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PubMed1998

A "word length effect" for sign language: further evidence for the role of language in structuring working memory.

We report a sign length effect in deaf users of American Sign Language that is analogous to the word length effect for speech. Lists containing long signs (signs that traverse relatively long distances) produced poorer memory performance than did lists of short signs (signs that do not change in location). Further, this length effect was eliminated by articulatory suppression (repetitive motion of the hands), and articulatory suppression produced an overall drop in performance. The pattern of results, together with previous findings (Wilson & Emmorey, 1997), provides evidence for a working memory system for sign language that consists of a phonological storage buffer and an articulatory rehearsal mechanism. This indicates a close equivalence of structure between working memory for sign language and working memory for speech. The implications of this equivalence are discussed.

Adult↗

PubMed2004

A relationship between cerebellar Purkinje cells and spatial working memory demonstrated in a lurcher/chimera mouse model system.

New emphasis has been placed upon cerebellar research because of recent reports demonstrating involvement of the cerebellum in non-motor cognitive behaviors. Included in the growing list of cognitive functions associated with cerebellar activation is working memory. In this study, we explore the potential role of the cerebellum in spatial working memory using a mouse model of Purkinje cell loss. Specifically, we make aggregation chimeras between heterozygous lurcher (Lc/+) mutant embryos and +/+ (wildtype) embryos and tested them in the delayed matching-to-position (DMTP) task. Lc/+ mice lose 100% of their Purkinje cells postnatally due to a cell-intrinsic gain-of-function mutation. Lc/+<->+/+ chimeras therefore have Purkinje cells ranging from 0 to normal numbers. Through histological examination of chimeric mice and observations of motor ability, we showed that ataxia is dependent upon both the number and distribution of Purkinje cells in the cerebellum. In addition, we found that Lc/+ mice, with a complete loss of Purkinje cells, have a generalized deficit in DMTP performance that is probably associated with their motor impairment. Finally, we found that Lc/+<->+/+ chimeric mice, as a group, did not differ from control mice in this task. Rather, surprisingly, analysis of their total Purkinje cells and performance in the DMTP task revealed a significant negative relationship between these two variables. Together, these findings indicate that the cerebellum plays a minor or indirect role in spatial working memory.

Animals↗

PubMed1993

Influence of working memory on adult age differences in matrix reasoning.

The four studies reported in this article, involving a total of 401 adults ranging between 18 and 80 years of age, were designed to investigate how working memory might mediate adult age differences in matrix reasoning tasks such as the Raven's Progressive Matrices Test. Evidence of this medication is available in the finding that statistical control of an index of working memory reduces the age-related variance in matrix reasoning performance by approximately 70 per cent. Because the age differences were nearly constant across items of varying difficulty, it was concluded that the factors responsible for variation in item difficulty were distinct from those responsible for the age differences. However, young adults were found to be more accurate than older adults at recognizing information presented earlier in the matrix reasoning trial, thereby supporting the interpretation that working memory exerts its influence by contributing to the preservation of information during subsequent processing.

Adolescent↗

PubMed1985

Effects of pesticides and drugs on working memory in rats: continuous non-match.

Effects of four pesticides (carbaryl, propoxur, chlordimeform, and deltamethrin) and two reference drugs, physostigmine and chlordiazepoxide, were measured on the performance of rats trained on a continuous non-match (CNM) delayed comparison, working memory procedure. These same compounds were also tested in analogous, large and small stimulus difference discrimination (i.e., non working-memory) procedures. The effects of the pesticides and physostigmine on CNM performance were qualitatively similar, and also similar to their effects on discrimination performance. As dosage of these compounds increased, only small effects on accuracy were observed, followed at still larger doses by an abrupt and non-selective decrease in all responding. The pesticides and physostigmine did not selectively affect working memory: the magnitude of their effects did not increase with intertrial interval, and the compounds were equally effective in disrupting discrimination and CNM performance. Effects of chlordiazepoxide on performance in the CNM and discrimination control procedures differed qualitatively from those of the pesticides and physostigmine.

Animals↗

PubMed2001

Dissociating retention and access in working memory: an age-comparative study of mental arithmetic.

In two experiments, young and older adults solved arithmetic chain tasks with single-digit operands, with or without a concurrent memory load of three or six digits. Variables in the arithmetic tasks had to be replaced by digits from the screen or from the memory set. A task-irrelevant concurrent load impaired neither speed nor accuracy of arithmetic in younger adults. In Experiment 2, this was also true for older adults. A large decrease in arithmetic performance was observed, however, when variables in the arithmetic task had to be substituted by digits from the memory list. Older adults had specific problems with this condition in Experiment 1, where the substitution involved two successive steps, but not in Experiment 2, where the substitution from memory could be done in a single step. The results are difficult to reconcile with models assuming a common resource for storage and processing. Rather, they are compatible with the hypothesis that a concurrent memory load interferes with a processing task only during the points of access to working memory. Further, even though access to working memory was found to be the critical source of concurrent-load interference, it was found to be insensitive to the effects of adult aging.

Adult↗

PubMed2005

Functional imaging of working memory in obstructive sleep-disordered breathing.

Functional magnetic resonance imaging was used to map cerebral activation in 16 patients with obstructive sleep-disordered breathing (OSDB) and 16 healthy subjects, during the performance of a 2-back verbal working memory task. Six patients with OSDB were reimaged after a minimum period of 8 wk of treatment with positive airway pressure. Working memory speed in OSDB was significantly slower than in healthy subjects, and a group average map showed absence of dorsolateral prefrontal activation, regardless of nocturnal hypoxia. After treatment, resolution of subjective sleepiness contrasted with no significant change in behavioral performance, persistent lack of prefrontal activation, and partial recovery of posterior parietal activation. These findings suggest that working memory may be impaired in OSDB and that this impairment is associated with disproportionate impairment of function in the dorsolateral prefrontal cortex. Nocturnal hypoxia may not be a necessary determinant of cognitive dysfunction, and sleep fragmentation may be sufficient. There may be dissociations between respiratory vs. cortical recovery and objective vs. subjective recovery. Hypofrontality may provide a plausible biological mechanism for a clinical overlap with disorders of mood and attention.

Adult↗

PubMed2000

Relationship between relaxation by guided imagery and performance of working memory.

This study tested the hypothesis that relaxation by guided imagery improves working-memory performance of healthy participants. 30 volunteers (both sexes, ages 17-56 years) were randomly assigned to one of three groups and administered the WAIS-III Letter-Number Sequencing Test before and after 10-min. treatment with guided imagery or popular music. The control group received no treatment. Groups' test scores were not different before treatment. The mean increased after relaxation by guided imagery but not after music or no treatment. This result supports the hypothesis that working-memory scores on the test are enhanced by guided imagery and implies that human information processing may be enhanced by prior relaxation.

Adolescent↗

PubMed2005

Mapping the developmental constraints on working memory span performance.

This study investigated the constraints underlying developmental improvements in complex working memory span performance among 120 children of between 6 and 10 years of age. Independent measures of processing efficiency, storage capacity, rehearsal speed, and basic speed of processing were assessed to determine their contribution to age-related variance in complex span. Results showed that developmental improvements in complex span were driven by 2 age-related but separable factors: 1 associated with general speed of processing and 1 associated with storage ability. In addition, there was an age-related contribution shared between working memory, processing speed, and storage ability that was important for higher level cognition. These results pose a challenge for models of complex span performance that emphasize the importance of processing speed alone.

Age Factors↗

PubMed2006

Stress, prefrontal cortex and environmental enrichment: studies on dopamine and acetylcholine release and working memory performance in rats.

The aim of the present study was to investigate whether environmental enrichment changes the effects of acute stress on both the release of dopamine and acetylcholine in the prefrontal cortex (PFC) and working memory performance. Male Wistar rats (3 months of age) were housed in enriched or control conditions during 12 months. Behavioural testing was carried out to assess working memory performance in a delayed alternation task (water escape T-maze). Horizontal and vertical motor activity were also monitored in the open field. After behavioural testing (open field and water T-maze), animals were implanted with guide cannula in the PFC to perform microdialysis experiments and to monitor dopamine and acetylcholine extracellular concentrations. Handling stress (40min) produced similar increases of extracellular concentrations of dopamine in the PFC of both enriched and control animals. In contrast, handling stress increased significantly the extracellular concentrations of acetylcholine in the PFC of control, but not enriched, animals. Exposing animals to a lit open field during 10min significantly reduced working memory performance assessed immediately in the water T-maze just in control animals, though these effects were not significantly different between both groups of animals. Spontaneous motor activity in the open field was lower in enriched compared to control animals. These results suggest that environmental enrichment changes acetylcholine, but not dopamine, reactivity to stress in the PFC.

Acetylcholine↗

PubMed1992

Reversal by 3,3',5-triido-L-thyronine of the working memory deficit, and the decrease in acetylcholine, glutamate and gamma-aminobutyric acid induced by ethylcholine aziridinium ion in mice.

The effect of 3,3',5-triiodo-L-thyronine (T3) on working memory in ethylcholine aziridinium ion (AF64A)-treated mice was studied in a delayed non-matching to sample task using a T-maze. After behavioural testing was completed, mice were killed by microwave irradiation and regional brain levels of acetylcholine, aspartate, glutamate, glutamine, glycine, taurine, and gamma-aminobutyric acid (GABA) were measured by high-performance liquid chromatography with electrochemical detection. Treatment with AF64A (7 nmol, i.c.v.) produced a deficit in working memory performance in the non-matching to sample task at 30 s delay, and decreased acetylcholine, glutamate, and GABA levels in the hippocampus, but not in the septum and cerebral cortex. Administration of T3 (0.3 mg/kg, p.o., once daily for 6 days) to AF64A-treated animals improved the deficit in working memory performance and reversed the decrease in acetylcholine, glutamate, and GABA levels in the hippocampus. These results indicate that the deficit in performance induced by AF64A can be improved by T3 administration.

Acetylcholine↗

PubMed1998

Monitoring working memory load during computer-based tasks with EEG pattern recognition methods.

We assessed working memory load during computer use with neural network pattern recognition applied to EEG spectral features. Eight participants performed high-, moderate-, and low-load working memory tasks. Frontal theta EEG activity increased and alpha activity decreased with increasing load. These changes probably reflect task difficulty-related increases in mental effort and the proportion of cortical resources allocated to task performance. In network analyses, test data segments from high and low load levels were discriminated with better than 95% accuracy. More than 80% of test data segments associated with a moderate load could be discriminated from high- or low-load data segments. Statistically significant classification was also achieved when applying networks trained with data from one day to data from another day, when applying networks trained with data from one task to data from another task, and when applying networks trained with data from a group of participants to data from new participants. These results support the feasibility of using EEG-based methods for monitoring cognitive load during human-computer interaction.

Adult↗

PubMed1997

Working memory impairments in traumatic brain injury: evidence from a dual-task paradigm.

Although many individuals with traumatic brain injury (TBI) perform well on standard neuropsychological tests, they often exhibit marked functional difficulties. The functions which are impaired seem to be analogous to the role of the central executive system (CES) in Baddeley's [Working Memory, 1986, Oxford University Press, New York] widely accepted model of working memory. The purpose of this study was to investigate CES function in individuals with TBI with a dual-task paradigm. We studied 25 non-demented persons who were at various stages in their recovery from severe TBI and compared their performance on a dual-task paradigm to a group of age-matched controls. Our dual-task paradigm measured performance on a simple visual reaction time task both alone (baseline) and during concurrent tasks of articulation or digit span. Subjects were also assessed with other neuropsychological tests of executive function. TBI patients had slower reaction times on the primary task when performed alone (P < 0.05) and greater decrements in performance during dual-task conditions (P < 0.01). They also exhibited significantly greater deficits than control subjects on other measures of executive function. Although correlations between dual-task performance and other executive measures were quite low, principle components analysis suggested that a common factor does exist between these measures. These findings support the conclusion that TBI patients have a working memory impairment that is due to dysfunction of the CES and which may be related to executive function deficits as measured by standard neuropsychological testing.

Adolescent↗

PubMed2006

The antisaccade task as an index of sustained goal activation in working memory: modulation by nicotine.

INTRODUCTION: The antisaccade task provides a laboratory analogue of situations in which execution of the correct behavioural response requires the suppression of a more prepotent or habitual response. Errors (failures to inhibit a reflexive prosaccade towards a sudden onset target) are significantly increased in patients with damage to the dorsolateral prefrontal cortex and patients with schizophrenia. Recent models of antisaccade performance suggest that errors are more likely to occur when the intention to initiate an antisaccade is insufficiently activated within working memory. Nicotine has been shown to enhance specific working memory processes in healthy adults. MATERIALS AND METHODS: We explored the effect of nicotine on antisaccade performance in a large sample (N = 44) of young adult smokers. Minimally abstinent participants attended two test sessions and were asked to smoke one of their own cigarettes between baseline and retest during one session only. RESULTS AND CONCLUSION: Nicotine reduced antisaccade errors and correct antisaccade latencies if delivered before optimum performance levels are achieved, suggesting that nicotine supports the activation of intentions in working memory during task performance. The implications of this research for current theoretical accounts of antisaccade performance, and for interpreting the increased rate of antisaccade errors found in some psychiatric patient groups are discussed.

Adult↗

PubMed2024

The effect of fampridine on working memory: a randomized controlled trial based on a genome-guided repurposing approach.

Working memory (WM), a key component of cognitive functions, is often impaired in psychiatric disorders such as schizophrenia. Through a genome-guided drug repurposing approach, we identified fampridine, a potassium channel blocker used to improve walking in multiple sclerosis, as a candidate for modulating WM. In a subsequent double-blind, randomized, placebo-controlled, crossover trial in 43 healthy young adults (ClinicalTrials.gov, NCT04652557), we assessed fampridine's impact on WM (3-back d-prime, primary outcome) after 3.5 days of repeated administration (10 mg twice daily). Independently of baseline cognitive performance, no significant main effect was observed (Wilcoxon P = 0.87, r = 0.026). However, lower baseline performance was associated with higher working memory performance after repeated intake of fampridine compared to placebo (rs = -0.37, P = 0.014, n = 43). Additionally, repeated intake of fampridine lowered resting motor threshold (F(1,37) = 5.31, P = 0.027, R2β = 0.01), the non-behavioral secondary outcome, indicating increased cortical excitability linked to cognitive function. Fampridine's capacity to enhance WM in low-performing individuals and to increase brain excitability points to its potential value for treating WM deficits.

Adult↗

PubMedDate not supplied

Dissociating mental transformations and visuo-spatial storage in working memory: evidence from representational neglect.

A study is reported of visuo-spatial working memory in two individuals suffering from a cognitive deficit known as unilateral spatial neglect, and seven healthy control participants. Both patients have difficulties reporting details on the left side of imaged representations, and one has an additional difficulty with perceptual input to the left of his body midline. All participants were asked to report the location and identity of objects presented in novel 2 x 2 arrays that were either present throughout or were described orally by the experimenter, with no visual input. On half of the trials, the report was to be made from the opposite perspective, requiring 180 degree mental rotation of the mentally represented array. The patients show an impaired ability to report details from the presented or the imagined left, but had no difficulty with mental rotation. Results point to a clear separation between the processes of perception and those of visuo-spatial working memory. Results also suggest that the patients might be suffering from damage to the system used for holding visuo-spatial representations rather than a difficulty with attending to elements of that representation.

Aged↗

PubMed1998

Human working memory capacity is 7+/-2 in a radial maze with distracting interruption: possible implication for neural mechanisms of declarative and implicit long-term memory.

Human participants were instructed to walk out along each of the arms of a 15-m in diameter, 8-arm radial maze once and only once. In order to approximate the circumstances under which laboratory rats remember visited sites, our human participants were asked to select arms in an unsystematic order. They scored an average of 7.6 to 7.8 correct choices, even if midway during a trial there was a 5-min interruption filled with a verbal-spatial interfering task (a scavenger hunt) or a 15-min interruption filled with a visuospatial task (a maze-running computer simulation). This finding extends our earlier research with humans in 13- or 17-arm radial mazes under nondelay conditions, in which we also found working memory (WM) capacity for about 7 to 9 places, the same as that of laboratory rats. We discuss earlier findings in other laboratories, showing that rats can successfully bridge long radial maze task interruptions of 5 or 8 h, and we compare our results also to those from studies in which human participants were not discouraged from reducing memory load by responding systematically in radial mazes. Because the radial maze task takes minutes to complete even under nondelay conditions its routine consideration as a working memory task in the animal literature alters the assumptions often made about the duration of WM in the human literature. Accumulating empirical findings about place-memory in humans, nonhuman mammals, and birds suggest it might be productive to reevaluate this theoretical issue with respect to present knowledge about the roles of the hippocampus and other brain structures in declarative memory and in procedural or implicit memory, while considering the hypothesis that some forms of information may exploit long-term memory in parallel with working memory.

Adolescent↗

PubMed2005

Fractionating working memory: consolidation and maintenance are independent processes.

In the present study, we required subjects to remember simple objects that were masked to interrupt consolidation and allow us to estimate the rate of information accrual in visual working memory. We compared a consolidation-baseline condition with a consolidation-during-maintenance condition in which subjects needed to remember a set of unmasked items and then were shown to-be-remembered masked items. We hypothesized that if the control processes of consolidation and maintenance are performed by common mechanisms, then consolidation should be less efficient when performed during maintenance than when performed alone. However, we found that an identical amount of information was encoded per unit time in the two conditions. These results indicate that working memory consolidation is not slowed by maintenance and suggest a two-step model of encoding in visual working memory.

Adolescent↗

PubMed2005

Haploinsufficiency of the arginine-vasopressin gene is associated with poor spatial working memory performance in rats.

Behavioral pharmacological studies have implicated a role for the neurophysin arginine-vasopressin in learning and memory. Vasopressin, and its analogues, can produce either improvements or impairments in mnemonic functions, effects that depend upon the agent administered, the memory process measured and the task employed. As recent data have implicated vasopressin in regulating the cognitive functions of the prefrontal cortex, we sought to determine whether changes in vasopressinergic tone would affect a form of memory that is dependent upon this brain region. To that end, we used a genetic approach to examine how haploinsufficiency of the vasopressin gene affects working memory performance. Specifically, we tested a naturally occurring null-mutant rat on an operant delayed-non-match-to-position task. Male and female heterozygous and wild-type rats were trained to perform this working memory task, and the effects of varying the delay across which they had to maintain task information were systematically varied. Although vasopressin-deficient rats omitted fewer trials and completed trials more quickly, they exhibited delay-dependent deficits of choice accuracy. The genotype effects were not modified by sex. Collectively, these data indicate that even partial vasopressin deficiency can trigger deficits of spatial working memory performance and add to the growing body of results supporting a regulatory control of neocortical-dependent cognitive functions by this neurohormone.

Analysis of Variance↗