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PubMed2002

Long-term study of chronic oral aluminum exposure and spatial working memory in rats.

The authors report an effort to advance animal models that mimic the cognitive decline of Alzheimer's disease. Rats were trained and repeatedly tested in a spatial delayed matching-to-position paradigm in the water maze, with the location of the submerged platform changing between, but not within, days. After Trial 1 (random search) and intertrial intervals of 30 s or 1 hr, memory was tested in Trial 2. Young rats quickly acquired this task and were repeatedly tested after different intervals over 7 months, with a slight increase in performance toward the end of testing, but no difference in latencies between delays. Oral long-term treatment of 1 group with 0.1% aluminum caused no delay-dependent working memory deficit. This testing protocol may enable between- and within-subject long-term assessment of spatial working memory before and after drug treatment and may prove useful in animal models of progressive cognitive decline.

Administration, Oral↗
PubMed2005

FROST: a distributed neurocomputational model of working memory maintenance.

Many studies suggest that the sustained activation underlying working memory (WM) maintenance is mediated by a distributed network that includes the prefrontal cortex and other structures (e.g., posterior parietal cortex, thalamus, globus pallidus, and the caudate nucleus). A computational model of WM, called FROST (short for FROntal-Striatal-Thalamic), is proposed in which the representation of items and spatial positions is encoded in the lateral prefrontal cortex. During delay intervals, activation in these prefrontal cells is sustained via parallel, prefrontal cortical-thalamic loops. Activation reverberates in these loops because prefrontal cortical excitation of the head of the caudate nucleus leads to disinhibition of the thalamus (via the globus pallidus). FROST successfully accounts for a wide variety of WM data, including single-cell recording data and human behavioral data.

Action Potentials↗
PubMed2005

Evidence for sustained attention and working memory in schizophrenia sharing a common mechanism.

Sustained attention and working memory (WM) are closely related functions that may share common mechanisms. The authors assessed sustained attention in schizophrenia patients and healthy comparison subjects using visuomotor tracking tasks under varying distractor loads. The attentional effort expended to deal with distractors was lower in patients and showed significant association with WM, executive function and negative symptoms in that group. It is proposed that the anterior attention system of sustained attention models and the executive function of the WM model describe the same or a closely related mechanism that is located in the prefrontal cortex (PFC) and is impaired in schizophrenia.

Adult↗
PubMed2005

Working memory span tasks: A methodological review and user's guide.

Working memory (WM) span tasks-and in particular, counting span, operation span, and reading span tasks-are widely used measures of WM capacity. Despite their popularity, however, there has never been a comprehensive analysis of the merits of WM span tasks as measurement tools. Here, we review the genesis of these tasks and discuss how and why they came to be so influential. In so doing, we address the reliability and validity of the tasks, and we consider more technical aspects of the tasks, such as optimal administration and scoring procedures. Finally, we discuss statistical and methodological techniques that have commonly been used in conjunction with WM span tasks, such as latent variable analysis and extreme-groups designs.

Group Processes↗
PubMed2003

Effects of methylphenidate on working memory in pigeons.

To assess the effects of methylphenidate on working memory, pigeons were trained in a delayed matching-to-sample task. Delay interval duration (0.2, 1, 3, 6, or 12 sec) was varied within sessions in order to separate delay-dependent from delay-independent effects of the drug on performance. A reduction in the sample response requirement from five responses to one response effectively reduced attention to the stimulus and impaired overall accuracy. Methylphenidate was administered in doses of 0.0 (saline control), 0.25, 2.5, and 10 mg/kg. Relative to performance with saline, accuracy was significantly reduced with 10 mg/kg methylphenidate to the same extent in both fixed ratio (FR) 1 and FR 5 conditions. The smaller doses had no effect, and there was no evidence that accuracy improved with drug administration. Intercepts and slopes of exponential functions fitted to measures of discriminability plotted as a function of delay showed that methylphenidate affected delay-independent aspects of performance (initial discriminability), but not delay-dependent aspects (rate of forgetting).

Animals↗
PubMed2003

Working memory for visual features and conjunctions in schizophrenia.

The visual working memory (WM) storage capacity of patients with schizophrenia was investigated using a change detection paradigm. Participants were presented with 2, 3, 4, or 6 colored bars with testing of both single feature (color, orientation) and feature conjunction conditions. Patients performed significantly worse than controls at all set sizes but demonstrated normal feature binding. Unlike controls, patient WM capacity declined at set size 6 relative to set size 4. Impairments with subcapacity arrays suggest a deficit in task set maintenance: Greater impairment for supercapacity set sizes suggests a deficit in the ability to selectively encode information for WM storage. Thus, the WM impairment in schizophrenia appears to be a consequence of attentional deficits rather than a reduction in storage capacity.

Adult↗
PubMed2001

Performance more than working memory disrupted by acute systemic inflammation in rats in appetitive tasks.

Evidence from molecular biology, epidemiology, behavioral pharmacology, and clinical science support the conclusion that brain inflammation contributes to the pathogenesis of cognitive symptoms in Alzheimer's disease (AD) and other neuropsychological disorders. Three different tests were conducted to determine whether the acute inflammatory response induced by systemic lipopolysaccharide (LPS) treatment is accompanied by a selective disruption of working memory functioning in rats. Doses of LPS sufficient to induce a thermoregulatory response were administered intraperitoneally and their effects on behavioral measures of symbolic working memory, spatial learning, and spatial memory consolidation, were assessed. LPS-induced immune activation was found not to significantly affect memory processes in any of the behavioral tests used. However, LPS-induced immune activation caused performance deficits consistent with a disruptive effect of LPS on motivation and arousal. These results suggest that sickness behavior induced by immune stimulation is not necessarily accompanied by selective impairment in memory processes. The importance of distinguishing cognitive disruption from performance impairment in interpreting the behavioral effects of inflammatory mediators is discussed.

Animals↗
PubMed2002

Time-dependent hierarchical organization of spatial working memory: a transcranial magnetic stimulation study.

The performance of memory-guided saccades with two different delays (3 and 30 s of memorization) was studied in seven healthy subjects. Double-pulse transcranial magnetic stimulation (dTMS) with an interstimulus interval of 100 ms was applied over the right dorsolateral prefrontal cortex (DLPFC) early (1 s after target presentation) and late (28 s after target presentation). Early stimulation significantly increased in both delays the percentage of error in amplitude (PEA) of contralateral memory-guided saccades compared to the control experiment without stimulation. dTMS applied late in the delay had no significant effect on PEA. Furthermore, we found a significantly smaller effect of early stimulation in the long-delay paradigm. These results suggest a time-dependent hierarchical organization of the spatial working memory with a functional dominance of DLPFC during the early memorization, independent from the memorization delay. For a long memorization delay, however, working memory seems to have an additional, DLPFC-independent component.

Adult↗
PubMed2003

Pantomimes are special gestures which rely on working memory.

The case of a patient is reported who presented consistently with overt deficits in producing pantomimes in the absence of any other deficits in producing meaningful gestures. This pattern of spared and impaired abilities is difficult to reconcile with the current layout of cognitive models for praxis. This patient also showed clear impairment in a dual-task paradigm, a test taxing the co-ordination aspect of working memory, though performed normally in a series of other neuropsychological measures assessing language, visuo-spatial functions, reasoning function, and executive function. A specific working memory impairment associated with a deficit of pantomiming in the absence of any other disorders in the production of meaningful gestures suggested a way to modify the model to account for the data. Pantomimes are a particular category of gestures, meaningful, yet novel. We posit that by their very nature they call for the intervention of a mechanism to integrate and synthesise perceptual inputs together with information made available from the action semantics (knowledge about objects and functions) and the output lexicon (stored procedural programmes). This processing stage conceived as a temporary workspace where gesture information is actively manipulated, would generate new motor programmes to carry out pantomimes. The model of gesture production is refined to include this workspace.

Aged↗
PubMed1991

Effects of adult age on structural and operational capacities in working memory.

Eight experiments were conducted in which young adults and older adults were asked to report the latest value of 1 of several continuously changing numeric or spatial variables. Accuracy of reporting the current value of the target variable was lower with increases in the number of potentially relevant variables and with increases in the number of required processing operations. Young and older adults exhibited similar effects of the number of potentially relevant variables (hypothesized to be sensitive to the structural capacity of working memory) and of the number of required processing operations (hypothesized to be sensitive to the operational capacity of working memory), but older adults were generally less accurate than young adults.

Adult↗
PubMed1995

Neural correlates of working memory in a visual letter monitoring task: an fMRI study.

Complex mental operations rely on the coordinated activity of widely distributed brain regions constituting neurocognitive networks. Using multislice echoplanar functional magnetic resonance imaging (fMRI) we have contrasted regional brain activity during a control and an experimental condition which differed with respect to the demands placed on verbal working memory. Subjects were seven right-handed healthy male volunteers. Analysis of group and individual data revealed activation in the anterior and posterior parasagittal cortex in all subjects, left parietal cortex (six subjects) and left dorsolateral prefontal cortex (five subjects). These results suggest that verbal working memory is subserved by a neurocognitive network comprising cortical regions involved in attention, executive function and short term mnemonic processes.

Adult↗
PubMed1997

Nicotinic antagonist administration into the ventral hippocampus and spatial working memory in rats.

Nicotinic acetylcholine receptors are important for maintaining optimal memory performance. In order to more fully characterize the involvement of nicotinic systems in memory, the contributions of nicotinic acetylcholine receptor subtypes were investigated. This study targeted the alpha 7 and alpha 4 beta 2 nicotinic receptors in the ventral hippocampus, an area known to be important for spatial working memory. Antagonists of alpha 7 and alpha 4 beta 2 receptors were locally infused into the ventral hippocampus of rats and the effects on memory were examined with the radial-arm maze. The subtype-specific competitive antagonists infused into separate groups of rats were methyllycaconitine citrate (an alpha 7 antagonist) and dihydro-beta-erythroidine hydrobromide (an alpha 4 beta 2 antagonist). Their effects on radial-arm maze performance were contrasted with the non-specific competitive antagonist, D-tubocurarine chloride. Significant deficits in radial-arm maze choice accuracy performance were found at 78.7 micrograms/side for methyllycaconitine and at 106.9 micrograms/side for dihydro-beta-erythroidine. Increased response latency was also seen at these doses. Tubocurarine induced seizures at doses previously reported to have no effect. Wet dog shakes were seen in most rats at 0.1 microgram/side with tubocurarine, 26.3 micrograms/side with methyllycaconitine and 106.9 micrograms/side with dihydro-beta-erythroidine. This study suggests that both alpha 7 and alpha 4 beta 2 nicotinic acetylcholine receptor subtypes are involved in working memory formation and that the hippocampus is a critical site for nicotinic cholinergic involvement in memory function, though the high doses of antagonists needed to produce the memory impairment may have had less than completely specific effects.

Aconitine↗
PubMed2001

Age, working memory, and on-line syntactic processing in sentence comprehension.

One hundred twenty-seven individuals who ranged in age from 18 to 90 years were tested on a reading span test and on measures of on-line and off-line sentence processing efficiency. Older participants had reduced working-memory spans compared with younger participants. The on-line measures were sensitive to local increases in processing load, and the off-line measures were sensitive to the syntactic complexity of the sentences. Older and younger participants showed similar effects of syntactic complexity on the on-line measures. There was some evidence that older participants were more affected than younger participants by syntactic complexity on the off-line measures. The results support the hypothesis that on-line processes involved in recognizing linguistic forms and determining the literal, preferred, discourse-coherent meaning of sentences constitute a domain of language processing that relies on its own processing resource or working-memory system.

Adolescent↗
PubMed1999

Neuronal correlates of parametric working memory in the prefrontal cortex.

Humans and monkeys have similar abilities to discriminate the difference in frequency between two mechanical vibrations applied sequentially to the fingertips. A key component of this sensory task is that the second stimulus is compared with the trace left by the first (base) stimulus, which must involve working memory. Where and how is this trace held in the brain? This question was investigated by recording from single neurons in the prefrontal cortex of monkeys while they performed the somatosensory discrimination task. Here we describe neurons in the inferior convexity of the prefrontal cortex whose discharge rates varied, during the delay period between the two stimuli, as a monotonic function of the base stimulus frequency. We describe this as 'monotonic stimulus encoding', and we suggest that the result may generalize: monotonic stimulus encoding may be the basic representation of one-dimensional sensory stimulus quantities in working memory. Thus we predict that other behavioural tasks that require ordinal comparisons between scalar analogue stimuli would give rise to monotonic responses similar to those reported here.

Animals↗
PubMed1993

"That man's father is my father's son": the roles of structure, strategy, and working memory in solving convoluted verbal problems.

Normative data (N = 896) collected on solutions to the traditional reasoning problem "Brothers and sisters have I none,/That man's father is my father's son" was the platform for a set of experiments to investigate the roles of problem structure, subject strategy, and working memory in error making in a class of verbal problems. The normative data revealed that the modal, but incorrect response to the brothers and sisters problem was "himself," whereas the correct response of "son" was given by only 17% of subjects for the traditional version above, rising to 40% for a reordered novel version. This problem's structure, identified as a double-modifier structure, was found to produce similar response patterns across a range of verbal problems. Results from (1) syntactical structure manipulations (e.g., "My father's son is the father of that man"), and (2) efforts to teach subjects to use a linear strategy (a sequence of steps), interpreted within a framework of Just and Carpenter's (1992) capacity theory of comprehension, suggested that working memory overload varies across within-structure modifications and subjects. Furthermore, this overload may be compounded by subjects' choices of strategy.

Adult↗
PubMedDate not supplied

A model of working memory: bridging the gap between electrophysiology and human brain imaging.

Human neuroimaging methods such as positron emission tomography and functional magnetic resonance imaging have made possible the study of large-scale distributed networks in the behaving human brain. Although many imaging studies support and extend knowledge gained from other experimental modalities such as animal single-cell recordings, there have also been a substantial number of experiments that appear to contradict the animal studies. Part of the reason for this is that neuroimaging is an indirect measure of neuronal firing activity, and thus interpretation is difficult. Computational modeling can help to bridge the gap by providing a substrate for making explicit the assumptions and constraints provided from other sources such as anatomy, physiology and behavior. We describe a large-scale model of working memory that we have used to examine a number of issues relating to the interpretation of imaging data. The gating mechanism that regulates engagement and retention of short-term memory is revised to better reflect hypothesized underlying neuromodulatory mechanisms. It is shown that in addition to imparting better performance for the memory circuit, this mechanism also provides a better match to imaging data from working memory studies.

Brain↗
PubMed2001

Cortical networks for working memory and executive functions sustain the conscious resting state in man.

The cortical anatomy of the conscious resting state (REST) was investigated using a meta-analysis of nine positron emission tomography (PET) activation protocols that dealt with different cognitive tasks but shared REST as a common control state. During REST, subjects were in darkness and silence, and were instructed to relax, refrain from moving, and avoid systematic thoughts. Each protocol contrasted REST to a different cognitive task consisting either of language, mental imagery, mental calculation, reasoning, finger movement, or spatial working memory, using either auditory, visual or no stimulus delivery, and requiring either vocal, motor or no output. A total of 63 subjects and 370 spatially normalized PET scans were entered in the meta-analysis. Conjunction analysis revealed a network of brain areas jointly activated during conscious REST as compared to the nine cognitive tasks, including the bilateral angular gyrus, the left anterior precuneus and posterior cingulate cortex, the left medial frontal and anterior cingulate cortex, the left superior and medial frontal sulcus, and the left inferior frontal cortex. These results suggest that brain activity during conscious REST is sustained by a large scale network of heteromodal associative parietal and frontal cortical areas, that can be further hierarchically organized in an episodic working memory parieto-frontal network, driven in part by emotions, working under the supervision of an executive left prefrontal network.

Adult↗
PubMed2003

Attention and working memory: a dynamical model of neuronal activity in the prefrontal cortex.

Cognitive behaviour requires complex context-dependent mapping between sensory stimuli and actions. The same stimulus can lead to different behaviours depending on the situation, or the same behaviour may be elicited by different cueing stimuli. Neurons in the primate prefrontal cortex show task-specific firing activity during working memory delay periods. These neurons provide a neural substrate for mapping stimulus and response in a flexible, context- or rule-dependent, fashion. We describe here an integrate-and-fire network model to explain and investigate the different types of working-memory-related neuronal activity observed. The model contains different populations (or pools) of neurons (as found neurophysiologically) in attractor networks which respond in the delay period to the stimulus object, the stimulus position ('sensory pools'), to combinations of the stimulus sensory properties (e.g. the object identity or object location) and the response ('intermediate pools'), and to the response required (left or right) ('premotor pools'). The pools are arranged hierarchically, are linked by associative synaptic connections, and have global inhibition through inhibitory interneurons to implement competition. It is shown that a biasing attentional input to define the current rule applied to the intermediate pools enables the system to select the correct response in what is a biased competition model of attention. The integrate-and-fire model not only produces realistic spiking dynamicals very similar to the neuronal data but also shows how dopamine could weaken and shorten the persistent neuronal activity in the delay period; and allows us to predict more response errors when dopamine is elevated because there is less different activity in the different pools of competing neurons, resulting in more conflict.

Animals↗