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The neural correlates of human working memory for haptically explored object orientations.

Skillful object manipulation requires that haptically explored spatial object characteristics like orientation be adequately represented in working memory. In the current functional magnetic resonance imaging study, healthy right-handed participants explored a bar-shaped reference object with the left hand, memorizing its orientation. After a variable delay (0.5, 5, or 10 s), participants used their right hand to match the orientation by rotating a second, identical object. In the first seconds of the delay, right sensorimotor cortex was active, whereas clusters in left anterior prefrontal cortex (aPFC) (Brodmann area 10) became dominant 2 s after the end of exploration, showing sustained activity for several seconds. In contrast, left parieto-occipital cortex was involved toward the end of the delay interval. Our results indicate that a dynamic network of brain areas subserves hapticospatial information processing in the delay between haptic stimulus exploration and orientation matching. We propose that haptic sensory traces, maintained in contralateral sensorimotor cortex, are transformed into more abstract hapticospatial representations in the early delay stages. Maintenance of these representations engages aPFC and parieto-occipital cortex. Whereas aPFC possibly integrates spatial and motor components of hapticospatial working memory, parieto-occipital cortex might be involved in orientation imagery, supporting working memory, and the preparation of haptic matching.

Adult↗

Commonalities and differences in the working memory components underlying letter and category fluency tasks: a dual-task investigation.

This study used a dual-task interference paradigm to test the hypothesis that different subcomponents of working memory differentially contribute to performance on letter fluency and category fluency tasks. College students (N = 96) performed each type of verbal fluency task in isolation and concurrently with I of 3 secondary tasks. The secondary tasks were chosen for their putative involvement in different working memory subcomponents. Two subsystems of working memory, the phonological loop and the visuospatial sketchpad, were identified as important contributors to fluency performance, especially to performance on letter fluency and category fluency tasks, respectively. Moreover, the results also suggest that the executive function, mental set shifting, may be deployed to perform both letter fluency and category fluency tasks.

Adolescent↗

Visual but not spatial working memory deficit in children with spina bifida.

Twenty children with spina bifida and twenty controls were assessed on a battery of visuospatial working memory tests. Children with spina bifida performed as well as the control group in the visuospatial test and in the forward and backward versions of the Corsi test, but were impaired in the 'House Visual Span.' This test, designed in our lab, provides specific information regarding visual ability to discriminate between pictorial targets and lures, and requires specific visual processing of stimuli. These results are discussed in terms of working memory models and are viewed as supporting the distinction between the visual and spatial components of working memory.

Adolescent↗

The effects of prelimbic and infralimbic lesions on working memory for visual objects in rats.

The present experiment investigated the effects of quinolinic acid (90 mM) lesions of the prelimbic-infralimbic cortices on working memory for visual objects and on acquisition of a visual object discrimination. In both tests a GO/NO-GO procedure was used. In the working memory task, rats were tested before and after surgery. A continuous recognition procedure was used to assess working memory, which involved successive exposure to different three-dimensional objects that could be displaced to receive a cereal reinforcement. Of the 12 object presentations/session, 4 objects were presented for a second time in which displacing the object did not result in a reinforcement. The number of trials between the first and second presentations of an object ranged from 0 to 3 (lags). Memory was assessed by the latency to displace an object during the second presentation. In the visual object discrimination, rats had successive exposure to two different objects. Displacement of one object resulted in a cereal reinforcement, while displacement of the other did not. The findings indicated that prelimbic-infralimbic lesions significantly impaired memory for visual objects across all lags. Prelimbic-infralimbic lesions did not impair acquisition of the visual object discrimination. The results suggest that the prelimbic-infralimbic areas are part of neural system important in the short-term memory for visual objects.

Animals↗

Individual and age-related differences in children's working memory.

The purpose of this study was to investigate the degree to which age-related and individual differences in children's working memory (WM) are due to a general or task-specific capacity system. Experiment 1 correlated children's (N = 146; age range 5-19 years) verbal and visual-spatial working memory performance with various intelligence and achievement measures. The results supporting a general system were that (1) visual-spatial and verbal WM measures were significantly intercorrelated with and without age partialed out and (2) both verbal and visual-spatial WM measures were significantly correlated with diverse achievement and intelligence measures. Experiment 2 compared three age groups (N = 192; 7-, 10-, and 13-year-olds) on working-memory performance tasks under initial, enhanced (cued), and maintenance conditions. The results supporting a general capacity system were that (1) age-related performance differences in WM were found on all conditions and not isolated to specific processes, (2) the maintenance measures (high-load condition) predicted the variance better in age-related performance than process measures, and (3) although individual differences in WM performance reflected two independent operations, these operations produced similar correlations to achievement within age groups. Overall, the results support a general capacity explanation of age-related and individual differences in children's WM performance.

Adolescent↗

Separate neural correlates for the mnemonic components of successive discrimination and working memory tasks.

We have used positron emission tomography to map the mnemonic components of two tasks at the extremes of the visual short-term/ working memory spectrum. The successive discrimination task requires only storage of a single item for very short time (ultra-short- term memory), while the 2back task requires both maintenance (i.e. storage and rehearsal) and manipulation of several items (working memory). We tested whether or not the storage component, common to the two tasks, engaged the same cerebral regions. To remove unnecessary confounds, we reduced the cues available to the subjects to a single elementary attribute, the orientation of a grating presented in central vision. This prevented subjects from using verbal strategies or vestibular cues and allowed equating of difficulty among tasks. Ultra-short-term memory for orientation engaged a large expanse of occipito-temporal cortex with a rate-dependent antero-posterior gradient: a fast trial rate engaged posterior regions, a slow trial rate anterior regions. On the other hand, working memory for orientation involved the left inferior parietal cortex, left dorsolateral prefrontal cortex and a left superior frontal sulcus region, and to a lesser degree the symmetrical right superior frontal region and a left superior parietal region. Direct comparison of the two orientation memory networks confirmed their functional segregation. We conclude that at least the storage of orientation information engages distinct regions depending on whether or not short-term memory/working memory involves rehearsal and/or manipulative processes.

Adult↗

Storage and processing working memory functions in Alzheimer-type dementia.

A selective deterioration of working memory functions has been suggested as an explanation of the cognitive decay occurring in normal ageing as well as in Alzheimer-type dementia. Recent studies have highlighted that elderly people's limitations in working memory functions may be better interpreted when analysing the specific characteristics of the cognitive process (i.e., passive storage or active manipulation of information). In the present study, we have adapted a procedure used to investigate age-related memory modifications, involving both verbal and visuo-spatial material in tasks tapping passive and active processes, to investigate the deterioration associated with Alzheimer's disease. A group of Alzheimer patients in the early stages of the disease were matched to a control group of healthy elderly. Results show that Alzheimer patients performed less accurately than the control group in all tasks. However, the deficit was maximised in the case of active processes, regardless of the type of material used (verbal or visuo-spatial). These data highlight the importance of considering the amount of active processing as the key variable when interpreting the decay in cognitive functions in the early stages of Alzheimer's disease.

Journal Article↗

[Working memory in healthy subjects and schizophrenics: studies using BOLD fMRT].

Functional magnetic resonance imaging uses the blood oxygen level-dependent effect (BOLD MRI) for noninvasive display of cerebral correlatives of cognitive function. The importance for the understanding of physiological and pathological processes is demonstrated by investigations of working memory in schizophrenics and healthy controls. Working memory is involved in processing rather than storage of information and therefore is linked to complex processes such as learning and problem solving. In schizophrenic psychosis, these functions are clearly restricted. Training effects in the working memory task follow an inverse U-shape function, suggesting that cerebral activation reaches a peak before economics of the brain find a more efficient method and activation decreases.

Brain↗

Models of functional organization of the lateral prefrontal cortex in verbal working memory: evidence in favor of the process model.

Research on the functional organization of the lateral prefrontal cortex (PFC) in working memory continues to be fairly equivocal between two major frameworks: organization-by-process or organization-by-material. Although there is fairly strong evidence for organization-by-process models from event-related fMRI studies, some investigators argue that the nature of the stimulus material better defines the functional organization of the lateral PFC, particularly in more ventral regions (BA 47/45/44). Specifically, the anterior region of the ventrolateral PFC (BA 47/45) is hypothesized to subserve semantic processing while the posterior region (BA 44) may subserve phonological processing. In the current event-related fMRI study, we directly compared process-related versus material-related organizational principles in a verbal working memory task. Subjects performed a modified delayed response task in which they (1) retained a list of five words or five nonwords during the delay period ("maintenance"), or (2) performed a semantic (size reordering) or phonological (alphabetical reordering) task on the word or nonword lists, respectively ("manipulation"). We did not find evidence during the delay period of our task to support claims of anterior-posterior specializations in the ventrolateral PFC for semantic versus phonological processing. Subjects did, however, display greater neuronal activity during the delay period of manipulation trials than maintenance trials in both the dorsolateral PFC and posterior ventrolateral regions. These data are more consistent with the process model of the organization of lateral PFC in verbal working memory.

Adolescent↗

Association between response inhibition and working memory in adult ADHD: a link to right frontal cortex pathology?

BACKGROUND: We sought to assess the relationship between response inhibition and working memory in adult patients with attention-deficit/hyperactivity disorder (ADHD) and neurosurgical patients with frontal lobe damage. METHODS: The stop-signal reaction time (SSRT) test and a spatial working memory (SWM) task were administered to 20 adult patients with ADHD and a group of matched controls. The same tasks were administered to 21 patients with lesions to right frontal cortex and 19 patients with left frontal lesions. RESULTS: The SSRT test, but not choice reaction time, was significantly associated with search errors on the SWM task in both the adult ADHD and right frontal patients. In the right frontal patients, impaired performance on both variables was correlated with the volume of damage to the inferior frontal gyrus. CONCLUSIONS: Response inhibition and working memory impairments in ADHD may stem from a common pathologic process rather than being distinct deficits. Such pathology could relate to right frontal-cortex abnormalities in ADHD, consistent with prior reports, as well as with the demonstration here of a significant association between SSRT and SWM in right frontal patients.

Adult↗

Brain connectivity related to working memory performance.

Several brain areas show signal decreases during many different cognitive tasks in functional imaging studies, including the posterior cingulate cortex (PCC) and a medial frontal region incorporating portions of the medial frontal gyrus and ventral anterior cingulate cortex (MFG/vACC). It has been suggested that these areas are components in a default mode network that is engaged during rest and disengaged during cognitive tasks. This study investigated the functional connectivity between the PCC and MFG/vACC during a working memory task and at rest by examining temporal correlations in magnetic resonance signal levels between the regions. The two regions were functionally connected in both conditions. In addition, performance on the working memory task was positively correlated with the strength of this functional connection not only during the working memory task, but also at rest. Thus, it appears these regions are components of a network that may facilitate or monitor cognitive performance, rather than becoming disengaged during cognitive tasks. In addition, these data raise the possibility that the individual differences in coupling strength between these two regions at rest predict differences in cognitive abilities important for this working memory task.

Adult↗

Alcohol attenuates load-related activation during a working memory task: relation to level of response to alcohol.

BACKGROUND: A low level of response to alcohol is a major risk factor for the development of alcohol dependence, but neural correlates of this marker are unclear. METHOD: Ten healthy volunteers were classified by median split on level of response to alcohol and underwent 2 sessions of functional magnetic resonance imaging following ingestion of a moderate dose of alcohol and a placebo. The blood oxygen level-dependent activation to an event-related visual working memory test was examined. RESULTS: The subjects exhibited longer response latencies and more errors as a function of increasing working memory load and showed a load-dependent increase in activation in dorsolateral prefrontal cortex, posterior parietal cortex, and visual cortex. Alcohol did not affect performance (errors or response latency), but attenuated the working memory load-dependent activation in the dorsolateral prefrontal cortex. During the placebo condition, individuals with a low level of response to alcohol showed greater activation in dorsolateral prefrontal cortex and posterior parietal cortex than those with a high level of response to alcohol. During the alcohol condition, groups showed similar attenuation of load-dependent brain activation in these regions. CONCLUSION: Low-level responders relative to high-level responders exhibited an increased working memory load-dependent activation in dorsolateral prefrontal cortex and posterior parietal cortex when not exposed to alcohol. This increase in brain response was attenuated in low-level responders after ingesting a moderate dose of alcohol.

Adult↗

Impairments on nonspatial self-ordered and externally ordered working memory tasks after lesions of the mid-dorsal part of the lateral frontal cortex in the monkey.

Monkeys with lesions of the mid-dorsal part of the lateral frontal cortex, which extends above the sulcus principalis as far as the midline (MDL lesions), were shown to exhibit severe and long-lasting impairments on certain nonspatial working memory tasks: the self-ordered and externally ordered tasks (experiments 1, 2, 3, 5, 6, and 8). These tasks, which were modeled on similar ones previously used with patients, measure the capacity to monitor, within working memory, self-generated choices and the occurrence of externally ordered stimuli. Monkeys with lesions of the adjacent posterior dorsolateral frontal cortex, which surrounds the arcuate sulcus (PA lesions), performed as well as the normal control animals on these tasks. Experiments 4 and 5 showed that the critical variable accounting for the impairment on the self-ordered and externally ordered working memory tasks by monkeys with MDL lesions is the size of the set of stimuli that must be monitored. Furthermore, the MDL lesions did not affect basic recognition memory (experiment 6), or primacy and recency mnemonic effects [i.e., the capacity to discriminate between the initial (or final) items and other items in a list of stimuli (experiments 4 and 7), or the capacity to select from a set of stimuli on the basis of a learned fixed sequence (experiment 9)]. Thus, lesions of the mid-dorsal part of the lateral frontal cortex give rise to an impairment in working memory that depends on the size of the set of the stimuli that have to be monitored.

Animals↗

Effects of modafinil on working memory processes in humans.

RATIONALE: Modafinil is a well-tolerated psychostimulant drug with low addictive potential that is used to treat patients with narcolepsy or attention deficit disorders and to enhance vigilance in sleep-deprived military personal. So far, understanding of the cognitive enhancing effects of modafinil and the relevant neurobiological mechanisms are incomplete. OBJECTIVES: The aim of this study was to investigate the effects of modafinil on working memory processes in humans and how they are related to noradrenergic stimulation of the prefrontal cortex. METHODS: Sixteen healthy volunteers (aged 20-29 years) received either modafinil 200 mg or placebo using a double blind crossover design. Two computerized working memory tasks were administered, a numeric manipulation task that requires short-term maintenance of digit-sequences and different degrees of manipulation as well as delayed matching task that assesses maintenance of visuo-spatial information over varying delay lengths. The battery was supplemented by standardized paper pencil tasks of attentional functions. RESULTS: Modafinil significantly reduced error rates in the long delay condition of the visuo-spatial task and in the manipulation conditions, but not in the maintenance condition of the numeric task. Analyses of reaction times showed no speed-accuracy trade-off. Attentional control tasks (letter cancellation, trail-making, catch trials) were not affected by modafinil. CONCLUSIONS: In healthy volunteers without sleep deprivation modafinil has subtle stimulating effects on maintenance and manipulation processes in relatively difficult and monotonous working memory tasks, especially in lower performing subjects. Overlapping attentional and working memory processes have to be considered when studying the noradrenergic modulation of the prefrontal cortex.

Adult↗

Working memory deficits and levels of N-acetylaspartate in patients with schizophreniform disorder.

OBJECTIVE: The authors used proton magnetic resonance spectroscopic imaging ((1)H-MRSI) to assess potential reductions of N-acetylaspartate (a marker of neuronal integrity) in the hippocampal area and dorsolateral prefrontal cortex of patients with schizophreniform disorder. In addition, they assessed the relationship between N-acetylaspartate levels and working memory deficits. METHOD: Twenty-four patients with DSM-IV schizophreniform disorder and 24 healthy subjects were studied. Subjects underwent (1)H-MRSI and were given the N-back working memory test. RESULTS: The schizophreniform disorder patients had selective reductions of N-acetylaspartate ratios in the hippocampal area and the dorsolateral prefrontal cortex, and a positive correlation was seen between N-acetylaspartate ratios in the dorsolateral prefrontal cortex and performance during the 2-back working memory condition. CONCLUSIONS: Similar to findings reported in schizophrenia studies, N-acetylaspartate reductions in the hippocampal area and the dorsolateral prefrontal cortex were seen in patients with schizophreniform disorder. Moreover, the results support other evidence that neuronal pathology in the dorsolateral prefrontal cortex accounts for a proportion of working memory deficits already present at illness outset.

Adult↗

The effects of d-cycloserine, a partial agonist at the glycine binding site, on spatial learning and working memory in scopolamine-treated rats.

The present study investigated the effect of d-cycloserine, a partial agonist at the glycine binding site on NMDA receptor complex, on the performance of scopolamine-treated adult rats in a water maze task assessing spatial learning and in a delayed non-matching to position task assessing working memory in a spatial context. In the spatial learning task, scopolamine (0.4 mg/kg, i.p.) impaired acquisition (increased escape latency and distance) and increased swimming speed of rats. D-cycloserine (1.0 mg/kg, i.p.) reversed the deficits in acquisition performance but not the increases in behavioral activity. In the working memory task, scopolamine (0.2 mg/kg, i.p.) produced deficits on nonmnemonic rather than on mnemonic performance factors; scopolamine delay-independently decreased the percent correct responses and reduced behavioral activity of rats. D-cycloserine (1.0, 3.0 and 10 mg/kg, i.p.) did not reverse these performance deficits. When administered alone, the moderate to higher doses of d-cycloserine had no effects on working memory but the lower dose produced slight deficits in mnemonic performance factors; the 1.0 mg/kg dose delay-dependently decreased the percent correct responses without affecting behavioral activity of rats. In the water maze task, d-cycloserine had no effects on acquisition performance or behavioral activity of rats. These results suggest that acute, systemic administration of d-cycloserine does not improve spatial learning or working memory. However, at appropriate doses this agent may be efficacious in disease states of central cholinergic hypofunction since 1.0 mg/kg d-cycloserine was able to reverse the scopolamine-induced deficits in acquisition.

Animals↗

Opioid modulation of working memory: intraseptal, but not intraamygdaloid, infusions of beta-endorphin impair performance in spatial alternation.

The effect of beta-endorphin on spatial working memory was examined following microinfusions of beta-endorphin into the medial septal area and central amygdaloid nucleus in Long-Evans male rats. Working memory was assessed by spatial alternation in a T-maze. beta-Endorphin, 250 and 1000 ng/site, respectively, and muscimol, 20 ng/site, were infused into the medial septal area or central amygdaloid nucleus prior to behavioral testing. The hippocampal theta rhythm was examined following intraseptal infusions of beta-endorphin and muscimol. In the medial septal area, beta-endorphin and muscimol impaired choice accuracy and reduced the power of hippocampal theta rhythm. The degree of reduction in the power of hippocampal theta rhythm was correlated with the magnitude of behavioral impairment of choice accuracy in spatial alternation. In the central amygdaloid nucleus, beta-endorphin (1000 ng) and muscimol (20 ng) did not affect choice accuracy. The results suggest that septal, but not amygdaloid, opioid, and GABAergic activity modulate spatial working memory and hippocampal physiology.

Amygdala↗

Remembering "what" brings along "where" in visual working memory.

Does a behavioral and anatomical division exist between spatial and object working memory? In this article, we explore this question by testing human participants in simple visual working memory tasks. We compared a condition in which there was no location change with conditions in which absolute location change and absolute plus relative location change were manipulated. The results showed that object memory was influenced by memory for relative but not for absolute location information. Furthermore, we demonstrated that relative space can be specified by a salient surrounding box or by distractor objects with no touching surfaces. Verbal memory was not influenced by any type of spatial information. Taken together, these results indicate that memory for "where" influences memory for "what." We propose that there is an asymmetry in memory according to which object memory always contains location information.

Humans↗