomus also scored at chance levels during the probe trial, about as poorly as mutant knockout mice considered to be deficient in spatial memory. These differences probably reflect differential styles of water maze learning rather than spatial memory deficits: C. glareolus appears to be superior in inhibiting behavior interfering with proper spatial search behavior, while M. oeconomus succeeds in escaping by using rapid circular swimming. We assume that size variations of the IIP-MF correspond to a mechanism stabilizing hippocampal processing during spatial learning or complex activities. This corresponds to the ecological lifestyle of the two species and is in line with previous observations on the role of the IIP-MF.

Animals↗
PubMed2003

Phonological and visuo-spatial working memory in individuals with intellectual disability.

Differences in the storage and rehearsal components of the phonological loop and visuo-spatial sketchpad were investigated in individuals with and without intellectual disability matched on memory span. The group with intellectual disability had specific difficulty in the rehearsal component of the phonological loop, as demonstrated by a weak word length effect compared to the group without intellectual disability. Groups did not differ in the storage component of the phonological loop as indexed by the phonological similarity effect. Also, groups did not differ in the storage or maintenance components of the visuo-spatial sketchpad, having comparable visual similarity and visual complexity effects. However, visual complexity task performance suggested that some aspects of visual processing surpass developmental level expectations for individuals with intellectual disability.

Adolescent↗
PubMed2004

Choline pivaloyl esters improve in rats cognitive and memory performances impaired by scopolamine treatment or lesions of the nucleus basalis of Meynert.

The effects of two choline pivaloyl esters, [2-(2,2-dimethylpropionyloxy)ethyl]trimethylammonium iodide (1) and [2-(2,2-dimethylpropionyloxy)ethyl]trimethylammonium 2,2-dimethylpropionate (2), on learning and memory impairments induced in rats by scopolamine or lesions of nucleus basalis magnocellularis (NBM) have been evaluated by object recognition and Morris water maze tests in comparison with Tacrine (THA). Both 1 and 2 restored discrimination in object recognition test for assessing working-episodic memory and improved spatial memory in scopolamine or NBM-lesioned rats as well. The positive effects produced by 1 and 2 on cognitive and memory deficits were well comparable with those evoked by THA, used as reference compound.

Acetylcholinesterase↗
PubMed1994

Spatial working memory over long retention intervals: dependence on sustained cholinergic activation in the septohippocampal or nucleus basalis magnocellularis-cortical pathways?

Previous direct neurochemical studies of the temporal dynamics of cholinergic activation in the septohippocampal and nucleus basalis magnocellularis-cortical pathways at various stages during repeated testing of mice with selective spatial reference or working memory protocols [Durkin and Toumane (1992), Behav. Brain Res. 50, 43-52] showed that the post-test durations of cholinergic activation in each pathway varied as a function of the type of memory tested and the level of task mastery. Since (i) the hippocampal formation is considered to constitute a critical component of a temporary memory buffer, and (ii) working memory items are not thought to be submitted to consolidation and permanent storage, we postulated that the duration of testing-induced cholinergic activation in the septohippocampal pathway may govern the maintenance of the working memory trace over the retention interval. In order to test directly this hypothesis C57 B1/6 mice were extensively trained (one trial/day, 25-30 days) on an identical selective working memory task to attain high levels of retention (> 80% correct), but using either 5 min (Group 1), or 60 min (Group 2) retention intervals. At various times (30 s-75 min) following the initial acquisition phase of the test, cholinergic activity in the hippocampus and frontal cortex was quantified using measures of high-affinity choline uptake. Whereas cholinergic activation was observed in both pathways at 30 s post-acquisition and throughout the 5 min retention interval in Group 1, the situation in Group 2 is different, activation of the septohippocampal pathway being maintained for only 15 min, while activation in the nucleus basalis magnocellularis-cortical pathway is maintained for the totality of the 1 h retention interval. The nucleus basalis magnocellularis-cortical cholinergic pathway, in addition to its role in long-term reference memory storage processes may, thus, via an intervention in the temporal encoding of information, also subsume a complementary intermediate-term buffer storage role in working memory situations requiring retention intervals in excess of 15 min in mice. This secondary, "backup", function of the nucleus basalis magnocellularis-cortical pathway would thus liberate the septohippocampal complex from its primary active role in the temporary maintenance and/or accessibility of the working memory trace in these particular cases requiring long retention intervals.

Acetylcholine↗
PubMed2006

The relationship between migratory behaviour, memory and the hippocampus: an intraspecific comparison.

It has been hypothesized that memory-demanding ecological conditions might result in enhanced memory and an enlarged hippocampus, an area of the brain involved in memory processing, either via extensive memory experience or through evolutionary changes. Avian migration appears to represent one of such memory-demanding ecological conditions. We compared two subspecies of the white-crowned sparrow: migratory Zonotrichia leucophrys gambelii and non-migratory Z. l. nuttalli. Compared to non-migratory Z. l. nuttalli, migratory Z. l. gambelii showed better memory performance on spatial one-trial associative learning tasks and had more hippocampal neurons. Migratory subspecies also had larger hippocampi relative to the remainder of the telencephalon but not relative to body mass. In adults, the differences between migratory and non-migratory sparrows were especially pronounced in the right hippocampus. Juvenile migratory Z. l. gambelii had relatively larger hippocampal volume compared to juvenile non-migratory Z. l. nuttalli. Adult migratory Z. l. gambelii had more neurons in their right hippocampus compared to juveniles but such differences were not found in non-migratory Z. l. nuttalli. Our results suggest that migratory behaviour might be related to enhanced spatial memory and an enlarged hippocampus with more neurons, and that differences in the hippocampus between migratory and non-migratory sparrows might be experience-dependent. Furthermore, for the first time our results suggest that the right hippocampus, which encodes global spatial information, might be involved in migratory behaviour.

Analysis of Variance↗
PubMed2005

Transitional information in spatial serial memory: path characteristics affect recall performance.

This study examined the role of stimulus characteristics in a visuospatial order reconstruction task in which participants were required to recall the order of sequences of spatial locations. The complexity of the to-be-remembered sequences, as measured by path crossing, path length, and angles, was found to affect serial memory, in terms of both recall accuracy and response times. The results demonstrate that not all sequences are remembered equally and that spatial characteristics of the sequences constitute an important variable in the understanding of visuospatial serial memory. More important, the data suggest that spatial path represents transitional information and that, as is the case in verbal serial memory, transitional information is of critical importance in serial memory.

Attention↗
PubMedDate not supplied

Short-term behavioral and electrophysiological consequences of underwater trauma.

In a previous work we found that a 30-s underwater trauma, following 8 days of training for a spatial memory task in the water maze, resulted in poor performance in the spatial memory task at both 1 h and 3 weeks after the trauma. Here we found that compared with naive animals and animals that were trained for the spatial learning task but were not traumatized, the traumatized rats showed impaired performance in a spatial learning task in the water maze 20 min after the trauma and a reduced level of dentate gyrus long-term potentiation (LTP) 40 min after high-frequency stimulation to the perforant path. We also found a positive correlation between the behavioral performance and hippocampal plasticity. The reduced ability to induce LTP suggests that the trauma-related behavioral impairment is mediated by hippocampal-dependent processes. The underwater trauma may provide an important and potentially powerful model for understanding the mechanisms underlying the relationship between stress, cognition, and learning.

Animals↗
PubMed2006

NADPH-diaphorase histochemical changes in the hippocampus, cerebellum and striatum are correlated with different modalities of exercise and watermaze performances.

Nitric oxide is involved in memory and motor learning. We investigated possible influences of exercise on spatial memory and NADPH-diaphorase (NADPH-d) histochemical activity in the hippocampus, striatum and cerebellum. Fifteen albino Swiss mice between the 22nd and 55th post-natal days were exercised in the following modalities: voluntary (V), acrobatic (A), acrobatic/voluntary (AV) and forced (F) and compared to inactive group (I). After the exercise period, all subjects were tested in the water maze for 3 days. Animal brains were processed for NADPH-d histochemistry. Densitometry of the neuropil of the hippocampus, striatum and cerebellum and morphometric analysis of NADPHd+ type I neurons of the striatum were done. Exercise groups presented higher levels of NADPH-d activity in the molecular and polymorphic layers of dentate gyrus and lacunosum molecular layer of CA1. The A group presented higher NADPH-d activity in the cerebellar granular layer than all other groups. Branching points and dendritic segment densities of NADPH-d type I neurons were higher in V, A and AV than in F and I groups. Exercise groups revealed best performances on water maze tests. Thus, different modalities of exercise increases in different proportions for the nitrergic activity in the hippocampus, striatum and cerebellum, and these changes seem to be beneficial to spatial memory.

Analysis of Variance↗
PubMed2003

One-trial memory for object-place associations after separate lesions of hippocampus and posterior parahippocampal region in the monkey.

In earlier studies of one-trial spatial memory in monkeys (Parkinson et al., 1988; Angeli et al., 1993), severe and chronic memory impairment for both object-place association and place alone was found after ablation of the hippocampal formation. The results appeared to provide the first clear-cut evidence in the monkey of the essential role of the hippocampus in spatial memory, but that interpretation neglected the inclusion in the lesion of the underlying posterior parahippocampal region. To determine the separate contributions of the hippocampus and posterior parahippocampal region to these spatial forms of one-trial memory, we trained 10 rhesus monkeys, as before, to remember the spatial positions of either two different trial-unique objects overlying two of the wells in a three-well test tray (object-place trials) or simply two of the three wells (place trials). Six of the monkeys then received ibotenic acid lesions restricted to the hippocampal formation (group H), and the four others received selective ablations of the posterior parahippocampal region (group P), comprising mainly parahippocampal cortex, parasubiculum, and presubiculum. Group H was found to be completely unaffected postoperatively on both types of trials, whereas group P sustained an impairment on both types equal in magnitude to that observed after the combined lesions in the original studies. Thus, contrary to the previous interpretation, one-trial memory for object-place association and, perhaps more fundamentally, one-trial memory for two different places appear to be critically dependent not on the hippocampal formation but rather on the posterior parahippocampal region.

Animals↗
PubMed2001

Upper/lower visual field asymmetry on a spatial relocation memory task.

The purpose of this study was to investigate whether the lower visual field advantage reported on a number of visual tasks depends on the activity of neural systems which process information from different spaces. To this end, a double dissociation logic was followed by observing the effects of visual and spatial interference on a relocation memory task performed by 80 volunteers. Results showed that participants were better at relocating stimuli presented in the lower than in the upper visual field. Moreover, a concurrent spatial task, but not a concurrent visual task, disrupted the visual field vertical asymmetry. Those findings confirm that the vertical asymmetry of visual field depends on the spatial processing of incoming stimuli.

Adult↗