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Working memory in children with reading disabilities.

This study investigated associations between working memory (measured by complex memory tasks) and both reading and mathematics abilities, as well as the possible mediating factors of fluid intelligence, verbal abilities, short-term memory (STM), and phonological awareness, in a sample of 46 6- to 11-year-olds with reading disabilities. As a whole, the sample was characterized by deficits in complex memory and visuospatial STM and by low IQ scores; language, phonological STM, and phonological awareness abilities fell in the low average range. Severity of reading difficulties within the sample was significantly associated with complex memory, language, and phonological awareness abilities, whereas poor mathematics abilities were linked with complex memory, phonological STM, and phonological awareness scores. These findings suggest that working memory skills indexed by complex memory tasks represent an important constraint on the acquisition of skill and knowledge in reading and mathematics. Possible mechanisms for the contribution of working memory to learning, and the implications for educational practice, are considered.

Aptitude↗

The functional neuroanatomy of human working memory revisited. Evidence from 3-T fMRI studies using classical domain-specific interference tasks.

In the present event-related functional magnetic resonance imaging study, the neural implementation of human working memory was reinvestigated using a factorial design with verbal and visuospatial item-recognition tasks each performed under single-task conditions, under articulatory suppression, and under visuospatial suppression. This approach allowed to differentiate between brain systems subserving domain-specific working memory processes and possible neural correlates of more "central" executive or storage functions. The results of this study indicate (1) a domain-specific functional-neuroanatomical organization of verbal and visuospatial working memory, (2) a dual architecture of verbal working memory in contrast to a unitary macroscopic architecture of visuospatial working memory, (3) possible neural correlates for a domain-unspecific "episodic buffer" in contrast to a failure to find brain areas attributable to a "central executive," and (4) competition for neuronal processing resources as the causal principle for the occurrence of domain-specific interference in working memory.

Acoustic Stimulation↗

Working memory after traumatic brain injury in children.

To investigate the effects of traumatic brain injury on working memory in children, we administered semantic (letter identity) and phonological (letter rhyme) N-back tasks to children who were on average 5 years post-mild (n = 54) or -severe (n = 26) traumatic brain injury and 44 typically developing children who were comparable in age. The correct detection of targets and false alarms were measured for each task. Memory load (which varied from 0 to 3 letters back) and age significantly affected the detection of targets and false alarms in both tasks. The severity of traumatic brain injury affected the correct detection of letters on the identity task and false alarms on the rhyme task. Traumatic brain injury severity also interacted with memory load in its effect on false alarms on the rhyme task. Traumatic brain injury results in impaired working memory and diminished inhibition in children. The N-back working memory task is feasible for administration to brain-injured children and potentially could be useful for studying brain activation associated with working memory and effects of drug therapy in this group of patients.

Adolescent↗

Transcranial magnetic stimulation of left prefrontal cortex impairs working memory.

OBJECTIVES: Several lines of evidence suggest that the prefrontal cortex is involved in working memory. Our goal was to determine whether transient functional disruption of the dorsolateral prefrontal cortex (DLPFC) would impair performance in a sequential-letter working memory task. METHODS: Subjects were shown sequences of letters and asked to state whether the letter just displayed was the same as the one presented 3-back. Single-pulse transcranial magnetic stimulation (TMS) was applied over the DLPFC between letter presentations. RESULTS: TMS applied over the left DLPFC resulted in increased errors relative to no TMS controls. TMS over the right DLPFC did not alter working memory performance. CONCLUSION: Our results indicate that the left prefrontal cortex has a crucial role in at least one type of working memory.

Adult↗

Updating in working memory: a comparison of good and poor comprehenders.

In this research, we examined the relation between reading comprehension and success in a working memory updating task. We tested the hypotheses that poor comprehenders' deficiencies are associated with a specific difficulty in the working memory updating process, particularly in controlling for information that is no longer relevant. In the first experiment, groups of poor and good comprehenders, ages 8-11 years, were administered a working memory updating task. In the second experiment a year later, a subgroup of participants involved in the first experiment was tested with a different updating task. In both experiments, poor comprehenders had less accurate recall performance and made more intrusion errors than did good comprehenders. Moreover, distinguishing intrusion errors on the basis of their permanence in memory, we found that poor comprehenders were more likely to intrude items that were maintained longer in memory than were good comprehenders. This type of error predicted reading comprehension abilities better than did working memory recall. This suggests that the relation between reading comprehension and working memory is mediated by the ability to control for irrelevant information.

Child↗

Mesial temporal spikes interfere with working memory.

The hippocampus and other mesial temporal structures support long-term memory and also are common foci for epilepsy. Recently it was shown that these brain structures may subserve the short-term storage and rehearsal processes called working memory in humans. We determined the accuracy of verbal and visuospatial working memory in the presence and in the absence of mesial temporal spikes in eight patients who had bilateral depth electrodes implanted to evaluate intractable epilepsy. Six of eight patients had declines in working memory performance during mesial temporal spiking, with the greatest disruption in spatial and verbal recall coincident with left hippocampal spikes (p = 0.019). Overall accuracy of working memory for all patients declined an average of 6% on spike trials. The two patients who did not have decreased accuracy during spike trials also had the best overall working memory performance. Mesial temporal spikes were not detected on extracranial recordings and yet may be associated with declines in working memory in some patients with epilepsy.

Action Potentials↗

Blockade of 5-HT1A receptors compensates loss of hippocampal cholinergic neurotransmission involved in working memory of rats.

NAN-190, a selective 5-HT1A receptor antagonist, had no effect on the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) in the working memory task with a three-panel runway setup, when injected bilaterlly at 0.32 or 1.0 micrograms/side into the dorsal hippocampus. Intrahippocampal administration of the muscarinic receptor antagonist scopolamine at 3.2 micrograms/side or the competitive NMDA receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) at 32 ng/side significantly increased the number of working memory errors. The increase in working memory errors induced by intrahippocampal scopolamine (3.2 micrograms/side) was reduced by concurrent infusion of 0.32 and 1.0 microgram/side NAN-190, an effect that reached significance only for the 1.0 microgram/side dose. In contrast, NAN-190 at 1.0 micrograms/side did not affect the increase in working memory errors when infused intrahippocampally together with 32 ng/side CPP. These results suggest that blockade of hippocampal 5-HT1A receptors does not affect impairment of working memory resulting from block of NMDA receptor-mediated neurotransmission, but that it can compensate deficiency of septohippocampal cholinergic activity involved in working memory performance of rats.

Animals↗

EEG synchronization likelihood in mild cognitive impairment and Alzheimer's disease during a working memory task.

OBJECTIVE: Synchronization likelihood analysis of resting state EEG has shown that cognitive dysfunction in Alzheimer's disease (AD) and its precursor mild cognitive impairment (MCI) are associated with a loss of functional connectivity in high (upper alpha and beta) frequency bands. Working memory tasks are known to change functional connectivity, but it is unknown whether this increases the differences between AD, MCI and healthy controls. Our objective was to investigate the behavior of synchronization likelihood of multichannel EEG in AD, MCI and cognitively healthy controls, both at rest and during a working memory task. METHODS: EEGs (200 Hz sample frequency, 21 channels, average reference) were recorded at rest as well as during a visual working memory task in 14 patients with AD according to the NINCDS-ADRDA criteria (mean age 76.4; SD 13.6), 11 patients with MCI according to the criteria of Petersen (mean age 78.4; SD 6.4) and 14 with subjective memory complaints but no demonstrable memory disturbance (mean age 61.6; SD 26.6). The synchronization likelihood was computed over 19 channels, comparing each channel with all the other channels for the 0.5-4, 4-8, 8-10, 10-12, 12-30, 30-50 Hz frequency bands. RESULTS: The synchronization likelihood was significantly decreased in the upper alpha (10-12) and beta (12-30) bands in AD compared to persons with subjective memory complaints. The working memory task scores strongly correlated with Mini-Mental State Examination scores. During the working memory task the synchronization likelihood was significantly higher in MCI compared to the control subjects in the lower alpha band (8-10 Hz). CONCLUSIONS: Decrease of beta band synchronization occurs in mild AD, both in a resting condition and during a working memory task. SIGNIFICANCE: Decrease of beta band synchronization in mild AD is a robust finding. The present study confirms our findings in a different cohort of patients, using alternative frequency bands. The diagnostic value of the synchronization likelihood in AD and MCI needs to be further established.

Aged↗

Genetic linkage and association between chromosome 1q and working memory function in schizophrenia.

Schizophrenia is substantially heritable, but specific susceptibility genes remain to be identified. Progress in this endeavor has been hindered by non-Mendelian transmission patterns, probable genetic heterogeneity, and an inability to detect premorbid and nonpenetrant carriers of predisposing genes. To circumvent these complexities, this study employed quantitative measures of liability, or "endophenotypes," within a sample of twins discordant for schizophrenia, drawn from the relatively genetically isolated population of Finland. A region on the distal portion of chromosome 1 has shown evidence for linkage to schizophrenia in two prior studies using Finnish patient samples. To elucidate further the nature and location of this potential susceptibility gene, linkage and association analyses were carried out across the chromosome 1 region of interest using quantitative neuropsychological measures of liability. Analyses with a composite measure of liability yielded suggestive evidence for linkage at marker D1S2833 (P = 0.04). Follow-up analyses of the individual trait measures showed that the Visual Span subtest of the Wechsler Memory Scale (WMS), an indicator of spatial working memory function, was uniquely sensitive to marker D1S2833 (P = 0.007). Association analysis confirmed that allelic variation in D1S2833 is associated with variation in spatial working memory performance as measured by the Visual Span subtest (P = 0.003), the significance of which was confirmed in an analysis of 10,000 Monte Carlo permutations. These data support the utility of this approach and provide evidence for a gene affecting spatial working memory function in schizophrenia patients and their unaffected co-twins.

Chromosomes, Human, Pair 1↗

Influence of working memory on patterns of motor related cortico-cortical coupling.

Working memory is implicated in various higher-order cognitive operations. We hypothesized that the availability of a temporal representation in working memory would limit the extent of cortico-cortical coupling necessary to undertake a self-paced rhythmic movement. To this end we examined modulations in cortico-cortical interactions as determined by EEG coherence during a delay interval and subsequent movement reproduction. Right hand movement was initially paced by a metronome beat every 0.9 s, followed by a delay interval, after which hand movement was repeated in an unpaced manner. Movement reproduction after a long (22.5 s, corresponding to 25 movement cycles) compared to a short (5.4 s, corresponding to 6 movement cycles) delay interval was associated with an increased degree of functional coupling in the beta frequency band (12-30 Hz) of the left (movement-driving) hemisphere (F3-FC3, F3-C3 and F3-P3 connections) as well as mesial regions (FCz-FC3, FCz-C3 and Cz-FC3 connections) even though overall behavioral characteristics were not influenced. In addition, analysis of the EEG coherence in the delay period revealed a bilateral frontal network (F3-F4, F3-FC4, F4-FC3 and FC3-FC4 connections). Activity in the latter tended to be synchronized in the theta band (4-8 Hz) and was significantly less strong at 22.5 s than 5.4 s. These data suggest that working memory may be partly subserved by synchronization in a bilateral frontal network and may provide an intrinsic contextual influence that shapes the pattern of cortico-cortical interaction during a given task.

Biomechanical Phenomena↗

The effects of clozapine and risperidone on spatial working memory in schizophrenia.

OBJECTIVE: The purpose of this investigation was to evaluate the effects of clozapine and risperidone on spatial working memory in patients with schizophrenia. METHOD: Spatial working memory performance was evaluated at baseline and after 17 and 29 weeks in 97 patients with schizophrenia participating in a multisite trial. RESULTS: Compared with baseline performance while receiving conventional antipsychotic medication, risperidone improved, and clozapine worsened, spatial working memory performance. CONCLUSIONS: The differential effects of these medications on spatial working memory may be due to the anticholinergic effects of clozapine and prefrontal dopamine-enhancing effects of risperidone.

Adult↗

Thought disorder, working memory and attention: interrelationships and the effects of neuroleptic medications.

Impairments in attention and vigilance, working memory and organization of speech (thought disorder) have been reliably observed in patients with schizophrenia. The response in these cognitive parameters to neuroleptic medications can be used to sharpen their characterization in neuropsychological terms. In particular, a review of the literature suggests that while working memory is relatively insensitive to neuroleptics, attention and thought disorder may improve with neuroleptic administration. On the basis of the response to typical and atypical neuroleptics, attention as deployed in the Continuous Performance Test may reflect response readiness rather than actual vigilance. Thought disorder, which is often assumed to be the result of impaired discourse planning due to a reduced capacity for working memory, does not covary with working memory, and the two parameters show different responses to neuroleptic medications. Rather, cognitive studies suggest that thought disorder may arise from abnormalities within the semantic system itself.

Antipsychotic Agents↗

Verbal and spatial working memory in older individuals: A positron emission tomography study.

Recent reviews of a substantial number of studies have partially resolved questions concerning the brain regions used by working memory for manipulation and representation. We report a large single experiment in middle-aged to older adults (n = 89), classified by hypertensive status. Our design addresses the question of regions related to manipulation and representation, most particularly comparing spatial and verbal working memory. A control, memory search, and 2-back running memory task were performed with identical stimuli and responses during whole-brain 15O water positron emission tomography (PET) scans. Letter or spatial position instructions created verbal or spatial working memory versions of the tasks. We assessed agreement with the literature using regions of interest that were defined by clusters of activation empirically derived from the literature by Wager and Smith (Wager, T.D. and Smith, E.E., Neuroimaging studies of working memory: a meta-analysis, Cognitive, Affective and Behavioral Neuroscience, 3 (2003) 255-274). Our results largely confirmed conclusions from the review on the organization of working memory into dorsal prefrontal manipulation and ventrolateral prefrontal maintenance areas and representation in dorsal and ventral paths. Specific verbal versus spatial comparisons were also concordant with prior work establishing posterior lateralized representation for different contents by working memory. The similarity of results between this older sample and results derived by others from younger participants is notable.

Aged↗

Differential effects of 5-HT3 receptor antagonism on working memory failure due to deficiency of hippocampal cholinergic and glutamatergic transmission in rats.

The muscarinic acetylcholine receptor antagonist scopolamine significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) in the working memory task with a three-panel runway setup, when injected bilaterally at 3.2 microg/side into the dorsal hippocampus. Concurrent infusion of the selective and potent 5-hydroxytryptamine3 (5-HT3) receptor antagonist Y-25130 (0.32 and 1.0 microg/side) significantly attenuated the increase in working memory errors induced by intrahippocampal 3.2 microg/side scopolamine. Intrahippocampal Y-25130 (1.0 microg/side) by itself did not affect working memory errors. On the other hand, intrahippocampal administration of the competitive NMDA receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) at 32 ng/side caused a significant increase in the number of working memory errors. However, Y-25130 at 1.0 microg/side did not affect the increase in working memory errors when infused intrahippocampally together with 32 ng/side CPP. These results suggest that antagonism of hippocampal 5-HT3 receptors is ineffective against working memory failure resulting from blockade of NMDA receptor-mediated neurotransmission, but that it can compensate deficiency of septohippocampal cholinergic activity involved in working memory function of rats.

Acetylcholine↗

The relationship of working memory, inhibition, and response variability in child psychopathology.

INTRODUCTION: The aim of this study was to investigate the relationship between working memory and inhibition in children with attention deficit hyperactivity disorder (ADHD), high-functioning autism (HFA), and Tourette syndrome (TS), compared to normally developing children. Furthermore, the contribution of variation in processing speed on working memory and inhibition was investigated in these childhood psychopathologies. METHOD: Four groups of children are reported in this study: 65 children with ADHD, 66 children with HFA, 24 children with TS, and 82 normal control children. All children were in the age range of 6-13 years. RESULTS: The relationship between working memory and inhibition was similar in children with ADHD, HFA, TS, and normally developing children. The relationship between both domains did not alter significantly for any of the groups, when variation in processing speed was taken into account. More symptoms of hyperactivity/impulsivity are related to a poorer inhibitory process and greater response variability. More symptoms of autism are related to a poorer working memory process. CONCLUSION: The current study showed that working memory, inhibition, and response variability, are distinct, but related cognitive domains in children with developmental psychopathologies. Research with experimental manipulations is needed to tackle the exact relationship between these cognitive domains.

Adolescent↗

Assessment of working memory abilities using an event-related brain potential (ERP)-compatible digit span backward task.

OBJECTIVE: This study investigated the effectiveness of an ERP-compatible Digit Span Backward (ERP-DB) task to determine working memory abilities in healthy participants. METHODS: Participants were administered both the standard digit span backward and ERP-DB tasks. The ERP-DB task was divided into two sections, consisting of 2, 4, 6 and 8 (Group 1) and 3, 5, and 7 (Group 2) set sizes. A set of digits was aurally presented, followed by a second set that either corresponded to the reverse order of the first set (correct condition) or had one digit in the sequence replaced by an incorrect digit (incorrect condition). RESULTS: Two posterior positive components were found to distinguish the two conditions; an earlier positive component (P200/P300) was elicited in the correct condition, whereas a comparatively robust and prolonged positive slow wave (PSW) was elicited in the incorrect condition. Furthermore, the PSW and the difference in PSW amplitude between incorrect and correct conditions (dPSW) dissipated as working memory load increased and were related to working memory capacity. CONCLUSIONS: The PSW, dPSW and P200/P300 components were found to be associated with working memory abilities and may have the potential to act as neurophysiological markers for the assessment of working memory capacity. SIGNIFICANCE: This research lends support for the utility of the ERP-DB task as a means of assessing working memory abilities, which may have implications for testing patients with expressive communication impairments.

Adult↗

Working memory constrains human cooperation in the Prisoner's Dilemma.

Many problems in human society reflect the inability of selfish parties to cooperate. The "Iterated Prisoner's Dilemma" has been used widely as a model for the evolution of cooperation in societies. Axelrod's computer tournaments and the extensive simulations of evolution by Nowak and Sigmund and others have shown that natural selection can favor cooperative strategies in the Prisoner's Dilemma. Rigorous empirical tests, however, lag behind the progress made by theorists. Clear predictions differ depending on the players' capacity to remember previous rounds of the game. To test whether humans use the kind of cooperative strategies predicted, we asked students to play the iterated Prisoner's Dilemma game either continuously or interrupted after each round by a secondary memory task (i.e., playing the game "Memory") that constrained the students' working-memory capacity. When playing without interruption, most students used "Pavlovian" strategies, as predicted, for greater memory capacity, and the rest used "generous tit-for-tat" strategies. The proportion of generous tit-for-tat strategies increased when games of Memory interfered with the subjects' working memory, as predicted. Students who continued to use complex Pavlovian strategies were less successful in the Memory game, but more successful in the Prisoner's Dilemma, which indicates a trade-off in memory capacity for the two tasks. Our results suggest that the set of strategies predicted by game theorists approximates human reality.

Biological Evolution↗

Adult age differences in self-ordered pointing task performance: contributions from working memory, executive function and speed of information processing.

This study investigated adult age differences in, and predictors of, the performance of a test of executive function, the Self-Ordered Pointing Task (SOPT; Petrides & Milner, 1982). Performance on the SOPT is thought to rely on high level working memory processes, therefore, measures reflecting the common operationalization of working memory, along with measures of executive function and speed of information processing, were investigated as predictors of SOPT performance. Younger (aged 17-48 years) and older (aged 65-88 years) adults completed a 16-item, 3-trial, modified version of Shimamura and Jurica's (1994) version of the SOPT, and tests assessing working memory, executive function and speed. Results showed that younger adults made fewer errors on the SOPT. There was no age difference in the frequency of use of a clustering strategy. Contrary to expectations, working memory was not a good predictor of individual or age differences in SOPT performance. Instead, speed of processing, and to a lesser extent, measures of perseverations, made larger unique and overlapping contributions to the variance. The SOPT and its association, or dissociation, with other measures of working memory may be useful for research into the nature of working memory and executive function and the theoretical links between them.

Adolescent↗