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PubMed1997

Clozapine reverses the spatial working memory deficits induced by FG7142 in monkeys.

The atypical neuroleptic, clozapine, has been shown to have encouraging, but mixed, effects on prefrontal cortical (PFC) cognitive deficits in schizophrenia, a stress-exacerbated disorder involving dopamine (DA) dysregulation. The current study examined the effects of acute clozapine pretreatment on the spatial working memory deficits induced by the pharmacological stressor, FG7142, in monkeys. Previous research has shown that FG7142 impairs spatial working memory in rats and monkeys through excessive DA receptor stimulation in the PFC (Murphy et al. 1996). Lower clozapine doses (1-3 mg/kg p.o.) reversed the FG7142-induced spatial working memory deficits, whereas doses in the clinical range (e.g., 6 mg/kg, p.o.) did not improve cognitive function in most animals. Clozapine alone produced a dose-related impairment in delayed response performance. These results from nonhuman primates suggest that the clozapine doses commonly used to treat schizophrenia may not be optimal for treating the PFC cognitive deficits associated with this illness.

Animals↗
PubMed1999

Problem-solving and spatial working memory in patients with schizophrenia and with focal frontal and temporal lobe lesions.

Problem-solving ability was investigated in 25 DSM-IIIR schizophrenic (SC) patients using the Tower of Hanoi (TOH) task. Their performance was compared to that of: (1) 22 patients with neurosurgical unilateral prefrontal lesions, 11 left (LF) and 10 right hemisphere (RF); (2) 38 patients with unilateral temporal lobectomies, 19 left (LT) and 19 right (RT); and (3) 44 matched control subjects. Like the RT and LF group, the schizophrenics were significantly impaired on the TOH. The deficit shown by the schizophrenic group was equivalent whether or not the problems to be solved included goal-subgoal conflicts, unlike the LF group who were impaired specifically on these problems. The nature of the SC deficit was also distinct from that of the RT group, in that the problem-solving deficit remained after controlling for the effects of spatial memory performance. This study indicates, therefore, that neither focal frontal nor temporal lobe damage sustained in adult life is a sufficient explanation for the problem-solving deficits found in patients with schizophrenia.

Adult↗
PubMed1999

A developmental functional MRI study of spatial working memory.

Functional magnetic resonance imaging (fMRI) was used to examine patterns of cortical activity in children during performance of a spatial working memory task. Six children (8-10 years) and six adults (19-26 years) searched a linear array of four boxes for the appearance of a dot. In the visual blocks, participants made no response. In the motor blocks, participants were instructed to indicate the location of the dot on each trial using a button-press response. In the working memory blocks, participants were instructed to indicate at which location the dot had appeared 1 or 2 trials previously. Both children and adults showed activity in the left precentral and postcentral gyri, as well as the right cerebellum for the motor condition as compared to the visual condition. Comparison of the memory and motor conditions revealed reliable activity in the right superior frontal gyrus (BA 8), right dorsolateral prefrontal cortex (BA 10/46), right superior parietal cortex, and bilateral inferior parietal cortex for both adults and children. These results suggest that spatial working memory tasks activate very similar cortical regions for school-age children and adults. The findings differ from previous imaging studies of nonspatial working memory tasks in that the prefrontal activations observed in the current work tend to be more dorsal. Results are discussed in light of the significant behavioral performance differences observed between child and adult participants.

Adult↗
PubMed2005

Genetic ablation of the mammillary bodies in the Foxb1 mutant mouse leads to selective deficit of spatial working memory.

Mammillary bodies and the mammillothalamic tract are parts of a classic neural circuitry that has been implicated in severe memory disturbances accompanying Korsakoff's syndrome. However, the specific role of mammillary bodies in memory functions remains controversial, often being considered as just an extension of the hippocampal memory system. To study this issue we used mutant mice with a targeted mutation in the transcription factor gene Foxb1. These mice suffer perinatal degeneration of the medial and most of the lateral mammillary nuclei, as well as of the mammillothalamic bundle. Foxb1 mutant mice showed no deficits in such hippocampal-dependent tasks as contextual fear conditioning and social transmission of food preference. They were also not impaired in the spatial reference memory test in the radial arm maze. However, Foxb1 mutants showed deficits in the task for spatial navigation within the Barnes maze. Furthermore, they showed impairments in spatial working memory tasks such as the spontaneous alternation and the working memory test in the radial arm maze. Thus, our behavioural analysis of Foxb1 mutants suggests that the medial mammillary nuclei and mammillothalamic tract play a role in a specific subset of spatial tasks, which require combined use of both spatial and working memory functions. Therefore, the mammillary bodies and the mammillothalamic tract may form an important route through which the working memory circuitry receives spatial information from the hippocampus.

Animals↗
PubMed2000

Collaborative activity between parietal and dorso-lateral prefrontal cortex in dynamic spatial working memory revealed by fMRI.

Functional MRI was used to determine how the constituents of the cortical network subserving dynamic spatial working memory respond to two types of increases in task complexity. Participants mentally maintained the most recent location of either one or three objects as the three objects moved discretely in either a two- or three-dimensional array. Cortical activation in the dorsolateral prefrontal (DLPFC) and the parietal cortex increased as a function of the number of object locations to be maintained and the dimensionality of the display. An analysis of the response characteristics of the individual voxels showed that a large proportion were activated only when both the variables imposed the higher level of demand. A smaller proportion were activated specifically in response to increases in task demand associated with each of the independent variables. A second experiment revealed the same effect of dimensionality in the parietal cortex when the movement of objects was signaled auditorily rather than visually, indicating that the additional representational demands induced by 3-D space are independent of input modality. The comodulation of activation in the prefrontal and parietal areas by the amount of computational demand suggests that the collaboration between areas is a basic feature underlying much of the functionality of spatial working memory.

Acoustic Stimulation↗
PubMed2006

SNAP-25 in hippocampal CA3 region is required for long-term memory formation.

SNAP-25 is a synaptosomal protein of 25 kDa, a key component of synaptic vesicle-docking/fusion machinery, and plays a critical role in exocytosis and neurotransmitter release. We previously reported that SNAP-25 in the hippocampal CA1 region is involved in consolidation of contextual fear memory and water-maze spatial memory (Hou et al. European J Neuroscience, 20: 1593-1603, 2004). SNAP-25 is expressed not only in the CA1 region, but also in the CA3 region, and the SNAP-25 mRNA level in the CA3 region is higher than in the CA1 region. Here, we provide evidence that SNAP-25 in the CA3 region is also involved in learning/memory. Intra-CA3 infusion of SNAP-25 antisense oligonucleotide impaired both long-term contextual fear memory and water-maze spatial memory, with short-term memory intact. Furthermore, the SNAP-25 antisense oligonucleotide suppressed the long-term potentiation (LTP) of field excitatory post-synaptic potential (fEPSP) in the mossy-fiber pathway (DG-CA3 pathway), with no effect on paired-pulse facilitation of the fEPSP. These results are consistent with the notion that SNAP-25 in the hippocampal CA3 region is required for long-term memory formation.

Animals↗
PubMed1997

Temporal and spatial context memory in patients with focal frontal, temporal lobe, and diencephalic lesions.

Patients with focal frontal, temporal lobe, or diencephalic lesions were investigated on measures of temporal (recency) and spatial (position) context memory, after manipulating exposure times to match recognition memory for targets (pictorial stimuli) as closely as possible. Patients with diencephalic lesions from an alcoholic Korsakoff syndrome showed significant impairment on the temporal context (recency) task, as did patients with frontal lesions penetrating the dorsolateral frontal cortex, according to MRI (and PET) evidence. Patients with temporal lobe lesions showed only a moderate (non-significant) impairment on this task, and patients with medial frontal lesions, or large frontal lesions not penetrating the dorsolateral cortical margins, performed as well as healthy controls at this task. On the spatial context memory task, patients with lesions in the temporal lobes showed significant impairment, and patients with right temporal lesions performed significantly worse than patients with left temporal lesions. Patients with diencephalic lesions showed only a modest (non-significant) impairment on this task, and the frontal lobe group performed normally. When a group of patients with temporal lobe lesions resulting from herpes encephalitis were examined separately, an identical pattern of results was obtained, the herpes group being significantly impaired on spatial memory and showing a trend towards impairment for temporal context memory. There were strong correlations between anterograde memory quotients and context memory performance (despite the use of an exposure time titration procedure) and a weak association in the frontal group with one frontal/executive task [corrected] (card-sorting perservations). It is predicted that correlations between temporal context memory and frontal/executive tasks will be greater in samples of patients all of whom have frontal lesions invading the dorsolateral cortical margin.

Adult↗
PubMed2004

SNAP-25 in hippocampal CA1 region is involved in memory consolidation.

As a synaptosomal protein, SNAP-25 plays a role in a number of neuronal functions including axonal growth, dendrite formation, fusion of synaptic vesicles with membrane and the expression of long-term potentiation (LTP) in the hippocampus. Using a learning/memory behavior screening, we identified SNAP-25 as one of the differentially expressed genes in the hippocampus upon behavioral training. The inhibition of SNAP-25 with intracerebroventricular antisense oligonucleotide caused a deficit in long- but not short-term memory for step-down inhibitory avoidance. Intra-CA1 infusion of the SNAP-25 antisense oligonucleotide impaired long-term contextual fear memory and spatial memory and interfered with the LTP of synaptic transmission in the CA1 region. The inhibitory effect on LTP was not mediated by a pre-synaptic mechanism because paired pulse facilitation of synaptic transmission was not affected after administration of the antisense oligonucleotide. Together, the results suggest that SNAP-25 in the CA1 region is involved in memory consolidation.

Animals↗
PubMed1996

Selective effects of nerve growth factor on spatial recent memory as assessed by a delayed nonmatching-to-position task in the water maze.

Nerve growth factor (NGF) ameliorates age-related deficits in certain types of memory in rats. Although the effects of NGF on reference memory are well documented, the influence of NGF on recent memory is less well understood. The issue of recent memory is of primary importance in the design of therapies for cognitive disorders, because this type of memory is impaired in elderly humans and is severely affected early in the course of Alzheimer's disease (AD). The present study was designed to evaluate the efforts of NGF on recent memory in a task that used escape from water as the motivating stimulus and used the same design as forced-choice recognition tasks given to humans. Fischer-344 rats, 4 months old (4MO) or 23 months old (23MO), were pretested in a new spatial recent memory task designed for the Morris water maze, a delayed nonmatching-to-position task, and infused intraventricularly with recombinant human NGF or vehicle. After 2 weeks of NGF infusion, no substantial changes in behavior were observed in either age group. However, NGF treatment extended over 4 weeks improved considerably the choice accuracy of 23MO rats to a level similar to the performance of 4MO rats. These results, together with our previous work (Markowska et al., 1994), indicate that the effects of NGF on spatial recent memory are more intense than on spatial reference memory. NGF suppressed the body weight gain in 4MO rats but did not affect 23MO rats. In 23MO rats, NGF mildly counteracted age-related deficits in inhibitory avoidance, but did not have an effect in young rats.

Aging↗
PubMed1995

Individual differences in spatial working memory in relation to schizotypy.

With a delayed-response task, spatial working memory function was assessed in normal students who were selected for schizotypy. The Wisconsin Card Sorting Test was also administered. Twenty-eight undergraduate students who scored high on the Perceptual Aberration Scale (PerAb) and 23 who scored low on this scale participated in this study. High PerAb students performed less accurately compared with the low PerAb controls on the delayed-response task, and they were more than twice as likely as low PerAb students to be impaired. The groups did not differ in the number of perseverative errors or number of categories achieved on the Wisconsin Card Sorting Test, but, as predicted, high PerAb students were less able to maintain set than were the low PerAb students. Neuropsychological implications of these data are discussed.

Adolescent↗
PubMed2006

Chronic intermittent ethanol exposure during adolescence blocks ethanol-induced inhibition of spontaneously active hippocampal pyramidal neurons.

BACKGROUND: Binge alcohol drinking among adolescents has been a serious public health problem. A model of binge alcohol, chronic intermittent ethanol exposure (CIEE), during adolescence significantly attenuates ethanol-induced spatial memory deficits in rats. However, the attenuation was absent following a 12-day ethanol-free period. Since spatial memory is hippocampal dependent, a reduction in ethanol-induced spatial memory impairments may be due to a reduction in the ability of ethanol to inhibit the firing rate of single hippocampal pyramidal neurons following CIEE. METHODS: Beginning on postnatal day 30 (P30), male adolescent Sprague-Dawley rats (Harlan) were administered 5.0 g/kg ethanol (n = 10, CIEE-treated group) or an equivolume saline (n = 10, CISE-treated group) every 48 hours for 20 days. Single hippocampal pyramidal neurons from 5 CIEE-treated rats and 5 CISE-treated rats were recorded on the day following completion of the chronic intermittent exposure procedure (animals now P50). Additionally, neurons from 5 CIEE-treated rats and 5 CISE-treated rats were recorded 12 days after the completion of the chronic intermittent exposure procedure (animals now P62). RESULTS: Ethanol exposure during adolescence completely blocked ethanol-induced inhibition of hippocampal pyramidal neurons in rats that were CIEE exposed. However, the effect of CIEE on hippocampal neurophysiology was time dependent. Specifically, neurons recorded from CIEE-treated rats after a 12-day ethanol-free period had similar maximal inhibition as neurons from CISE-treated animals, although the time to reach inhibition was significantly greater in neurons from CIEE-treated rats. CONCLUSION: Chronic ethanol exposure during adolescence produces a reduction, or tolerance, to ethanol-induced inhibition of hippocampal pyramidal neural activity. Although the tolerance was greatly reversed after a 12-day ethanol-free period, neurons from CIEE animals inhibited slower than neurons from CISE animals. Since the hippocampus is known to be involved not only in spatial memory, but also in many other types of memory formation, the altered hippocampal functions because of CIEE during adolescence should be taken as a serious warning for society.

Action Potentials↗
PubMedDate not supplied

Nurse-computer interaction: staff performance outcomes.

The purpose of this study was to examine the relationship of nurses' cognitive and demographic characteristics to their information retrieval speed, accuracy, and subjective screen satisfaction during on-line interactions with three different computer screens. One hundred ten randomly selected female clinical nurses interacted with computer screens of varying information densities. Age, spatial memory, and spatial visualization were significant predictors for nurses' practiced and overall performance speeds. Age was an important variable across screens; the cognitive variables, however, differed according to screen types. Age was a predictor of nurses' practiced accuracy, while both age and spatial visualization predicted overall accuracy scores. Perceptual speed was not a significant predictor in any equations, and none of the nurse characteristics predicted subjective screen satisfaction.

Adult↗
PubMed2006

Impaired spatial reference memory and increased exploratory behavior in P301L tau transgenic mice.

The neuropathological hallmark shared between Alzheimer's disease (AD) and familial frontotemporal dementia (FTDP-17) are neurofibrillary tangles (NFT) which are composed of filamentous aggregates of the microtubule-associated protein tau. Their formation has been reproduced in transgenic mice, which express the FTDP-17-associated mutation P301L of tau. In these mice, tau aggregates are found in many brain areas including the hippocampus and the amygdala, both of which are characterized by NFT formation in AD. Previous studies using an amygdala-specific test battery revealed an increase in exploratory behavior and an accelerated extinction of conditioned taste aversion in these mice. Here, we assessed P301L mice in behavioral tests known to depend on an intact hippocampus. Morris water maze and Y-maze revealed intact spatial working memory but impairment in spatial reference memory at 6 and 11 months of age. In addition, a modest disinhibition of exploratory behavior at 6 months of age was confirmed in the open field and the elevated O-maze and was more pronounced during aging.

Aging↗
PubMed2002

Maintenance and manipulation in spatial working memory: dissociations in the prefrontal cortex.

Two experiments were conducted to compare thec ries of the functional organization of spatial working memory within the human prefrontal cortex. In Experiment I, memory set size for locations was parametrically varied, allowing for the assessment of BOLD signal across maintenance requirements. In the sec ond experiment, manipulation of spatial information held in working memory was contrasted with simple maintenance of that information. Both experiment evoked significant activity in a distributed spatia working memory network. Although dorsolateral prefrontal activation increased monotonically with memory set size, this region was differentially engaged in task conditions involving explicit manipulation of in ternal representations. Activation in the superior frontal sulcal region was associated with maintenance of spatial information, increasing with memory se size. In contrast, ventrolateral prefrontal activation was present only at the highest memory set size, possibly due to the differential use of organizational strategies with more complex stimuli. These results sup port claims that the dorsolateral prefrontal cortex is involved in the manipulation of internal representa tions and that the superior frontal sulcal region is involved in the maintenance of spatial information but they suggest a complex role for the ventrolatera prefrontal region.

Algorithms↗
PubMed1990

Is memory for spatial location automatically encoded?

Naveh-Benjamin (1987, 1988) has shown that memory for spatial location does not meet the criteria for automatic encoding as claimed by Hasher and Zacks (1979). Age, intention, concurrent processing demands, practice, strategies, and individual differences affected memory for location. These variables should have affected effortful but not automatic processing. The experiments reported in the present paper, in which a different task was used, showed that intention, practice, and concurrent processing demands did not affect memory for location. I concluded that (1) the location task used by Naveh-Benjamin included effortful subtasks and also incidental cover or concurrent processing tasks that interfered directly with performance, and (2) the variables that he manipulated may not have affected the encoding of location. The need to differentiate processes from task performance in analyzing the automaticity issue is discussed. The dominant mode for remembering location is automatic, but such information may also be remembered voluntarily.

Adult↗
PubMed1996

The effects of discrete cingulum bundle lesions in the rat on the acquisition and performance of two tests of spatial working memory.

Rats received one of three different surgeries in which radiofrequency lesions were made in the cingulum bundle. These consisted of either: (i) two pairs of bilateral lesions at the mid and posterior levels of the tract (M + PCB, n = 9); (ii) a single pair of bilateral lesions at the posterior level of the tract (PCB, n = 5); or (iii) a single lesion in each hemisphere, one at a posterior level the other at a mid level (CCB, n = 6). Twelve other animals acted as surgical controls (SHAM). None of the groups of animals with cingulum bundle lesions was impaired on either the acquisition or performance of an automated delayed nonmatching-to-position task in an operant chamber. In fact, following combination of the three cingulum bundle groups it was found that the lesions resulted in a small, but significant improvement in performance of this task when compared with the SHAM animals. All three groups with tract lesions were, however, impaired on an alternation task in a T-maze. This double dissociation between the two tests of spatial working memory, coupled with the comparable scores of the three lesion groups, is seen as showing that the cingulum bundle is part of a neuroanatomical circuit subserving aspects of allocentric spatial memory. The relative mildness of the alternation deficit in the present study also suggests that the bundle must be completely destroyed bilaterally to produce a pronounced deficit.

Animals↗
PubMed2004

Attentional cueing reverses deficits in spatial working memory task performance in chronic low dose MPTP-treated monkeys.

Chronic low dose MPTP-treated monkeys develop difficulty in performing spatial working memory tasks. Since these tasks have both attentional and memory components, the extent to which task performance deficits are attentional or memory in nature was examined. Using a modified variable delayed response (VDR) task, employment of an attentional cue prior to stimulus presentation significantly improved task performance, suggesting a strong attentional component to the deficit in spatial working memory task performance. These findings suggest that procedures to enhance attention may be useful in ameliorating some of the "memory" deficits associated with early Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2005

Neuropsychological evidence for separating components of visuo-spatial working memory.

There is increasing evidence to support the idea that visuo-spatial working memory can be segregated into separate cognitive subsystems. However, the nature of these systems remains unclear. In this paper we report data from two brain injured patients suggesting that information about visual appearance is retained in a different subsystem from information about spatial location, and that this differential processing can be observed when the style of presentation (sequential or simultaneous) is controlled.

Adolescent↗