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Transient spatial deficit associated with bilateral lesions of the lateral mammillary nuclei.

The mammillary bodies have long been implicated in spatial memory, and lesions of this structure in rats can impair some spatial memory tasks. The mammillary bodies, however, comprise two main nuclei that have different electrophysiological and anatomical properties. It is therefore possible that they have different functions. The present study determined whether selective lesions of one of these components, the lateral mammillary nucleus, are sufficient to induce spatial memory deficits. While selective lateral mammillary nuclei lesions induced deficits on a working memory task in the water maze, this impairment was milder and not as persistent as that seen with complete mammillary body lesions. Furthermore, lateral mammillary nuclei lesions did not impair T-maze alternation, which is sensitive to complete mammillary body lesions. From these results it appears that lesions confined to the lateral mammillary nuclei are sufficient to produce mild impairments when rapid, new spatial learning is at a premium. At the same time, the remaining mammillary nuclei also contribute to spatial learning, though this may be in a qualitatively different manner.

Animals↗

Visual and spatial working memory dissociation: evidence from Williams syndrome.

This study aimed at investigating the possible dissociation between visual and spatial working memory (WM) by means of two different experiments. In the first experiment, a WM test for visual material and for spatial information was given to a group of 202 normally developing children (chronological age 7 years 5 months, SD 1.6 years; 109 males, 93 females). Results document a different developmental trend in the two span tests. In the second experiment, we presented the same visual and spatial WM tests to a group of 13 individuals with Williams syndrome (WS), seven males and six females (chronological age mean 18 years 3 months, SD 5.1; mental age mean 7 years 2 months, SD 1.5 years), and to a control group of 26 typically developing children 14 males and 12 females matched for mental age (mean 7 years 2 months, SD 1.4). The results of this second experiment show that, on average, the spatial span obtained by individuals with WS was significantly lower than control participants, but visual span was comparable in the two groups. Our data support the hypothesis of a dissociation within the visuo-spatial sketch pad slave system in the WM model.

Amnesia↗

The role of spatial working memory in inhibition of return: evidence from divided attention tasks.

Inhibition of return (IOR) refers to a bias against returning attention to a location that has been recently attended. In the present experiments, we examined the role of working memory in IOR by introducing secondary tasks (in the temporal interval between the cue and the target) that involved a working memory component. When the secondary task was nonspatial in nature (monitoring odd digits or adding digits), IOR was present, although overall reaction times were greater in the presence of the secondary task. When the task involved a spatial working memory load (remembering the directionality of arrows or the orientation of objects), IOR was eliminated. However, when the participants had incentive to process the directionality of an arrow but did not have to use any memory system, IOR persisted at peripheral locations. Overall, the results suggest that IOR is partially mediated by a spatial working memory system.

Attention↗

Cortical oscillatory activity during spatial echoic memory.

In human magnetoencephalogram, we have found gamma-band activity (GBA), a putative measure of cortical network synchronization, during both bottom-up and top-down auditory processing. When sound positions had to be retained in short-term memory for 800 ms, enhanced GBA was detected over posterior parietal cortex, possibly reflecting the activation of higher sensory storage systems along the hypothesized auditory dorsal space processing stream. Additional prefrontal GBA increases suggested an involvement of central executive networks in stimulus maintenance. The present study assessed spatial echoic memory with the same stimuli but a shorter memorization interval of 200 ms. Statistical probability mapping revealed posterior parietal GBA increases at 80 Hz near the end of the memory phase and both gamma and theta enhancements in response to the test stimulus. In contrast to the previous short-term memory study, no prefrontal gamma or theta enhancements were detected. This suggests that spatial echoic memory is performed by networks along the putative auditory dorsal stream, without requiring an involvement of prefrontal executive regions.

Acoustic Stimulation↗

Executive processes in visual and spatial working memory tasks.

Three experiments are reported, which have investigated the nature of the cognitive mechanisms that underlie performance on specific visuo-spatial working memory tasks, with the emphasis on exploring the extent of central executive involvement. Experiments 1 and 2 employed oral random digit generation as an executive task within a dual-task paradigm. The results of both experiments indicated that visuo-spatial tasks that involve sequential processing of information show more interference with random digit generation than do visuo-spatial tasks that involve simultaneous processing. The third experiment substituted oral random digit generation for executive tasks that did not involve memory for serial order (vigilance tasks adapted from Vandierendonck, De Vooght, & Van der Goten, 1998b). The results indicated significant interference between the vigilance tasks and the sequential visuo-spatial task, but not with the simultaneous visuo-spatial task. Overall the results of the three experiments are interpreted as indicating that serial sequential visuo-spatial tasks involve executive resources to a significantly greater extent than do simultaneous visuo-spatial tasks, and that this can have implications for studies that attempt to make use of such tasks to fractionate separable visual and spatial components within working memory.

Adolescent↗

Elevations of endogenous kynurenic acid produce spatial working memory deficits.

Kynurenic acid (KYNA) is a tryptophan metabolite that is synthesized and released by astrocytes and acts as a competitive antagonist of the glycine site of N-methyl-D-aspartate receptors at high concentrations and as a noncompetitive antagonist of the alpha7-nicotinic acetylcholine receptor at low concentrations. The discovery of increased cortical KYNA levels in schizophrenia prompted the hypothesis that elevated KYNA concentration may underlie the working memory dysfunction observed in this population that has been attributed to altered glutamatergic and/or cholinergic transmission. The present study investigated the effect of elevated endogenous KYNA on spatial working memory function in rats. Increased KYNA levels were achieved with intraperitoneal administration of kynurenine (100 mg/kg), the precursor of KYNA synthesis. Rats were treated with either kynurenine or a vehicle solution prior to testing in a radial arm maze task at various delays. Elevations of endogenous KYNA resulted in increased errors in the radial arm maze. In separate experiments, assessment of locomotor activity in an open field and latency to retrieve food reward from one of the maze arms ruled out the possibility that deficits in the maze were attributable to altered locomotor activity or motivation to consume food. These results provide evidence that increased KYNA levels produce spatial working memory deficits and are among the first to demonstrate the influence of glia-derived molecules on cognitive function. The implications for psychopathological conditions such as schizophrenia are discussed.

Animals↗

[Establishment of analogous oxidative damaged Alzheimer's disease rat model and effect of tiaoxin recipe on it].

OBJECTIVE: To establish a convenient, economical and practical analogous oxidative damaged Alzheimer's disease rat model (AD model) for exploring the effect of Tiaoxin Recipe (TXR) on the spatial memory capacity and beta-amyloid protein (A beta) deposition in the model. METHODS: The AD model was established by left ventricular injection of DHF-FeCl3-ADP. Spatial memory and learning capacity of the model rat was observed by Morris water maze method, A beta deposition in its cerebral cortex was observed by immunohistochemistry, and the effect of TXR was analysed. RESULTS: Compared with the normal group, the spatial memory capacity in the model group was obviously decreased, with A beta widely deposited in cortex, immunohistochemical examination showed that the number of A beta positive cells and their mean optic density significantly increased. TXR displayed significantly improving effect on the above-mentioned changes. CONCLUSION: The oxidative damaged model could not only express the clinical characteristics (short-term memory impairment), but also partially reflex the pathological changes (A beta deposition) of AD, is an economical and practical analogous AD model. TXR has the effects of improving spatial memory impairment and lowering A beta deposition in the AD model rats.

Alzheimer Disease↗

Smaller subcortical volumes and cognitive deficits in children with prenatal methamphetamine exposure.

The purpose of this pilot study was to examine possible neurotoxic effects of prenatal methamphetamine (Meth) exposure on the developing brain and on cognition. Meth-exposed children (n=13) and unexposed control subjects (n=15) were evaluated with MRI. Global brain volumes and regional brain structures were quantified. Ten Meth-exposed and nine unexposed children also completed neurocognitive assessments. Meth-exposed children scored lower on measures of visual motor integration, attention, verbal memory and long-term spatial memory. There were no differences among the groups in motor skills, short delay spatial memory or measures of non-verbal intelligence. Despite comparable whole brain volumes in each group, the Meth-exposed children had smaller putamen bilaterally (-17.7%), smaller globus pallidus (left: -27%, right: 30%), smaller hippocampus volumes (left: -19%, right: -20%) and a trend for a smaller caudate bilaterally (-13%). The reduction in these brain structures correlated with poorer performance on sustained attention and delayed verbal memory. No group differences in volumes were noted in the thalamus, midbrain or the cerebellum. In summary, compared with the control group, children exposed to Meth prenatally exhibit smaller subcortical volumes and associated neurocognitive deficits. These preliminary findings suggest prenatal Meth exposure may be neurotoxic to the developing brain.

Adolescent↗

Impaired learning in a spatial working memory version and in a cued version of the water maze in rats with MPTP-induced mesencephalic dopaminergic lesions.

A lesion in the substantia nigra pars compacta (SNc) of rats induced by intra-nigral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused specific loss of dopamine and its nonconjugated metabolites in the dorsal striatum and in the prefrontal cortex (PFC), but not in the hippocampus or the ventral striatum (nucleus accumbens). This lesion did not alter the motor performance of the rats or learning of a spatial reference memory task in the water maze but impaired learning of a spatial working memory task and also of a cued version of the water maze. The results are discussed by relating the selective memory deficits observed in these water maze tasks to the PFC, dorsal striatum, and hippocampus. Some parallels between the memory deficits in these SNc-lesioned rats and Parkinson's disease patients are also discussed.

Animals↗

Hippocampal N-methyl-D-aspartate receptor-mediated encoding and retrieval processes in spatial working memory: delay-interposed radial maze performance in rats.

In order to clarify the role of hippocampal N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors in different stages of spatial working memory, we first assessed the rats' performance in a delay-interposed eight-arm radial maze task (experiment 1). When a delay was interposed after the first four correct choices, rats showed more errors in the second-half performance depending on the length of delay; however, they did not show any significant increase of error choices until the delay was beyond 2 h. We then tested the effect of 2-amino-5-phosphonopentanoic acid (AP5), a competitive NMDA receptor antagonist, and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX)-disodium, an AMPA receptor antagonist, on a standard (no delay-interposed) radial maze task (experiment 2). The drug effect was maintained 15-30 min but it completely disappeared 60 min after dorsal hippocampal microinjection. Based on these findings we finally investigated the effects of hippocampal AP5 and NBQX administered at different stages of 2 h delay-interposed radial maze task on the second-half performance (experiment 3). AP5 immediately before the first-half and before the second-half performance significantly impaired the correct choices, but the treatment immediately after the first-half performance did not, while NBQX impaired them in all three conditions. Results suggest that hippocampal NMDA receptors play an important role in encoding and retrieval processes of spatial working memory, while AMPA receptor activation is necessary not only in these processes but also in consolidation/retention process.

2-Amino-5-phosphonovalerate↗

Selective interference with verbal and spatial working memory in young and older adults.

Young and older adults were administered digit and location memory span tasks with and without verbal and spatial secondary tasks. Age differences were greater in location span than in digit span; however, there were no age differences in either the magnitude or pattern of effects of secondary tasks. There were also no age differences in the effects of secondary tasks on a combined (digit and location) task. On the digit and location span tasks, both young and older adults showed only domain-specific interference: naming colors selectively interfered with memory for digits, leaving memory for locations unaffected; pointing to matching colors selectively interfered with memory for locations, leaving memory for digits unimpaired. The results of the present study suggest a greater age deficit in spatial working memory than in verbal working memory, but provide no evidence of an age deficit in susceptibility to interference by secondary tasks in either domain.

Adolescent↗

Relationship of behavioural and symptomatic syndromes in schizophrenia to spatial working memory and attentional set-shifting ability.

BACKGROUND: Behavioural syndromes (thought disturbance, social withdrawal, depressed behaviour and antisocial behaviour) offer a different perspective from that of symptomatic syndromes on the disability that may be associated with schizophrenia. Few studies have assessed their relationship with neuropsychological deficits. We hypothesized that these syndromes may represent behavioural manifestations of frontal-subcortical impairments, previously described in schizophrenia. METHOD: Long-stay inpatients (n=54) and community patients (n=43) with enduring schizophrenia were assessed, using measures of symptoms and behaviour and tests of executive functioning. The relationship between syndromes and neuropsychological function was assessed using multiple regression and logistic regression analyses. RESULTS: Significant associations were found between performance on the spatial working memory task and the psychomotor poverty symptomatic syndrome, and between attentional set-shifting ability and both disorganization symptoms and the thought disturbance behavioural syndrome. These results were not explained by the effect of premorbid IQ, geographical location, length of illness or antipsychotic medication. Length of illness was an independent predictor of attentional set-shifting ability but not of working memory performance. CONCLUSION: The specific relationship between negative symptoms and spatial working memory is consistent with involvement of the dorsolateral prefrontal cortex. The associations between difficulty with set-shifting ability and both disorganization symptoms and behaviours may reflect inability to generalize a rule that had been learned and impaired ability to respond flexibly. The specific relationship of illness duration to set-shifting ability may suggest progressive impairment on some executive tasks. The nature of these relationships and their neurobiological and rehabilitation implications are considered.

Adult↗

Hierarchical coding in the perception and memory of spatial layouts.

Two experiments were performed to investigate the organization of spatial information in perception and memory. Participants were confronted with map-like configurations of objects which were grouped by color (Experiment 1) or shape (Experiment 2) so as to induce cognitive clustering. Two tasks were administered: speeded verification of spatial relations between objects and unspeeded estimation of the Euclidean distance between object pairs. In both experiments, verification times, but not distance estimations, were affected by group membership. Spatial relations of objects belonging to the same color or shape group were verified faster than those of objects from different groups, even if the spatial distance was identical. These results did not depend on whether judgments were based on perceptually available or memorized information, suggesting that perceptual, not memory processes were responsible for the formation of cognitive clusters.

Adult↗

Spatial working memory capacity in unilateral neglect.

It has been proposed recently that a deficit in keeping track of spatial locations may contribute to the severity of unilateral neglect in some right hemisphere stroke patients. However, performance on traditional spatial working memory (SWM) tasks (e.g. Corsi blocks) might be confounded by failure to encode leftward locations, rather than a true deficit of maintaining locations in SWM. Here we introduced new procedures for circumventing this to measure SWM capacity in neglect. In a first experiment, 20 right hemisphere stroke patients (10 with and 10 without neglect) were tested on a computerized vertical variant of the Corsi task. Sequences of spatial locations in a vertical column were displayed and participants had to tap out the remembered sequence on a touchscreen. Patients with left neglect were impaired on this vertical SWM task compared with all control groups. However, poor performance on this task (as for Corsi blocks) might involve impaired memory for stimulus sequence, or poor visuomotor control of manual responding, rather than reduced SWM capacity per se. A second experiment therefore employed a purer measure of vertical SWM. After the displayed sequence, a single location was now probed visually, with observers judging verbally (yes/no) if it had been in the preceding sequence. Hence order no longer mattered, and no spatial motor response was required. Again, the neglect group was impaired relative to all others, now with very little overlap between the performances of individual neglect patients versus individuals in control groups. Poor performance on the second task, which provides a purer measure of SWM capacity, correlated with severity of left neglect on cancellation tasks (but not on line bisection), consistent with recent proposals that SWM deficits can exacerbate left neglect on visual search tasks when present conjointly. Lesion anatomy indicated that neglect patients with a SWM deficit were most likely to have damage to parietal white matter, plus, in the second experiment, to the insula also. These findings demonstrate that an impairment in SWM capacity can contribute to the neglect syndrome in patients with stroke involving regions within the right parietal lobe and insula.

Adult↗

Impaired retention of preoperatively acquired spatial reference memory in homing pigeons following hippocampal ablation.

Hippocampal-parahippocampal-ablated homing pigeons have been shown to suffer a retrograde loss of information used in the recognition of their home loft. Here we report that the range of retrograde deficits includes spatial reference memory in the form of information gained from repeated training sites that can be used to direct a homeward orientation response. Following 8 training releases from each of two sites, 28 of 42 homing pigeons underwent hippocampal-parahippocampal ablation. In the subsequent test releases from the two sites, untreated controls whose navigational map was rendered temporarily dysfunctional by an anosmic procedure showed no impairment in determining the home direction, indicating the successful retention and utilization of directionally useful information around the release sites. Hippocampal-ablated controls who were not rendered anosmic and thus had access to their navigational map also showed no impairment in determining the home direction, indicating no general impairment in initial orientation as a result of hippocampal ablation. In contrast, hippocampal-ablated pigeons whose navigational map was rendered temporarily dysfunctional failed to successfully orient homeward from the training sites, indicating impairment in the retention and/or implementation of directional information gathered at the release sites during training. The data reveal a spatial reference memory deficit involving pre-ablation acquired directional information in homing pigeons following hippocampal ablation.

Animals↗

Animal models of memory impairment.

Memory impairment in the elderly resembles a mild temporal lobe dysfunction. Alterations in the hippocampal formation are also a probable basis for cognitive deficits in some animal models of ageing. For example, aged rats are impaired in hippocampal-dependent tests of spatial memory. Recent studies have revealed considerable structural integrity in the aged hippocampus, even in aged rats with the most impaired spatial memory. In contrast, atrophy/loss of cholinergic neurons in the basal forebrain and deficiency in cholinergic transduction in hippocampus correlate with the severity of spatial memory impairment in aged rats. This evidence supports the longstanding view that age-related loss of memory has a cholinergic basis. In this context, it is somewhat surprising that the use of a selective cholinergic immunotoxin in young rats to further test this hypothesis has revealed normal spatial memory after removing septo-hippocampal cholinergic neurons. Young rats with immunotoxic lesions, however, have other behavioural impairments in tests of attentional processing. These lines of research have implications for understanding the neurobiological basis of memory deficits in ageing and for selecting an optimal behavioural setting in which to examine therapies aimed at restoring neurobiological function.

Animals↗

fMRI reveals alteration of spatial working memory networks across adolescence.

Recent studies have described neuromaturation and cognitive development across the lifespan, yet few neuroimaging studies have investigated task-related alterations in brain activity during adolescence. We used functional magnetic resonance imaging (fMRI) to examine brain response to a spatial working memory (SWM) task in 49 typically developing adolescents (25 females and 24 males; ages 12-17). No gender or age differences were found for task performance during SWM. However, age was positively associated with SWM brain response in left prefrontal and bilateral inferior posterior parietal regions. Age was negatively associated with SWM activation in bilateral superior parietal cortex. Gender was significantly associated with SWM response; females demonstrated diminished anterior cingulate activation and males demonstrated greater response in frontopolar cortex than females. Our findings indicate that the frontal and parietal neural networks involved in spatial working memory change over the adolescent age range and are further influenced by gender. These changes may represent evolving mnemonic strategies subserved by ongoing adolescent brain development.

Adolescent↗

Cognitive function in aged ovariectomized female rhesus monkeys.

To determine whether ovariectomy exacerbates age-related cognitive decline, the performance of 6 aged monkeys that had been ovariectomized early in life (OVX-Aged) was compared to that of 8 age-matched controls with intact ovaries (INT-Aged) and that of 5 young controls with intact ovaries (INT-Young) in tasks of visual recognition memory, object and spatial memory, and executive function. The OVX-Aged monkeys were marginally more impaired than the INT-Aged monkeys on the delayed nonmatching-to-sample with a 600-s delay. In contrast, they performed significantly better than the INT-Aged controls on the spatial condition of the delayed recognition span test. The hypothesis that prolonged estrogenic deprivation may exaggerate the age-related decline in visual recognition memory will require additional support. However, the findings suggest that long-term ovariectomy may protect against the development with aging of spatial memory deficits.

Aging↗