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PubMed2000

Relationship among discharges of neighboring neurons in the rat prefrontal cortex during spatial working memory tasks.

The relationship among discharges of neurons that were recorded simultaneously with tetrodes in the rat medial prefrontal cortex was analyzed. Spatial working memory tasks were divided into several distinct stages based on the behavioral correlates of individual neurons, and interneuronal correlation of signal (mean discharge rate at each stage) and noise (trial-to-trial deviation from the signal) was calculated. Behavioral correlates of neighboring neurons were quite heterogeneous and, accordingly, average signal correlation was relatively low ( approximately 0.16). Noise correlation was even lower ( approximately 0.06), but neuronal noise was more correlated among the neurons with similar signals. Spikes underlying the signal and noise correlation among the prefrontal cortical neurons were loosely synchronized over a few hundred milliseconds. These results suggest that neighboring prefrontal cortical neurons process largely independent information and have weakly correlated noise and that precisely synchronized spikes play a relatively minor role in producing the correlated signal and noise among these neurons.

Action Potentials↗
PubMed2005

The contribution of implicit and explicit memory to the effects of errorless learning: a comparison between young and older adults.

There is evidence that the prevention of errors during learning might be helpful in improving an impaired memory performance, both in amnesia as well as in normal age-related memory decline. Although errorless learning is a promising technique for use in rehabilitation practice, the underlying mechanisms are unclear. That is, it has been suggested that the beneficial effects of errorless learning operate through implicit memory, whereas others implicate that it is explicit memory that is responsible for the enhanced memory performance after errorless learning. The current study examined the contribution of implicit and explicit memory function to the memory performance after errorless and errorful learning using the process-dissociation procedure. A group of young adults (N=40) was compared to a matched group of older individuals (N=40) on a spatial memory task (i.e., learning the locations of everyday objects in a room). The results clearly show age-related decline in explicit spatial memory, while implicit spatial memory was unaffected. Furthermore, the young group benefited from errorless learning compared to errorful learning, while the older group did not show a difference between the two learning conditions. Also, it was found that the effects of errorful learning were related to explicit memory function, and not implicit processing, corroborating and extending recent findings.

Adult↗
PubMed2006

Visual long-term memory for spatial frequency?

It has been suggested that a visual long-term memory based on a sensory representation of the stimulus accounts for discrimination performance when the reference and the test stimuli are separated in time. Decision processes involved in setting response criteria, however, may also contribute to discrimination performance. In the present study, it is shown that under proper control, spatial frequency discrimination thresholds from a group of observers, each performing on a single trial, are significantly higher for a 2-h than for a 5-sec retention interval, whereas thresholds from individual observers performing in repeated trials with a 2-h retention interval are considerably lower. The results suggest that discrimination performance may depend on the retention of task-relevant information, such as a response criterion, rather than on visual memory of the stimulus. It is concluded that it is risky to postulate a high-fidelity long-term visual memory for spatial frequency on the basis of psychophysical group discrimination thresholds.

Decision Making↗
PubMedDate not supplied

Prefrontal cortex and working memory for spatial response, spatial location, and visual object information in the rat.

In the first experiment, rats were trained on a working memory task for a spatial response (right-left turn) information using a delayed matching-to-sample procedure. Following lesions of the medial prefrontal cortex (MPF), which includes anterior cingulate and medial precentral cortex, there was a profound working memory deficit even at the shortest delay. In the second experiment, rats were trained on a working memory task for spatial location information using a delayed matching-to-sample procedure. Following lesions of the MPF, there was only a mild working memory deficit, whereas following dorsal hippocampal lesions there was a profound working memory deficit even at the shortest delay. In the third experiment, rats were trained on a working memory task for visual object information using a delayed nonmatching-to-sample procedure. Following lesions of the MPF, there were no working memory deficits, whereas following lesions of the prelimbic and infralimbic cortex there was a profound working memory deficit even at the shortest delay. The results suggest that different neural subregions of the prefrontal cortex mediate working memory for specific attribute information.

Animals↗
PubMed2003

Role of central cholinergic receptor sub-types in spatial working memory: a five-arm maze task in mice provides evidence for a functional role of nicotinic receptors in mediating trace access processes.

A delayed-matching spatial working memory protocol in a 5-arm maze was used to test the hypothesis of differential roles for central nicotinic and muscarinic cholinergic receptors in mediating task performance. In experiment 1, using a within subjects-repeated design, groups of C57Bl/6 mice, previously trained to criterion with a 4 h retention interval separating presentation and test phases, received i.p. injections of either saline, scopolamine (0.8 mg/kg), mecamylamine (8.0 mg/kg), or the combination of scopolamine and mecamylamine before re-testing. Injections were given either, a) 15 min pre-presentation or, b) 30 s, c) 15 min, d) 3 h 45 min post-presentation in order to differentially affect the acquisition, trace maintenance and recall phases. Significant decreases in correct responses were observed for each drug treatment but the effects were a function of the time of treatment. Results of condition d), (i.e.15 min before retention test) confirm previous reports of severe disruption by each antagonist and their combination on retention. However, conditions a-c) show a constant disruption by scopolamine, increasing disruption by mecamylamine, whereas the combined treatment was without effect. Although the data show that central nicotinic and muscarinic antagonists both modulate working memory performance, they indicate first, that scopolamine-induced "amnesia" results, not from selective post-synaptic M1 muscarinic blockade but from indirect over-activation of nicotinic receptors. Second, the observation of high levels of retention although nicotinic and muscarinic receptors had undergone combined blockade during a large part of the retention interval is incompatible with the concept that test-induced activation of central cholinergic neurones mediates memory trace maintenance. Finally, taken with data from experiment 2, using a short (20 min) treatment-to-test interval, we conclude that central nicotinic receptors play a key role in attentional processes enabling working memory trace access during retrieval.

Animals↗
PubMed1993

Memory for spatial locations, motor responses, and objects: triple dissociation among the hippocampus, caudate nucleus, and extrastriate visual cortex.

Based on behavioral procedures aimed at measuring working or data-based memory for spatial location, response, and visual object information, it is shown that there is a triple dissociation among the hippocampus, caudate nucleus, and extrastriate visual cortex in mediating spatial location, response, and visual object information, respectively. The hippocampus appears to subserve only spatial location, the caudate nucleus only response, and the extrastriate visual cortex only visual object information. The results support the neurobiological foundation of the attribute memory model.

Animals↗
PubMed2004

Event-related potentials in young and elderly adults during a visual spatial working memory task.

The P300 event-related brain potential (ERP) was examined in 14 young (20-29 years of age) and 16 elderly (60-82 years of age) subjects during the performance of a visuospatial memory task requiring recognition of locations. Elderly and young adults exhibited similar recognition accuracy, but recognition reaction times were significantly slower in the elderly. Midline P300 amplitudes recorded in response to visuospatial probe stimuli were significantly attenuated in the elderly, and, depending on the nature of the probe, P300 latency-derived indices indicated that both cognitive and motoric slowness characterized visuospatial recognition in the aged. The results, discussed in relation to neural mechanisms supporting working memory function, suggest that alterations in attention and processing speed may play a role in visual-spatial working memory deficits associated with normal and pathological aging.

Adult↗
PubMed2007

Calcium/calmodulin kinase kinase beta has a male-specific role in memory formation.

The calcium/calmodulin (CaM) kinase cascade regulates gene transcription, which is required for long-term memory formation. Previous studies with Camkk2 null mutant mice have shown that in males calcium/calmodulin kinase kinase beta (CaMKKbeta) is required for spatial memory formation and for activation of the transcription factor cyclic AMP-responsive element binding protein (CREB) in the hippocampus by spatial training. Here we show that CaMKKbeta is not required for spatial memory formation in female mice as female Camkk2 null mutants were not impaired in spatial memory formation and they had the same level of hippocampal CREB phosphorylation after spatial training as female wild-type mice. Furthermore, we show that male but not female Camkk2 null mutants were impaired in long-term potentiation (LTP) at hippocampal CA1 synapses. Finally, a transcriptional analysis of male Camkk2 null mutants led to the identification of a gene, glycosyl phosphatidyl-inositol anchor attachment protein 1 (GAA1), whose hippocampal mRNA expression was up-regulated by spatial and contextual training in male but not in female wild-type mice. Taken together, we conclude that CaMKKbeta has a male-specific function in hippocampal memory formation and we have identified male-restricted transcription occurring during hippocampal memory formation.

Animals↗
PubMed2006

Spatial learning and goldfish telencephalon NMDA receptors.

Recent results have demonstrated that the mammalian hippocampus and the dorso-lateral telencephalon of ray-finned fishes share functional similarities in relation to spatial memory systems. In the present study, we investigated whether the physiological mechanisms of this hippocampus-dependent spatial memory system were also similar in mammals and ray-finned fishes, and therefore possibly conserved through evolution in vertebrates. In Experiment 1, we studied the effects of the intracranial administration of the noncompetitive NMDA receptor antagonist MK-801 during the acquisition of a spatial task. The results indicated dose-dependent drug-induced impairment of spatial memory. Experiment 2 evaluated if the MK-801 produced disruption of retrieval of a learned spatial response. Data showed that the administration of MK-801 did not impair the retrieval of the information previously stored. The last experiment analyzed the involvement of the telencephalic NMDA receptors in a spatial and in a cue task. Results showed a clear impairment in spatial learning but not in cue learning when NMDA receptors were blocked. As a whole, these results indicate that physiological mechanisms of this hippocampus-dependent system could be a general feature in vertebrate, and therefore phylogenetically conserved.

Animals↗
PubMed1999

Hand-centred coding of target location in visuo-spatial working memory.

The aim of the present experiment was to determine the frame of reference used to encode a visually specified target location, in a simple, visuo-spatial short-term-memory task, using delayed manual pointing. Subjects were required to remember the location of a single, visually presented stimulus, over delays of 3 and 30 s, and to recall its location by pointing to it with the tip of a stylus with eyes closed. There were two starting positions for the hand: one near the body, proximal to the target area, the other far from the body, i.e., beyond the target area. Two groups of twelve subjects participated in the experiment. One group observed the target locations in the light, the other group observed the target LEDs in the dark. The results showed a large (between 10-30%) and consistent undershoot of the remembered target location with respect to the hand's starting position, in the sagittal axis, both when the hand started from the near and from the far position. That is, from the far starting position. pointing errors lay consistently beyond the actual target location as seen from the subject's viewpoint. Further, this undershoot error in the remembered target location increased over time delay. These results are in favour of the hypothesis that the visual target locations were encoded in a hand-centred frame of reference in spatial short-term memory. They also implicate the use of motor- or action-related representations in visuo-spatial working memory.

Adult↗
PubMedDate not supplied

Cognitive changes associated with supplementation of testosterone or dihydrotestosterone in mildly hypogonadal men: a preliminary report.

This study prospectively examined changes in cognition in hypogonadal men given testosterone (T) or older hypogonadal men given dihydrotestosterone (DHT) gel. A battery of cognitive tests assessing verbal and spatial memory, language, and attention was administered at baseline (prior to medication) and again at days 90 and 180 of treatment for men receiving T gel and at baseline and days 30 and 90 of treatment for men receiving DHT gel. For men receiving T gel, circulating total T and estradiol (E(2)) were significantly raised compared with baseline, and a significant improvement in verbal memory was observed. For men receiving DHT gel, serum DHT levels increased and T levels decreased significantly compared with baseline, and a significant improvement in spatial memory was observed. The results suggest that beneficial changes in cognition can occur in hypogonadal men using T replacement levels and DHT treatment, and these changes in cognition can be reliably measured during a relative steady-state dose level. Further, our results suggest that aromatization of T to E(2) may regulate verbal memory in men, whereas nonaromatizable androgens may regulate spatial memory.

Adult↗
PubMed2006

[Spatial orientation memory: evaluation in patents with Alzheimer disease and temporal lobe epilepsy].

Experimental studies have identified pyramidal cells in hippocampus in rats with participation in the spatial orientation memory (SOM), which are named location cells. This study had the purpose to adapt a test based in these experiments in order to check the performance of SOM and the participation of hippocampus into SOM in patients with mesial temporal sclerosis (MTS). The research was divided into two studies: the first one the test was adapted, and in order to check its capacity to investigate the deficits of SOM, it has applied in groups of 10 (ten) subjects, one group with patients that have Alzheimer disease and the other one with healthy elderly (p<0.001). The second study has evaluated the participation of hippocampus into SOM in 43 patients (23 with mesial temporal sclerosis (MTS) and 20 submitted to selective amygdala hippocampectomy (SAH)) and 23 healthy volunteers with p<0,05 between MTS and SAH and between controlled and SAH. It was shown that the test of SOM is suitable to evaluate deficits, but it seems the SOM is not a specific function of human hippocampus.

Adult↗
PubMed2003

The effects of Ginkgo biloba extracts on the memory and motor functions of rats with chronic cerebral insufficiency.

The main goal of the current study was to investigate the effects of two Ginkgo leaf extracts, EGb 761 and an extract of local Ginkgo leaf (LGb), on the memory and motor functions of rats with chronic cerebral insufficiency (produced by bilateral common carotid artery ligation). After the operation, spatial memory and motor functions were tested for over 80 days. Tests included (1) radial-arm maze test for testing spatial memory and locomotor activity and (2) muscle force and hind limbs for escape. The results indicate that both EGb 761 and LGb improved spatial memory from the second week after operation, but only EGb 761 delayed deterioration of motor functions from the fifth week after operation.

Animals↗
PubMed2005

Gender and adolescent alcohol use disorders on BOLD (blood oxygen level dependent) response to spatial working memory.

AIMS: To determine how alcohol use differentially affects brain functioning in male and female adolescents. METHODS: Adolescents with alcohol use disorders (AUDs; 7 female, 11 male) and control adolescents without AUDs (9 female, 12 male), aged 14-17 years, performed spatial working memory and vigilance tasks during functional magnetic resonance imaging. RESULTS: Gender, AUD and their interaction were significantly associated with brain activation patterns to the tasks. There were interactions in the superior frontal, superior temporal, cingulate and fusiform regions, in which female and male adolescents with AUDs showed a different brain response from each other and control subjects. Overall, female adolescents with AUDs showed a greater departure from normal activation patterns than male adolescents with AUD. CONCLUSIONS: Adolescent alcohol involvement may affect male and female brains differently, and adolescent females may be somewhat more vulnerable to adverse alcohol effects. With continued drinking, these adolescents may be at an increased risk for behavioural deficits.

Adolescent↗
PubMed1999

Korean red ginseng saponins with low ratios of protopanaxadiol and protopanaxatriol saponin improve scopolamine-induced learning disability and spatial working memory in mice.

The effects of two ginseng saponins having a different ratio of protopanaxadiol (PD) and protopanaxatriol saponins (PT) on the learning impairment induced by scopolamine, and learning and memory in mice were investigated in a passive avoidance task and a Morris water maze task. The ratio of PD and PT was 1.24 and 1.46, respectively. Before training, the ginseng saponins were administered intraperitoneally at doses of 50 and 100 mg/kg. The two saponins improved the scopolamine-induced learning impairment at different dosages in mice, 50 and 100 mg/kg, respectively. However, the two saponins did not show a favorable effect on learning and memory in normal mice. Korean red ginseng saponin with a low PD/PT ratio had an improving effect on spatial working memory, but the saponin with a high PD/PT ratio did not. This finding suggests that the PD/PT ratio of the ginseng saponins may be an important factor in the pharmacological role of red ginseng as a medicinal herb.

Animals↗
PubMed1997

Stimulation and blockade of alpha1 adrenoceptors affect behavioural activity, but not spatial working memory assessed by delayed non-matching to position task in rats.

The present study investigated the role of alpha1 adrenergic receptors in the modulation of working memory and behavioural activity by assessing the effects of alpha1 adrenergic receptor stimulation or blockade on the performance of rats in a delayed non-matching to position task. St-587 (a putative agonist of alpha1 adrenoceptors) at a dose of 100 microg/kg slightly increased choice accuracy (per cent correct responses) of rats, but the effect was delay-independent which is interpreted as an improvement in choice accuracy and non-mnemonic (non-working memory) in character. Neither St-587 (300 or 1000 microg/kg) nor prazosin (a prototype antagonist of alpha1 adrenoceptors) (100 or 300 microg/kg) significantly affected the choice accuracy of rats in this task. Prazosin 300 microg/kg lengthened the latency for correct responses in the working memory task but did not affect food collection latencies. This combination of effects may reflect decreased motor output. St-587 300 and 1000 microg/kg, but not prazosin, increased food collection latencies in the working memory task. Thus, the present results suggest that alpha1 adrenergic receptors do not play any important role in spatial working memory as assessed using the delayed non-matching to position task, but that modulation of alpha1 adrenoceptors may affect motor activity and motivation in rats.

Adrenergic alpha-Agonists↗
PubMed2004

Behavioral effects of CD40-CD40L pathway disruption in aged PSAPP mice.

We have shown that, when an amyloid-beta peptide (Abeta) overproducing transgenic mouse model (PSAPP) of Alzheimer's disease (AD) is treated with a depleting antibody against CD40L, it causes marked attenuation of Abeta pathology associated with decreased amyloidogenic processing of amyloid precursor protein (APP) and increased cerebral clearance of Abeta. Here, we report that, when PSAPP mice receive a regimen of anti-CD40L antibody commencing at an age associated with initial Abeta deposition, they demonstrate superior spatial memory on the standard water maze and radial arm water maze tasks, as well as exhibiting superior non-spatial memory in the object recognition test, as compared to control PSAPP mice. Furthermore, PSAPP mice treated with an anti-CD40L antibody regimen commencing at an age associated with extensive Abeta deposition demonstrate superior spatial memory on the standard water maze task, as compared to control PSAPP mice. Disruption of CD40L activity has beneficial effects on pathology and cognitive behavior in the PSAPP mouse model, providing support for the therapeutic potential of interrupting the CD40-CD40L interaction in AD.

Aging↗
PubMed2001

Functional neuroanatomy of visuo-spatial working memory in Turner syndrome.

Turner syndrome (TS), a genetic disorder characterized by the absence of an X chromosome in females, has been associated with cognitive and visuo-spatial processing impairments. We utilized functional MRI (fMRI) to investigate the neural substrates that underlie observed deficits in executive functioning and visuo-spatial processing. Eleven females with TS and 14 typically developing females (ages 7-20) underwent fMRI scanning while performing 1-back and 2-back versions of a standard visuo-spatial working memory (WM) task. On both tasks, TS subjects performed worse than control subjects. Compared with controls, TS subjects showed increased activation in the left and right supramarginal gyrus (SMG) during the 1-back task and decreased activation in these regions during the 2-back task. In addition, decreased activation in the left and right dorsolateral prefrontal cortex (DLPFC) and caudate nucleus was observed during the 2-back task in TS subjects. Activation differences localized to the SMG, in the inferior parietal lobe, may reflect deficits in visuo-spatial encoding and WM storage mechanisms in TS. In addition, deficits in the DLPFC and caudate may be related to deficits in executive function during WM performance. Together these findings point to deficits in frontal-striatal and frontal-parietal circuits subserving multiple WM functions in TS.

Adolescent↗