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PubMed2003

GluR-A-Deficient mice display normal acquisition of a hippocampus-dependent spatial reference memory task but are impaired during spatial reversal.

Acquisition and reversal of a spatial discrimination were assessed in an appetitive, elevated plus-maze task in 4 groups of mice: knockout mice lacking the AMPA receptor subunit GluR-A (GluR1), wild-type controls, mice with cytotoxic hippocampal lesions, and controls that had undergone sham surgery. In agreement with previous studies using tasks such as the water maze, GluR-A(-/-) mice were unimpaired during acquisition of the spatial discrimination task, whereas performance in the hippocampalgroup remained at chance levels. In contrast to their performance during acquisition, the GluR-A(-/-) mice displayed a mild deficit during reversal of the spatial discrimination and were profoundly impaired during discrete trial, rewarded-alternation testing on the elevated T maze. The latter result suggests a short-term, flexible spatial working memory impairment in GluR-A(-/-) mice, which might also underlie their mild deficit during spatial reversal.

Animals↗

PubMed1999

Impairment of olfactory identification in obsessive-compulsive disorder.

BACKGROUND: Olfactory identification ability has been associated with processing in the orbitofrontal cortex (OFC), an area that has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). Although olfactory sensitivity is normal in patients with OCD, no study has investigated olfactory identification in this disorder. METHODS: A group of 20 subjects with OCD and 23 age- and education-matched controls performed a standardized test of olfactory identification. They also performed computerized tests of spatial memory span, spatial working memory and spatial recognition memory that have been shown previously to be sensitive to cognitive deficits in patients with OCD. RESULTS: Performance on the olfactory identification task, spatial recognition task and spatial span task was significantly worse in the OCD group than controls. CONCLUSIONS: While impairment in spatial cognition is consistent with previous studies of OCD, its significance for brain-behaviour models of OCD is unclear. However, the finding of abnormal olfactory identification in patients with OCD is consistent with the hypothesis that there is a disruption to processing at the level of the OFC in the disorder.

Adult↗

PubMedDate not supplied

Dissociating verbal and spatial working memory using PET.

Three experiments used position emission tomography (PET) to study the neural basis of human working memory. These studies ask whether different neural circuits underly verbal and spatial memory. In Experiment 1, subjects had to retain for 3 sec. either the names of four letters (verbal memory) or the positions of three dots (spatial memory). The PET results manifested a clear cut double dissociation, as the verbal task activated primarily left-hemisphere regions whereas the spatial task activated only right-hemisphere regions. In Experiment 2, the identical sequence of letters was presented in all conditions, and what varied was whether subjects had to remember the names of the letters (verbal memory) or their positions in the display (spatial memory). In the verbal task, activation was concentrated more in the left than the right hemisphere; in the spatial task, there was substantial activation in both hemispheres, though in key regions, there was more activation in the right than the left hemisphere. Experiment 3 studied only verbal memory, and showed that a continuous memory task activated the same regions as the discrete verbal task used in Experiment 1. Taken together, these results indicate that verbal and spatial working memory are implemented by different neural structures.

Humans↗

PubMed2005

Social isolation stress impairs passive avoidance learning in senescence-accelerated mouse (SAM).

Despite cumulative evidence showing the detrimental effect of psychosocial stress on the learning/memory functions in dementia diseases, the precise neurobiological mechanisms behind such an effect remain unclear. Mice of the senescence-accelerated mice prone 10 (SAMP10) strain, a neurodegenerative dementia model, were chronically exposed to social isolation stress from the age of 5 weeks. At the age of 12 weeks, conditioning memory and spatial memory were evaluated by one-trial passive avoidance and Y-maze tests, respectively. Chronic social isolation stress significantly reduced conditioning memory but did not affect spatial memory. Although further behavioral tasks using an elevated plus maze and a pain threshold test exhibited stress-induced analgesia, an analysis of covariance excluded the possibility that such analgesia might contribute to the stress-induced impairment of conditioning memory. In addition, endocrinological and immunohistochemical analysis revealed that isolation stress elevated the serum corticosterone levels and inhibited the increase in c-Fos expression in the central amygdaloidal nucleus (CeA) that is required for conditioning memory during passive avoidance learning. In conclusion, chronic social isolation stress exacerbated conditioning memory in SAM mice, probably through a glucocorticoid-mediated decrease in neural activation in the CeA.

Aging↗

PubMed2005

Verbal and spatial working memory in autism.

Verbal and spatial working memory were examined in high-functioning children, adolescents, and adults with autism compared to age and cognitive-matched controls. No deficit was found in verbal working memory in the individuals with autism using an N-back letter task and standardized measures. The distinction between the N-back task and others used previously to infer a working memory deficit in autism is that this task does not involve a complex cognitive demand. Deficits were found in spatial working memory. Understanding the basis for the dissociation between intact verbal working memory and impaired spatial working memory and the breakdown that occurs in verbal working memory as information processing demands are increased will likely provide valuable insights into the neural basis of autism.

Adolescent↗

PubMed1996

Serial order in spatial immediate memory.

Serial order effects in spatial memory are investigated in three experiments. In the first an analysis of errors in recall data suggested that immediate transpositions were the most common error and that order errors over 2 or 3 adjacent items accounted for the majority of errors in recall. The first and last serial positions are less error-prone than is the middle position in sets of six and seven items. A second experiment investigated recognition of transpositions and found that immediate transpositions were hardest to recognize but that a traditional serial position effect was not found. This may be due to the difficulty of maintaining one set of spatial items when another set is presented for comparison. A probe experiment, in which subjects were asked to recognize whether a single item came from a memory set and then to assign it to its position in the set indicated that the first and last positions were remembered more accurately than were central positions. The combination of serial order data in recall and position data suggests that there are similarities between serial order and position effects in the verbal and spatial domains and that serial order in spatial sequences is position-based.

Adult↗

PubMed2001

Ethanol-induced impairments in spatial working memory are not due to deficits in learning.

BACKGROUND: Acute ethanol administration impairs spatial reference memory and spatial working memory. However, the experimental designs previously used to test spatial working memory fail to make a distinction between the acquisition, or learning, of spatial information and the retention of this information. This study demonstrates that acute ethanol administration impairs spatial working memory, by using a novel experimental design that eliminates the confound between the learning of new spatial information and the testing of this information. METHODS: Long-Evans male rats received three forced trials to the same place for food reward on an elevated radial arm maze. Subjects were then given six free-choice trials in the first acquisition session, followed by a 30-min consolidation period before an additional six free-choice trials were administered-the retention session. Animals were trained to a criterion of five of six correct in both the acquisition and retention over 2 consecutive days. Once criteria were obtained, subjects received either saline or one of three ethanol doses immediately after the acquisition session to investigate whether ethanol alters retention of the learned spatial information. RESULTS: Acute ethanol administration impaired spatial working memory. Rats tested under saline and low-dose ethanol (1.0 g/kg) made significantly more place choices than rats tested under moderate- or high-dose ethanol (1.5 and 2.0 g/kg, respectively). Ethanol produced a temporary impairment in that no significant differences were found when subjects were retrained and retested 24 hr after initial testing. CONCLUSIONS: These results demonstrate that acute ethanol administration impairs spatial working memory and that such a deficit is not contingent on a learning impairment. These results support earlier findings that acute ethanol administration impairs spatial working memory but provide a significant advance by validating a novel training procedure that allows for direct investigation of working memory. Ethanol's impairment of both spatial working memory and spatial reference memory strengthens the similarities between memory impairments due to ethanol administration and memory impairments due to hippocampal lesions.

Animals↗

PubMed1997

Impaired spatial information processing in aged monkeys with preserved recognition memory.

Spatial information processing was examined in a non-human primate model of cognitive aging, using procedures formally similar to tasks designed for rats. The test apparatus was a large open field containing eight reward locations. Monkeys rapidly learned to visit each location once per trial, and probe manipulations confirmed that young animals navigated according to the distribution of cues surrounding the maze. In contrast, aged monkeys solved the task using a response sequencing strategy, independent of extramaze spatial information. Object recognition memory was normal in the aged group. The results reveal substantial correspondence in the cognitive effects of aging across rat and primate models, and they establish appropriate procedures for testing the long-standing proposal that the role of the hippocampus in normal spatial learning is similarly conserved.

Aging↗

PubMed1990

The effects of aging in rats on working and reference memory performance in a spatial holeboard discrimination task.

The effects of aging on spatial memory performance of rats was studied in a holeboard task in which 4 of 16 holes were baited with food. Brown-Norway rats of five ages (4, 13, 19, 25, and 30 months) received a total of 80 acquisition trials. A clear age-related decline of spatial working and reference memory performance was found. The decline was most profound between 19 and 25 months of age. The speed of visiting holes and the development of a preferred pattern of hole-visits did not influence spatial discrimination performance. Correlational analysis supported the view that the working and reference memory measures represent distinct aspects of spatial memory.

Aging↗

PubMed2000

Eye movement task measures inhibition and spatial working memory in adults with schizophrenia, ADHD, and a normal comparison group.

Schizophrenia and attention deficit/hyperactivity disorder (ADHD) are both associated with deficits in inhibition and working memory, although in ADHD the working memory deficit is hypothesized to be secondary to the inhibitory deficit. This similarity in cognitive processes has been paralleled by similarities across the two groups in the performance of working memory and inhibition tasks. The delayed oculomotor response task is an alternative task, which may allow greater separation of working memory from inhibitory components, and thus its use may provide additional information on primary vs. secondary deficits in these disorders. Ten young adult ADHD sufferers, 10 schizophrenic subjects, and 10 normal subjects were matched on age, gender, and education. Eye movements were recorded during delayed oculomotor response tasks with 1- and 3-s delays. Both the ADHD and the schizophrenic subjects demonstrated dis-inhibition (an increased percentage of premature saccades); however only schizophrenic subjects demonstrated an impaired working memory (decreased spatial accuracy of the remembered saccade). The results are consistent with the hypothesis that working memory is a primary deficit in schizophrenia, but secondary to the inhibitory deficit in ADHD.

Adult↗

PubMed2006

Modification of spatial recognition memory and object discrimination after chronic administration of haloperidol, amitriptyline, sodium valproate or olanzapine in normal and anhedonic rats.

In the present study we have investigated the effects of a chronic administration of olanzapine (Ola) on visual and spatial memory in normal and anhedonic rats. The effects of Ola have been compared to those of the typical antipsychotic Hal, the tricyclic antidepressant amitriptyline (Ami), and the mood stabilizer VPA. Anhedonia (assessed by reduction of sucrose preference) was induced by administration of a chronic mild stress (CMS) protocol, in which rats were exposed sequentially, over a period of 4 wk, to a variety of unpredictable mild stressors. The spatial memory was evaluated by testing the ability of the rats to discriminate a familiar vs. a novel environment, while the visual memory was assessed by testing the ability of the rats to discriminate familiar vs. novel objects. In CMS-free rats, VPA (5 or 30 mg/kg.d), Ola (0.02 or 0.1 mg/kg.d), Ami (2 mg/kg.d) and Hal (0.2 mg/kg.d) caused no detectable modifications of visual memory, whereas VPA (5 mg/kg.d), Ami (2 mg/kg.d) and Ola (0.02 mg/kg.d) did not modify spatial memory performance. In our experimental conditions, the administration of the CMS protocol caused an impairment of both visual and spatial memory. The chronic treatment of anhedonic rats with Ola (0.02 mg/kg.d) or Ami (2 mg/kg.d) prevented, at least in part, the stress-induced impairment of visuospatial performance. In conclusion, the results of the present preclinical study seem to indicate that the chronic administration of low doses of Ola or Ami has the potential to lead to substantial cognitive benefits in depressed patients.

Amitriptyline↗

PubMed1994

Evidence for spatial working memory in honeybees (Apis mellifera).

Spatial working memory (the ability to represent multiple locations in a flexible, dynamic manner) has been studied in a range of vertebrate species. The results of 3 experiments indicate that this ability also exists in at least one invertebrate (honeybees; Apis mellifera). Individual honeybees collected sugar solution from a matrix of 6 locations. They avoided revisits to locations previously depleted of solution more accurately than expected by chance. The results rule out several nonmemorial explanations for this ability, and it is therefore best explained by a spatial working memory system that allows discrimination of previously visited locations from those not yet visited. These results substantially expand the range of species in which spatial working memory has been demonstrated.

Animals↗

PubMed2002

Spatial working memory and the brainstem cholinergic innervation to the anterior thalamus.

The anteroventral thalamic nucleus (AV) has a role in spatial memory, but the influence of the prominent brainstem cholinergic projection to this region is unknown. Here, spatial memory in a 12-arm radial maze was examined after 0.15 microl bilateral AV infusions of scopolamine. In part one, rats visited six arms singly (the phase 1 arms) and, after a 10 min delay, were allowed free choice to both phase 1 arms and the remaining six baited arms (phase 2 arms). Scopolamine (10 microg) administered during the delay increased errors to both phase 1 and phase 2 arms, whereas PBS infusions increased phase 1 arm errors only. The PBS effect was the result of inserting the internal cannulas alone and not the infusion. The same dose of scopolamine (10 microg) infused before maze testing (part two: no phase 1 arms, no delay) also impaired spatial memory over and above the effects of both PBS and no-infusion, which did not differ markedly. Part two also showed that choice latency and choice strategies were unaffected by PBS and scopolamine. Cannulation and infusion procedures in both parts one and two did not produce any negative carryover effects across multiple control (no internal cannula) sessions, and a trypan blue manipulation indicated that infusions were restricted to the AV region. This study provides the first direct evidence that the brainstem cholinergic innervation to the limbic thalamus influences learning and memory, which may have important implications for human neurological conditions such as alcohol-related disorders and schizophrenia.

Animals↗

PubMed2004

The where and how of attention-based rehearsal in spatial working memory.

Rehearsal in human spatial working memory is accomplished, in part, via covert shifts of spatial selective attention to memorized locations ("attention-based rehearsal"). We addressed two outstanding questions about attention-based rehearsal: the topography of the attention-based rehearsal effect, and the mechanism by which it operates. Using event-related fMRI and a procedure that randomized the presentation of trials with delay epochs that were either filled with a flickering checkerboard or unfilled, we localized the effect to extrastriate areas 18 and 19, and confirmed its absence in striate cortex. Delay-epoch activity in these extrastriate regions, as well as in superior parietal lobule and intraparietal sulcus, was also lateralized on unfilled trials, suggesting that attention-based rehearsal produces a baseline shift in areas representing the to-be-remembered location in space. No frontal regions (including frontal eye fields) demonstrated lateralized activity consistent with a role in attention-based rehearsal.

Adolescent↗

PubMed1997

Pattern of neuropsychologic dysfunction in inactive systemic lupus erythematosus.

The pattern of neuropsychological dysfunction in patients with inactive systemic lupus erythematosus (SLE) was examined. Fifty-eight subjects with inactive SLE and 47 healthy controls were administered a standardized neuropsychological test battery. Summary scores reflecting 18 different cognitive processes were derived. Subjects were designated cognitively impaired if three or more summary scores differed significantly from premorbid estimates of cognitive functioning. Cognitive impairment was identified in 43% of subjects with inactive SLE and 19% of healthy controls. Subjects with inactive SLE, as a group, performed significantly worse than healthy controls on measures of auditory verbal memory, visual spatial memory, psychomotor speed, and motor functioning. A significantly greater proportion of subjects with inactive SLE than healthy controls was impaired only on a measure of visual spatial memory. Cognitive impairment in subjects with inactive SLE was associated with increasing age. There were no associations between cognitive impairment and current depressive symptoms or current corticosteroid use. These findings suggest that cognitive dysfunction occurs frequently in inactive SLE. The variability of performance of subjects with inactive SLE is consistent with the heterogeneity of CNS involvement in the disease.

Adult↗

PubMed2004

A secreted form of the beta-amyloid precursor protein (sAPP695) improves spatial recognition memory in OF1 mice.

The beta-amyloid precursor protein (APP) plays a central role in Alzheimer's disease (AD) and appears to be a multifunctional protein. Secreted forms of APP (sAPP) have memory-enhancing effects in certain behavioral paradigms. To investigate sAPP's role in spatial memory processes, we adapted a spatial recognition task and evaluated (1) the performance of OF1 mice after massed training (single 15-min acquisition session) and distributed training (three 5-min acquisition sessions), (2) the decline of spatial recognition performance by introducing different delays (5min, 1, 3, and 24h) between the acquisition and retention phases, and (3) the effects of sAPP(695) on spatial recognition memory. In the present study, mice selectively reacted to a change in the spatial configuration of five objects. Indeed, 3min post-acquisition, mice performed similarly in the massed and distributed versions of the task, by re-exploring the two displaced objects only, whereas mice exposed to the same spatial configuration did not. Additionally, all mice did react to a novel object in a subsequent object recognition phase. Mice detected object displacements 5min, 1h, or 3h post-acquisition, but no more at a 24h-delay. Finally, mice treated with sAPP(695) intracerebroventricularly at a dose of 0.5pg/4microL/mouse, 20-min pre-acquisition or 5-min post-acquisition, still reacted to a spatial change in objects position 24h post-acquisition, in marked contrast to NaCl-treated mice. Our data demonstrate that sAPP(695) significantly improves a form of spatial memory, and confirms the hypothesis of an action of this protein on early memory processes.

Amyloid beta-Protein Precursor↗

PubMed1999

The cerebellum and cognition: cerebellar lesions do not impair spatial working memory or visual associative learning in monkeys.

Anatomical studies in non-human primates have shown that the cerebellum has prominent connections with the dorsal, but not the ventral, visual pathways of the cerebral cortex. Recently, it has been shown that the dorsolateral prefrontal cortex (DPFC) and cerebellum are interconnected in monkeys. This has been cited in support of the view that the cerebellum may be involved in cognitive functions, e.g. working memory. Six monkeys (Macaca fascicularis) were therefore trained on a classic test of working memory, the spatial delayed alternation (SDA) task, and also on a visual concurrent discrimination (VCD) task. Excitotoxic lesions were made in the lateral cerebellar nuclei, bilaterally, in three of the animals. When retested after surgery the lesioned animals were as quick to relearn both tasks as the remaining unoperated animals. However, when the response times (RT) for each task were directly compared, on the SDA task the monkeys with cerebellar lesions were relatively slow to decide where to respond. We argue that on the SDA task animals can prepare their responses between trials whereas this is not possible on the VCD task, and that the cerebellar lesions may disrupt this response preparation. We subsequently made bilateral lesions in the DPFC of the control animals and retested them on the SDA task. These monkeys failed to relearn the task. The results show that, unlike the dorsal prefrontal cortex, the cerebellum is not essential for working memory or the executive processes that are necessary for correct performance, though it may contribute to the preparation of responses.

Animals↗

PubMed1993

Complex figure recall in the elderly: a deficit in memory or constructional strategy?

Spatial memory declines with age. This study investigated the hypothesis that the decline in spatial memory in the elderly is due to a dysfunction in frontal lobe-mediated planning and organization. The copy and recall ability of 49 elderly subjects and 20 younger subjects was assessed using the Rey-Osterrieth Figure. In addition, the manner of construction, (e.g., the order that each line was produced) was compared between groups. Despite comparable performance with the younger subjects when copying the figure, older subjects performed significantly worse than younger subjects when asked to reproduce the figure from memory. However, this was not due to the organizational strategies they used while copying the figure. They constructed the figure in the same manner as the younger subjects. Therefore, the spatial memory deficits in the elderly are not due to an abnormal organizational strategy. These results are discussed in relation to those of patients with frontal lobe damage and preliminary data from subjects with mild dementia.

Adult↗