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At least 613 records · Page 34Linked to original sources
PubMed1998

Cortical dysfunction in schizophrenia during auditory word and tone working memory demonstrated by functional magnetic resonance imaging.

BACKGROUND: Verbal learning and memory deficits are among the most severe cognitive deficits observed in schizophrenia. We have demonstrated that such deficits do not extend to working memory for tones in a substantial number of patients even when verbal working memory is impaired. In this study we used functional magnetic resonance imaging to study the neural basis of this dissociation of auditory verbal and nonverbal working memory in individuals with schizophrenia. METHODS: While undergoing functional magnetic resonance imaging, 12 schizophrenic patients and 12 matched control subjects performed auditory Word Serial Position Task and Tone Serial Position Task. RESULTS: Both tasks produced activation in frontal cortex and temporal and parietal lobes of the cerebrum in both groups. While robust activation was observed in the left inferior frontal gyrus (areas 6, 44, and 45) in the control group during the Word Serial Position Task, activation in the patient group was much reduced in these areas and failed to show the same task-specific activation as in controls. Reduced activation in patients was not confined to the inferior frontal gyrus, but also extended to a medial area during the Tone Serial Position Task and to premotor and anterior temporal lobe areas during both tasks. CONCLUSIONS: These findings support the hypothesis that abnormalities in cortical hemodynamic response in the inferior frontal gyrus underlie the verbal working memory deficit in schizophrenia. The relationship of verbal working memory deficits to other cognitive functions suggests that abnormal functioning in the speech-related areas may reflect a critical substrate of a broad range of cognitive dysfunctions associated with schizophrenia.

Adult↗
PubMed2002

Delay modulates spectral correlates in the human EEG of non-verbal auditory working memory.

Studies using neuroimaging and electro- and magnetoencephalographic techniques have begun to identify the brain structures and dynamics that underlie auditory working memory. However, past research has not clearly characterized how the neural dynamics varies with the delay over which auditory information must be maintained. We used electroencephalogram band power as a measure of relative neuronal synchrony during a non-verbal auditory working memory task. Comparing the working memory task with a control recognition task, the relative synchrony in bilateral theta and alpha bands was unchanged using a two second delay. However, five and ten second delays produced increases and decreases in relative synchrony, respectively. The memory task also induced greater synchronization in beta and gamma bands over the right temporal cortex during the two and five second delays. The results suggest that the cortical dynamics that underlie auditory working memory are highly dependent upon a duration-dependent encoding strategy.

Acoustic Stimulation↗
PubMed2000

Processing speed, working memory, and IQ: a developmental model of cognitive deficits following cranial radiation therapy.

IQ decrements following cranial radiation therapy (CRT) for acute lymphoblastic leukemia (ALL) are most apparent years after treatment. The authors examined a developmental model for delayed deficits by evaluating the relationship between processing speed, working memory, and IQ in long-term survivors of childhood ALL (n = 27) compared with demographically matched controls (n = 27). The ALL group treated with CRT showed deficits in IQ, working memory, and processing speed relative to controls. Differences in IQ between the CRT group and controls were mediated by differences in working memory. Processing speed did not fully account for the working memory deficit in the CRT group. Participants with ALL treated only with chemotherapy showed similar working memory and processing speed as matched controls. Data suggest that deficits in processing speed and working memory following CRT may underlie declines in IQ.

Adolescent↗
PubMed2004

Time constraints and resource sharing in adults' working memory spans.

This article presents a new model that accounts for working memory spans in adults, the time-based resource-sharing model. The model assumes that both components (i.e., processing and maintenance) of the main working memory tasks require attention and that memory traces decay as soon as attention is switched away. Because memory retrievals are constrained by a central bottleneck and thus totally capture attention, it was predicted that the maintenance of the items to be recalled depends on both the number of memory retrievals required by the intervening treatment and the time allowed to perform them. This number of retrievals:time ratio determines the cognitive load of the processing component. The authors show in 7 experiments that working memory spans vary as a function of this cognitive load.

Adult↗
PubMed1997

Reflection of working memory: ERP mnemonic effects.

The study of working memory often utilizes a delayed matching to sample paradigm (DMS). Typically in the matching condition, the test and sample stimuli are identical, raising the possible confound of retinotopic projections for the matching stimuli in contrast to the non-matching stimuli. In the present study, 65 healthy subjects performed a modified delayed matching to sample task while monitoring their ERP waveforms. The stimuli consisted of 60 different sample stimuli (S1) and 60 different test stimuli (S2). Half of the S2s were complementary to the sample stimuli (Fit), the other half of the S2s were not complementary (Nonfit). After S2, the subjects pressed one of the buttons to indicate whether the test stimulus fits the sample stimulus. Our statistical results indicated that the ERPs to sample stimuli differed from the ERPs to test stimuli from 200 ms poststimulus to the end of the recording epoch. The ERPs to fitting stimuli were significantly different from those to non-fitting stimuli from 200 to 400 ms poststimulus. The ERP patterns in the present study may reflect ERP mnemonic effect for working memory. Our results ruled out the retinotopic confound as a potential mediator variable, and are in agreement with other animal or human neurophysiological studies on memory.

Adult↗
PubMedDate not supplied

Effects of neuromodulation in a cortical network model of object working memory dominated by recurrent inhibition.

Experimental evidence suggests that the maintenance of an item in working memory is achieved through persistent activity in selective neural assemblies of the cortex. To understand the mechanisms underlying this phenomenon, it is essential to investigate how persistent activity is affected by external inputs or neuromodulation. We have addressed these questions using a recurrent network model of object working memory. Recurrence is dominated by inhibition, although persistent activity is generated through recurrent excitation in small subsets of excitatory neurons. Our main findings are as follows. (1) Because of the strong feedback inhibition, persistent activity shows an inverted U shape as a function of increased external drive to the network. (2) A transient external excitation can switch off a network from a selective persistent state to its spontaneous state. (3) The maintenance of the sample stimulus in working memory is not affected by intervening stimuli (distractors) during the delay period, provided the stimulation intensity is not large. On the other hand, if stimulation intensity is large enough, distractors disrupt sample-related persistent activity, and the network is able to maintain a memory only of the last shown stimulus. (4) A concerted modulation of GABA(A) and NMDA conductances leads to a decrease of spontaneous activity but an increase of persistent activity; the enhanced signal-to-noise ratio is shown to increase the resistance of the network to distractors. (5) Two mechanisms are identified that produce an inverted U shaped dependence of persistent activity on modulation. The present study therefore points to several mechanisms that enhance the signal-to-noise ratio in working memory states. These mechanisms could be implemented in the prefrontal cortex by dopaminergic projections from the midbrain.

Action Potentials↗
PubMed2002

The synchronization of the human cortical working memory network.

A verbal reasoning problem at the intersection of verbal working memory, problem-solving, and language comprehension was examined using event-related fMRI to distinguish differences in the differential timing of the response of the various cortical regions that compose the working memory network. Problems were developed such that the process demand as well as the timing of the manipulation of the contents of working memory (i.e., a demanding computation) was varied. Activation was observed in several regions including the dorsolateral prefrontal cortex, the inferior frontal gyrus, and the parietal lobe. Examination of the MR amplitude response revealed that the regions do not all activate simultaneously; instead, their activation time courses reveal differential responses that correspond to their theoretical processing role in the problem-solving task. The coordination of cortical area responses reveals how the various cortical regions synchronize and collaborate in order to accomplish a given cognitive function.

Adult↗
PubMed2005

Functional connectivity reveals load dependent neural systems underlying encoding and maintenance in verbal working memory.

One of the main challenges in working memory research has been to understand the degree of separation and overlap between the neural systems involved in encoding and maintenance. In the current study we used a variable load version of the Sternberg item recognition test (two, four, six, or eight letters) and a functional connectivity method based on constrained principal component analysis to extract load-dependent neural systems underlying encoding and maintenance, and to characterize their anatomical overlap and functional interaction. Based on the pattern of functional connectivity, constrained principal component analysis identified a load-dependent encoding system comprising bilateral occipital (Brodmann's area (BA) 17, 18), bilateral superior parietal (BA 7), bilateral dorsolateral prefrontal (BA 46), and dorsal anterior cingulate (BA 24, 32) regions. For maintenance, in contrast, constrained principal component analysis identified a system that was characterized by both load-dependent increases and decreases in activation. The structures in this system jointly activated by maintenance load involved left posterior parietal (BA 40), left inferior prefrontal (BA 44), left premotor and supplementary motor areas (BA 6), and dorsal cingulate regions (BA 24, 32), while the regions displaying maintenance-load-dependent activity decreases involved bilateral occipital (BA 17, 18), posterior cingulate (BA 23) and rostral anterior cingulate/orbitofrontal (BA 10, 11, 32) regions. The correlation between the encoding and maintenance systems was strong and negative (Pearson's r = -.55), indicting that some regions important for visual processing during encoding displayed reduced activity during maintenance, while subvocal rehearsal and phonological storage regions important for maintenance showed a reduction in activity during encoding. In summary, our analyses suggest that separable and complementary subsystems underlie encoding and maintenance in verbal working memory, and they demonstrate how constrained principal component analysis can be employed to characterize neuronal systems and their functional contributions to higher-level cognition.

Adolescent↗
PubMed2003

[Reading comprehension and working memory: structural equation modeling approach].

We examined the relationship among intelligence, working memory, and reading comprehension using structural equation modeling (SEM). Ninety-six participants were instructed to perform two reading comprehension tests and six cognitive tasks: two verbal intelligence subtests, two spatial intelligence subtests, and two reading span tasks. Three latent variables that were called verbal ability, spatial ability, and working memory were derived from the six cognitive tasks. SEM demonstrated that the latent variables of working memory and verbal ability contribute to reading comprehension, suggesting that central executive functioning related to attention control was mediated among these cognitive abilities.

Adolescent↗
PubMed2003

Gamma oscillations correlate with working memory load in humans.

Functional imaging of human cortex implicates a diverse network of brain regions supporting working memory - the capacity to hold and manipulate information for short periods of time. Although we are beginning to map out the brain networks supporting working memory, little is known about its physiological basis. We analyzed intracranial recordings from two epileptic patients as they performed a working memory task. Spectral analyses revealed that, in both patients, gamma (30-60 Hz) oscillations increased approximately linearly with memory load, tracking closely with memory load over the course of the trial. This constitutes the first evidence that gamma oscillations, widely implicated in perceptual processes, support the maintenance of multiple items in working memory.

Brain Mapping↗
PubMed1992

Schizophrenics show spatial working memory deficits.

The present study demonstrates that schizophrenics are impaired on spatial delayed-response tasks, analogous to those that have been used to assess the working memory function of the dorsolateral prefrontal cortex in rhesus monkeys. Schizophrenic patients and two control groups, normal subjects and bipolar psychiatric patients, were tested on the oculomotor version of the memory task, a haptic version of the same task, and two control tasks: a sensory task that did not require working memory and a digit span test. The schizophrenic patients showed marked deficits relative to the two control groups in both the oculomotor and haptic delayed-response tasks. They were not, however, impaired on the digit span test, which taps verbal working memory as well as voluntary attention, and on the sensory control task, in which their responses were guided by external cues rather than by spatial working memory. These findings provide direct evidence that schizophrenics suffer a loss in representational processing and that this deficit is modality independent. These data on spatial working memory add to the growing evidence for involvement of the dorsolateral prefrontal cortex in schizophrenic disease.

Adult↗
PubMed2002

Attenuation of working memory and spatial acquisition deficits after a delayed and chronic bromocriptine treatment regimen in rats subjected to traumatic brain injury by controlled cortical impact.

Cognitive impairments are pervasive and persistent sequelae of human traumatic brain injury (TBI). In vivo models of TBI, such as the controlled cortical impact (CCI) and fluid percussion (FP), are utilized extensively to produce deficits reminiscent of those seen clinically with the hope that empirical study will lead to viable therapeutic interventions. Both CCI and FP produce spatial learning acquisition deficits, but only the latter has been reported to impair working memory in rats tested in the Morris water maze (MWM). We hypothesized that a CCI injury would impair working memory similarly to that produced by FP, and that delayed and chronic treatment with the D2 receptor agonist bromocriptine would attenuate both working memory and spatial learning acquisition deficits. To test these hypotheses, isoflurane-anesthetized adult male rats received either a CCI (2.7 mm deformation, 4 m/sec) or sham injury, and 24 h later were administered bromocriptine (5 mg/kg, i.p.) or vehicle, with continued daily injections until all behavioral assessments were completed. Motor function was assessed on beam balance and beam walking tasks on postoperative days 1-5 and cognitive function was evaluated in the MWM on days 11-15 for working memory (experiment 1) and on days 14-18 for spatial learning acquisition (experiment 2). Histological examination (hippocampal CA1 and CA3 cell loss/survival and cortical lesion volume) was conducted 4 weeks after surgery. All injured groups exhibited initial impairments in motor function, working memory, and spatial learning acquisition. Bromocriptine did not affect motor function, but did ameliorate working memory and significantly attenuated spatial acquisition deficits relative to the injured vehicle-treated controls. Additionally, the injured bromocriptine-treated group exhibited significantly more morphologically intact CA3 neurons than the injured vehicle-treated group (55.60 +/- 3.10% vs. 38.34 +/- 7.78% [p = 0.03]). No significant differences were observed among TBI groups in CA1 cell survival (bromocriptine, 40.26 +/- 4.74% vs. vehicle, 29.13 +/- 6.63% [p = 0.14]) or cortical lesion volume (bromocriptine, 17.78 +/- 0.62 mm3 vs. vehicle, 19.01 +/- 1.49 mm3 [p > 0.05]). These data reveal that CCI produces working memory deficits in rats that are similar to those observed following FP, and that the delayed and chronic bromocriptine treatment regimen conferred cognitive and neural protection after TBI.

Animals↗
PubMed1998

Concurrent activation of hippocampal glycine and polyamine sites of the N-methyl-D-aspartate receptor synergistically reverses working memory deficits in rats.

Intrahippocampal administration of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (0.18 microg/side) significantly increased the number of errors in the working memory task with a three-panel runway setup. The increase in working memory errors by intrahippocampal MK-801 was significantly attenuated by concurrent infusion of D-cycloserine (1.0 microg/side) or spermidine (10 microg/side), agonists of the glycine and polyamine modulatory sites on the NMDA receptor/channel complex, respectively. Combined injection of the behaviorally ineffective doses of 0.1 microg/side D-cycloserine and 0.32 microg/side spermidine synergistically reduced intrahippocampal MK-801-induced increase in working memory errors. The combination of D-cycloserine and spermidine also synergistically attenuated the increase in working memory errors resulting from intrahippocampal injection of the muscarinic acetylcholine receptor antagonist scopolamine (3.2 microg/side). These results suggest that positive modulation of the NMDA receptor/channel through activation of the glycine and polyamine sites can synergistically compensate deficiency of hippocampal NMDA and muscarinic receptor-mediated neurotransmission involved in working memory function.

Animals↗
PubMed1992

Interference in memory for tonal pitch: implications for a working-memory model.

The degree of interference caused by different kinds of stimuli on memory for tonal pitch was studied. Musically trained and untrained subjects heard a sequence of two tones separated by an interval of 5 sec. The tones were either identical in pitch or differed by a semitone. Subjects had to decide whether the tones were identical or not. The interval was filled with tonal, verbal, or visual material under attended and unattended conditions. The results revealed clear group differences. Musically trained subjects' retention of the first test tone was only affected by the interposition of other tones. In contrast, the performance of musically untrained subjects was also affected by verbal and visual items. The findings are discussed in the framework of Baddeley's (1986) working-memory model.

Adult↗
PubMed2006

Mechanisms underlying working memory for novel information.

In this Opinion article we describe a theory that the brain mechanisms underlying working memory for novel information include a buffer in parahippocampal cortices. Computational modeling indicates that mechanisms for maintaining novel information in working memory could differ from mechanisms for maintaining familiar information. Electrophysiological data suggest that the buffer for novel information depends on acetylcholine. Acetylcholine activates single-cell mechanisms that underlie persistent spiking of neurons in the absence of synaptic transmission, allowing maintenance of information without prior synaptic modification. fMRI studies and lesion studies suggest that parahippocampal regions mediate working memory for novel stimuli, and the effects of cholinergic blockade impair this function. These intrinsic mechanisms in parahippocampal cortices provide an important alternative to theories of working memory based on recurrent synaptic excitation.

Acetylcholine↗
PubMed1997

The alpha-1 adrenergic agonist, cirazoline, impairs spatial working memory performance in aged monkeys.

The alpha-1 adrenergic agonist, cirazoline, was examined for effects on spatial working memory performance in aged rhesus monkeys. Cirazoline has additional high affinity for imidazoline receptors and has good brain penetrance when administered systemically. Spatial working memory was assessed using the variable delayed response task, a test dependent upon prefrontal cortical function in monkeys. Low doses of cirazoline (0.00001-0.001 mg/kg) impaired delayed response performance significantly. This impairment did not appear to result from nonspecific changes in behavior, because cirazoline had no significant effect on performance of control trials where the delay was "0" s, and had no significant effect on behavioral ratings. Impairment was reversed by pretreatment with the alpha-1 adrenergic antagonist, prazosin, consistent with drug actions at alpha-1 adrenergic receptors. In contrast, preliminary data suggest that higher cirazoline doses (0.001-0.01 mg/kg) occasionally produced improved performance that was not reversed by prazosin, but rather, by the imidazoline/alpha-2 adrenergic antagonist, idazoxan. The finding that alpha-1 adrenergic receptor stimulation impairs spatial working memory performance complements previous research demonstrating that alpha-2 adrenergic receptor stimulation improves working memory, and suggests that norepinephrine may have opposing actions at alpha-1 vs. alpha-2 receptors in the prefrontal cortex as it does in the hypothalamus and thalamus.

Adrenergic alpha-1 Receptor Agonists↗
PubMed2005

Directing spatial attention in mental representations: Interactions between attentional orienting and working-memory load.

Orienting spatial attention to locations in the extrapersonal world has been intensively investigated during the past decades. Recently, it was demonstrated that it is also possible to shift attention to locations within mental representations held in working memory. This is an important issue, since the allocation of our attention is not only guided by external stimuli, but also by their internal representations and the expectations we build upon them. The present experiment used behavioural measures and event-related functional magnetic resonance imaging to investigate whether spatial orienting to mental representations can modulate the search and retrieval of information from working memory, and to identify the neural systems involved, respectively. Participants viewed an array of coloured crosses. Seconds after its disappearance, they were cued to locations in the array with valid or neutral cues. Subsequently, they decided whether a probe stimulus was presented in the array. The behavioural results indicated that orienting of spatial attention within working memory attenuates the well-known effect of decreasing performance when memory load is increased. So "internal" spatial orienting seems to highlight information or facilitate search within working memory, which leads to advantages in retrieval. Imaging enabled the separation of brain areas supporting spatial orienting functions from those sensitive to working-memory load. Orienting of spatial attention to the contents of working memory activated posterior parietal cortex bilaterally, the insula, and lateral and medial frontal cortices.

Adult↗
PubMed1994

Working-memory capacity and reading comprehension in young and older adults.

This study investigates the role of working-memory capacity in reading comprehension in young and older subjects. A task yielding separate measures for processing and storage components was used to assess working-memory capacity. A French version of the Nelson-Denny test was administered as a measure of abilities that underlie reading comprehension. In the working-memory task, recall performances were lower in older subjects. Nevertheless, the intercorrelations suggested that the age-related impairment was probably linked to the processing component. Mean scores on the reading-comprehension test did not differ between groups. However, scores were correlated with processing time on the working-memory task in younger subjects, but with storage capacity in older subjects.

Adult↗