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Enhancement of working memory in aged monkeys by a sensitizing regimen of dopamine D1 receptor stimulation.

A natural consequence of aging is a loss of dopamine function and associated deficits in working memory in both human and nonhuman primates. Specifically, deficiency of D1 receptor signaling has been implicated in age-related cognitive decline. Here, we report that an intermittent, sensitizing regimen of the D1 dopamine agonist ABT-431 dramatically enhances working memory performance in aged rhesus monkeys, while either producing impairment or having little effect on performance in young adult monkeys. Importantly, cognitive enhancement in the aged monkeys was still evident for >1 year after cessation of D1 treatment. Because intermittent exposure to low doses of amphetamine and other stimulants has been shown to enhance responsiveness to subsequent stimulant exposure, our findings suggest that sensitization of D1 signaling may provide a novel neurobiological mechanism for improving a core cognitive process in conditions in which dopamine function has deteriorated, such as in normal aging and Parkinson's disease.

Age Factors↗

Different working memory capacity in normal young adults for visual and tactile letter recognition task.

Thirty-nine young adult participants performing the visual and tactile n-back working memory task were compared. In the visual task, letters were presented on a computer screen and in the tactile task, plastic letters embedded on a board were explored tactually. The amount of incorrect responses increased with increasing memory load in both tasks, but was significantly lower in the visual task. Subgrouping the participants with extreme performances into "skilled" and "poor" performers showed that the best performance was found among "skilled" visual performers, and the worst one among "poor" tactile performers. There was more interindividual variation among tactile than visual performance. We conclude that tactile working memory capacity, measured here by letter recognition and letter memory, is generally more limited and shows more variability than visual memory in normal sighted participants.

Adolescent↗

Prefrontal cortex lesions augment the location-related firing properties of area TE/perirhinal cortex neurons in a working memory task.

It has previously been proposed that prefrontal cortex may have some role in keeping temporal cortex-based representations "on-line" during a working memory task. To test this hypothesis, the effects of electrolytic prefrontal cortex lesions on the firing of area TE and perirhinal cortex (PRC) neurons were examined while rats performed a delayed non-match to position task in the T-maze. The behavioural performance of control (n = 4) and lesioned (n = 4) animals were similar during this task, and many neurons displayed a statistically significant location-related variation in firing rate during the sample (44/56 neurons) and test (39/56 neurons) phases. Units from prefrontal-lesioned animals (82%) were more likely to display a significant variation in firing across the maze compared to controls (50%; P < 0.01), and to have more discrete location-related properties (50% of neurons) compared to the control (5%) group (P < 0.0005). This finding suggests that prefrontal cortex normally modulates the transmission and/or processing of spatial information in area TE/PRC during a working memory task. Modulation could be mediated through direct connections between the structures or via prefrontal control of subcortical structures. This finding has implications for our understanding of prefrontal-temporal involvement in memory and cognitive disorders.

Action Potentials↗

Theta coupling in the human electroencephalogram during a working memory task.

The role of coupling between prefrontal and temporo-parietal brain areas within the theta frequency range of the human electroencephalogram was explored in a working memory task. During encoding of visual information higher theta amplitudes were observed in the right compared to the left hemisphere. Retrieval of visuospatial and verbal information elicited a more bilateral activation pattern. These effects were accompanied by theta coupling between dorsolateral prefrontal and right posterior temporal electrode sites during encoding. During retrieval prefrontal and bilateral temporo-parietal brain areas were coupled. These results support the idea of working memory functions being dependent on distributed prefrontal-temporal networks.

Acoustic Stimulation↗

Vagal influence on working memory and attention.

The aim of the present study was to investigate the effect of vagal tone on performance during executive and non-executive tasks, using a working memory and a sustained attention test. Reactivity to cognitive tasks was also investigated using heart rate (HR) and heart rate variability (HRV). Fifty-three male sailors from the Royal Norwegian Navy participated in this study. Inter-beat-intervals were recorded continuously for 5 min of baseline, followed by randomized presentation of a working memory test (WMT) based on Baddeley and Hitch's research (1974) and a continuous performance test (CPT). The session ended with a 5-min recovery period. High HRV and low HRV groups were formed based on a median split of the root mean squared successive differences during baseline. The results showed that the high HRV group showed more correct responses than the low HRV group on the WMT. Furthermore, the high HRV group showed faster mean reaction time (mRT), more correct responses and less error, than the low HRV group on the CPT. Follow-up analysis revealed that this was evident only for components of the CPT where executive functions were involved. The analyses of reactivity showed a suppression of HRV and an increase in HR during presentation of cognitive tasks compared to recovery. This was evident for both groups. The present results indicated that high HRV was associated with better performance on tasks involving executive function.

Adult↗

Age, memory load, and individual differences in working memory as determinants of class-inclusion reasoning.

We studied the effects of individual differences in speak-span scores and variations in memory demands on the class-inclusion performance of 10-, 13-, and 15-year-old children. The speak-span task was an age-appropriate modification of Daneman and Carpenter's (1980) reading-span task and was considered to be a measure of global resources. The age variable was assumed to be a global index of skill development, and some of the specific skills hypothesized to be important in class-inclusion reasoning were estimated using a mathematical model. The results from both regression analyses and the mathematical model indicated that differences in age, speak span, and memory load all affected performance. Surprisingly, the effects of speak span and memory load were independent. However, the effects of each of these variables depended on the age level of the participants. Based on these findings, we argued that (a) resources vary continuously with age, (b) both skill level and global resources should be varied in developmental studies of problem solving, and (c) resource theories (e.g., Norman & Shallice, 1986) should be modified to account for developmental change.

Adolescent↗

Functional role of entorhinal cortex in working memory processing.

Our learning and memory system has the challenge to work in a world where items to learn are dispersed in space and time. From the information extracted by the perceptual systems, the learning system must select and combine information. Both these operations may require a temporary storage where significance and correlations could be assessed. This work builds on the common hypothesis that hippocampus and subicular, entorhinal and parahippocampal/postrhinal areas are essential for the above-mentioned functions. We bring up two examples of models; the first one is modeling of in vivo and in vitro data from entorhinal cortex layer II of delayed match-to-sample working memory experiments, the second one studying mechanisms in theta rhythmicity in EC. In both cases, we discuss how cationic currents might be involved and relate their kinetics and pharmacology to behavioral and cellular experimental results.

Animals↗

Psychosocial stress impairs working memory at high loads: an association with cortisol levels and memory retrieval.

Stress and cortisol are known to impair memory retrieval of well-consolidated declarative material. The effects of cortisol on memory retrieval may in particular be due to glucocorticoid (GC) receptors in the hippocampus and prefrontal cortex (PFC). Therefore, effects of stress and cortisol should be observable on both hippocampal-dependent declarative memory retrieval and PFC-dependent working memory (WM). In the present study, it was tested whether psychosocial stress would impair both WM and memory retrieval in 20 young healthy men. In addition, the association between cortisol levels and cognitive performance was assessed. It was found that stress impaired WM at high loads, but not at low loads in a Sternberg paradigm. High cortisol levels at the time of testing were associated with slow WM performance at high loads, and with impaired recall of moderately emotional, but not of highly emotional paragraphs. Furthermore, performance at high WM loads was associated with memory retrieval. These data extend previous results of pharmacological studies in finding WM impairments after acute stress at high workloads and cortisol-related retrieval impairments.

Adult↗

Spatial working memory score of humans in a large radial maze, similar to published score of rats, implies capacity close to the magical number 7 +/- 22.

To compare the working memory (WM) capacity of humans to rats, we tested humans with a 17-arm radial maze and, in a follow up experiment, with a 13-arm radial maze. Both mazes were 15.2 meters in diameter, painted on a grassy field. In one version of the 13-arm experiment, we required a concurrent nonsense vocalization to impede subjects' use of language to remember locations. Subjects were instructed to choose arms of the radial maze unsystematically--as rats generally appear to do--and to visit the end of each arm only once. In additional procedures, we tested working memory capacity in a verbal task that is more analogous to the radial maze than is the typical ordered recall test. Subjects were asked to try to recite a sequence of 17 numbers (i.e., 18 through 34) or letters (A through Q) in unsystematic order, with no repeats. In another experiment subjects recited 13 numbers (14-26) or letters (A-M). In all tests, subjects were allowed only as many responses as there were distinct items (17 or 13, respectively). Average correct-response (nonrepeat) scores were 14.4 for the 17-arm maze and 14.1 for both of the verbal 17-item tests; these scores are close to the reported score for rats in a 17-arm radial maze. Average scores were between 10.8 and 11.4 in all of the 13-item maze and recitation tasks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of nitrendipine on reference and working memory of rats in three-panel runway.

This study was designed to investigate whether calcium-channel blocker, nitrendipine affects memory of rats in three-panel runway test. Nitrendipine (2-4 mg kg(-1), intra peritoneally (i.p.)) neither enhanced nor impaired reference and working memory performances of young adult rats. However, it improved impairment in reference memory induced by anticholinergic drug scopolamine (3 mg kg(-1), i.p.) while it had no effects on impairment in working memory induced by the same drug. The results suggest that nitrendipine may be of benefit in the treatment of memory disturbances resulted from cholinergic deficit.

Animals↗

Activity in ventrolateral and mid-dorsolateral prefrontal cortex during nonspatial visual working memory processing: evidence from functional magnetic resonance imaging.

Whole-brain functional magnetic resonance imaging was used to study five healthy human subjects while they performed two nonspatial visual working memory tasks and one control task. In the first memory task, the subjects were required to view a sequence of three pattern stimuli, randomly selected from a familiar set of four stimuli, and then identify which one of three simultaneously presented stimuli was the one that had not been presented in the previous array. In the other task, the subjects were required to observe an identical sequence of three randomly selected pattern stimuli and then to respond by selecting those same stimuli in the order presented. In comparison to a baseline control task, increases in signal intensity were observed, bilaterally, in the mid-dorsolateral frontal cortex and in the right ventrolateral frontal cortex in both memory tasks. When the two tasks were compared directly, however, the first memory task, which had the higher monitoring requirement, yielded significantly greater signal intensity changes in area 9/46 of the right mid-dorsolateral frontal cortex. These results provide further evidence for the precise functional contribution made by the mid-dorsolateral frontal cortex in visual working memory tasks and concur closely with findings in nonhuman primates.

Adult↗

Spatial working memory deficits in children at ages 3-4 who were low birth weight, preterm infants.

The aim of this study was to investigate attention and perceptual and spatial working memory abilities in preterm, low birth weight preschool children without evident brain disorders as determined by normal cerebral ultrasound findings and normal motor development. The authors evaluated 19 preterm and 19 typically developing children who were matched for IQ and chronological age. Results indicated that children born prematurely without major neurological deficits and with a normal cognitive level may have specific difficulty in sustained attention, visuospatial processing, and spatial working memory when evaluated at ages 3-4. This finding is relevant for understanding the qualitative aspects of cognitive development in preterm children and the neurobiological substrate underlying this development.

Attention↗

Reversible inactivation of the medial septum or nucleus basalis impairs working memory in rats: a dissociation of memory and performance.

Lidocaine-induced inactivation of the medial septum immediately after training or prior to testing in a delay radial-arm maze task produced deficits in spatial working memory that reflected impaired acquisition of the task. Injection of lidocaine into the nucleus basalis magnocellularis produced a profile of behavioral changes that indicated that temporary inactivation of this structure impaired the behavioral expression of information already stored in working memory. This appears to reflect an impairment in processes that are required for performance (i.e., attention, motivation, sensorimotor function) of the task but not for retrieval of stored information. Site-specific inactivation of the basal forebrain should help to reveal the involvement of its component structures in different aspects of cognitive function.

Analysis of Variance↗

Through a narrow window: working memory capacity and the detection of covariation.

The samples of data that people use in their attempts to detect relationships in the environment are limited in size by working memory capacity. The implications of that constraint are explored by analyzing the sampling distribution of the most common measure of relationship--the product moment correlation (Pearson's rxy). This distribution is skewed when the population correlation differs from zero (i.e., when a correlation exists), and the more so, the smaller the sample. As both the median and the mode of the sampling distribution are more extreme than the population value, it follows that samples likely to be encountered indicate a correlation stronger than that in the population. Thus, the limited capacity of working memory may serve as an amplifier that helps people to avoid missing strong relationships. As the distribution is more skewed the smaller the sample size, the effect suggests an explanation for the fact that young children detect meaningful covariation fairly rapidly.

Cognition↗

Selective fimbria and thalamic lesions differentially impair forms of working memory in rats.

Several series of experiments were designed to compare the effects of selective lesions of the fimbria or of thalamic nuclei on three different tasks involving working memory in rats: object recognition, place recognition, and the radial arm maze test. The main effects of fimbria lesions were as follows: they produced deficits in the radial maze; object recognition was spared or even facilitated, whereas place recognition was impaired. Electrolytic lesions of either centromedian-parafascicularis (CM-Pf) or dorsomedialis (DM) nuclei produced highly significant deficits in the radial maze test but spared object and place recognition. Ibotenate lesions of the CM-Pf had no effect on any test, which means that the critical structure in the effects of the electrolytic lesions of the CM-Pf was the fasciculus retroflexus (FR). These data may contribute two main points to animal models of hippocampal and thalamic amnesia: (1) different forms of working memory in rats might have different neural bases and (2) the FR may be involved in learning and memory processes.

Animals↗

In two species, females exhibit superior working memory and inferior reference memory on the water radial-arm maze.

Male and female mice and rats were tested on a water escape version of the radial-arm maze designed to measure working and reference memory. In both species, females exhibited superior working memory during acquisition, and were better able to handle a higher memory load. However, male mice and rats exhibited better reference memory than females during the asymptotic portion of testing. Our data suggest that females may be better at working memory when both working and reference memory information must be learned simultaneously, and males better at reference memory when it has been differentiated from working memory.

Animals↗

Working memory in infancy: six-month-olds' performance on two versions of the oculomotor delayed response task.

The capacity of 6-month-old infants to maintain information in working memory for several seconds was studied using two versions of an oculomotor delayed response task. Infants were presented with either a cue stimulus in a target location (Experiment 1), or an abstract, central stimulus (Experiment 2) which could be used to predict the peripheral location in which an attractive target stimulus subsequently appeared. Eye movements during delay periods from 600 to 5000 ms were recorded. The results indicated that infants maintained information about stimulus locations in working memory for 3-5 s. These results imply maturity of regions of the prefrontal cortex closely associated with a similar task used in neurophysiological and neuroimaging studies.

Association Learning↗