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PubMed1999

Verbal working memory deficit in Parkinson's disease subjects.

The aim of the present work was to evaluate verbal working memory in patients affected by Parkinson's disease (PD). In particular, tests that explore the functionality of the Articulatory Loop and of the Central Executive during verbal tasks were given. PD patients displayed normal phonological similarity, word length and word frequency effects in a Word span task, thus demonstrating adequate retention capacity of the phonological store, normal functioning of the articulatory rehearsal mechanism and a normal contribution of lexical-semantic knowledge to verbal immediate recall. In the Brown-Peterson task, PD patients showed abnormal performance decay on the letter recall task when articulatory rehearsal was inhibited by a serial subtraction concurrent task. These data provide evidence for normal functioning of the Articulatory Loop in PD patients. However, when the verbal recall task is more attention demanding, PD patients show deficient performance levels, presumably due to depleted processing resources by the Central Executive.

Adult↗
PubMedDate not supplied

Does strategy knowledge influence working memory in children with mathematical disabilities?

This study investigated the relationship between working memory (WM), declarative strategy knowledge, and math achievement in children with and without mathematical disabilities (MD). Experiment 1 examined the relationship between strategy knowledge, verbal WM, and visual-spatial WM in children with MD as a function of initial, gain, and maintenance conditions. The results showed that after partialing the influence of reading, stable strategy choices rather than specific strategy knowledge was related to verbal and visual-spatial WM span in high demand (maintenance) conditions. Experiment 2 compared children with MD to a group of chronological age-matched children and a group of math ability-matched children on the same conditions as Experiment 1. Age-matched children's verbal and visual-spatial WM performance was superior to that of children with MD, whereas WM performance was statistically comparable between children with MD and younger children matched on math ability. The selection of expert strategies was related to high WM span scores in the initial conditions. After controlling for reading achievement in a regression analysis, verbal and visual-spatial WM, stable verbal strategy choices, and expert strategy choices related to visual-spatial processing all contributed independent variance to math achievement. Overall, these results suggest that WM and math achievement are related to strategy knowledge.

Aptitude↗
PubMed1996

Contrasting effects of fetal CA1 and CA3 hippocampal grafts on deficits in spatial learning and working memory induced by global cerebral ischaemia in rats.

Functional effects of fetal hippocampal field grafts were assessed in rats with spatial learning and memory impairments following global cerebral ischaemia. Experiment 1 examined effects of grafts dissected from fields CA1 and CA3 at embryonic day 19 and from the dentate gyrus at postnatal day 1. Cell suspensions (15,000 cells/site) were implanted bilaterally at two points above the dorsal CA1 area two weeks after four-vessel occlusion (electrocoagulation of the vertebral arteries followed the 24 h later by occlusion of the carotid arteries for 15 min). Histological examination showed that CA1 neuronal loss (60-70%) was equivalent in all ischaemic groups and that 80% of CA1 and 60% of CA3 grafts survived and were sited appropriately in the alveus or corpus callosum above the area of ischaemic CA1 damage in the host, but there was no survival of dentate grafts. Results from rats with poor pyramidal cell graft survival were excluded, but those from rats with non-surviving dentate grafts were retained as an additional control group. Acquisition in the water maze was examined nine and 25 weeks after transplantation, and spatial working memory was assessed in three-door runway and water maze matching-to-position tasks 19 and 28 weeks after grafting, respectively. For water maze acquisition rats were trained with two trails/day and a 10 min inter-trial interval for 10-12 days to locate a submerged platform. Ischaemic rats with CA1 grafts learned the platform position as rapidly as non-ischaemic controls, searched appropriately in the training quadrant and were accurate in heading towards the platform, but were initially impaired on recall of the precise platform position on probe trials with the platform removed. Performance of ischaemic controls and groups with CA3 and non-surviving dentate graft groups was significantly impaired relative to controls and to the CA1 grafted group. The CA1 grafted group was also as successful as controls in matching-to-position in the water maze and substantially superior to the other ischaemic groups, assessed using three trials/day, with a 30-s inter-trial interval and a different platform position on each day. In a more complex matching-to-position task in the three-door runway, the performance of the CA1 grafted group was significantly impaired relative to controls, although superior to that of the other ischaemic control and graft groups. Functional recovery with CA1, but not CA3, grafts in ischaemic rats was replicated in a second experiment which assessed water maze acquisition and working memory at 10 and 14 weeks after transplantation, in rats with 90% graft survival. These results indicate that long-lasting, task-dependent improvements can be seen in ischaemic rats with CA1 fetal grafts in both aversively and appetitively motivated spatial learning tasks. The findings suggest that functional recovery requires homotypic replacement of CA1 cells damaged by ischaemia, rather than provision of structurally similar glutamate-releasing CA3 pyramidal cells.

Animals↗
PubMed2007

Aging, focus switching, and task switching in a continuous calculation task: evidence toward a new working memory control process.

This study examined switching of the focus of attention in working memory in relation to global task switching in a continuous calculation task using two rules (midpoint and up-and-down) in a group of 25 younger adults and a group of 23 older adults. Age differences emerged in accuracy when participants worked on two strings simultaneously (necessitating a focus switch); focus switching did not interact with age in the response time domain. No age differences were obtained for global task switching. Ex-Gaussian decomposition showed a shift due to focus switching in all parameters, but a shift in leading edge only for task switching. The results suggest that task switching and focus switching rely on different processes, and that there is a specific age-related deficit in focus switching.

Adolescent↗
PubMedDate not supplied

Prenatal phenytoin exposure and spatial navigation in offspring: effects on reference and working memory and on discrimination learning.

Previous research has shown that rats exposed to phenytoin (PHT) in utero demonstrate abnormal circling, decreased learning, hyperactivity, and delayed air righting reflex development. The effects of prenatal PHT on offspring learning have been found on multiple-T mazes (Biel and Cincinnati types) and on spatial navigation (Morris maze). However, the specificity of the latter effects is unknown. Herein, we tested the effects of prenatal PHT in a Morris maze using six different procedures: cued versus spatial reference memory-based learning, cued versus spatial working memory-based learning, and cued versus spatial discrimination learning. PHT-exposed offspring showed increased preweaning mortality, growth reduction, and abnormal circling as noted in previous studies. PHT offspring were separated into those exhibiting circling and those not. PHT noncircling offspring demonstrated impaired reference memory-based spatial learning (acquisition and reversal), but no other effects. By contrast, PHT circling offspring demonstrated not only impaired reference memory-based spatial learning, but also impaired cued platform learning, impaired spatial discrimination, and impaired working memory-based learning. These data confirm that prenatal PHT induces a specific reference memory-based spatial learning deficit even in asymptomatic (noncircling) offspring that is distinct from the impairment induced in littermates exhibiting the circling impairment.

Analysis of Variance↗
PubMed1999

Working memory is more sensitive than declarative memory to the acute effects of corticosteroids: a dose-response study in humans.

The effects of various doses (40 microg/kg/hr, 300 microg/kg/hr, 600 microg/kg/hr or placebo) of hydrocortisone on tasks assessing working and declarative memory function were measured in 4 groups of 10 young men. During the infusion, participants were given an item-recognition working memory task, a paired-associate declarative memory task, and a continuous performance task used to control possible concomitant effects of corticosteroids on vigilance. The results revealed significant acute effects of the highest dose of hydrocortisone on working memory function, without any significant effect on declarative memory function or arousal-vigilance performance. These results suggest that working memory is more sensitive than declarative memory to the acute elevations of corticosteroids, which could explain the detrimental effects of corticosteroids on acquisition and consolidation of information, as reported in the literature.

Adrenocorticotropic Hormone↗
PubMed2003

Spatio-temporal working-memory and short-term object-location tasks use different memory mechanisms.

Spatial short-term memory for objects' locations was investigated in a spatial relocation task. During maintenance, dynamic visual noise or spatial tapping were administered as visual or spatial secondary tasks, respectively. Because memory for location should tap the visual component of working memory, a visual but not a spatial secondary task should impair location memory. In fact, neither of the tasks impaired memory (Experiment 1), although the expected dissociation between visual and spatial components was clearly confirmed for a spatio-temporal main task (Corsi test) (Experiment 2). We then contrasted location memory for pictures of objects and of nonsense figures under visual interference. Real objects were relocated much better than nonsense figures, and visual noise was again ineffective (Experiment 3). When spatial tapping was combined with the same material (Experiment 3a), again no influence on memory for locations of objects was observed and only a small influence on remembering nonsense figures. We suggest that the Corsi and the relocation VSWM-tasks use different memory mechanisms. The configuration of objects is reconstructed from perceptual records in an episodic buffer, provided by the same structures that enable visual memory after longer intervals. Rehearsal is not necessary for the persistence of these traces. In contrast, in the Corsi task remembering, a temporal sequence across homogeneous locations needs spatio-temporal marking and therefore active rehearsal of the locations by shifting spatial attention. A spatially demanding secondary task during retention interrupts this rehearsal.

Adult↗
PubMed1983

Specific reading retardation and working memory: a review.

Research into the memory deficit of retarded readers is examined within a working memory framework. Although much of the evidence in this area is confusing, there is fairly consistent evidence that reading retardation can be associated with a deficit in long-term storage of phonological information. This deficit may affect retarded readers' ability to utilize the articulatory loop, a short-term store which appears to play an important role in certain aspects of normal reading acquisition. On the other hand, there is fairly consistent evidence that retarded readers perform normally at storing non-verbal information and the semantic aspects of verbal information in long-term memory. Problems with current research strategies are discussed and suggestions for future research directions are made.

Attention↗
PubMed2001

A neural correlate of working memory in the monkey primary visual cortex.

The brain frequently needs to store information for short periods. In vision, this means that the perceptual correlate of a stimulus has to be maintained temporally once the stimulus has been removed from the visual scene. However, it is not known how the visual system transfers sensory information into a memory component. Here, we identify a neural correlate of working memory in the monkey primary visual cortex (V1). We propose that this component may link sensory activity with memory activity.

Animals↗
PubMed1995

Concurrent blockade of beta-adrenergic and muscarinic receptors disrupts working memory but not reference memory in rats.

In order to clarify the interactions between monoaminergic and cholinergic systems in working and reference memory functions, the effects of administration of the alpha, beta-adrenergic, D1-, D2-dopaminergic or serotonergic receptor antagonist together with the muscarinic receptor antagonist scopolamine on this behavior were examined using a three-panel runway task. Both in working and reference memory tasks, the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) was significantly increased by 0.32 mg/kg scopolamine, but not by the doses up to 0.18 mg/kg. The beta-adrenergic antagonist propranolol at 10 mg/kg had no effect on the number of working memory errors. Combined administration of 10 mg/kg propranolol and scopolamine at 0.1 and 0.18 mg/kg significantly increased the number of working memory errors. However, in a reference memory task, propranolol at 10 mg/kg did not affect the number of errors, whether administered alone or together with 0.1 mg/kg scopolamine. Other monoaminergic receptor antagonists, including the alpha-adrenergic antagonist phentolamine (3.2 and 10 mg/kg), D1-antagonist SCH23390 (0.032 and 0.056 mg/kg). D2-antagonist sulpiride (100 mg/kg) and serotonin antagonist cinanserin (10 and 32 mg/kg) had no significant effect on working or reference memory errors, whether they were administered independently or in combination with scopolamine at 0.1 mg/kg. These results suggest that beta-adrenergic/muscarinic interactions play an important role in mediating processes involved in working memory performance of rats.

Adrenergic beta-Antagonists↗
PubMed1989

In vivo modulation of septo-hippocampal cholinergic activity in mice: relationships with spatial reference and working memory performance.

Dopaminergic afferents to the septum mediate a tonic and trans-synaptic inhibitory control on the cholinergic neurones of the septo-hippocampal pathway. Lesion of these afferents using 6-hydroxydopamine (6-OHDA) results in a chronic and specific increase of hippocampal cholinergic activity in mice. The consequence of this in vivo modulation of hippocampal cholinergic activity on the acquisition of both a spatial discrimination and a working memory (delayed non-matching to place) task in an 8-arm radial maze by C57BL/6 mice were investigated. Combined neurochemical and behavioural analyses revealed significant correlations between hippocampal sodium-dependent high-affinity choline uptake activation induced by testing and performance measures. In the first experiment 6-OHDA-treated mice compared to control and vehicle-injected mice showed a transient (day 2) but significant facilitation of their spatial discrimination performance which appears to be better related to the working but not to the reference memory component of the task. This hypothesis is strengthened by the results of the second experiment which shows an amelioration of working memory performance when the septo-hippocampal cholinergic pathway is specifically activated in vivo.

Afferent Pathways↗
PubMed2000

Practice-related functional activation changes in a working memory task.

The effects of practice on the functional anatomy of a visuospatial working memory (VSWM) task were studied using functional Magnetic Resonance Imaging (fMRI). Functional imaging was conducted as subjects completed a moderate (Experiment 1) or extensive (Experiment 2) amount of practice on a delayed-match-to-sample task. While improvement in task performance was seen with practice, the task's dependence upon VSWM did not change. Activations in frontal (inferior, middle, and precentral gyri and superior frontal sulcus), parietal (intra-parietal sulcus, inferior parietal lobule, and precuneus) and cingulate (anterior and posterior) regions were observed as were bilateral insular and occipital activations. With the exception of the posterior cingulate, practice produced activation decreases in these regions, thus providing little evidence for a re-organization of the functional neuroanatomy. Fewer regions passing statistical criteria were observed at the end of practice relative to early in practice. Regions that were lost were mostly posterior (occipital and precuneus) but also included the left middle frontal gyrus, left precentral gyrus, and right insula suggesting that a more precise VSWM functional map can be observed once processes specific to encountering a novel task are removed. Little further activation changes were observed after extensive practice. These results suggest, minimally, that practice effects should be considered so as to avoid incorrectly attributing functional activation to a cognitive process of interest. Further, these data show that the dynamics of functional change can be tracked while a task is being learned and as an important cognitive process becomes more skilled.

Adult↗
PubMed1997

A parametric study of prefrontal cortex involvement in human working memory.

Although recent neuroimaging studies suggest that prefrontal cortex (PFC) is involved in working memory (WM), the relationship between PFC activity and memory load has not yet been well-described in humans. Here we use functional magnetic resonance imaging (fMRI) to probe PFC activity during a sequential letter task in which memory load was varied in an incremental fashion. In all nine subjects studied, dorsolateral and left inferior regions of PFC were identified that exhibited a linear relationship between activity and WM load. Furthermore, these same regions were independently identified through direct correlations of the fMRI signal with a behavioral measure that indexes WM function during task performance. A second experiment, using whole-brain imaging techniques, both replicated these findings and identified additional brain regions showing a linear relationship with load, suggesting a distributed circuit that participates with PFC in subserving WM. Taken together, these results provide a "dose-response curve" describing the involvement of both PFC and related brain regions in WM function, and highlight the benefits of using graded, parametric designs in neuroimaging research.

Adolescent↗
PubMed1999

Load-dependent roles of frontal brain regions in the maintenance of working memory.

Brain imaging studies have suggested a critical role for prefrontal cortex in working memory (WM) tasks that require both maintainenance and manipulation of information over time in delayed-response WM tasks. In the present study, functional magnetic resonance imaging (fMRI) was used to examine whether prefrontal areas are activated when only maintenance is required in a delayed-response WM task, without the overt requirement to manipulate the stored information. In two scans, six subjects performed WM tasks in which, on each trial, they (1) encoded 1, 3, or 6 to-be-remembered letters, (2) maintained these letters across a 5-second unfilled delay, and (3) determined whether a single probe letter was or was not part of the memory set. Activation of left caudal inferior frontal gyrus was observed, relative to the 1-letter task, when subjects were required to maintain 3 letters in WM. When subjects were required to maintain 6 letters in WM, additional prefrontal areas, most notably middle and superior frontal gyri, were activated bilaterally. Thus, increasing the amount of to-be-maintained information, without any overt manipulation requirement, resulted in the recruitment of wide-spread frontal-lobe regions. Inferior frontal gyrus activation was left-hemisphere dominant in both the 3- and 6-letter conditions, suggesting that such activation reflected material-specific verbal processes. Activation in middle and superior frontal gyri appeared only in the 6-letter condition and was right-hemisphere dominant, suggesting that such activation reflected material-independent executive processes.

Adult↗
PubMed1991

The competitive NMDA antagonist AP5, but not the non-competitive antagonist MK801, induces a delay-related impairment in spatial working memory in rats.

Rats were trained to alternate responses on a discrete trial working memory task on a T-maze. In Experiment 1, the rats were then matched for choice accuracy and allocated to three treatment groups. These were: implantation of osmotic minipumps for intraventricular infusion of either (a) 15 mM D-2-amino-5-phosphonopentanoic acid (AP5) or (b) artificial cerebrospinal fluid (VEH); and an unoperated control group (UNOP). In Phase 1 we assessed alternation performance with a minimal delay between responses: the UNOP and VEH rats continued to choose accurately; the AP5 rats showed an impairment of choice accuracy, but recovered over days. In Phase 2 a 20-s delay between responses was enforced, and choice accuracy was assessed following injections either of saline or of Milacemide HCl (10 mg/kg). There was now a severe and enduring impairment of choice accuracy in the AP5 group, but Milacemide injections did not affect performance in any of the treatment groups. In Experiment 2 rats were trained in a similar way, and then given intraperitoneal injections of MK801 or of physiological saline in a within-subjects design and tested for T-maze performance with a minimal or a 20-s delay between responses. In the first Phase, MK801 was given 10-min before behavioural testing commenced; in the second Phase, it was given 28-40 min before behavioural testing commenced. The outcome depended critically on the time between drug injection and testing. There was a significant drug-induced impairment of choice accuracy in both Phases; but in Phase 1 there was no impairment in testing with a minimal retention interval and an impairment with a 20-s retention both retention intervals. We conclude that AP5, but not MK801, interferes with temporary memory storage in a delay-dependent manner.

2-Amino-5-phosphonovalerate↗
PubMed2005

Neuropsychological evidence for separating components of visuo-spatial working memory.

There is increasing evidence to support the idea that visuo-spatial working memory can be segregated into separate cognitive subsystems. However, the nature of these systems remains unclear. In this paper we report data from two brain injured patients suggesting that information about visual appearance is retained in a different subsystem from information about spatial location, and that this differential processing can be observed when the style of presentation (sequential or simultaneous) is controlled.

Adolescent↗
PubMed2002

Duration of dogs' (Canis familiaris) working memory in search for disappearing objects.

Two experiments explored the duration of dogs' working memory in an object permanence task: a delay was introduced between the disappearance of a moving object behind a box and the beginning of the search by the animal. In experiment 1, the dogs were tested with retention intervals of 0, 10, 30, and 60 s. Results revealed that the dogs' accuracy declined as a function of the length of the retention interval but remained above chance for each retention interval. In experiment 2, with new subjects, longer retention intervals (0, 30, 60, 120, and 240 s) were presented to the dogs. Results replicated findings from experiment 1 and revealed that the dogs' accuracy remained higher than chance level with delays up to 240 s. In both experiments, the analysis of errors also showed that the dogs searched as a function of the proximity of the target box and were not subject to intertrial proactive interference. In the discussion, we explore different alternatives to explain why dogs' search behaviour for hidden objects decreased as a function of the retention intervals.

Animals↗
PubMed2005

Pattern of impaired working memory during major depression.

BACKGROUND: The aim of this study was to assess working memory (WM) in patients with major depressive disorder (MDD), using a robust parametric WM task (the n-back task). METHODS: Twenty patients with MDD and twenty healthy controls completed a visual version of the paradigm, comprising four levels of task difficulty (i.e. 0-, 1-, 2-, and 3-back). Performance accuracy and reaction time (RT) were measured at each difficulty level. RESULTS: In comparison with controls, patients with MDD exhibited slower RTs (F((1,38)) = 25.16, p < 0.001), and reduced accuracy (F((1,38)) = 5.93, p < 0.001). There was no diagnosis-specific effect of task difficulty on performance accuracy. However, the faster response to memory (1-3-back) than to shadowing (0-back) tasks observed in controls was not as pronounced in patients. CONCLUSIONS: These observations support a relatively specific impairment of WM/central executive function in MDD, which may potentially mediate the diverse pattern of cognitive dysfunction noted in MDD. The parametric n-back task is applicable to subjects with MDD and yields results interpretable across the dimensions of task difficulty and performance in controls and patients.

Adult↗