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PubMedDate not supplied

The computational role of dopamine D1 receptors in working memory.

The prefrontal cortex (PFC) is essential for working memory, which is the ability to transiently hold and manipulate information necessary for generating forthcoming action. PFC neurons actively encode working memory information via sustained firing patterns. Dopamine via D1 receptors potently modulates sustained activity of PFC neurons and performance in working memory tasks. In vitro patch-clamp data have revealed many different cellular actions of dopamine on PFC neurons and synapses. These effects were simulated using realistic networks of recurrently connected assemblies of PFC neurons. Simulated D1-mediated modulation led to a deepening and widening of the basins of attraction of high (working memory) activity states of the network, while at the same time background activity was depressed. As a result, self-sustained activity was more robust to distracting stimuli and noise. In this manner, D1 receptor stimulation might regulate the extent to which PFC network activity is focused on a particular goal state versus being open to new goals or information unrelated to the current goal.

Animals↗
PubMed2005

Visuo-spatial working memory deficits in current and former users of MDMA ('ecstasy').

Verbal working memory and executive deficits have been observed in ecstasy users. The present study sought to establish whether these also extended to visuo-spatial working memory. Thirty-six current ecstasy users, 12 former users (abstinent for at least 6 months) and 31 individuals that had never used ecstasy were tested on a maintenance plus type visuo-spatial working memory task. The task required participants to recall a sequence of specially marked cells in a four-by-four matrix display while at the same time performing a concurrent visual judgement task. Both the current and former user groups registered impairments relative to nonusers. These remained significant following statistical controls for a range of potentially confounding variables including the use of various other drugs during the 3 months prior to testing. Users were unimpaired on a simple spatial span measure suggesting that the deficits observed reflected the executive aspects of the spatial working memory task. Also consistent with executive involvement, statistical controls for measures of verbal working memory performance (computation span) removed half of the ecstasy-related variance in spatial working memory. The possibility that the pattern of results obtained might reflect some general impairment in information processing efficiency is discussed.

Adult↗
PubMed2004

Animal models of working memory: insights for targeting cognitive dysfunction in schizophrenia.

BACKGROUND AND RATIONALE: Working memory performance is considered to be a core deficit in schizophrenia and the best predictor of social reintegration and propensity for relapse. This cardinal cognitive process is critical for human reasoning and judgment and depends upon the integrity of prefrontal function. Prefrontal dysfunction in schizophrenia has been linked to altered dopaminergic and glutamatergic transmission. However, to date, antipsychotics provide no substantial relief from the debilitating cognitive consequences of this disease. OBJECTIVES: This review examines the key rodent and non-human primate models for elucidating the neural mechanisms of working memory and their neuromodulation. We compare the physiology and pharmacology of working memory between the normal state and experimentally induced models of prefrontal dysfunction and evaluate their relevance for schizophrenia. RESULTS AND CONCLUSIONS: Rodent models have demonstrated the significance of aberrant dopaminergic and glutamatergic signaling in medial prefrontal cortex for working memory. However, there is some question as to the extent to which rodent tests of working memory tap into the same process that is compromised in schizophrenia. Non-human primates provide an unexcelled model for the study of influences on prefrontal function and working memory due to the high degree of homology between human and non-human primates in the relationship between prefrontal cortex and higher cognitive capacities. Moreover, non-human primate models of prefrontal dysfunction including amphetamine sensitization, subchronic phencyclidine, and neurodevelopmental insult are ideal for the analysis of novel compounds for the treatment of cognitive dysfunction in schizophrenia, thereby facilitating the translation between preclinical drug development and clinical trials.

Amphetamine↗
PubMed1998

Temporal limits of spatial working memory in humans.

An essential feature attributed to working memory is the labile and transient nature of its representations. Using an oculomotor task, we examined the stability of spatial working memory in 16 normal human subjects. Eye movements towards remembered spatial cues (memory-guided saccades) were electro-oculographically recorded after memorization delays that varied unpredictably between 0.5 and 30s. A peaked time-course of saccadic targeting errors, with maximal errors around 20s delay, was found, showing that delay-dependent decay of spatial information in working memory occurs, but is time-limited and reverts significantly beyond delays of about 20s. These data (i) indicate temporal limits of spatial working memory and (ii) provide the first behavioural evidence for the existence of two parallely generated mental representations of space that successively control memory-guided behaviour in humans.

Adult↗
PubMed1999

Control of resolution and perception in working memory.

Mechanisms underlying and controlling resolution and perception in working memory are studied by means of a pulse-coupled network model. It is shown that the adaptivity, i.e. the degree to which previous activity affects the ability to fire, of the excitatory units can control several aspects of the network dynamics in a coordinated way to enable multiple items to be resolved and perceived in working memory. One basic aspect is the complexity of the dynamics that regulates the temporal resolution of several items. The slow NMDA-receptor-mediated component of synaptic couplings to excitatory units facilitates successive activations of a given item. The dimension of the activated subspace of the complete available neural representation space is gradually decreased as adaptivity is reduced. It is also shown that the formation of perception by sufficiently intense and coherent activation of different features of an object can be controlled concurrently with resolution by the adaptivity. The mechanisms derived can account for the observed capacity of working memory with respect to number of items consciously resolved and also for the observed temporal separation of different items. Numerous observations link neuromodulators to cognitive functions and to various brain disorders involving working memory. Based on the influence of various neuromodulators on neuronal adaptivity, the model can also account for neuromodulatory regulation of working memory functions.

Animals↗
PubMed2006

Working memory: linking capacity with selectivity.

Working memory is one of the most intensively studied psychological processes, but little is known about what distinguishes individuals in their working memory capacity. Recent evidence from electroencephalogram recordings suggests that one crucial component of this variation is our ability to exclude irrelevant information.

Electroencephalography↗
PubMed2005

Cerebellar damage produces selective deficits in verbal working memory.

The cerebellum is often active in imaging studies of verbal working memory, consistent with a putative role in articulatory rehearsal. While patients with cerebellar damage occasionally exhibit a mild impairment on standard neuropsychological tests of working memory, these tests are not diagnostic for exploring these processes in detail. The current study was designed to determine whether damage to the cerebellum is associated with impairments on a range of verbal working memory tasks, and if so, under what circumstances. Moreover, we assessed the hypothesis that these impairments are related to impaired rehearsal mechanisms. Patients with damage to the cerebellum (n = 15) exhibited a selective deficit in verbal working memory: spatial forward and backward spans were normal, but forward and backward verbal spans were lower than controls. While the differences were significant, digit spans were relatively preserved, especially in comparison to the dramatic reductions typically observed in classic 'short-term memory' patients with perisylvian brain damage. The patients tended to be more impaired on a verbal version compared to a spatial version of a working memory task with a long delay and this impairment was correlated with overall symptom and dysarthria severity. These results are consistent with a contribution of the cerebellum to rehearsal and suggest that inclusion of a delay before recall is especially detrimental in individuals with cerebellar damage. However, when we examined markers of rehearsal (i.e. word-length and articulatory suppression effects) in an immediate serial recall task, we found that qualitative aspects of the patients' rehearsal strategies were unaffected. We propose that the cerebellum may contribute to verbal working memory during the initial phonological encoding and/or by strengthening memory traces rather than by fundamentally subserving covert articulatory rehearsal.

Adult↗
PubMed2000

Distinguishing the functional roles of multiple regions in distributed neural systems for visual working memory.

We have investigated the human neural systems for visual working memory using functional magnetic resonance imaging to distinguish sustained activity during memory delays from transient responses related to perceptual and motor operations. These studies have identified six distinct frontal regions that demonstrate sustained activity during memory delays. These regions could be distinguished from brain regions in extrastriate cortex that participate more in perception and from brain regions in medial and lateral frontal cortex that participate more in motor control. Moreover, the working memory regions could be distinguished from each other based on the relative strength of their participation in spatial and face working memory and on the relative strength of sustained activity during memory delays versus transient activity related to stimulus presentation. These results demonstrate that visual working memory performance involves the concerted activity of multiple regions in a widely distributed system. Distinctions between functions, such as perception versus memory maintenance, or spatial versus face working memory, are a matter of the degree of participation of different regions, not the discrete parcellation of different functions to different modules.

Brain Mapping↗
PubMed2000

Distinguishing the functional roles of multiple regions in distributed neural systems for visual working memory.

We have investigated the human neural systems for visual working memory using functional magnetic resonance imaging to distinguish sustained activity during memory delays from transient responses related to perceptual and motor operations. These studies have identified six distinct frontal regions that demonstrate sustained activity during memory delays. These regions could be distinguished from brain regions in extrastriate cortex that participate more in perception and from brain regions in medial and lateral frontal cortex that participate more in motor control. Moreover, the working memory regions could be distinguished from each other based on the relative strength of their participation in spatial and face working memory and on the relative strength of sustained activity during memory delays versus transient activity related to stimulus presentation. These results demonstrate that visual working memory performance involves the concerted activity of multiple regions in a widely distributed system. Distinctions between functions, such as perception versus memory maintenance, or spatial versus face working memory, are a matter of the degree of participation of different regions, not the discrete parcellation of different functions to different modules.

Animals↗
PubMed2003

Age-related deficits in mice performing working memory tasks in a water maze.

This study determined whether mice exhibit spatial working memory deficits with increased age. C57BL/6JNia mice of 3 different ages were tested in the Morris water maze with 2 protocols designed to assess immediate and delayed working memory abilities. Young mice required multiple trials in order to show improvements in the working memory task. Deficits in immediate working memory were detected in both 10- and 24- to 26-month-old mice. Reference memory deficits and declines in performance in the delayed working memory task were only seen in 24- to 26-month-olds. This increased susceptibility of immediate working memory processes to the aging process in mice may be related to their need for more rehearsal in the water maze than other species.

Aging↗
PubMed2005

Spatial working memory and planning ability: contrasts between schizophrenia and bipolar I disorder.

Working memory may be conceptualized as a multi-component system involving the active maintenance and manipulation of stored information in the service of planning/guiding behaviour. Impaired spatial working memory is a robust finding in schizophrenia patients which has been related to an impairment in frontostriatal connectivity. The purpose of this study was to examine the specificity of this impairment by comparing the mnemonic and executive aspects of working memory performance in schizophrenia and bipolar disorder with psychotic features, focusing particularly on the functional dynamics between task components. Twenty-four patients with schizophrenia, 14 patients with bipolar I disorder (manic phase) and 33 healthy control subjects were assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB): including the spatial working memory (between search errors and strategy scores) spatial span (storage capacity) and spatial planning (Stockings of Cambridge: accuracy and latency) tasks. Both patient groups were impaired on the spatial span task, which requires the maintenance and retrieval of stored information. In contrast, only schizophrenia patients showed a significant deficit in between search errors, which requires both maintenance and manipulation of information in working memory. That is, they exhibited both a mnemonic and an executive dysfunction. Spatial span was particularly important to accurate planning ability in bipolar patients. In contrast, in patients with schizophrenia poor spatial working memory was a significant predictor of planning impairments, consistent with failures in goal selection, evaluation and/or execution. Furthermore, initial planning time was positively correlated with the latency to complete a planning sequence. This pattern of slow cognitive processing in schizophrenia patients only, resembled that reported previously in patients with basal ganglia disorders. These findings are discussed in terms of a possible common disturbance in fronto-parietal circuitry in the two disorders together with a specific disturbance of fronto-striatal circuitry in schizophrenia, that is not present in bipolar disorder.

Adult↗
PubMed2005

Cerebrocerebellar networks during articulatory rehearsal and verbal working memory tasks.

Converging evidence has implicated the cerebellum in verbal working memory. The current fMRI study sought to further characterize cerebrocerebellar participation in this cognitive process by revealing regions of activation common to a verbal working task and an articulatory control task, as well as regions that are uniquely activated by working memory. Consistent with our model's predictions, load-dependent activations were observed in Broca's area (BA 44/6) and the superior cerebellar hemisphere (VI/CrusI) for both working memory and motoric rehearsal. In contrast, activations unique to verbal working memory were found in the inferior parietal lobule (BA 40) and the right inferior cerebellum hemisphere (VIIB). These findings provide evidence for two cerebrocerebellar networks for verbal working memory: a frontal/superior cerebellar articulatory control system and a parietal/inferior cerebellar phonological storage system.

Adult↗
PubMed2006

Postural responses to specific types of working memory tasks.

Standing participants performed working memory tasks that varied along three dimensions: (1) type of information presented (verbal or visual); (2) the primary cognitive process engaged (encoding or rehearsal); and (3) interference that targeted the working memory components (phonological loop and visual sketchpad) believed primarily active during rehearsal. Postural sway variability decreased during rehearsal and increased during encoding. The effects during encoding, but not during rehearsal, differed for verbal versus visual material. Changes in cognitive activity were also associated with changes in the temporal patterns of postural sway. The results suggest postural control is sensitive to the type of cognitive task performed.

Adolescent↗
PubMedDate not supplied

Audiospatial and visuospatial working memory in 6-13 year old school children.

The neural processes subserving working memory, and brain structures underlying this system, continue to develop during childhood. We investigated the effects of age and gender on audiospatial and visuospatial working memory in a nonclinical sample of school-aged children using n-back tasks. The results showed that auditory and visual working memory performance improves with age, suggesting functional maturation of underlying cognitive processes and brain areas. The gender differences found in the performance of working memory tasks suggest a larger degree of immaturity in boys than girls at the age period of 6-10 yr. The differences observed between the mastering of auditory and visual working memory tasks may indicate that visual working memory reaches functional maturity earlier than the corresponding auditory system.

Age Factors↗
PubMed1998

Dissociation of mnemonic and perceptual processes during spatial and nonspatial working memory using fMRI.

Neuroimaging studies in humans have consistently found robust activation of frontal, parietal, and temporal regions during working memory tasks. Whether these activations represent functional networks segregated by perceptual domain is still at issue. Two functional magnetic resonance imaging experiments were conducted, both of which used multiple-cycle, alternating task designs. Experiment 1 compared spatial and object working memory tasks to identify cortical regions differentially activated by these perceptual domains. Experiment 2 compared working memory and perceptual control tasks within each of the spatial and object domains to determine whether the regions identified in experiment 1 were driven primarily by the perceptual or mnemonic demands of the tasks, and to identify common brain regions activated by working memory in both perceptual domains. Domain-specific activation occurred in the inferior parietal cortex for spatial tasks, and in the inferior occipitotemporal cortex for object tasks, particularly in the left hemisphere. However, neither area was strongly influenced by task demands, being nearly equally activated by the working memory and perceptual control tasks. In contrast, activation of the dorsolateral prefrontal cortex and the intraparietal sulcus (IPS) was strongly task-related. Spatial working memory primarily activated the right middle frontal gyrus (MFG) and the IPS. Object working memory activated the MFG bilaterally, the left inferior frontal gyrus, and the IPS, particularly in the left hemisphere. Finally, activation of midline posterior regions, including the cingulate gyrus, occurred at the offset of the working memory tasks, particularly the shape task. These results support a prominent role of the prefrontal and parietal cortices in working memory, and indicate that spatial and object working memory tasks recruit differential hemispheric networks. The results also affirm the distinction between spatial and object perceptual processing in dorsal and ventral visual pathways.

Adult↗
PubMed1991

The implications of congenital deafness for working memory.

A model of the working memory of the congenitally deaf was built based on Baddeley's model. Following an examination of the literature pertaining to encoding used by the congenitally deaf, I concluded that a model of the working memory of the deaf must include subsystems for articulatory, sign, and visual encoding. By highlighting the inherent flexibility of a model such as Baddeley's, the proposed model allows for applications to the deaf, other special, and hearing populations.

Deafness↗
PubMed2003

Short-term, delayed, and working memory are impaired during hypoglycemia in individuals with type 1 diabetes.

OBJECTIVE: To examine the effects of acute insulin-induced hypoglycemia on short-term, delayed, and working memory in individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS: A hyperinsulinemic glucose clamp was used to maintain arterialized blood glucose level at either 4.5 mmol/l (euglycemia) or 2.5 mmol/l (hypoglycemia) on two separate occasions in 16 adults with type 1 diabetes. The participants completed tests of immediate and delayed verbal memory, immediate and delayed visual memory, and working memory during each experimental condition. Two other mental tests, the Trail Making B Test and the Digit Symbol Test, were also administered. RESULTS: Performance in tests of immediate verbal and immediate visual memory was significantly impaired during hypoglycemia. The effect of hypoglycemia on working memory and delayed memory was more profound. Performance in the nonmemory tests, the Trail Making B Test, and the Digit Symbol Test also deteriorated during hypoglycemia. CONCLUSIONS: All of the memory systems examined in the present study were affected significantly by acute hypoglycemia, particularly working memory and delayed memory. Mild (self-treated) hypoglycemia is common in individuals with insulin-treated diabetes; therefore, these observed effects of hypoglycemia on memory are of potential clinical importance because they could interfere with many everyday activities.

Acute Disease↗
PubMed2003

Working memory and executive functions in transient global amnesia.

Transient global amnesia (TGA) is usually considered to produce a profound impairment of long-term episodic memory, while at the same time sparing working memory. However, this neuropsychological dissociation has rarely been examined in detail. While a few studies have assessed some components of working memory in TGA, the results that have been obtained are far from conclusive. To clarify this issue, we carried out a comprehensive investigation of working memory in 10 patients during a TGA attack. In the first study, we report the results from three patients examined with a battery of neuropsychological tests designed to assess each of the three subcomponents of Baddeley's model of working memory. In a second study, seven different patients underwent neuropsychological investigations that focused specifically on the central executive system, using a protocol derived from a study by Miyake and colleagues. Our findings showed that subcomponents of working memory, such as the phonological loop and visuo-spatial sketch pad, were spared in TGA patients. Specific executive functions that entailed inhibitory control, dual task performance, updating and shifting mechanisms were also found to be normal. However, we found significantly impaired performance for the Brown-Peterson test, and that TGA patients were significantly impaired in the recollection of their episodic memories. They also made reduced numbers of 'remember' compared with 'know' judgments in the episodic memory test several days after TGA. On the basis of our findings, it would appear that the episodic memory deficit during TGA is not related to elementary aspects of executive functioning. Our data also highlight the nature of the cognitive mechanisms involved in the Brown-Peterson task, which may well depend on long-term memory (such as the process of semantic encoding). Lastly, the selective deficit in recollective episodic memories observed in TGA may be principally related to medial temporal lobe abnormalities that have been reported in this syndrome.

Aged↗