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Is speed of processing or working memory the primary information processing deficit in multiple sclerosis?

OBJECTIVE: To examine whether processing speed or working memory is the primary information processing deficit in persons with MS. DESIGN: Case-control study. SETTING: Hospital-based specialty clinic. PARTICIPANTS: 215 adults with clinically definite MS. MAIN OUTCOME MEASURE: Mean demographically corrected T-scores, prevalence rates of impairment and relative risk of impaired Processing Speed and Working Memory Index Scores from the WAIS-WMS III. RESULTS: Deficits in Processing Speed were much more common than Working Memory in all comparisons. This was observed for both relapsing remitting (RRMS) and secondary progressive MS (SPMS) subjects, but accentuated in the latter group. CONCLUSIONS: Results strongly suggest that the primary information processing deficit in persons with MS is in speed of processing.

Adult↗

Effects of music listening and relaxation instructions on arousal changes and the working memory task in older adults.

The purpose of this study was to examine the effects of subject-preferred music and relaxation instructions on older adults' arousal and working memory. Fifteen female older adults participated in 10 minutes of all 3 experimental conditions: (a) subject-preferred music, (b) relaxation instructions, and (c) silence control. Four subcategories of arousal level, energy, tiredness, tension, and calmness, were measured before and after experimental treatment using the Activation-Deactivation Adjective Check List by Thayer (1978). After each experimental condition, subjects had a working memory test by Daneman and Carpenter (1980). Results of the 2 x 3 repeated measures analysis of variances indicated that music increased subjects' energy levels, but relaxation and silence significantly decreased energy levels. Relaxation and silence increased their tiredness and calmness levels. All experimental conditions decreased subjects' tension levels. The scores in the working memory test were not significantly different among experimental conditions. Results did not indicate clear relationships between four subcategories of arousal levels and working memory scores. Results indicated that subject-preferred music has potentials to increase older adults' energetic arousal and reduce tension.

Aged↗

The relationship between measures of working memory and sentence comprehension in patients with Alzheimer's disease.

Patients with dementia of the Alzheimer's type (DAT) and age- and education-matched older volunteers were tested on a battery of working memory tests, as well as on two tests of sentence comprehension. Patients had reduced spans and impaired central executive processes in working memory but showed normal effects of phonological and articulatory variables on span. On the sentence comprehension tasks, DAT patients showed effects of the number of propositions in a sentence but not of syntactic complexity. Impairment in the central executive processes of working memory in DAT patients was correlated with the effect of the number of propositions in a sentence on the sentence comprehension tasks. The results suggest that patients with DAT have working memory impairments that are related to their ability to map the meanings of sentences onto depictions of events in the world.

Aged↗

Hippocampal stimulation disrupts spatial working memory even 8 h after acquisition.

The present experiment used hippocampal stimulation to determine the temporal gradient of consolidation of spatial working memory. Rats were trained to perform a spatial working memory task on a radial maze with 12 arms. Each rat went to the ends of 6 arms to obtain a food reward. After 8 h, the rat chose among all the arms to find the ones not previously chosen (and consequently still having food). During some test sessions, the hippocampus was stimulated electrically either at a current level just high enough to produce an electrophysiological seizure, or at a current level below this seizure threshold. Stimulation occurred at one of five intervals (0 to 8 h) following the completion of the first six choices. During other test sessions, the hippocampus was not stimulated. After seizure stimulation, the number of retroactive errors (returning to arms chosen prior to stimulation) increased at all delay intervals; the number of proactive errors (returning to arms chosen after stimulation) increased only with the delay of 8 h. Subthreshold stimulation had no influence on either type of error. These results indicate that normal hippocampal function is required for the maintenance of spatial information in working memory, and that the time course of consolidation of this information is significantly greater than that seen in other types of memory, or consolidation may not take place at all.

Animals↗

Spatial working memory in asymptomatic HIV-infected subjects.

Many clinical and research findings converge to indicate that frontal lobe, basal ganglia, and related neuronal connections are primarily involved in human immunodeficiency virus (HIV) infection; frontal lobe, mainly the prefrontal cortex, has a specialized role in working memory processes. This study focused on neuropsychological evaluation of the spatial component of working memory in a sample of 34 asymptomatic HIV-infected subjects as compared with 34 age- and sex-matched seronegative control subjects. A computer-administered test assessing spatial working memory was used for the neuropsychological evaluation. The findings did not show any spatial working memory impairment during the asymptomatic phase of HIV infection.

Adult↗

Disturbing visual working memory: electrophysiological evidence for a role of the prefrontal cortex in recovery from interference.

Single cell recordings in monkeys support the notion that the lateral prefrontal cortex (PFC) controls reactivation of visual working memory representations when rehearsal is disrupted. In contrast, recent fMRI findings yielded a double dissociation for PFC and the medial temporal lobe (MTL) in a letter working memory task. PFC was engaged in interference protection during reactivation while MTL was prominently involved in the retrieval of the letter representations. We present event-related potential data (ERP) that support PFC involvement in the top-down control of reactivation during a visual working memory task with endogenously triggered recovery after visual interference. A differentiating view is proposed for the role of PFC in working memory with respect to endogenous/exogenous control and to stimulus type. General implications for binding and retention mechanisms are discussed.

Adult↗

The effects of acute tyrosine and phenylalanine depletion on spatial working memory and planning in healthy volunteers are predicted by changes in striatal dopamine levels.

RATIONALE: Dopamine (DA) is considered important in the modulation of tasks of spatial working memory. However, the findings from studies in humans to date are mixed. While this may be due to the characteristics of the tasks used, it is also possible that these findings are explained by variable central effects of the manipulations used. OBJECTIVE: To test the effects of acute tyrosine and phenylalanine depletion (TPD, which reduces synthesis and release of brain DA) on cognitive function and relate changes in performance accuracy to the central effects of TPD measured with [11C]raclopride positron emission tomography (PET). METHODS: Fourteen participants were given tests of spatial working memory, planning, verbal memory span and trial-and-error learning after acute TPD, seven of whom also received PET scans to measure changes in striatal DA levels. RESULTS: Although TPD produced a clear reduction in tyrosine and phenylalanine availability to the brain, no impairments on any of the cognitive tests were observed. However, changes in spatial working memory and planning accuracy after TPD showed a highly significant relationship with the changes in striatal DA levels. CONCLUSIONS: Our findings suggest that the effects of TPD on spatial working memory and planning may be unreliable due to the variability of the changes in brain DA levels achieved with this manipulation.

Adult↗

Age-related deficits as working memory load increases: relationships with growth factors.

Young and aged female rats were tested on a water radial-arm maze designed to measure performance as working memory load increased, followed by brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin 3 (NT3) protein assessments in hippocampus and frontal cortex. Aged rats showed deficiencies in both working and reference memory. There were also profound age-related working memory load effects. Aged rats made more errors as working memory load increased and showed learning only during early trials when memory load was low, while young rats exhibited learning over all trials. Neurotrophin assessment showed that frontal cortex NGF and BDNF levels were positively, and hippocampal NT3 negatively, correlated with number of errors made during specific trials in aged animals. Comparison to untested rats showed that testing increased NT3, but not BDNF or NGF, protein levels in both age groups. Findings suggest that young rats learn to handle a higher working memory load as testing progresses, while aged rats do not, and that frontal cortex and hippocampal neurotrophin levels may relate to working memory proficiency in aged female rats.

Aging↗

Working memory span and situation model processing.

This study looked at how comprehension and memory processing at the situation model level is related to traditional measures of working memory capacity, including the word span, reading span, operation span, and spatial span tests. Issues of particular interest were the ability to remember event descriptions, the detection and memory of functional relationships, the detection of inconsistencies, sensitivity to causal connectivity, and memory for surface form, textbase, and situation-specific content. There was little evidence that traditional measures of working memory span were directly related to processing at the situation model level. However, working memory span was related to our few textbase-level tests.

Cognition↗

Contributions of subregions of the prefrontal cortex to working memory: evidence from brain lesions in humans.

We investigated working memory in patients with focal brain damage involving subregions of the prefrontal cortex (PFC). Lesions in the dorsal portion of lateral PFC or the ventromedial portion of orbital PFC did not impair performance in tasks that required maintenance and monitoring of object or spatial information. Larger lesions involving both ventral and dorsal parts of the lateral PFC impaired maintenance and monitoring of spatial and object information, with more severe deficits observed in the spatial tasks. The results support a distributed localization of function in lateral PFC during working memory.

Adult↗

Working memory capacity in schizophrenia: a parametric fMRI study.

Impaired working memory (WM) function in schizophrenia has been associated with abnormal activation of the dorsolateral prefrontal cortex (DLPFC). It is, however, not clear whether abnormal activation is a sign of DLPFC pathology, or a correlate of poor performance. We address this question by examining activity in the WM brain system at different levels of task difficulty. A parametric fMRI paradigm is used to examine how the WM system responds to increasing load. A parametric fMRI design with four levels of a spatial N-back task was used to examine the relationships between working memory load, functional output (performance) and brain activity in 10 schizophrenic patients on atypical antipsychotic medication and to compare these to 10 healthy controls. In spite of increasingly poor performance in schizophrenic patients, activity increased normally in DLPFC and inferior parietal cortex bilaterally and in anterior cingulate, with increasing load. At 3-back, activity dropped in DLPFC in comparison with controls, but not in the other regions. The results indicate that peak activation of the WM-system is reached at a lower processing load in schizophrenic patients than in healthy controls. As a decline of DLPFC activity at high processing loads in itself is not abnormal, WM dysfunction in schizophrenia appears to be the result of an impaired functional output of the whole WM system, causing elevation of the effective burden imposed by WM tasks.

Adult↗

D-cycloserine, a glycine site agonist, reverses working memory failure by hippocampal muscarinic receptor blockade in rats.

D-Cycloserine, a partial agonist at the glycine binding site on the NMDA receptor/channel complex, did not affect 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 1 or 10 microg/side into the dorsal hippocampus. Intrahippocampal administration of the muscarinic receptor antagonist scopolamine (3.2 microg/side) significantly increased the number of working memory errors. The increase in working memory errors induced by intrahippocampal 3.2 microg/side scopolamine was significantly reduced by concurrent infusion of 1 and 10 microg/side D-cycloserine. These results suggest that positive modulation of the NMDA receptor/channel through activation of the glycine site can compensate dysfunction of hippocampal cholinergic neurotransmission involved in working memory function.

Animals↗

Effect of the BDNF V166M polymorphism on working memory in healthy adolescents.

Brain-derived neurotrophic factor (BDNF) may play a role in modulating memory function and there is growing evidence that the BDNF V166M polymorphism may influence episodic memory in humans. However, previous association studies examining this polymorphism and working memory are inconsistent. The current study examined this association in a large sample of adolescent twin-pairs and siblings (785 individuals from 439 families). A range of measures (event-related potential, general performance and reaction time) was obtained from a delayed-response working-memory task and total association was examined using the quantitative transmission disequilibrium tests (QTDT) program. Analyses had approximately 93-97% power (alpha= 0.05) to detect an association accounting for as little as 2% of the variance in the phenotypes examined. Results indicated that the BDNF V166M polymorphism is not associated with variation in working memory in healthy adolescents.

Adolescent↗

Voluntazy and automatic attentional control of visual working memory.

Previous studies of attention-directing cues have focused largely on the effects of cuing on perceptual processes, but cuing may also influence the transfer of perceptual representations into visual working memory. In the present study, we examined this potential role of cues, using both predictive and non-predictive cues in the context of a visual working memory task. Each trial began with a cue, followed by an array of six colored squares, a delay interval, and then a probe square presented at th e location of one of the squares in the previous array. The subjects were required to indicate whether the color of the probe square was the same as the color of the square that had previously been presented at the same location. Performance on this working memory task was more accurate when the cued location was probed than when an uncued location was probed, even when the cued location was no more likely to be probed than any of the uncued locations. An additional experiment using the abrupt-onset paradigm of Yantis and Jonides (1984) yielded similar results. Thus, visual transients may automatically influence the transfer of perceptual representations into visual working memory.

Adolescent↗

Seeking the neural substrates of visual working memory storage.

It is widely assumed that the prefrontal cortex (PFC) is a critical site of working memory storage in monkeys and humans. Recent reviews of the human lesion literature and recent neuroimaging results, however, challenge this view. To test these alternatives, we used event-related fMRI to trace the retention of working memory representation of target faces across three delay periods that were interposed between the presentation of each of four stimuli. Across subjects, only posterior fusiform gyrus demonstrated reliable retention of target-specific activity across all delay periods. Our results suggest that no part of frontal cortex, including PFC, stores mnemonic representation of faces reliably across distracted delay periods. Rather, working memory storage of faces is mediated by a domain-specific network in posterior cortex.

Adult↗

Converging evidence that stereotype threat reduces working memory capacity.

Although research has shown that priming negative stereotypes leads to lower performance among stigmatized individuals, little is understood about the cognitive mechanism that accounts for these effects. Three experiments tested the hypothesis that stereotype threat interferes with test performance because it reduces individuals' working memory capacity. Results show that priming self-relevant negative stereotypes reduces women's (Experiment 1) and Latinos' (Experiment 2) working memory capacity. The final study revealed that a reduction in working memory capacity mediates the effect of stereotype threat on women's math performance (Experiment 3). Implications for future research on stereotype threat and working memory are discussed.

Adult↗

Alterations in the functional anatomy of working memory in adult attention deficit hyperactivity disorder.

OBJECTIVE: The authors used a functional neuroimaging study with a working memory probe to investigate the pathophysiology of attention deficit hyperactivity disorder (ADHD). Their goal was to compare regional cerebral blood flow (rCBF) changes related to working memory in adults with and without ADHD. METHOD: Using [(15)O]H(2)O positron emission tomography (PET) studies, the authors compared the sites of neural activation related to working memory in six adult men diagnosed with ADHD and six healthy men without ADHD who were matched in age and general intelligence. RESULTS: Task-related changes in rCBF in the men without ADHD were more prominent in the frontal and temporal regions, but rCBF changes in men with ADHD were more widespread and primarily located in the occipital regions. CONCLUSIONS: These data suggest the use of compensatory mental and neural strategies by subjects with ADHD in response to a disrupted ability to inhibit attention to nonrelevant stimuli and the use of internalized speech to guide behavior.

Adult↗

EEG correlates of verbal and nonverbal working memory.

BACKGROUND: Distinct cognitive processes support verbal and nonverbal working memory, with verbal memory depending specifically on the subvocal rehearsal of items. METHODS: We recorded scalp EEG while subjects performed a Sternberg task. In each trial, subjects judged whether a probe item was one of the three items in a study list. Lists were composed of stimuli from one of five pools whose items either were verbally rehearsable (letters, words, pictures of common objects) or resistant to verbal rehearsal (sinusoidal grating patterns, single dot locations). RESULTS: We found oscillatory correlates unique to verbal stimuli in the theta (4-8 Hz), alpha (9-12 Hz), beta (14-28 Hz), and gamma (30-50 Hz) frequency bands. Verbal stimuli generally elicited greater power than did nonverbal stimuli. Enhanced verbal power was found bilaterally in the theta band, over frontal and occipital areas in the alpha and beta bands, and centrally in the gamma band. When we looked specifically for cases where oscillatory power in the time interval between item presentations was greater than oscillatory power during item presentation, we found enhanced beta activity in the frontal and occipital regions. CONCLUSION: These results implicate stimulus-induced oscillatory activity in verbal working memory and beta activity in the process of subvocal rehearsal.

Journal Article↗