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Effects of excitotoxic thalamic intralaminar nuclei lesions on attention and working memory.

In rats, lesions of the thalamic intralaminar nuclei (ILn) impair measures of working memory, but it is unclear whether alterations of attention contribute to the mnemonic deficits. The present experiment tested the effects of ILn lesions on a two-lever attention task that required discrimination of visual signals and non-signals. Rats were trained presurgically in the task and then received sham surgery or infusions of n-methyl-d-aspartate (NMDA) into the ILn to induce excitotoxic lesions. ILn lesions transiently decreased accurate detection of signals. ILn lesions also increased omissions. Compared to sham-lesioned rats, ILn-lesioned animals were not differentially affected when task demands were increased by presenting a visual distracter. Finally, a retention interval was incorporated into the task to assess whether the lesions affected acquisition of a working memory version of this behavioral paradigm. Unlike sham-lesioned animals, ILn-lesioned rats did not demonstrate a significant improvement in signal detection when a retention interval was introduced. The transient lesion-induced deficits in the attention task suggest that, in rats, the ILn may contribute to aspects of attentional processing, but through neural re-organization or activity in other regions, there is compensation for the loss of ILn functioning. The ILn appear to be necessary for maintaining performance when working memory demands are increased.

Analysis of Variance↗

The effects of muscarinic cholinergic receptor blockade in the rat anterior cingulate and Prelimbic/Infralimbic cortices on spatial working memory.

Previous findings indicate that cholinergic input to the medial prefrontal cortex may modulate mnemonic processes. The present experiment determined whether blockade of muscarinic cholinergic receptors in the rodent anterior cingulate and prelimbic/infralimbic cortices impairs spatial working memory. In a 12-arm radial maze, a working memory for spatial locations task was employed using a continuous recognition go/no-go procedure. Rats were allowed to enter 12 arms for a reinforcement. Of the 12 arm presentations, 3 or 4 arms were presented for a second time in a session that did not contain a reinforcement. The number of trials between the first and second presentations of an arm ranged from 0 to 6 (lags). Infusions of scopolamine (1, 5, and 10 microgram), a muscarinic cholinergic antagonist, into the prelimbic/infralimbic cortices, but not the anterior cingulate cortex, significantly impaired spatial working memory in a lag- and dose-dependent manner. The deficit induced by scopolamine (10 microgram) was attenuated by concomitant intraprelimbic/infralimbic injections of oxotremorine (2 microgram) a muscarinic cholinergic agonist. A separate group of rats was tested on a successive spatial discrimination task. Injections of scopolamine (1, 5, and 10 microgram) into the prelimbic/infralimbic cortices did not impair performance on the spatial discrimination task. These findings suggest that muscarinic transmission in the prelimbic/infralimbic cortices, but not the anterior cingulate cortex, is important for spatial working memory.

Analysis of Variance↗

Influence of processing speed on adult age differences in working memory.

Two studies are reported in which adults ranging from 18 to 80 years of age performed tasks designed to measure working memory functioning and perceptual comparison speed. The results from both studies indicated that statistical control of the measures of perceptual comparison speed greatly attenuated the age-related variance in measures of working memory even when working memory was assessed under self-paced conditions. Additional results in the second study supported the hypothesis that the speed influence was manifested in the rate of activating information rather than in the rate at which it was lost as a function of time or other processing.

Adolescent↗

Visuospatial working memory and the processing of spatial descriptions.

The dual-task paradigm was used to determine whether the spatial, visual and verbal components of working memory are engaged in the processing of spatial descriptions. Participants listened to route or survey descriptions of urban-like spatial environments and then drew corresponding maps. The position of each new landmark was described either in terms of the direction to move toward this landmark (route descriptions) or its relative location with regard to the previously mentioned landmark (survey descriptions). Route and survey descriptions resulted in similar recall performance in the absence of an interfering task and landmarks were consistently less well recalled than their associated moves/locations. The pattern of interference resulting from the secondary tasks indicated that the processing of landmarks called upon both the visual and spatial components of working memory in the route perspective, whereas the processing of moves/locations essentially relied on the spatial component in both the route and the survey perspectives. The verbal component of working memory was only involved in the processing of landmarks in the survey perspective. The results suggest that distinct cognitive processes support memory for route and survey descriptions, and that distinct working memory resources support the processing of landmarks and landmark positions.

Adult↗

Working memory in individuals with HIV infection.

The central executive component (CE) of Baddeley's working memory model (Baddeley, 1992) was evaluated in 26 asymptomatic human immunodeficiency virus-infected individuals (HIV+) and 23 HIV-control subjects using a dual-task working memory paradigm. The HIV+ and HIV- groups showed an equivalent reduction in performance on both the primary task (visual vigilance) and the secondary task (letter span) when they were performed concurrently relative to when either task was performed alone. This result suggested normal CE functioning in these HIV+ subjects. In contrast, the HIV+ subjects had significantly longer response latencies on reaction time measures relative to the HIV- control group. These findings indicated that slowed processing in early stage HIV-infected individuals is not associated with a working memory deficit.

AIDS Dementia Complex↗

Working memory as an emergent property of the mind and brain.

Cognitive neuroscience research on working memory has been largely motivated by a standard model that arose from the melding of psychological theory with neuroscience data. Among the tenets of this standard model are that working memory functions arise from the operation of specialized systems that act as buffers for the storage and manipulation of information, and that frontal cortex (particularly prefrontal cortex) is a critical neural substrate for these specialized systems. However, the standard model has been a victim of its own success, and can no longer accommodate many of the empirical findings of studies that it has motivated. An alternative is proposed: Working memory functions arise through the coordinated recruitment, via attention, of brain systems that have evolved to accomplish sensory-, representation-, and action-related functions. Evidence from behavioral, neuropsychological, electrophysiological, and neuroimaging studies, from monkeys and humans, is considered, as is the question of how to interpret delay-period activity in the prefrontal cortex.

Animals↗

Dynamics of population code for working memory in the prefrontal cortex.

Some neurons (delay cells) in the prefrontal cortex elevate their activities throughout the time period during which the animal is required to remember past events and prepare future behavior, suggesting that working memory is mediated by continuous neural activity. It is unknown, however, how working memory is represented within a population of prefrontal cortical neurons. We recorded from neuronal ensembles in the prefrontal cortex as rats learned a new delayed alternation task. Ensemble activities changed in parallel with behavioral learning so that they increasingly allowed correct decoding of previous and future goal choices. In well-trained rats, considerable decoding was possible based on only a few neurons and after removing continuously active delay cells. These results show that neural activity in the prefrontal cortex changes dynamically during new task learning so that working memory is robustly represented and that working memory can be mediated by sequential activation of different neural populations.

Action Potentials↗

Bidirectional modulation of spatial working memory by ethanol.

BACKGROUND: It is common knowledge that ethanol causes cognitive and memory impairments. Although these deficits are attributed to its central depressant properties, ethanol has biphasic effects and at low doses can produce excitatory actions. METHODS: Here we examined whether ethanol could have biphasic effects on performance in a delayed alternation task in a T-maze, a behavioral test of working memory. RESULTS: A dose-response study showed that intermediate doses of ethanol (1 g/kg) were associated with impairments of working memory in rats, as assessed at short intertrial intervals (10 sec). In contrast, at longer delays (120 sec), when the delayed alternation performance was reduced markedly in controls, a lower dose of ethanol (0.5 g/kg) significantly improved working memory. CONCLUSIONS: These results demonstrate a dose-dependent, bidirectional effect of ethanol on working memory and implicate the prefrontal cortex, the site of working memory function, as a target of ethanol action. The cognitive improvements caused by low, excitatory doses of ethanol may be perceived as rewarding and could have relevance for chronic ethanol consumption in humans.

Animals↗

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

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

Adolescent↗

Working memory.

It is suggested that working memory comprises a system for the temporary storage and manipulation of information, forming an important link between perception and controlled action. Evidence is presented for a three-component model, comprising an attentional control system, the central executive, and two subsidiary slave systems. One of these the, the visuo-spatial sketch pad holds and manipulates spatial information, while the other, the phonological loop performs a similar function for auditory and speech-based information. Evidence is presented for the view that the phonological loop has evolved as a mechanism to facilitate the acquisition of language.

Animals↗

Working memory: trouble in mind.

Visual working memory has been found to depend on interactions between the prefrontal cortex and visual association areas; the neurons involved can be modulated by dopamine. These new findings have relevance for the treatment of Parkinson's disease and schizophrenia.

Animals↗

Maintenance versus manipulation in verbal working memory revisited: an fMRI study.

Working memory (WM) is the ability to keep a limited amount of information "on line" for immediate use during short intervals. Verbal WM has been hypothesized to consist of neuroanatomically segregated components, i.e., maintenance (storage, rehearsal, and matching) and manipulation (reordering or updating), corresponding to ventrolateral and dorsolateral prefrontal cortex. Previous imaging studies of maintenance vs manipulation processes in WM have produced inconsistent results, which may have been due to methodological issues such as low statistical power and the use of insertion (subtraction) designs. In the present functional magnetic resonance imaging study we used parametric versions of both a prototypical maintenance task (Sternberg) and a prototypical manipulation task (n-letter back task) in 21 healthy subjects. Increased signal correlated with load common for both tasks was found in bilateral dorsolateral and anterior prefrontal, left ventrolateral prefrontal, and bilateral parietal regions. Workload x task interactions were found in bilateral dorsolateral prefrontal cortex for manipulation vs maintenance, but also for responding vs encoding (storage) in the maintenance task. Therefore, our data support a functional rather than a neuroanatomical distinction between maintenance and manipulation, given our finding that these tasks differentially activate virtually identical systems.

Adult↗

Training of working memory in children with ADHD.

Working memory (WM) capacity is the ability to retain and manipulate information during a short period of time. This ability underlies complex reasoning and has generally been regarded as a fixed trait of the individual. Children with attention deficit hyperactivity disorder (ADHD) represent one group of subjects with a WM deficit, attributed to an impairment of the frontal lobe. In the present study, we used a new training paradigm with intensive and adaptive training of WM tasks and evaluated the effect of training with a double blind, placebo controlled design. Training significantly enhanced performance on the trained WM tasks. More importantly, the training significantly improved performance on a nontrained visuo-spatial WM task and on Raven's Progressive Matrices, which is a nonverbal complex reasoning task. In addition, motor activity--as measured by the number of head movements during a computerized test--was significantly reduced in the treatment group. A second experiment showed that similar training-induced improvements on cognitive tasks are also possible in young adults without ADHD. These results demonstrate that performance on WM tasks can be significantly improved by training, and that the training effect also generalizes to nontrained tasks requiring WM. Training improved performance on tasks related to prefrontal functioning and had also a significant effect on motor activity in children with ADHD. The results thus suggest that WM training potentially could be of clinical use for ameliorating the symptoms in ADHD.

Adolescent↗

Is there a relationship between task demand and storage space in tests of working memory capacity?

This paper considers working memory capacity, critically examining the hypothesis that counting span (the ability to count arrays of objects and store count totals) reflects a trade-off in resources available for processing and short-term storage. Previous evidence interpreted as favouring this hypothesis has confounded task difficulty with counting time. Experiment 1 validated a manipulation of the attentional demands of counting in which target objects were differentiated from non-targets by either a single feature (colour) or a feature conjunction (a combination of line orientations). The results confirmed that the two presentations involved qualitatively different attentional loads. Experiment 2 used these displays to compare counting span for children aged 6 to 11, both with and without an adjustment of target numerosity to control for differences in processing time. At all ages, span was lower when counting took longer, but there was no difference between feature and conjunction arrays once counting time was accounted for. These results argue against a resource trade-off interpretation of counting span. Rather, they support a hypothesis of resource-switching among children, implying that counting span acts as a measure of time-based forgetting.

Adult↗

Dynamic cortical networks of verbal and spatial working memory: effects of memory load and task practice.

Working memory (WM), the ability to briefly retain and manipulate information in mind, is central to intelligent behavior. Here we take advantage of the high temporal resolution of electrophysiological measures to obtain a millisecond timescale view of the activity induced in distributed cortical networks by tasks that impose significant WM demands. We examined how these networks are affected by the type and amount of information to be remembered, and by the amount of task practice. Evoked potentials (EPs) were obtained from eight subjects performing spatial and verbal versions of a visual n-back WM task (n = 1, 2, 3) on each of three testing days. In well-trained subjects, WM tasks elicited transient responses reflecting different subcomponents of task processing, including transient (lasting 0.02-0.3 s) task-sensitive and load-sensitive EPs, as well as sustained responses (lasting 1-1.5 s), including the prestimulus Contingent Negative Variation (CNV), and post-stimulus frontal and parietal Slow Waves. The transient responses, with the exception of the P300, differed between the verbal and spatial task versions, and between trials with different response requirements. The P300 and the Slow Waves were not affected by task version but were affected by increased WM load. These results suggest that WM emerges from the formation of a dynamic cortical network linking task-specific processes with non-specific, capacity-limited, higher-order attentional processes. Practice effects on the EPs suggested that practice led to the development of a more effective cognitive strategy for dealing with lower-order aspects of task processing, but did not diminish demands made on higher order processes. Thus a simple WM task is shown to be composed of numerous elementary subsecond neural processes whose characteristics vary with type and amount of information being remembered, and amount of practice.

Adult↗

Effects of chronic alcohol consumption on spatial reference and working memory tasks.

The aim of this work was to determine the spatial memory impairments induced by chronic alcohol consumption in rats. The alcoholization process began on the 21st postnatal day and alcohol concentrations were gradually increased to reach a concentration of 20% that was maintained for 4 mon. Behavioral tests were performed in the Morris Water Maze (MWM). The first study assessed the effects of chronic alcohol intake on two reference memory tasks (a place learning with multiple trials and a new place learning carried out in the same experimental context). Alcohol-treated animals presented no overall impairment in their ability to process spatial information. Deficits were restricted to reduced behavioral flexibility in spatial strategies. The second study assessed working memory in two tasks in which information about platform location was only valid for one trial. In the first working memory task, the animals had to perform one trial per day and in the second task they were submitted to four trials per day. At the end of the second experiment, all animals were trained in a visual-cued task. In the second experiment, the most important deficits in alcohol-treated animals occur in spatial working memory tasks, and this impairment was independent of the intertrial interval used. In the second spatial working memory task, performance of the alcohol-treated animals in the earlier trials affected their performance in subsequent trials, suggesting that a process of proactive interference had taken place. The visual-cued task demonstrated that these behavioral impairments were produced without visuoperceptive impairments.

Adaptation, Psychological↗

Working memory performance in poor outcome schizophrenia: relationship to age and executive functioning.

Performance on the Letter-Number Sequencing (LNS) and Wisconsin Card Sorting Tests (WCST) have been shown to be significantly correlated in patients with schizophrenia, a relationship postulated to be due to working memory demands of the two tests (Gold, Carpenter, Randolph, Goldberg, & Weinberger, 1997). An alternative explanation for the association between these two tests is their sorting demands, in that both require sorting of information albeit in slightly different ways. If the latter explanation is valid, then working memory tasks that do not require sorting or other conceptualization demands should be less predictive of WCST performance than LNS. These hypotheses were examined in 34 poor outcome patients with schizophrenia, one-half of whom were over the age of 65. Patients were evaluated on Digit Span Forward, spatial working memory, LNS, and the WCST. It was found that WCST performance was significantly associated with performance on the LNS but no other working memory task. Age related performance differences were greatest on the WCST Categories and floor effects were noted on this test in one-half of the subjects. Analyses predicting WCST Categories in subjects whose scores were greater than zero (n = 16) also demonstrated that LNS, but not Digit Span or spatial working memory (any delay) predicted WCST performance. These findings indicate that LNS may be an index of executive functioning, particularly in patients who cannot perform the WCST.

Adult↗

Effects of histidine on working memory deficits induced by the 5-HT1A-receptor agonist 8-OH-DPAT.

We investigated the effects of histidine on spatial memory deficits induced by the 5-HT1A-receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Working memory deficits were elicited by 8-OH-DPAT without affecting reference memory. Histidine improved the working memory deficit induced by 8-OH-DPAT at doses causing a significant increase in brain histamine content. This finding suggests that the histaminergic system regulates 8-OH-DPAT-induced working memory deficit.

8-Hydroxy-2-(di-n-propylamino)tetralin↗