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PubMed1999

Schizophrenic subjects activate dorsolateral prefrontal cortex during a working memory task, as measured by fMRI.

BACKGROUND: Neuroimaging studies of schizophrenic subjects performing working memory (WM) tasks have demonstrated a relative hypoactivity of prefrontal cortex compared with normal subjects. METHODS: Using functional magnetic resonance imaging (fMRI), we compared dorsolateral prefrontal cortex (DLPFC) activation in 12 schizophrenic and 10 normal subjects during rewarded performance of a WM task. Subjects performed a modified version of the Sternberg Item Recognition Paradigm (SIRP), a continuous performance, choice reaction time (RT) task that requires WM. We compared a high WM load condition with a nonWM choice RT condition and with a low WM load condition. RESULTS: Schizophrenic subjects performed the tasks better than chance but worse than normal subjects. They showed greater activation than normal subjects in the left DLPFC but did not differ in the right DLPFC or in the control region. In the schizophrenic group, left DLPFC activation was inversely correlated with task performance, as measured by errors. CONCLUSIONS: These findings contrast with previous studies that demonstrated task-related hypofrontality in schizophrenia. Task parameters that may contribute to this difference are discussed. We hypothesize that the performance and activation differences we observed are also manifestations of prefrontal dysfunction in schizophrenia. They reflect inefficient functioning of the neural circuitry involved in WM.

Adult↗
PubMed2002

Age and skilled performance: contributions of working memory and processing speed.

In this study, we examined the interrelationships among age, working memory (WM), processing speed, and the development of skilled performance. Younger (M=20.5) and older (M=68.9) adults were trained on an alphabet arithmetic task (Haider & Frensch, 1996) administered across three consecutive days. Although older adults were slower than younger adults, both age groups' response latencies decreased as a result of practice. Contrary to expectations, WM and processing speed were significantly correlated with performance late in training. Partial correlations suggested that age differences in performance at the end of training were mediated by individual differences in cognitive processing speed.

Adult↗
PubMed2000

Functional neuroanatomy of spatial working memory in children.

Functional magnetic resonance imaging (fMRI) was used to examine spatial working memory in 8- to 11-year-old children tested under three conditions. In the visual condition, children were asked to examine the location of a dot on a screen. In the motor condition, children were instructed to push a button that corresponded to the location of a dot presented on a screen. In the memory condition, children were asked to remember the location of a dot presented 1 or 2 trials previously. Subtracting the activation of the motor condition from the memory condition revealed activity in the dorsal aspects of the prefrontal cortex and in the posterior parietal and anterior cingulate cortex. These findings were also obtained in the analysis of the memory minus visual conditions except that motor cortex activation was also observed. These findings parallel those reported in comparable studies of adults and suggest that fMRI may be a useful means of examining function-structure relations in developmental populations.

Adult↗
PubMed2001

A controlled-attention view of working-memory capacity.

In 2 experiments the authors examined whether individual differences in working-memory (WM) capacity are related to attentional control. Experiment 1 tested high- and low-WM-span (high-span and low-span) participants in a prosaccade task, in which a visual cue appeared in the same location as a subsequent to-be-identified target letter, and in an antisaccade task, in which a target appeared opposite the cued location. Span groups identified targets equally well in the prosaccade task, reflecting equivalence in automatic orienting. However, low-span participants were slower and less accurate than high-span participants in the antisaccade task, reflecting differences in attentional control. Experiment 2 measured eye movements across a long antisaccade session. Low-span participants made slower and more erroneous saccades than did high-span participants. In both experiments, low-span participants performed poorly when task switching from antisaccade to prosaccade blocks. The findings support a controlled-attention view of WM capacity.

Adult↗
PubMed1992

Daily glucose injections facilitate performance of a win-stay water-escape working memory task in mice.

In an experiment that compared 3 versions of a working memory task, male C57BL/6 mice given either 3 (n = 7) or 5 (n = 7) opportunities (test runs) per trial to choose the escape choice section of a maze acquired a win-stay (spatial matching-to-sample) water-escape task. Mice given only 1 test run per trial (n = 6) were unable to perform above chance level. In a 2nd experiment, 14 mice from the 1st experiment were tested for performance on the 3-test-run version of the task. Each mouse was tested for 12 consecutive days with each of 4 doses of glucose (0, 50, 100, & 250 mg/kg ip) given 30 min before testing. The two higher doses increased the percentage of correct test run choices on all 3 daily test runs across the 12 days of testing. Daily glucose injections facilitated the use of trial-dependent information.

Animals↗
PubMed2006

The time course of consolidation in visual working memory.

How long does it take to form a durable representation in visual working memory? Several theorists have proposed that this consolidation process is very slow. Here, we measured the time course of consolidation. Observers performed a change-detection task for colored squares, and shortly after the presentation of the first array, pattern masks were presented at the locations of each of the colored squares to disrupt representations that had not yet been consolidated. Performance on the memory task was impaired when the delay between the colored squares and the masks was short, and this effect became larger when the number of colored squares was increased. The rate of consolidation was approximately 50 ms per item, which is considerably faster than previous proposals.

Adolescent↗
PubMed2003

Theoretical implications of articulatory duration, phonological similarity, and phonological complexity in verbal working memory.

The phonological-loop model provides a prominent theoretical description of verbal working memory. According to it, serial recall accuracy should be inversely related to the articulatory duration and phonological similarity of verbal items in memorized sequences. Initial tests of these predictions by A. D. Baddeley and colleagues (e.g., A. D. Baddeley, N. Thomson, & M. Buchanan, 1975) appeared to support the phonological-loop model, but subsequent researchers have obtained conflicting data that putatively disconfirm its assumptions. Such conflicts may have stemmed from less than ideal measurements of articulatory duration and phonological similarity. This article discusses these concerns and proposes new theoretically principled methods for measuring articulatory duration and phonological similarity. Two experiments that used these methods in the context of a verbal serial recall task are reported. The results of these experiments confirm and extend the predictions of the phonological-loop model while disarming previous criticisms of it.

Adult↗
PubMed2002

Temporal structure in neuronal activity during working memory in macaque parietal cortex.

Many cortical structures have elevated firing rates during working memory, but it is not known how the activity is maintained. To investigate whether reverberating activity is important, we studied the temporal structure of local field potential (LFP) activity and spiking from area LIP in two awake macaques during a memory-saccade task. Using spectral analysis, we found spatially tuned elevated power in the gamma band (25-90 Hz) in LFP and spiking activity during the memory period. Spiking and LFP activity were also coherent in the gamma band but not at lower frequencies. Finally, we decoded LFP activity on a single-trial basis and found that LFP activity in parietal cortex discriminated between preferred and anti-preferred direction with approximately the same accuracy as the spike rate and predicted the time of a planned movement with better accuracy than the spike rate. This finding could accelerate the development of a cortical neural prosthesis.

Action Potentials↗
PubMed2004

Directed forgetting in working memory: age-related differences.

This study explored the effects of ageing on working memory by means of the directed forgetting procedure designed by Reed (1970). Memory for a letter trigram was compared in conditions where it was either presented alone (single-item), or followed by a second trigram to be recalled (interference), or followed by a second trigram to be forgotten (directed forgetting). The results clearly indicated that elderly participants inhibited the no-longer-relevant information less efficiently (recall in the single-item condition - recall in the directed forgetting condition), as predicted by the model of Hasher and Zacks (1988). However, the results also demonstrated that sensitivity to interference (recall in the single-item condition - recall in the interference condition) increased in the condition in which no inhibition was directly required.

Adult↗
PubMed2002

Rapid distributed fronto-parieto-occipital processing stages during working memory in humans.

Cortical potentials were recorded from implanted electrodes during a difficult working memory task requiring rapid storage, modification and retrieval of multiple memoranda. Synchronous event-related potentials were generated in distributed occipital, parietal, Rolandic and prefrontal sites beginning approximately 130 ms after stimulus onset and continuing for >500 ms. Coherent phase-locked, event-related oscillations supported interaction between these dorsal stream structures throughout the task period. The Rolandic structures generated early as well as sustained potentials to sensory stimuli in the absence of movement. Activation peaks and phase lags between synaptic populations suggested that perceptual processing occurred exclusively in the visual association cortex from approximately 90 to 130 ms, with its results projected to fronto-parietal areas for interpretation from approximately 130 to 280 ms. The direction of interaction then appeared to reverse from approximately 300 to 400 ms, consistent with mental arithmetic being performed by fronto-parietal areas operating upon a visual scratch pad in the dorsolateral occipital cortex. A second reversal, from approximately 420 to 600 ms, may have represented an updating of memoranda stored in fronto-parietal sites. Lateralized perisylvian oscillations suggested an articulatory loop. Anterior cingulate activity was evoked by feedback signals indicating errors. These results indicate how a fronto-centro-parietal 'central executive' might interact with an occipital visual scratch pad, perisylvian articulatory loop and limbic monitor to implement the sequential stages of a complex mental operation.

Adolescent↗
PubMed2006

Brain activity related to working memory and distraction in children and adults.

In order to retain information in working memory (WM) during a delay, distracting stimuli must be ignored. This important ability improves during childhood, but the neural basis for this development is not known. We measured brain activity with functional magnetic resonance imaging in adults and 13-year-old children. Data were analyzed with an event-related design to isolate activity during cue, delay, distraction, and response selection. Adults were more accurate and less distractible than children. Activity in the middle frontal gyrus and intraparietal cortex was stronger in adults than in children during the delay, when information was maintained in WM. Distraction during the delay evoked activation in parietal and occipital cortices in both adults and children. However, distraction activated frontal cortex only in children. The larger frontal activation in response to distracters presented during the delay may explain why children are more susceptible to interfering stimuli.

Adolescent↗
PubMed2007

Working memory specific activity in auditory cortex: potential correlates of sequential processing and maintenance.

Working memory (WM) tasks involve several interrelated processes during which past information must be transiently maintained, recalled, and compared with test items according to previously instructed rules. It is not clear whether the rule-specific comparisons of perceptual with memorized items are only performed in previously identified frontal and parietal WM areas or whether these areas orchestrate such comparisons by feedback to sensory cortex. We tested the latter hypothesis by focusing on auditory cortex (AC) areas with low-noise functional magnetic resonance imaging in a 2-back WM task involving frequency-modulated (FM) tones. The control condition was a 0-back task on the same stimuli. Analysis of the group data identified an area on right planum temporale equally activated by both tasks and an area on the left planum temporale specifically involved in the 2-back task. A region of interest analysis in each individual revealed that activation on the left planum temporale in the 2-back task positively correlated with the task performance of the subjects. This strongly suggests a prominent role of the AC in 2-back WM tasks. In conjunction with previous findings on FM processing, the left lateralized effect presumably reflects the complex sequential processing demand of the 2-back matching to sample task.

Adult↗
PubMed1999

Isodirectional tuning of adjacent interneurons and pyramidal cells during working memory: evidence for microcolumnar organization in PFC.

Studies on the cellular mechanisms of working memory demonstrated that neurons in dorsolateral prefrontal cortex (dPFC) exhibit directionally tuned activity during an oculomotor delayed response. To determine the particular contributions of pyramidal cells and interneurons to spatial tuning in dPFC, we examined both individually and in pairs the tuning properties of regular-spiking (RS) and fast-spiking (FS) units that represent putative pyramidal cells and interneurons, respectively. Our main finding is that FS units possess spatially tuned sensory, motor, and delay activity (i. e., "memory fields") similar to those found in RS units. Furthermore, when recorded simultaneously at the same site, the majority of neighboring neurons, whether FS or RS, displayed isodirectional tuning, i.e., they shared very similar tuning angles for the sensory and delay phases of the task. As the trial entered the response phase of the task, many FS units shifted their direction of tuning and became cross-directional to adjacent RS units by the end of the trial. These results establish that a large part of inhibition in prefrontal cortex is spatially oriented rather than being untuned and simply regulating the threshold response of pyramidal cell output. Moreover, the isodirectional tuning between adjacent neurons supports a functional microcolumnar organization in dPFC for spatial memory fields similar to that found in other areas of cortex for sensory receptive fields.

Action Potentials↗
PubMed1995

Individual differences in working memory strategies for reading expository text.

This study investigated whether individual differences in working memory (WM) span are associated with different WM management strategies during the reading of expository text. In Experiment 1, probe questions were presented on line during reading to determine whether thematic information was maintained in WM throughout comprehension. The data indicated that readers across the range of WM span maintained thematic information in WM throughout the reading of a given passage. In Experiment 2, sentence reading times and accuracy for both topic and detail questions were measured in two conditions: when topic sentences were present and when topic sentences were absent. Subjects performed similarly across the range of WM span in the topic-present condition, but lower span subjects performed more poorly on detail questions in the topic-absent condition. In Experiment 3, the topic-present condition of the second experiment was replicated, except that subjects expected to receive questions about details only. Thematic processing and retention of topic and detail information all increased with span. Taken together, these results suggest that, for more difficult text processing tasks, high- and low-span subjects adopt different WM management strategies and these strategies influence what is learned from reading the text.

Adult↗
PubMed1998

Effect of normal aging on the manipulation of information in working memory.

The goal of this study is to examine the central executive of working memory in normal aging, specifically focusing on its capacities to manipulate or modify the format of the to-be-recalled material. The central executive was measured with the alphabetical span procedure, during which subjects were asked to recall a random series of words in their alphabetical order. The storage demand was equalized across subjects by adjusting the list lengths according to individual span. Experiments 1, 2, and 3 showed that elderly subjects were not impaired in manipulating information, relative to young controls, even when the difficulty of the task was increased. In Experiment 4, validity was tested by asking young subjects to perform the task under the conditions of full or divided attention. Alphabetical recall was more impaired than direct recall during the divided attention condition, which suggests a larger involvement of the central executive component in the former. These results are discussed in relation to the hypothesis of a central executive impairment being associated with normal aging.

Adult↗
PubMed2001

Functional neuroanatomy of auditory working memory in schizophrenia: relation to positive and negative symptoms.

Functional brain imaging studies of working memory (WM) in schizophrenia have yielded inconsistent results regarding deficits in the dorsolateral prefrontal (DLPFC) and parietal cortices. In spite of its potential importance in schizophrenia, there have been few investigations of WM deficits using auditory stimuli and no functional imaging studies have attempted to relate brain activation during auditory WM to positive and negative symptoms of schizophrenia. We used a two-back auditory WM paradigm in a functional MRI study of men with schizophrenia (N = 11) and controls (N = 13). Region of interest analysis was used to investigate group differences in activation as well as correlations with symptom scores from the Brief Psychiatric Rating Scale. Patients with schizophrenia performed significantly worse and were slower than control subjects in the WM task. Patients also showed decreased lateralization of activation and significant WM related activation deficits in the left and right DLPFC, frontal operculum, inferior parietal, and superior parietal cortex but not in the anterior cingulate or superior temporal gyrus. These results indicate that in addition to the prefrontal cortex, parietal cortex function is also disrupted during WM in schizophrenia. Withdrawal-retardation symptom scores were inversely correlated with frontal operculum activation. Thinking disturbance symptom scores were inversely correlated with right DLPFC activation. Our findings suggest an association between thinking disturbance symptoms, particularly unusual thought content, and disrupted WM processing in schizophrenia.

Adult↗
PubMedDate not supplied

Evidence for quantitative domain dominance for verbal and spatial working memory in frontal and parietal cortex.

Neuroimaging studies in humans have shown that different working memory (WM) tasks recruit a common bilateral fronto-parietal cortical network. Animal studies as well as neuroimaging studies in humans have suggested that this network, in particular the prefrontal cortex, is preferentially recruited when material from different domains (e.g. spatial information or verbal/object information) has to be memorized. Early imaging studies have suggested qualitative dissociations in the prefrontal cortex for spatial and object/verbal WM, either in a left-right or a ventral-dorsal dimension. However, results from different studies are inconsistent. Moreover, recent fMRI studies have failed to find evidence for domain dependent dissociations of WM-related activity in prefrontal cortex. Here we present evidence from two independent fMRI studies using physically identical stimuli in a verbal and spatial WM task showing that domain dominance for WM does indeed exist, although only in the form of quantitative differences in activation and not in the form of a dissociation with different prefrontal regions showing mutually exclusive activation in different domains. Our results support a mixed dimension model of domain dominance for WM within the prefrontal cortex, with left ventral prefrontal cortex (PFC) supporting preferentially verbal WM and right dorsal PFC supporting preferentially spatial WM. The concept of domain dominance is discussed in the light of recent theories of prefrontal cortex function.

Adult↗
PubMed2002

Topographic segregation and convergence of verbal, object, shape and spatial working memory in humans.

This functional magnetic resonance imaging study investigates commonalties and differences in working memory (WM) processes employing different types of stimuli. We specifically sought to characterize topographic convergence and segregation with respect to prefrontal cortex involvement using verbal, spatial, real object and shape memory items in a two-back WM task. Both the dorsolateral and ventrolateral prefrontal cortices are conjointly activated across all stimulus types. No stimulus-specific differences in the activation patterns of the prefrontal cortex could be demonstrated giving support to the view of an amodal prefrontal involvement during WM processes. However, extra-frontal regions specialized on feature processing and involved in the preprocessing of the stimuli were selectively activated by these different subtypes of WM. These selectively activated regions are assigned to parts of the ventral and dorsal stream.

Adult↗