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PubMed2006

Evidence for a double dissociation between spatial-simultaneous and spatial-sequential working memory in visuospatial (nonverbal) learning disabled children.

The paper describes the performance of three children with specific visuospatial working memory (VSWM) impairments (Study 1) and three children with visuospatial (nonverbal) learning disabilities (Study 2) assessed with a battery of working memory (WM) tests and with a number of school achievement tasks. Overall, performance on WM tests provides evidence of a double dissociation between spatial-simultaneous processes, underpinning the memorization item positioning in a spatial configuration, and spatial-sequential processes, which allow memorization of the presentation order. In both groups of children of the two studies, a selective impairment either on spatial-sequential or on spatial-simultaneous working memory tasks was observed. These data support the existence of -simultaneous and -sequential modality-dependent processes in visuospatial working memory and confirm the importance of distinguishing between different subtypes of visuospatial (nonverbal) learning-disabled children.

Child↗

PubMedDate not supplied

A neural model of working memory processes in normal subjects, Parkinson's disease and schizophrenia for fMRI design and predictions.

A computational model was previously developed to investigate the role of parallel basal ganglia-thalamocortical loops in solving tasks that rely on working memory. Different lesions are applied to the model in order to investigate the working memory deficits observed in Parkinson's disease and schizophrenia. The simulations predict that the working memory deficits observed in Parkinson's disease result from a local dysfunction within the brain due to a problem in the disinhibitory process arising from the basal ganglia. They also predict that the working memory deficits observed in schizophrenia involve many cortical and subcortical areas and result from a problem in selecting items in working memory which are stored in basal ganglia-thalamocortical loops. The simulations predict the temporal unfolding of neuronal activity in different brain regions, both in the normal case and in the two disease states. A specific event-related functional magnetic resonance imaging study was elaborated to test some of those predictions.

Basal Ganglia↗

PubMed2004

Brain activation patterns associated with working memory in relapsing-remitting MS.

BACKGROUND: Patients with multiple sclerosis (MS) show changes in brain activation patterns during visual and motor tasks that include decreases in the typical local network for a function and increases in other brain regions. OBJECTIVE: To determine whether brain activation patterns associated with working memory are affected by MS. METHODS: Activation of working memory circuitry was examined using an fMRI n-back task in adults with mild relapsing-remitting MS (RRMS; n = 10) and demographically matched healthy controls (n = 10). RESULTS: Group differences in brain activation emerged during both low- and high-demand conditions (p < 0.001). Overall, patients showed less activation than controls in core prefrontal and parietal regions of working memory circuitry, and greater activation in other regions within and beyond typical working memory circuitry, including bilateral medial frontal, cingulate, parietal, bilateral middle temporal, and occipital regions. CONCLUSIONS: Relative to controls, patients with mild RRMS showed shifts in brain activation patterns within and beyond typical components of working memory circuitry.

Adult↗

PubMed2000

Prolonged reaction time to a verbal working memory task predicts increased power of posterior parietal cortical activation.

We used multislice functional magnetic resonance imaging (fMRI) to investigate the association between behavioral and neurophysiological measures of working memory task performance in 20 right-handed male healthy volunteers. Images were acquired over a 5-min period at 1.5 Tesla. We used a periodic design, alternating 30-s blocks of the "n-back" working memory task with 30-s blocks of a sensorimotor control task to activate verbal working memory systems. The power of functional response to the task was estimated by sinusoidal regression at each voxel. The relationship between power of fMRI response and mean reaction time over all 11 working memory trials was explored by multiple regression, with age and mean reaction time to the control task as covariates, at voxel and regional levels of analysis. All subjects were able to perform the n-back task accurately. A spatially distributed network was activated, including dorsolateral prefrontal cortex, inferior frontal gyrus, lateral premotor cortex, and supplementary motor area (SMA) in the frontal lobes. More posteriorly, there were major foci of activation in parietal and occipitoparietal cortex, precuneus, lingual, and fusiform gyri of the ventral occipital lobe, inferior temporal gyrus, and cerebellum. The power of functional response was positively correlated with reaction time in bilateral posterior parietal cortex (Talairach coordinates in x, y, z (mm) 35, -44, 37 and -32, -56, 42), indicating that subjects who found the task difficult, and responded with a slower reaction time, tended to activate these regions more powerfully. One interpretation of this regionally specific relationship between prolonged reaction time and increased power of posterior parietal activation is consistent with prior studies identifying similar areas of parietal cortex as the site of the phonological storage function in verbal working memory.

Adult↗

PubMed2006

Working memory capacity and a notorious brain teaser: the case of the Monty Hall Dilemma.

The Monty Hall Dilemma (MHD) is an intriguing example of the discrepancy between people's intuitions and normative reasoning. This study examines whether the notorious difficulty of the MHD is associated with limitations in working memory resources. Experiment 1 and 2 examined the link between MHD reasoning and working memory capacity. Experiment 3 tested the role of working memory experimentally by burdening the executive resources with a secondary task. Results showed that participants who solved the MHD correctly had a significantly higher working memory capacity than erroneous responders. Correct responding also decreased under secondary task load. Findings indicate that working memory capacity plays a key role in overcoming salient intuitions and selecting the correct switching response during MHD reasoning.

Adolescent↗

PubMed2005

Reversal of clozapine effects on working memory in rats with fimbria-fornix lesions.

Clozapine is an effective antipsychotic drug, but its effects on cognitive function are unclear. Previously, we found that clozapine caused a working memory deficit, which was reversed by nicotine. Hippocampal systems are important in determining clozapine effect on memory. In the current study, the memory effects of clozapine and nicotine administration were determined in rats with lesions of the fimbria-fornix, a fiber bundle which carries cholinergic and other projections between the septum and the hippocampus. Female Sprague-Dawley rats were trained on a win-shift procedure in the radial-arm maze, in which each arm entry was rewarded once per session. Then, 13 rats received bilateral knife-cut lesions of the fimbria-fornix, while 14 rats underwent sham surgery. The rats were tested after subcutaneous injections with combinations of clozapine (0 and 1.25 mg/kg) and nicotine (0, 0.2, and 0.4 mg/kg). In sham-operated rats, clozapine caused a significant (P<0.005) working memory impairment. Fimbria-fornix lesions also caused a significant (P<0.05) memory impairment. Interestingly, clozapine had the opposite effect on working memory in the lesioned vs sham-operated rats. In contrast to its effects in controls, clozapine (1.25 mg/kg) significantly (P<0.05) attenuated the working memory deficit caused by fimbria-fornix lesions. Nicotine (0.2 mg/kg) did not quite significantly improve memory in lesioned rats. The effects of clozapine and nicotine were not additive in the lesioned rats. This study demonstrates the efficacy of clozapine in improving working memory in fimbria-fornix-lesioned rats, whereas it causes impairments in intact rats. Therapeutic treatment with clozapine in people with malfunctions of the hippocampus such as seen in schizophrenia may improve cognitive performance, whereas the same doses of clozapine may impair memory in individuals without hippocampal malfunction.

Animals↗

PubMed2005

The impact of clinical depression on working memory.

INTRODUCTION: Both Channon, Baker, and Robertson (1993) and Hartlage, Alloy, Vazquez, and Dykman (1993) claim that working memory impairment in depressed patients is limited to Baddeley's (1996) central executive and does not affect either the phonological loop or the visuospatial scratchpad. Our key questions were: (1) is there an impairment of working memory in depression and which elements does it effect; (2) is another major clinical group also affected and in what ways, and finally, (3) how do these groups vary when compared with each other and with normals? Thus we sought to locate a depression-specific effect and define its extent. METHODS: We tested 35 depressed patients, using both 24 anxiety patients and 29 normal controls as comparisons. Several tasks were used so that we could differentiate between the three key aspects of working memory. RESULTS: Contrary to Channon et al., we found that depression affects the allocation of attention and all elements of working memory. The depression group showed a distinct performance profile, with impairments occurring on measures of both the phonological loop and visuospatial sketch pad. On measures of central executive functioning, both depression and anxiety groups showed comparable levels of impairment when compared with the control group. CONCLUSIONS: We propose that the source of general disruption in both depressed and anxious patients may be a competition between attempts to direct attentional resources to the task in hand and away from the distractive and intrusive effects of automatic negative thoughts.

Journal Article↗

PubMed2002

[A neuro-psychological test (T-K-W test) for dementia based on working memory theory and item-response theory: its development and construction].

The purpose of the present study was to develop a new neuro-psychological test for evaluating the severity of dementia based on the newly-developed theory of working memory. In Study I, twelve candidate test items, including experimental tasks used in our previous developmental studies and test items newly developed for this study, were administered to twenty four demented patients. In Study II, the same twelve test items as used in Study I were administered to eighteen normative-aged volunteers to identify the baseline of difficulty of each test item. The normative-aged group, in marked contrast to the demented group, responded correctly to nearly all of these items. These items, therefore, proved to have a discriminating power between dementia patients and normative-aged. After examining thoroughly the result of factor analysis of test scores, the difficulty of the items, and the feasibility and communicability of instructions for each item, the authors finally chose five items to construct the test. Four of these five items were ones originally developed by ourselves. In Study III, the final version of the test composed of the above five items was administered to one hundred demented patients of various etiologies. The test scores were analyzed according to the method of principal factor analysis and the theory of working memory. The results of factor analysis showed the factor pattern of a typical homogeneous test that measures a single dimension of working memory capacity. The authors, therefore, decided to apply to the test scores an item-response theory that postulates test homogeneity as a prerequisite. Based on this theory, parameters of discrimination and difficulty of each item were estimated. In addition, the scale value of each examinee, i.e. working memory capacity, was estimated from his or her response pattern to the items. When the administration of the whole test is difficult in a clinical setting, this theory makes it possible to estimate the scale value of an examinee from even a single item, though inevitably with lower reliability. Owing to the adaptability of this test, its practical utility as a measurement tool was much improved. Further, the test items and their subitems were analyzed in terms of the theory of working memory. The resulting high agreement between item difficulty and working memory demand confirmed the validity of the theoretical analysis. In addition, the result of discriminant analysis with thirty-one subitem scores of five items showed that the test discriminated correctly 79.3% of DAT and VD.

Aged↗

PubMed1997

Ventral prefrontal cortex is not essential for working memory.

It is widely held that the prefrontal cortex is important for working memory. It has been suggested that the inferior convexity (IC) may play a special role in working memory for form and color (). We have therefore assessed the ability of monkeys with IC lesions to perform visual pattern association tasks and color-matching tasks, both with and without delay. In experiment 1, six monkeys were trained on a visual association task with delays of up to 2 sec. Conservative IC lesions that removed lateral area 47/12 in three animals had no effect on the task. Further experiments showed that these lesions had no effect on the postoperative new learning of a color-matching task with delays of up to 2 sec or versions of the visual association task involving delays of up to 8 sec. In experiment 2, larger lesions of both areas 47/12 and 45A were made in the three control animals. This lesion caused a profound deficit in the ability to relearn simultaneous color matching, but subsequent matching with delays of up to 8 sec was clearly unimpaired. We suggest that the IC may be more important for stimulus selection and attention as opposed to working memory.

Animals↗

PubMed2002

No spatial working memory deficit in beta-amyloid-exposed rats. A longitudinal study.

Two experiments are described assessing whether long-term intraventricular or intrahippocampal administration of beta-amyloid protein 1-40 (beta A1-40) affects spatial working memory in rats monitored in a longitudinal study using the open-field water maze. A delayed matching-to-position procedure (DMTP) was employed in which platform locations were semi-randomly altered between days but were kept constant over the four trials on each day. Intertrial intervals (ITIs) were either 30 s or 1 h between Trials 1 and 2 (all other intervals = 30 s), with Trial 2 performance being an index for spatial working memory. Animals were trained before and tested repeatedly at various intervals after application of various compounds (see below) in five successive test sessions (TSs). In Experiment 1, beta A1-40 was applied after a challenge with long-term oral exposure to aluminium (Al; as 0.1% sulfate in drinking water). This in itself did not affect spatial working memory at any delay, despite of the more than 6 months of intake. beta A1-40 administered alone via intracerebroventricular (icv) minipumps (20 micrograms in 250 microliters) led to a small increase in latencies to find the platform, which recovered to control levels 3 months after minipumps were exhausted. Application of beta A1-40 in Al-exposed animals led to a subtle and progressive decline in working memory. This deterioration was reversed by the nootropic compound nefiracetam, which had no effect on the Al only group. In Experiment 2, well-trained rats were bilaterally implanted with intra-hippocampal minipumps containing beta A1-40 or reverse sequence beta A40-1. This did not impair spatial working memory in the DMTP task, measured either directly after minipumps were exhausted, or 2 weeks later. When intraperitoneally (i.p.) injected with a low concentration of the muscarinic antagonist scopolamine (0.2 mg/kg), a dose that was not effective alone, animals in the beta A1-40 group were amnesic. These data suggest that intra-hippocampal beta A1-40 administration alters cholinergic transmission, but these alterations may be mild and thus do not lead to obvious working memory deficits in a DMTP task in well-trained animals.

Administration, Oral↗

PubMed1988

Activation of the hippocampus and dentate gyrus by working-memory: a 2-deoxyglucose study of behaving rhesus monkeys.

The 2-deoxyglucose method was used to examine metabolic activity in the hippocampus, dentate gyrus, and amygdala of rhesus monkeys performing working-memory and control tasks. A working-memory group was tested on 1 of 3 tasks requiring trial-by-trial updating of information: delayed spatial response, delayed spatial alternation, or delayed object alternation. A control group was tested either on an associative memory problem, visual pattern discrimination, or a sensory-motor task that did not have an explicit mnemonic component. Local cerebral glucose utilization (LCGU) in specific layers of the dentate gyrus and the CA1 and CA3 sectors of the hippocampus, as well as in 7 distinct nuclei of the amygdala, was measured and compared across groups. Metabolic rate in specific layers of the dentate gyrus and the CA3 and CA1 fields of the hippocampus was enhanced in the working-memory compared with the control group: LCGU was between 18 and 24% higher in the granule cell and molecular layers of the dentate gyrus and in the molecular and radiatum layers of CA1 and CA3 in the hippocampus. In contrast, no significant group differences in LCGU were found for any of the 7 amygdaloid nuclei examined: the lateral, lateral basal, medial basal, accessory basal, cortical, central, and medial nuclei. These results are consistent with previous evidence showing that lesions of the hippocampus affect memory selectively, producing deficits on some memory problems while sparing others. Our findings further suggest that working-memory may be a common denominator among those tasks that are sensitive to hippocampal damage in monkeys. The contribution of the amygdala to performance on memory tasks, on the other hand, appears to be independent of the specific type of memory process that is engaged.

Amygdala↗

PubMed2005

Duration of cats' (Felis catus) working memory for disappearing objects.

This study explored the duration of cats' working memory for hidden objects. Twenty-four cats were equally divided into four groups, which differed according to the type of visual cues displayed on and/or around the hiding boxes. During eight sessions, the four groups of cats were trained to locate a desirable object hidden behind one of the four boxes placed in front of them. Then, the cats were tested with retention intervals of 0, 10, 30 and 60 s. Results revealed no significant differences between the groups during training or testing. In testing, the cats' accuracy to locate the hidden object rapidly declined between 0 and 30 s but remained higher than chance with delays of up to 60 s. The analysis of errors also indicated that the cats searched as a function of the proximity of the target box and were not subjected to intertrial proactive interference. This experiment reveals that the duration of cats' working memory for disappearing objects is limited and the visual cues displayed on and/or around the boxes do not help the cats to memorize a hiding position. In discussion, we explore why the duration of cats' working memory for disappearing objects rapidly declined and compare these finding with those from domestic dogs. The irrelevance of visual cues displayed on and around the hiding boxes on cats' retention capacity is also discussed.

Animals↗

PubMed2001

Basal ganglia dysfunction, working memory, and sentence comprehension in patients with Parkinson's disease.

To investigate the role of the basal ganglia in working memory and sentence comprehension, 14 patients with Parkinson's disease (PD) were administered experimental measures of semantic and phonological working memory, and a measure of sentence comprehension, while receiving dopaminergic medications and after a period of withdrawal from these medications. An age- and education- matched control group (N=14) received the same measures. Comparison with control subjects revealed deficits in patients with PD in sentence processing regardless of medication status, but no deficits in working memory. In contrast to previous studies, withdrawal of dopaminergic medications had no significant impact on task- related working memory functions or on sentence comprehension. Results suggest that basal ganglia dysfunction does not solely account for sentence comprehension deficits seen in PD.

Aged↗

PubMed1984

Hippocampal afterdischarge interferes with storage of spatial information in a working memory test.

In an attempt to impair spatial working memory by reversible functional blockade rather than by irreversible lesion of the hippocampus, eight male hooded rats were trained to asymptotic performance of 1.2 to 1.4 errors per trial in the spatial 12-choice apparatus ( Bure s et al. 1982), formally similar to the radial maze. The rats were implanted with hippocampal stimulating and recording electrodes, which were used for eliciting and monitoring hippocampal afterdischarge (HAD) lasting for at least 20 s. In Experiment 1, HAD elicited 1 or 10 min before testing increased the incidence of errors to 2.75 or 2.50 per trial, respectively, but the performance still remained above chance level (4.18). In Experiment 2, interruption of the trial by 1, 10, 20 and 30 min intervals inserted between choices 6 and 7 increased the incidence of errors in choices 7 to 12 to 1.0, 1.5, 2.1 and 2.5, respectively. HAD elicited immediately after choice 6 increased error incidence in the subsequent 6 choices performed after 1-min or 10-min intervals to 3.1 or 2.75, respectively, i.e. to the chance level of 3 errors in 6 choices. It is concluded that HAD elicits transient shortening of the memory span for newly acquired spatial information (anterograde effect) and erases the current spatial working memory record (retrograde effect).

Action Potentials↗

PubMed2003

Signal strength determines the nature of the relationship between perception and working memory.

Neurophysiological and behavioral studies have shown that perception and memory share neural substrates and functional properties. But are perception and the active working memory of a stimulus one and the same? To address this question in the spatial domain, we compared the percept and the working memory of the position of a target stimulus embedded within a surround of moving dots. Motion in a particular direction after the target's offset biased the memory of target location in the same direction. However, motion simultaneous with a high-contrast, perceptually strong target biased the percept of target location in the opposite direction. Thus, perception and working memory can be modified by motion in qualitatively different ways. Manipulations to strengthen the memory trace had no effect on the direction of the memory bias, indicating that memory signal strength can never equal that of the percept of a strong stimulus. However, the percept of a weak stimulus was biased in the direction of motion. Thus, although perception and working memory are not inherently different, they can differ behaviorally depending on the strength of the perceptual signal. Understanding how a changing surround biases neural representations in general, and postsensory processes in particular, can help one understand past reports of spatial mislocalization.

Computer Simulation↗

PubMed2003

Spatial, object, and affective working memory in social anhedonia: an exploratory study.

The domain-specificity of working memory was examined in psychosis-prone individuals with elevated social anhedonia scores. A group of individuals with deviant scores on the revised Social Anhedonia Scale (n=43) were compared with a normal control group (n=39) on delayed match-to-sample tasks involving spatial, identity, and affective information. The social anhedonia group performed less well on the spatial and emotion delayed match-to-sample tasks relative to the normally hedonic group. The two groups did not differ in terms of their performance on the identity delayed match-to-sample task. Although the social anhedonia group reported less positive affect, greater negative affect, and more alexithymic tendencies relative to the control group, there were no significant associations between these personality traits and working memory performance. In summary, the findings suggest that poorer working memory performance is not domain-specific in socially anhedonic individuals. The authors conclude that the socially anhedonic group's relatively poor performance on the emotion delayed match-to-sample task reflects difficulty and/or inefficiency in handling cognitively taxing tasks.

Adolescent↗

PubMed1986

The effects of hippocampal lesions upon spatial and non-spatial tests of working memory.

A series of experiments examined the proposal that the primary effect of hippocampal damage in rats is to disrupt working memory. Although extensive hippocampal lesions produced a severe impairment in forced-choice alternation--a test of spatial working memory--the same lesions did not impair the acquisition of a non-spatial test of working memory--delayed non-matching-to-sample. This test of object recognition required the rats to select that arm in a Y-maze which contained unfamiliar stimuli. Rats with hippocampal lesions were able to learn and perform this task at normal rates, even with retention delays of as long as 60 s. Two additional experiments helped confirm that the animals had indeed learnt a non-spatial test of working memory. The final experiment examined whether hippocampal lesions resulted in an increased sensitivity to proactive interference. It was found that repetition of test stimuli within a session, which increased interference, did attenuate recognition performance but there was no evidence that the animals with hippocampal lesions were differentially affected.

Animals↗

PubMed2005

Remembered duration: working memory and the reproduction of intervals.

On the basis of attention allocation models of time estimation, the role of working memory in prospective duration reproduction is explored. In four experiments, adult participants performed a counting task (duration, 400 sec) that allowed coordinative and sequential demands on working memory to be varied. After completing the counting task, the participants reproduced the time that they had worked on this task It emerged that (1) increased coordinative demands on working memory (but not increased sequential demands) reduced the accuracy of prospective duration reproduction (Experiments 1 and 2), (2) presenting context information during the reproduction phase enhanced the accuracy of the reproduced duration (Experiment 3), and (3) individual differences in coordinative working memory capacity affected duration reproduction in the same direction as the experimental manipulation of coordinative task demands (Experiment 4). The results suggest that attention allocation models of time estimation may benefit from taking a more differentiated view of the types of attentional demands that affect temporal cognition.

Adolescent↗