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PubMed2004

Inferior temporal, prefrontal, and hippocampal contributions to visual working memory maintenance and associative memory retrieval.

Higher order cognition depends on the ability to recall information from memory and hold it in mind to guide future behavior. To specify the neural mechanisms underlying these processes, we used event-related functional magnetic resonance imaging to compare brain activity during the performance of a visual associative memory task and a visual working memory task. Activity within category-selective subregions of inferior temporal cortex reflected the type of information that was actively maintained during both the associative memory and working memory tasks. In addition, activity in the anterior prefrontal cortex and hippocampus was specifically enhanced during associative memory retrieval. These data are consistent with the view that the active maintenance of visual information is supported by activation of object representations in inferior temporal cortex, but that goal-directed associative memory retrieval additionally depends on top-down signals from the anterior prefrontal cortex and medial temporal lobes.

Adolescent↗

PubMed2005

Activity in human medial temporal lobe associated with encoding process in spatial working memory revealed by magnetoencephalography.

Animal studies have suggested that working memory may be affected after lesions in the medial temporal lobe, although this assumption has not been corroborated by neuropsychological studies in humans. However, very recently, several functional neuroimaging studies in humans have successfully observed activation of the medial temporal lobe during working memory tasks. The main aim of this study was to investigate the contribution of the medial temporal lobe to the encoding process in spatial working memory. To address this issue we registered the neuromagnetic brain patterns of eight adult volunteers while they performed a spatial working memory task and more perceptual task using identical stimuli. After a initial phase (between 200 and 400 ms) without differences in activation, the medial temporal lobe showed a sustained activity, more evident in the right hemisphere, lasting up to 800 ms during the encoding stage of the spatial working memory task, while the activation in the perceptual task terminated earlier (approximately 400 ms after stimulus onset). The finding of a continued activation of the medial temporal lobe strongly suggests the contribution of this brain region to encoding operations in working memory.

Adult↗

PubMed1993

Effect of age and strain on working memory in mice as measured by win-shift paradigm.

Working memory is disrupted in Alzheimer's disease and stroke; therefore, any therapeutic drug should restore deficits in working memory. The win-shift foraging paradigm has been demonstrated to be a model of working memory in rats. In the present study, this paradigm was adapted to mice because of the greater ease and economy of testing potential drugs in mice and the wider availability of strains of aged mice with naturally occurring working memory deficits. This study has demonstrated strain differences in the working memory trace and that age induces a deficit that can be detected at 11 months of age in mice. Tacrine and physostigmine enhance the memory trace in normal mice and physostigmine can reverse age-induced working memory deficits in subjects with mild and moderate deficits but not in subjects with severe deficits.

Aging↗

PubMed1995

Nicotinic and muscarinic receptors in the rat prefrontal cortex: differential roles in working memory, response selection and effortful processing.

The aim of the present study was to evaluate the effects of cholinergic receptor blockade in the rat prefrontal cortex on cognitive processes. The nicotinic antagonists neuronal bungarotoxin and dihydro-beta-erythroidine and the muscarinic antagonist scopolamine were injected into the prelimbic area of the prefrontal cortex. Their behavioural effects were assessed in a T-maze to test reference memory (visual discrimination task) and working memory in delayed matching (MTS) and non-matching to sample (NMTS) tasks. Neuronal bungarotoxin produced a significant decrease in working memory performance in the MTS task but not in the NMTS task. In contrast, scopolamine impaired working memory in both MTS and NMTS tasks. Reference memory was not altered by any of the cholinergic antagonists. These results demonstrate a differential role of nicotinic and muscarinic receptors in the rat prefrontal cortex. Nicotinic transmission appears to be important in delayed response tasks requiring effortful processing for response selection, while the muscarinic system is involved in general working memory processes.

Acetylcholine↗

PubMedDate not supplied

The relationships between working memory and long-term memory.

Recent studies have led to the proposal that working memory operates not as a gateway between sensory input and long-term memory but as a workspace. The core of argument is that access to acquired knowledge and prior learning occurs before information becomes available to working memory. This proposition is a way to accommodate Baddeley's multiple component working memory model and the view that considers that working memory is nothing other than temporary activations of representations and procedures in long-term memory. However, this 'workspace' conception of working memory raises the question of the relationships between the central executive system and long-term memory.

Humans↗

PubMed2001

Individual differences in working memory: introduction to the special section.

This special section includes a set of 5 articles that examine the nature of inter- and intraindividual differences in working memory, using working memory span tasks as the main research tools. These span tasks are different from traditional short-term memory spans (e.g., digit or word span) in that they require participants to maintain some target memory items (e.g., words) while simultaneously performing some other tasks (e.g., reading sentences). In this introduction, a brief discussion of these working memory span tasks and their characteristics is provided first. This is followed by an overview of 2 major theoretical issues that are addressed by the subsequent articles--(a) the factors influencing the inter- and intraindividual differences in working memory performance and (b) the domain generality versus domain specificity of working memory--and also of some important issues that must be kept in mind when readers try to evaluate the claims regarding these 2 theoretical issues.

Attention↗

PubMed2006

Dorsolateral prefrontal cortex promotes long-term memory formation through its role in working memory organization.

Results from neuroimaging studies have shown that the dorsolateral prefrontal cortex (DLPFC) implements processes critical for organizing items in working memory (WM). Based on its role in WM, we hypothesized that the DLPFC should contribute to long-term memory (LTM) formation by strengthening associations among items that are organized in WM. We conducted an event-related functional magnetic resonance imaging (fMRI) study to test this hypothesis by investigating prefrontal activity during performance of two different WM tasks: on "rehearse" trials, participants actively maintained triplets of words during a brief delay, whereas on "reorder" trials, participants actively organized each triplet during the delay. After scanning, subjects performed an LTM test on words presented during both WM conditions. Behavioral results showed that WM processing in the reorder condition enhanced LTM by strengthening inter-item associations. fMRI results showed that DLPFC activity specifically during reorder trials was predictive of subsequent LTM. In contrast, activity in the posterior ventrolateral prefrontal cortex was predictive of LTM for words studied on both reorder and rehearse trials. These results support the view that the DLPFC contributes to LTM formation through its role in organization of information in WM.

Adult↗

PubMedDate not supplied

Working memory and novel word learning in children with hearing impairment and children with specific language impairment.

BACKGROUND: Working memory is considered to influence a range of linguistic skills, i.e. vocabulary acquisition, sentence comprehension and reading. Several studies have pointed to limitations of working memory in children with specific language impairment. Few studies, however, have explored the role of working memory for language deficits in children with hearing impairment. AIMS: The first aim was to compare children with mild-to-moderate bilateral sensorineural hearing impairment, children with a preschool diagnosis of specific language impairment and children with normal language development, aged 9-12 years, for language and working memory. The special focus was on the role of working memory in learning new words for primary school age children. METHODS & PROCEDURES: The assessment of working memory included tests of phonological short-term memory and complex working memory. Novel word learning was assessed according to the methods of. In addition, a range of language tests was used to assess language comprehension, output phonology and reading. OUTCOMES & RESULTS: Children with hearing impairment performed significantly better than children with a preschool diagnosis of specific language impairment on tasks assessing novel word learning, complex working memory, sentence comprehension and reading accuracy. No significant correlation was found between phonological short-term memory and novel word learning in any group. The best predictor of novel word learning in children with specific language impairment and in children with hearing impairment was complex working memory. Furthermore, there was a close relationship between complex working memory and language in children with a preschool diagnosis of specific language impairment but not in children with hearing impairment. CONCLUSIONS: Complex working memory seems to play a significant role in vocabulary acquisition in primary school age children. The interpretation is that the results support theories suggesting a weakened influence of phonological short-term memory on novel word learning in school age children.

Adolescent↗

PubMed2004

Search for cognitive trait components of schizophrenia reveals a locus for verbal learning and memory on 4q and for visual working memory on 2q.

Research to identify predisposing genes for complex diseases relying solely on clinical diagnosis is probably not ideal. Here, we analyzed genome-wide data for 168 schizophrenia families using neuropsychological variables associated with disease susceptibility, with the aid of SOLAR, a program for variance-component analysis. The linkage signal was greatly accentuated by application of the quantitative traits compared with diagnosis. We found evidence for a locus for verbal learning and memory on 4q21 (Z=3.01, Z(mp)=3.84 and empiric P=0.031 for delayed memory; Z=2.96, Z(mp)=3.4 and P=0.026 for verbal learning) and suggestive evidence for visual working memory on 2q36 (Z=2.80, Z(mp)=2.08 and P=0.093). In addition, some evidence emerged for a locus for recognition memory on 10p13, visual attention on 15q22 and executive function on 9p22 in the complete sample, as well as for delayed memory on 8q12, semantic clustering and intrusions on 1q42 and visual attention on 3p25 in the genealogically distinctive sample subsets. Of the loci linked to schizophrenia in diverse populations, in addition to the earlier mentioned regions, some evidence of linkage was observed for 2q, 6q, 7q, 11q, 13q, 14q, 18q and 22q. Our results reveal initial information on the effect of the loci associated with schizophrenia in multiple studies, and emphasize the value of trait components in the search for susceptibility loci for complex diseases.

Analysis of Variance↗

PubMed1998

Working memory and aphasia.

This study investigated the relationship between working memory capacity and reading comprehension in aphasia. A measurement of working memory capacity was obtained using a modified version of Daneman and Carpenter's (1980) Reading Span Task. Sets of sentences ranging in length from one to six words were presented to 22 aphasic subjects who were required to retain the terminal words following each sentence for subsequent recognition. The maximum number of words retrieved was used as an index of working memory capacity. Two versions of the task (listening and reading) were presented depending on the subjects' ability to read. Strong positive correlations were found between working memory capacity, reading comprehension, and language function. These results support the notion that the ability of aphasic individuals to comprehend language is predictable from their working memory capacities.

Adult↗

PubMed1992

Adults' reading comprehension: effects of syntactic complexity and working memory.

Two experiments investigated the relationship between working memory and reading comprehension. In the first, college students, 18 to 26 years of age, and adults, 60 to 92 years of age, were given a battery of tests of working memory, a standard timed reading comprehension test, and a reading test designed to explore how syntactic complexity affects comprehension. In a follow-up study, the adults were retested on a modified version of the syntax comprehension text. Age group declines in working memory and reading comprehension were obtained in Experiment I; age group declines in reading rate but not comprehension were obtained in Experiment II. The results suggest that working memory limitations affect elderly adults' ability to process complex syntactic constructions, lowering comprehension in the timed test (Experiment I) and reducing reading rates in the untimed test (Experiment II).

Adolescent↗

PubMed2000

Nature of the working memory deficit in fragile-X syndrome.

Working memory performance in a group of young Fragile X males with FMR-1 full mutation was compared to a learning disabled comparison group comprising Down's syndrome males and two control groups of mainstream schoolchildren. Performance was assessed on a battery of tasks tapping the three components of working memory-phonological loop, visual-spatial sketch pad, and the central executive. The results indicated that the Fragile X group displayed a general impairment on working memory tasks that cannot be attributed to a single working memory component per se. Instead, the results suggest that Fragile X males have a working memory deficit that may be attributed to how much attentional resource a specific task requires and their overall available executive capacity, irrespective of the working memory subsystem.

Adolescent↗

PubMed2002

Tracking the time-course of attentional involvement in spatial working memory: an event-related potential investigation.

Spatial working memory is a cognitive brain mechanism that enables the temporary maintenance and manipulation of spatial information. Recent neuroimaging and behavioral studies have led to the proposal that directed spatial attention is the mechanism by which location information is maintained in spatial working memory. Yet it is unclear whether attentional involvement is required throughout the period of active maintenance or is only invoked during discrete task-phases such as mnemonic encoding. In the current study, we aimed to track the time-course of attentional involvement during spatial working memory by recording event-related brain potentials (ERPs) from healthy volunteers. In Experiment 1, subjects performed a delayed-recognition task. Each trial began with the presentation of a brief stimulus (S1) that indicated the relevant location that subjects were to maintain in working memory. A 4.8-5.3 sec delay interval followed during which a single task-irrelevant probe was presented. The delay interval concluded with a test item (S2) to which subjects made a response indicating whether the S2-location was the same as the S1-memory location. To determine if attention was differentially engaged during discrete phases of the trial, task-irrelevant probes were presented early (400-800 msec following S1-offset) or late (2600-3000 msec following S1-offset) during the delay interval. Sensory-evoked ERPs (P1 and N1) elicited by these irrelevant probes showed attention-like modulations with greater amplitude responses for probes occurring at the S1-memory locations in comparison to probes presented at other locations. This pattern was obtained for both early- and late-delay probes. Probe-evoked activity during delayed-recognition trials was similar to activity observed when spatial attention was explicitly focused on a location in visual space (Experiment 2). These results are consistent with a model of spatial working memory in which perceptual level selective attention is utilized throughout the entire period of active maintenance to keep relevant spatial information in mind.

Adolescent↗

PubMed2001

High levels of estradiol disrupt conditioned place preference learning, stimulus response learning and reference memory but have limited effects on working memory.

The present study investigated the effects of high levels of estradiol in female rats on four different radial arm maze tasks: the hippocampus-dependent spatial working-reference memory task; the prefrontal cortex-hippocampus dependent delayed win-shift task; the striatum-dependent cued win-stay task; and the amygdala-dependent conditioned place preference task. Ovariectomized female rats were injected daily with either 10 microg of estradiol benzoate or sesame oil vehicle approximately 4 h prior to testing. In Experiment 1, treatment with estradiol disrupted learning on the spatial working-reference memory task by increasing the number of reference memory errors to reach criterion. In Experiment 2, treatment with estradiol had no significant effect on the delayed win-shift task. In Experiment 3, treatment with estradiol resulted in impaired performance on a striatum-dependent cued win-stay task. In Experiment 4, treatment with estradiol impaired the acquisition of a conditioned place-preference task. Taken together these findings suggest that high levels of estradiol inhibit reference memory, stimulus response learning, and amygdala-dependent appetitive conditioning while having little effect on working memory.

Amygdala↗

PubMed2006

Working memory deficits in adults with ADHD: is there evidence for subtype differences?

BACKGROUND: Working memory performance is important for maintaining functioning in cognitive, academic and social activities. Previous research suggests there are prevalent working memory deficits in children with attention deficit hyperactivity disorder (ADHD). There is now a growing body of literature characterizing working memory functioning according to ADHD subtypes in children. The expression of working memory deficits in adults with ADHD and how they vary according to subtype, however, remains to be more fully documented. METHODS: This study assessed differences in working memory functioning between Normal Control (NC) adults (N = 18); patients with ADHD, Combined (ADHD-CT) Type ADHD (N = 17); and ADHD, Inattentive (ADHD-IA) Type (N = 16) using subtests from the Wechsler Adult Intelligence Scale-III and Wechsler Memory Scale-III and the Paced Auditory Serial Addition Task (PASAT). RESULTS: The ADHD groups displayed significant weaknesses in contrast to the NC group on working memory tests requiring rapid processing and active stimulus manipulation. This included the Letter-Number-Sequencing test of the Wechsler scales, PASAT omission errors and the longest sequence of consecutive correct answers on the PASAT. No overall ADHD group subtype differences emerged; however differences between the ADHD groups and the NC group varied depending on the measure and the gender of the participants. Gender differences in performance were evident on some measures of working memory, regardless of group, with males performing better than females. CONCLUSION: In general, the data support a dimensional interpretation of working memory deficits experienced by the ADHD-CT and ADHD-IA subtypes, rather than an absolute difference between subtypes. Future studies should test the effects of processing speed and load on subtype performance and how those variables interact with gender in adults with ADHD.

Journal Article↗

PubMed2005

Rehabilitation of verbal working memory after left hemisphere stroke.

PRIMARY OBJECTIVE: To assess a rehabilitation programme of working memory. RESEARCH DESIGN: Single case multiple-baseline-across-behaviour design in a patient with chronic stroke suffering from a specific impairment of working memory. METHODS: Rehabilitation included training of storage and processing components of verbal working memory. Outcome was assessed with specific working memory tests, non-specific tasks requiring working memory, non-target tasks not requiring working memory and questionnaires addressing daily-life functioning. This assessment was performed twice before the experimental therapy and once after. RESULTS: Cognitive measures were stable before therapy. A statistically significant improvement was found for target measures and for daily-life skills. In contrast, no change was found on non-target tasks. CONCLUSION: Improvement was not apparently related to spontaneous recovery, since performance was stable before therapy. This study suggests that specific cognitive training may improve working memory in patients with brain injury.

Activities of Daily Living↗

PubMed2005

Delta(9)-THC administered into the medial prefrontal cortex disrupts the spatial working memory.

RATIONALE: Delta(9)-Tetrahydrocannabinol (Delta(9)-THC) disrupts working memory. The prefrontal cortex (PFC) is involved in the processing of working memory, and its medial portion (mPFC) is part of a brain reward circuit as constituted by the mesocorticolimbic dopaminergic system. OBJECTIVE: This study examined the involvement of the mPFC in the effects of Delta(9)-THC on spatial working memory. METHODS: Ten male Wistar rats well-trained in a radial arm maze and with bilateral cannula implanted in the mPFC received Delta(9)-THC intra-cortically (Delta(9)-THC IC) at doses of 0 (VEH), 32, 100 or 180 microg, 5 min before a 5-s or a 1-h delayed task in order to measure a short- or long-term spatial working memory, respectively. By contrast, 11 other animals received Delta(9)-THC intraperitoneally (Delta(9)-THC IP) at doses of 0 (VEH), 0.32, 1 or 1.8 mg/kg, 30 min before a 5-s or a 1-h delayed task. Additionally, after a 15-day washout, the effect of an IP or IC pre-exposure of Delta(9)-THC was examined by repeating both dose-effect curves in a crossover order for the routes of administration. RESULTS: Delta(9)-THC IP produced significantly larger number of errors at doses of 0.32 or 1 mg/kg as compared to VEH in the 1-h post-delay performance. Delta(9)-THC 100 microg IC also produced significantly larger number of errors as compared to VEH and also to the other doses (32 or 180 microg) IC in the 1-h post-delay performance. Previous exposure to Delta(9)-THC IP or IC did not significantly affect the disruptive effect of this cannabinoid. CONCLUSIONS: Delta(9)-THC administered directly in the mPFC impaired 1-h delayed task in the radial arm maze in a manner similar to that observed for its systemic administration, suggesting that the mPFC is involved in the disruptive effects of Delta(9)-THC on spatial working memory.

Animals↗

PubMed2006

Visual-spatial learning and memory in schizotypal personality disorder: continued evidence for the importance of working memory in the schizophrenia spectrum.

Verbal episodic memory deficits, a well-established feature of the schizophrenia spectrum, have also been found in individuals with schizotypal personality disorder (SPD), although visual-spatial episodic memory has proven harder to examine. To address this, we administered the Visual Object Learning Test (VOLT), a measure of visual-spatial learning and memory, as well as the California Verbal Learning Test (CVLT) and a verbal working memory test, to 50 individuals with SPD, 19 with other personality disorders (OPD), and 17 healthy volunteers. Compared to both other groups, individuals with SPD learned verbal and visual-spatial information at a reduced rate and recalled fewer words and objects after a long delay. Verbal working memory performance eliminated diagnostic differences in these episodic memory domains. These findings suggest that it is possible to detect both auditory and visual processing episodic memory abnormalities in the spectrum and that these deficits are uniformly a function of verbal working memory impairments.

Adult↗