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PubMed2003

Visual but not spatial working memory deficit in children with spina bifida.

Twenty children with spina bifida and twenty controls were assessed on a battery of visuospatial working memory tests. Children with spina bifida performed as well as the control group in the visuospatial test and in the forward and backward versions of the Corsi test, but were impaired in the 'House Visual Span.' This test, designed in our lab, provides specific information regarding visual ability to discriminate between pictorial targets and lures, and requires specific visual processing of stimuli. These results are discussed in terms of working memory models and are viewed as supporting the distinction between the visual and spatial components of working memory.

Adolescent↗

PubMed1990

Rats exposed prenatally to alcohol exhibit impairment in spatial navigation test.

Prenatal exposure to ethanol causes learning disabilities and low I.Q. scores. The objective of the present studies was to investigate whether exposure of rats to ethanol in utero, would induce a deficit in spatial memory in adult life. Pregnant rats were fed with an ethanol diet from day 1 of pregnancy till parturition. Control rats were either pair-fed with an isocaloric sucrose diet or were fed with lab-chow ad libitum. On the first day of birth, offspring exposed to ethanol in utero were placed with a control mother fed with lab-chow, while offspring of the lab-chow fed dams were placed with ethanol-treated dams. At 40, 60 and 90 days postnatally, behavioral testing was performed using the Morris swim maze, a test of spatial memory. Results indicated that the offspring exposed to ethanol in utero presented deficits in spatial memory processes. Ethanol did not completely block the learning of the swim maze task but the alcohol-exposed offspring exhibited longer latencies to perform the task, swam longer distances prior to locating and climbing onto the platform, and when the platform was removed, searched for it in all 4 quadrants of the pool. Restricted caloric intake during gestation and maternal behavior in early postnatal life also induced deficits in the performance on the swim maze task. However, these deficits were mild and short-lasting being absent at 60 and 90 days of age. In contrast, the deficits induced by ethanol were more severe and longer-lasting, being present in adult life.

Animals↗

PubMed2007

Propranolol blocks chronic risperidone treatment-induced enhancement of spatial working memory performance of rats in a delayed matching-to-place water maze task.

RATIONALE: Atypical antipsychotics improve cognitive function, including working memory, in schizophrenia. Some atypical antipsychotics have been reported to activate the locus coeruleus and induce beta-adrenoceptor antagonist sensitive c-Fos-like immunoreactivity in the prefrontal cortex. MATERIALS AND METHODS: The present study investigated the effects of chronic treatment of rats with risperidone (1 mg kg(-1) day(-1) s.c.), clozapine (10 mg kg(-1) day(-1) s.c.), or acidified saline vehicle control for 2, 4, or 8 weeks on spatial working memory performance in a delayed matching-to-place water maze task with a 60-s inter-trial retention interval with and without acute challenge with propranolol (10 mg/kg i.p.). RESULTS: Treatment with risperidone for 8 weeks, but not 2 or 4 weeks, significantly improved working memory performance. In contrast, treatment with clozapine for up to 8 weeks did not improve working memory. Acute challenge with propranolol blocked the improvement in working memory produced by chronic treatment with risperidone, but had no significant effect on performance in saline- or clozapine-treated animals. CONCLUSIONS: The delayed matching-to-place water maze task may prove valuable in the investigation of the behavioural pharmacology of the cognitive effects of antipsychotic drugs. These data suggest that beta adrenoceptors may contribute to the cognitive effects of chronic treatment with atypical antipsychotics.

Adrenergic beta-Antagonists↗

PubMed2006

Questionnaire ratings of attention-deficit/hyperactivity disorder (ADHD) in adults are associated with spatial working memory.

OBJECTIVE: Data related to brain function may have the potential to improve the reliability and validity of assessments for the aetiologically and clinically heterogeneous syndrome of attention-deficit/hyperactivity disorder (ADHD). This study investigated associations between questionnaire assessments of behavioural features of adults with ADHD and an aspect of neurocognitive performance which has been reported to be impaired in adults with ADHD. METHODS: Fifty-nine adult patients with a DSM-IV diagnosis of ADHD, and their informants, completed questionnaires related to aspects of severity of ADHD. Associations were examined between questionnaire ratings and performance on a computer-administered task of spatial working memory (SWM). RESULTS: Correlations between ratings of ADHD and SWM indicated moderate but significant correlations for patients' ratings, but not for informants' ratings. Also, patients who reported a past history of 'self-harm' (N=33) had a significantly worse mean performance on both measures of SWM (p=0.004, 0.003). CONCLUSIONS: The results indicate that aspects of impulsivity, i.e. self-ratings of 'emotive' behaviour (involving rapid response to stimuli and marked reactivity of mood) and of past 'self-harm', show relatively strong associations with SWM performance in adults selected on the basis of an ADHD diagnosis. A profile of neurocognitive performances may have a role in the assessment of ADHD.

Adult↗

PubMed2006

Enhancing cognition after stress with gene therapy.

Hippocampal function is essential for the acquisition, consolidation, and retrieval of spatial memory. High circulating levels of glucocorticoids (GCs), the adrenal steroid hormones secreted during stress, have been shown to impair both acquisition and retrieval and can either impair or enhance consolidation, depending on experimental conditions. In contrast, estrogen can enhance spatial memory performance and can block the deleterious effects of GCs on such performance. We therefore constructed a chimeric gene ("ER/GR") containing the hormone-binding domain of the GC receptor and the DNA binding domain of the estrogen receptor; as a result, ER/GR transduces deleterious GC signals into beneficial estrogenic ones. We show here that acute immobilization stress, before acquisition and retrieval phases, increases latencies for male rats in a hidden platform version of the Morris water maze. This impairment is blocked by hippocampal expression of the ER/GR transgene. ER/GR expression also blocks decreases in platform crossings caused by acute stress, either after acquisition or before retrieval. Three days of stress before acquisition produces an estrogen-like enhancement of performance in ER/GR-treated rats. Moreover, ER/GR blocks the suppressive effects of GCs on expression of brain-derived neurotrophic factor (BDNF), a growth factor central to hippocampal-dependent cognition and plasticity, instead producing an estrogenic increase in BDNF expression. Thus, ER/GR expression enhances spatial memory performance and blocks the impairing effects of GCs on such performance.

Analysis of Variance↗

PubMed1999

Spatial working memory assessment by a visual-manual delayed response task: a controlled study in schizophrenia.

'Working memory' dysfunction has been proposed as a central cognitive feature in schizophrenia. To further explore this issue we developed a computerized easy and fast to administer test using the standard keyboard as visual-manual subject-computer interface along a delayed-response paradigm. The test has been administered to 25 patients who met the DSM-III-R criteria for schizophrenia and 25 healthy control subjects matched as possible for sex. The data confirm the visuo-spatial 'working memory' dysfunction in schizophrenic patients. The test maintains the discriminative capacity of similar previously devised tasks with the advantages of being usable on almost every standard computer and shorter and more acceptable for severely disabled patients also. The test can be considered an useful tool to study the 'working memory' impairment in the cognitive deficit of schizophrenia.

Adult↗

PubMed2006

Spatial working memory in obsessive-compulsive disorder improves with clinical response: A functional MRI study.

To date, only a few studies have examined whether executive dysfunctions in obsessive-compulsive disorder (OCD) are state or trait dependent and almost none of these studies have used functional neuroimaging techniques. We conducted a functional MRI study before and after 12 weeks of pharmacological treatment in 14 psychotropic-free patients with OCD without comorbidity. Subjects performed a spatial variant of a working memory task with four increasing levels of difficulty (n-back task). Responders and non-responders did not differ in clinical and demographical characteristics or brain activation patterns before treatment. Performance improved only in responders and was associated with a change in the overall pattern of brain activity during the task. We found no correlations between (changes in) scores on symptom scales, brain activity and performance. Our preliminary findings suggests that spatial working memory deficits in OCD and their functional anatomical correlates, as assessed with a spatial n-back task, are, at least to some extent, state dependent.

Adult↗

PubMed2002

Long-term study of chronic oral aluminum exposure and spatial working memory in rats.

The authors report an effort to advance animal models that mimic the cognitive decline of Alzheimer's disease. Rats were trained and repeatedly tested in a spatial delayed matching-to-position paradigm in the water maze, with the location of the submerged platform changing between, but not within, days. After Trial 1 (random search) and intertrial intervals of 30 s or 1 hr, memory was tested in Trial 2. Young rats quickly acquired this task and were repeatedly tested after different intervals over 7 months, with a slight increase in performance toward the end of testing, but no difference in latencies between delays. Oral long-term treatment of 1 group with 0.1% aluminum caused no delay-dependent working memory deficit. This testing protocol may enable between- and within-subject long-term assessment of spatial working memory before and after drug treatment and may prove useful in animal models of progressive cognitive decline.

Administration, Oral↗

PubMed2001

The conjoint importance of the hippocampus and anterior thalamic nuclei for allocentric spatial learning: evidence from a disconnection study in the rat.

A disconnection procedure was used to test whether the hippocampus and anterior thalamic nuclei form functional components of the same spatial memory system. Unilateral excitotoxic lesions were placed in the anterior thalamic (AT) nuclei and hippocampus (HPC) in either the same (AT-HPC Ipsi group) or contralateral (AT-HPC Contra group) hemispheres of rats. The behavioral effects of these combined lesions were compared in several spatial memory tasks sensitive to bilateral hippocampal lesions. In all of the tasks tested, T-maze alternation, radial arm maze, and Morris water maze, those animals with lesions placed in the contralateral hemispheres were more impaired than those animals with lesions in the same hemisphere. These results provide direct support for the notion that the performance of tasks that require spatial memory rely on the operation of the anterior thalamus and hippocampus within an integrated neural network.

Animals↗

PubMed2006

Chimpanzees (Pan troglodytes) remember the location of a hidden food item after altering their orientation to a spatial array.

Two chimpanzees (Pan troglodytes) had a direct view of an experimenter placing a food item beneath one of several cups within a horizontal spatial array. The chimpanzees then were required to move around the spatial array, shifting their orientation to the array by 180 degrees . Both chimpanzees remembered the location of the food item. In the next experiment, a visual barrier was placed between the chimpanzees and the spatial array after the food item had been hidden to prevent visual tracking of the location of the object during the chimpanzees' movement. One chimpanzee remembered the location of the hidden item in this variation. These results demonstrate another capacity for spatial memory in this species that complements data indicating chimpanzee spatial memory for invisible displacements, array rotations, and array transpositions.

Animals↗

PubMed1996

Test anxiety and working memory system.

The purpose was to examine the effect of test anxiety on deficits in the articulatory loop in the working memory system. We used a verbal memory task to occupy the articulatory loop and a spatial memory task to occupy the visuospatial scratch pad. 17 highly test-anxious and 19 low-anxiety subjects performed both tasks under an anxiety-inducing situation during which they were observed by a monitor camera. Percentage of correct responses and reaction times were measured as indices of task performance. Highly anxious subjects reported feeling worry and cognitive self-concern more than the low-anxiety group. Highly anxious subjects showed a longer mean reaction time on the verbal memory task than the low-anxiety group. On the spatial memory task there was no difference in quality of performance. This finding might suggest that anxiety such as worry and cognitive self-concern interferes with information processing in the articulatory loop of the working memory system.

Achievement↗

PubMed2006

What is the functional significance of chronic stress-induced CA3 dendritic retraction within the hippocampus?

Chronic stress produces consistent and reversible changes within the dendritic arbors of CA3 hippocampal neurons, characterized by decreased dendritic length and reduced branch number. This chronic stress-induced dendritic retraction has traditionally corresponded to hippocampus-dependent spatial memory deficits. However, anomalous findings have raised doubts as to whether a CA3 dendritic retraction is sufficient to compromise hippocampal function. The purpose of this review is to outline the mechanism underlying chronic stress-induced CA3 dendritic retraction and to explain why CA3 dendritic retraction has been thought to mediate spatial memory. The anomalous findings provide support for a modified hypothesis, in which chronic stress is proposed to induce CA3 dendritic retraction, which then disrupts hypothalamic-pituitary-adrenal axis activity, leading to dysregulated glucocorticoid release. The combination of hippocampal CA3 dendritic retraction and elevated glucocorticoid release contributes to impaired spatial memory. These findings are presented in the context of clinical conditions associated with elevated glucocorticoids.

Adaptation, Physiological↗

PubMed1999

Architecture and dynamics of the primate prefrontal cortical circuit for spatial working memory.

In the experimental protocol of working memory tasks using a monkey as a subject, tuned activity of the prefrontal cortical neurons that is sustained during the delay period is a neuronal substrate of the working memory. This study addresses the question as to how this tuned activity is formed and maintained in the prefrontal cortex by means of computer simulations of the dynamics of a model prefrontal cortical circuit. The model assumes that pyramidal cells receive two types of intracortical inhibition, "parallel" and "anti-parallel", in accordance with recent experimental findings. The parallel and anti-parallel refer to the relationship between the preferred directions of presynaptic interneurons and postsynaptic pyramidal cells. The following three factors are suggested to be crucial for the formation and maintenance of spatial working memory: cortical amplification of the activity due to excitatory closed-loop circuitry, suppression of excessive excitation by the parallel inhibition, and sharpening of the activity profile by the anti-parallel inhibition.

Journal Article↗

PubMed2007

Layout geometry in the selection of intrinsic frames of reference from multiple viewpoints.

Four experiments investigated the roles of layout geometry in the selection of intrinsic frames of reference in spatial memory. Participants learned the locations of objects in a room from 2 or 3 viewing perspectives. One view corresponded to the axis of bilateral symmetry of the layout, and the other view(s) was (were) nonorthogonal to the axis of bilateral symmetry. Judgments of relative direction using spatial memory were quicker for imagined headings parallel to the symmetric axis than for those parallel to the other viewing perspectives. This advantage disappeared when the symmetric axis was eliminated. Moreover, there was more consistency across participants in the selection of intrinsic axes when the layout contained an axis of bilateral symmetry than when it did not. These results indicate that the layout geometry affects the selection of intrinsic frames of reference supporting the intrinsic model of spatial memory proposed by W. Mou and T. P. McNamara (2002) and by A. L. Shelton and T. P. McNamara (2001).

Female↗

PubMed1996

Differences in hippocampal volume among food storing corvids.

The hippocampal complex (hippocampus and parahippocampalis) is known to play a role in spatial memory in birds and is known to be larger in food-storing versus non-storing birds. In the present study, we investigated the relative volume of the hippocampal complex in four food-storing corvids: gray-breasted jays (Aphelocoma ultramarina), scrub jays (Aphelocoma coerulescens), pinyon jays (Gymnorhinus cyanocephalus), and Clark's nutcrackers (Nucifraga columbiana). The results show that Clark's nutcrackers have a larger hippocampal complex, relative to both body and total brain size, than the other three species. Clark's nutcrackers rely more extensively on stored food in the wild than the other three species. Clark's nutcrackers also perform better during cache recovery and operant tests of spatial memory than scrub jays. Thus, greater hippocampal volume is associated with better performance in laboratory tests of spatial memory and with stronger dependence on food stores in the wild.

Animals↗

PubMed1999

Simultaneous evaluation of spatial working memory and motivation by the allocentric place discrimination task in the water maze in rats.

In order to evaluate learning and memory deficits separately from and simultaneously with motivational, motor and sensory impairments in identical animals, we developed the allocentric place discrimination task test using a water maze in rats. For this assessment task, two similar, visible platforms, one was fixed and the other was floating, were simultaneously present in a pool, and the working memory of the allocentric place discrimination task was evaluated. After training, the task accuracy was high about 85% correct and animals were used repeatedly. The accuracy decreased significantly when the pool was surrounded with a black curtain. Muscarinic receptor antagonist scopolamine 0.5 mg/kg selectively impaired the accuracy. Muscle relaxant dantrolene 10 mg/kg selectively decreased swimming speed. Under low motivational condition (warm water), still time increased and swimming speed decreased, but the accuracy was not affected. Similar to warm water, opioid receptor agonist morphine 15 mg/kg increased still time and decreased swimming speed. These results suggest that the allocentric place discrimination task is useful in evaluating spatial working memory ability independently of and concurrently with also visual, motor ability and motivation in identical animals.

Analgesics, Opioid↗

PubMed1992

Chronic cerebrovascular insufficiency induces dementia-like deficits in aged rats.

Young and aged rats were subjected to cerebrovascular insufficiency (CVI) for 3 and 9 weeks. At the end of each time period, local cerebral blood flow (lCBF), spatial memory function, 31P- and 1H-NMR spectroscopy and imaging of the brains were evaluated in vivo. Morphometric counts of CA1 hippocampal neuron damage and staining for glial fibrillary acidic protein (GFAP) were done post-mortem. Results show that after 3 weeks of CVI, cortical and hippocampal lCBF was significantly reduced in young and aged animals respectively. In addition, young and aged rats at 3 weeks following CVI showed spatial memory deficits in the Morris water maze and elevation of 31P-phosphomonoester as measured by non-invasive NMR spectroscopy. At the same time period, in vivo 1H-microimaging (MRI) of brains showed areas of high signal intensity (suggesting local edema) localized asymmetrically to the right hippocampal region in young and aged CVI rats. Morphometry of the hippocampal CA1 sector at post-mortem confirmed the in vivo MRI changes and demonstrated that a significant percentage of the CA1 pyramidal cells were damaged after CVI. Nine weeks after CVI, hippocampal CBF reductions, spatial memory impairment, spectroscopic-microimaging changes and CA1 sector cell damage continued to be observed in the aged animals but were resolved in the young rat brains. In addition, GFAP immunoreaction progressively increased in the hippocampus of aged rats subjected to CVI for 9 weeks. It is concluded that cognitive, metabolic and morphologic damage was significantly more severe and longer lasting in aged than young rat brain after chronic CVI. The deficits observed in this rat model appear to mimic the early pathology reported in Alzheimer's disease and suggest that the present model could provide fundamental clues relative to the etiology and possible management of this dementia.

Aging↗

PubMed2004

Methylene blue improves brain oxidative metabolism and memory retention in rats.

Methylene blue (MB) increases mitochondrial oxygen consumption and restores memory retention in rats metabolically impaired by inhibition of cytochrome c oxidase. This study tested two related hypotheses using biochemical and behavioral techniques: (1) that low-level MB would enhance brain cytochrome c oxidation, as tested in vitro in brain homogenates and after in vivo administration to rats and (2) that corresponding low-dose MB would enhance spatial memory retention in normal rats, as tested 24 h after rats were trained in a baited holeboard maze for 5 days with daily MB posttraining injections. The biochemical in vitro studies showed an increased rate of brain cytochrome c oxidation with the low but not the high MB concentrations tested. The in vivo administration studies showed that the corresponding MB low dose (1 mg/kg) increased brain cytochrome c oxidation 24 h after intraperitoneal injection, but not after 1 or 2 h postinjection. In the behavioral studies, spatial memory retention in probe trials (percentage of visits to training-baited holes compared to total visits) was significantly better for MB-treated than saline control groups (66% vs. 31%). Together the findings suggest that low-dose MB enhances spatial memory retention in normal rats by increasing brain cytochrome c oxidase activity.

Animals↗