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[Functional magnetic resonance tomography during the activation of working memory].

AIMS: Functional magnetic resonance imaging was used in conjunction with a letter detection task for the study of working memory in 16 normal subjects. Because of movement artifacts, data from only 9 subjects were analysed. METHODS: In the activation task, subjects responded by pressing a button whenever any presented letter was the same as the second last in the sequence. In the control condition, the subjects had to respond to a fixed letter. Hence, the activation condition and the control condition differed only subjectively, i.e., regarding the task demand, whereas the stimuli and the type and frequency of response were identical. RESULTS: The activation condition produced significant activation in the dorsolateral prefrontal cortex (Brodmann's areas 10, 46, and 9). CONCLUSIONS: In contrast to experimental tasks previously used rather extensively to study the prefrontal cortex, the present paradigm is characterized by its simplicity, interpretability, and its ties to known neurophysiology of the frontal cortex.

Adult↗

The neural basis of task-switching in working memory: effects of performance and aging.

We studied the performance of young and senior subjects on a well known working memory task, the Operation Span. This is a dual-task in which subjects perform a memory task while simultaneously verifying simple equations. Positron-emission tomography scans were taken during performance. Both young and senior subjects demonstrated a cost in accuracy and latency in the Operation Span compared with performing each component task alone (math verification or memory only). Senior subjects were disproportionately impaired relative to young subjects on the dual-task. When brain activation was examined for senior subjects, we found regions in prefrontal cortex that were active in the dual-task, but not in the component tasks. Similar results were obtained for young subjects who performed relatively poorly on the dual-task; however, for young subjects who performed relatively well in the dual-task, we found no prefrontal regions that were active only in the dual-task. Results are discussed as they relate to the executive component of task switching.

Adult↗

Parieto-frontal interactions in visual-object and visual-spatial working memory: evidence from transcranial magnetic stimulation.

This study aimed to investigate whether transcranial magnetic stimulation (TMS) can induce selective working memory (WM) deficits of visual-object versus visual-spatial information in normal humans. Thirty-five healthy subjects performed two computerized visual n-back tasks, in which they were required to memorize spatial locations or abstract patterns. In a first series of experiments, unilateral or bilateral TMS was delivered on posterior parietal and middle temporal regions of both hemispheres after various delays during the WM task. Bilateral temporal TMS increased reaction times (RTs) in the visual-object, whereas bilateral parietal TMS selectively increased RTs in the visual-spatial WM task. These effects were evident at a delay of 300 ms. Response accuracy was not affected by bilateral or unilateral TMS of either cortical region. In a second group of experiments, bilateral TMS was applied over the superior frontal gyrus (SFG) or the dorsolateral prefrontal cortex (DLPFC). TMS of the SFG selectively increased RTs in the visual-spatial WM task, whereas TMS of the DLPFC interfered with both WM tasks, in terms of both accuracy and RTs. These effects were evident when TMS was applied after a delay of 600 ms, but not one of 300 ms. These findings confirm the segregation of WM buffers for object and spatial information in the posterior cortical regions. In the frontal cortex, the DLPFC appears to be necessary for WM computations regardless of the stimulus material.

Adult↗

A meta-analysis of working memory impairments in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: To determine the empirical evidence for deficits in working memory (WM) processes in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). METHOD: Exploratory meta-analytic procedures were used to investigate whether children with ADHD exhibit WM impairments. Twenty-six empirical research studies published from 1997 to December, 2003 (subsequent to a previous review) met our inclusion criteria. WM measures were categorized according to both modality (verbal, spatial) and type of processing required (storage versus storage/manipulation). RESULTS: Children with ADHD exhibited deficits in multiple components of WM that were independent of comorbidity with language learning disorders and weaknesses in general intellectual ability. Overall effect sizes for spatial storage (effect size = 0.85, CI = 0.62 - 1.08) and spatial central executive WM (effect size = 1.06, confidence interval = 0.72-1.39) were greater than those obtained for verbal storage (effect size = 0.47, confidence interval = 0.36-0.59) and verbal central executive WM (effect size = 0.43, confidence interval = 0.24-0.62). CONCLUSION: Evidence of WM impairments in children with ADHD supports recent theoretical models implicating WM processes in ADHD. Future research is needed to more clearly delineate the nature, severity, and specificity of the impairments to ADHD.

Adolescent↗

The neural substrate of orientation working memory.

We have used positron emission tomography (PET) to identify the neural substrate of two major cognitive components of working memory (WM), maintenance and manipulation of a single elementary visual attribute, i.e., the orientation of a grating presented in central vision. This approach allowed us to equate difficulty across tasks and prevented subjects from using verbal strategies or vestibular cues. Maintenance of orientations involved a distributed fronto-parietal network, that is, left and right lateral superior frontal sulcus (SFSl), bilateral ventrolateral prefrontal cortex (VLPFC), bilateral precuneus, and right superior parietal lobe (SPL). A more medial superior frontal sulcus region (SFSm) was identified as being instrumental in the manipulative operation of updating orientations retained in the WM. Functional connectivity analysis revealed that orientation WM relies on a coordinated interaction between frontal and parietal regions. In general, the current findings confirm the distinction between maintenance and manipulative processes, highlight the functional heterogeneity in the prefrontal cortex (PFC), and suggest a more dynamic view of WM as a process requiring the coordinated interaction of anatomically distinct brain areas.

Adult↗

Neural correlates of vibrotactile working memory in the human brain.

Recent neurophysiological studies in macaques identified a network of brain regions related to vibrotactile working memory (WM), including somatosensory, motor, premotor, and prefrontal cortex. In these studies, monkeys decided which of two vibrotactile stimuli that were sequentially applied to their fingertips and separated by a short delay had the higher vibration frequency. Using the same task, the objective of the present study was to identify the neural correlates related to the different task periods (encoding, maintenance, and decision making) of vibrotactile WM in the human brain. For this purpose, we used event-related functional magnetic resonance imaging and contrasted WM trials with a control condition of vibrotactile stimulation that did not require maintenance and decision making. We found that vibrotactile WM has a similar but not identical neural organization in humans and monkeys. Consistent with neurophysiological data in monkeys and behavioral studies in humans, the primary somatosensory and the ventral premotor cortex exhibited increased activity during encoding. Maintenance of a vibrotactile memory trace evoked activity in the premotor and ventrolateral prefrontal cortex. Decision making caused activation in the somatosensory, premotor, and lateral prefrontal cortex. However, human vibrotactile WM recruited additional areas. Decision making activated a broader network than that studied thus far in monkeys. Maintenance and decision making additionally activated the inferior parietal lobe. Although the different task components evoked activity in distinctive neural networks, there was considerable overlap of activity, especially regarding maintenance and decision making, indicating that similar neural mechanisms are required for the subprocesses related to these task components.

Adult↗

[Working memory and complex activities of everyday life in the initial stages of Alzheimer's disease].

INTRODUCTION: Evaluation of the working memory (WM) permits analysis of the degree of anterograde amnesia and fixation deficit present in patients with Alzheimer s disease (AD). Complex activities of everyday life (AEL) are also affected early. There is a close relation between the degree of cognitive deterioration and loss of functional competence in AEL. OBJECTIVE: To analyze the degree of memory loss and performance in carrying out complex AEL in patients with AD and mild cognitive disorder. PATIENTS AND METHODS: Evaluation of functional disorder, using Pfeffer s functional activity questionnaire (FAQ), and cognitive evaluation, using the WM examination protocol in a group of 36 patients. RESULTS: In the total MT (4.2+/-5.7) there were significant differences between patients with age associated memory impairment (AAMI) (11+/-7) and possible EA (3.2+/-4.6) and between AAMI and probable AD (2.8+/-4.8). The functional evaluation of the AEL (FAQ) gave a mean of 8.5+/-7.1. There were significant differences between probable AD (11+/-8) and possible EA (6+/-4) with the group AAMI 1+/-1.8. There was significant correlation between FAQ and total WM ( 0.70, p= 0.0001). It was found that patients with high FAQ scores had lower total WM scores. CONCLUSION: FAQ and WM have high correlation and are useful instruments for the evaluation of patients with cognitive deterioration at the initial stages.

Activities of Daily Living↗

Individual differences in working memory within a nomological network of cognitive and perceptual speed abilities.

It has become fashionable to equate constructs of working memory (WM) and general intelligence (g). Few investigations have provided direct evidence that WM and g measures yield similar ordering of individuals. Correlational investigations have yielded mixed results. The authors assess the construct space for WM and g and demonstrate that WM shares substantial variance with perceptual speed (PS) constructs. Thirty-six ability tests representing verbal, numerical, spatial, and PS abilities; the Raven Advanced Progressive Matrices; and 7 WM tests were administered to 135 adults. A nomological representation for WM is provided through a series of cognitive and PS ability models. Construct overlap between PS and WM is further investigated with attention to complexity, processing differences, and practice effects.

Adolescent↗

Working memory and inhibitory control in early childhood: Contributions from physiology, temperament, and language.

This study examined the cognitive skills of working memory and inhibitory control (WMIC) in relation to physiological functioning, temperament, and language in early childhood. WMIC skills were assessed in twenty-five 4 1/2-year-old children using the day--night Stroop-like task and the yes--no task; each task required the child to remember two rules and to inhibit a dominant response. Electroencephalogram (EEG) and heart period (HP) were recorded during baseline and WMIC tasks. An increase in 6- to 9-Hz EEG power from baseline to task was found for the medial frontal region. In addition, a decrease in HP (i.e., an increase in heart rate) was found from baseline to task. Associations were found between performance on the WMIC tasks and scales of the Children's Behavioral Questionnaire (CBQ) related to the effortful control of behavior. The Peabody Picture Vocabulary Test-III (PPVT-III) distinguished between high and low WMIC performance. Results of a discriminant function analysis indicated that physiology, temperament, and language were able to correctly predict 90% of WMIC performance.

Arousal↗

Working memory for letters, shapes, and locations: fMRI evidence against stimulus-based regional organization in human prefrontal cortex.

Investigations of working memory (WM) systems in the frontal cortex have revealed two stimulus dimensions along which frontal cortical representations may be functionally organized. One hypothesized dimension dissociates verbal from nonverbal WM processes, dividing left from right frontal regions. The second hypothesized dimension dissociates spatial from nonspatial WM, dividing dorsal from ventral frontal regions. Here we used functional magnetic resonance imaging to probe WM processes associated with three different types of stimuli: letters (verbal and nonspatial), abstract shapes (nonverbal and nonspatial), and locations (nonverbal and spatial). In a series of three experiments using the "n-back" WM paradigm, direct statistical comparisons were made between activation patterns in each pairwise combination of the three stimulus types. Across the experiments, no regions that demonstrated responses to WM manipulations were discovered to be unique to any of the three stimulus types. Therefore, no evidence was found to support either a left/right verbal/nonverbal dissociation or a dorsal/ventral spatial/nonspatial dissociation. While this could reflect a limitation of the present behavioral and imaging techniques, other factors that could account for the data are considered, including subjects' strategy selection, encoding of information into WM, and the nature of representational schemes in prefrontal cortex.

Adolescent↗

Differential working memory load effects after mild traumatic brain injury.

The objective of this study was to explore the effects of increasing working memory (WM) processing load on previously observed abnormalities in activation of WM circuitry shortly after mild traumatic brain injury (MTBI). Brain activation patterns in response to increasing WM processing load (auditory n-back: 0-, 1-, 2-, and 3-back conditions) were assessed with fMRI in 18 MTBI patients within 1 month of their injury and in 12 healthy controls. Performance accuracy on these tasks was also measured. Brain activation patterns differed between MTBI patients and controls in response to increasing WM processing loads. Controls maintained their ability to increase activation in regions of WM circuitry with each increase in WM processing load. MTBI patients showed disproportionately increased activation during the moderate processing load condition, but very little increase in activation associated with the highest processing load condition. Task performance did not differ significantly between groups on any task condition. MTBI patients showed a different pattern of allocation of processing resources associated with a high processing load condition compared to healthy controls, despite similar task performance. This suggests that injury-related changes in ability to activate or modulate WM processing resources might underlie some of the memory complaints after MTBI.

Adolescent↗

Interference between velocity-dependent and position-dependent force-fields indicates that tasks depending on different kinematic parameters compete for motor working memory.

Humans demonstrate motor learning when exposed to changes in the dynamics of movement or changes in the visuomotor map. However, when two opposing dynamic transformations are learned in succession, the memory of the first is overwritten by learning of the second; the same is true for two opposing visuomotor rotations. This retrograde interference is not seen for all combinations of transformations, however. When a dynamic transformation is learned subsequent to a visuomotor rotation, the presence or absence of interference appears to depend crucially on the structure of the dynamic task: a force-field dependent on the position of the hand produces interference, whereas an inertial load applied lateral to the hand does not. To explain these results, it has been hypothesized that two transformations can be learned without interference if they depend on two different kinematic parameters of movement (such as position and velocity of the hand). Here we demonstrate, contrary to this hypothesis, interference between a dynamic transformation that depends on the position of the hand and one that depends on its velocity. However, the interference was found to be incomplete, supporting the view that the ability to retain motor memories for different tasks depends on the degree to which their representations conflict in working memory.

Adaptation, Physiological↗

Functional significance of delay-period activity of primate prefrontal neurons in relation to spatial working memory and reward/omission-of-reward expectancy.

The lateral prefrontal cortex (LPFC) is important in cognitive control. During the delay period of a working memory (WM) task, primate LPFC neurons show sustained activity that is related to retaining task-relevant cognitive information in WM. However, it has not yet been determined whether LPFC delay neurons are concerned exclusively with the cognitive control of WM task performance. Recent studies have indicated that LPFC neurons also show reward and/or omission-of-reward expectancy-related delay activity, while the functional relationship between WM-related and reward/omission-of-reward expectancy-related delay activity remains unclear. To clarify the functional significance of LPFC delay-period activity for WM task performance, and particularly the functional relationship between these two types of activity, we examined individual delay neurons in the primate LPFC during spatial WM (delayed response) and non-WM (reward-no-reward delayed reaction) tasks. We found significant interactions between these two types of delay activity. The majority of the reward expectancy-related neurons and the minority of the omission-of-reward expectancy-related neurons were involved in spatial WM processes. Spatial WM-related neurons were more likely to be involved in reward expectancy than in omission-of-reward expectancy. In addition, LPFC delay neurons observed during the delayed response task were not concerned exclusively with the cognitive control of task performance; some were related to reward/omission-of-reward expectancy but not to WM, and many showed more memory-related activity for preferred rewards than for less-desirable rewards. Since employing a more preferred reward induced better task performance in the monkeys, as well as enhanced WM-related neuronal activity in the LPFC, the principal function of the LPFC appears to be the integration of cognitive and motivational operations in guiding the organism to obtain a reward more effectively.

Animals↗

Deficits of working memory during mental calculation in patients with Parkinson's disease.

Using the dual task paradigm, previous studies have suggested that working memory (WM) deficit is due to depleted attention resources in patients with Parkinson's disease (PD). The aim of this study is to establish whether the WM problems in PD are due to reduced attentional set-shifting resources rather than depletion of attention resources. The task design attempts to eliminate confounding of the deficits in dealing with novel material, a problem documented in PD, by concentrating on WM tasks of mental calculation that are familiar to subjects in daily living. We also administered attention tasks, the Trail Making Test (TMT) that relies primarily on attentional set-shifting and the Kana (Japanese syllabogram) Pick-out Test instead primarily depending on depleted attention resources for allocation. A total of 24 patients with PD and 24 normal controls participated in this study. The PD group showed deficits in mental calculation span and in attentional set-shifting in the TMT-b.Considering the common deficits in alternating processing of mental calculation and TMT-b in PD, the results suggested that the central executive dysfunction in PD during mental calculations was due to reduced attentional set-shifting resources for rapidly alternating operations, rather than the depletion of attentional resources.

Adult↗

Spatial working memory deficit in unilateral neglect.

Based on the similarity of brain areas lesioned in neglect and those activated by spatial working memory (WM) tasks in normals, we hypothesized that neglect may involve spatial WM impairments. A left neglect patient with right inferior frontal and basal ganglia damage performed cancellation tasks, making either highly visible marks (to provide a reminder of visited items), or invisible marks (so only spatial WM could represent cancelled items). Invisible marks led to repeated cancellations for targets that differed only in location, but not for targets with memorable unique identities, suggesting a deficit of spatial WM, with non-spatial WM spared. Neglect was greater for cancellation with invisible marks, consistent with a role for deficient spatial WM in cancellation deficits, but contrary to account solely in terms of attention capture by salient visible marks made in ipsilesional space.

Attention↗

Hypothesized neural dynamics of working memory: several chunks might be marked simultaneously by harmonic frequencies within an octave band of brain waves.

The capacity of working memory (WM) for up to about seven simple items holds true both for humans and other species, and may depend upon a common characteristic of mammalian brains. This paper develops the conjecture that each WM item is represented by a different brain wave frequency. The binding-by-synchrony hypothesis, now being widely investigated, holds that the attributes of a single cognitive element cohere because electroencephalogram (EEG) synchrony temporarily unifies their substrates, which are distributed among different brain regions. However, thought requires keeping active more than one cognitive element, or WM "chunk," at a time. If there is indeed a brain wave frequency code for cognitive item-representations that are copresent within the same volume of neural tissue, the simple mathematical relationships of harmonies could provide a basis for maintaining distinctness and for orderly changes. Thus, a basic aspect of music may provide a model for an essential characteristic of WM. Music is a communicative phenomenon of "intermediate complexity," more highly organized than the firing patterns of individual neurons but simpler than language. If there is a distinct level of neural processing within which the microscopic physiological activity of neurons self-organizes into the macroscopic psychology of the organism, it might require such moderate complexity. Some of the obvious properties of music--orderly mixing and transitions among limited numbers of signal lines-are suggestive of properties that a dynamic neural process might need in order to organize and reorganize WM markers, but there are a number of additional, nonobvious advantageous properties of summating sinusoids in music-like relationships. In particular, harmonies register a stable periodic signal in the briefest possible time. Thus, the regularity of summating sinusoids whose frequencies bear harmony ratios suggests a particular kind of tradeoff between parallel and serial processing. When there are few copresent waves, at EEG frequencies, this sort of parallel coding retains behaviorally meaningful brief periods. A necessary companion hypothesis is that the brain wave frequencies underlying WM are confined to a single octave; that is, the upper and lower bounds of the band are in the ratio of 2:1. This hypothesized restriction, suggested by an empirical property of EEG bands that has been widely reported but rarely commented upon, has the important property of precluding spurious difference rhythms. A restriction to an octave, of "harmonious" frequency-markers for WM items, also seems consistent with a great deal of behavioral data suggesting that WM comprises a rapidly fading trace process in which only up to three or four item-representations are strongly activated simultaneously. There is also an additional, sequential renewal-or-revision process, within which up to another three or four items are being actively refreshed by rehearsal or replaced. Such serial processing may involve a less stringent octave band crowding problem.

Animals↗

M2 muscarinic acetylcholine receptor knock-out mice show deficits in behavioral flexibility, working memory, and hippocampal plasticity.

Muscarinic acetylcholine receptors are known to play key roles in facilitating cognitive processes. However, the specific roles of the individual muscarinic receptor subtypes (M1-M5) in learning and memory are not well understood at present. In the present study, we used wild-type (M2+/+) and M2 receptor-deficient (M2-/-) mice to examine the potential role of M2 receptors in learning and memory and hippocampal synaptic plasticity. M2-/- mice showed significant deficits in behavioral flexibility and working memory in the Barnes circular maze and the T-maze delayed alternation tests, respectively. The behavioral deficits of M2-/- mice were associated with profound changes in neuronal plasticity studied at the Schaffer-CA1 synapse of hippocampal slices. Strikingly, short-term potentiation (STP) was abolished, and long-term potentiation (LTP) was drastically reduced after high-frequency stimulation of M2-/- hippocampi. Treatment of M2-/- hippocampal slices with the GABA(A) receptor antagonist, bicuculline, restored STP and significantly increased LTP. Whole-cell recordings from CA1 pyramidal cells demonstrated a much stronger disinhibition of GABAergic than glutamatergic transmission in M2-/- hippocampi, which was particularly prominent during stimulus trains. Increased strength of GABAergic inhibition is thus a likely mechanism underlying the impaired synaptic plasticity observed with M2-/- hippocampi. Moreover, the persistent enhancement of excitatory synaptic transmission in CA1 pyramidal cells induced by the transient application of a low concentration of a muscarinic agonist (referred to as LTP(m)) was totally abolished in M2-/- mice. Because impaired muscarinic cholinergic neurotransmission is associated with Alzheimer's disease and normal aging processes, these findings should be of considerable therapeutic relevance.

Amnesia↗

Age-related differences in executive control of working memory.

In two experiments, we used dual-task methodology to assess the effect of aging on executive control of working memory. We hypothesized that (1) age-related dual-task costs would be observed even when individual tasks represent different perceptual modalities; (2) age would modulate the effect of increased temporal overlap on dual-task performance; and (3) the vulnerability of specific memory mechanisms to interference would be age related. We found that aging was associated with disproportionate dual-task costs that increased when extending the overlap between individual tasks. The effect of interference with encoding, and arguably output, was disproportionately larger in old than in young individuals. Ensuring that individual tasks represent different perceptual modalities is important but insufficient when using dual-task methodology to assess the effect of aging on executive function. The degree of temporal overlap between individual tasks and the sensitivity of specific memory operations to interference should be considered, as well.

Adult↗

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