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PubMed1995

Activation of prefrontal cortex in children during a nonspatial working memory task with functional MRI.

Functional magnetic resonance imaging (fMRI) was used to examine the pattern of activity of prefrontal cortex in prepubertal children during performance of a nonspatial working memory task. The children observed sequences of letters and responded whenever a letter repeated with exactly one nonidentical letter intervening. In a comparison task, subjects monitored similar sequences of letters for any occurrence of a single, prespecified target letter. Location of activation closely approximated that observed in a recent fMRI study with adults using exactly the same task. Activation of the inferior and middle frontal gyri was reliably observed within individual subjects during performance of the working memory task relative to the comparison task. Activation increased and decreased with a time course that was highly consistent with the task manipulations and correlated with behavioral performance. To our knowledge, this study is one of the first to demonstrate the applicability of fMRI to a normative developmental population. Issues of age dependence of the hemodynamic responses of fMRI are discussed.

Adult↗
PubMedDate not supplied

The development of nonverbal working memory and executive control processes in adolescents.

The prefrontal cortex modulates executive control processes and structurally matures throughout adolescence. Consistent with these events, prefrontal functions that demand high levels of executive control may mature later than those that require working memory but decreased control. To test this hypothesis, adolescents (9 to 20 years old) completed nonverbal working memory tasks with varying levels of executive demands. Findings suggest that recall-guided action for single units of spatial information develops until 11 to 12 years. The ability to maintain and manipulate multiple spatial units develops until 13 to 15 years. Strategic self-organization develops until ages 16 to 17 years. Recognition memory did not appear to develop over this age range. Implications for prefrontal cortex organization by level of processing are discussed.

Adolescent↗
PubMed1993

Reserpine impairs spatial working memory performance in monkeys: reversal by the alpha 2-adrenergic agonist clonidine.

Repeated daily treatment with the catecholamine-depleting agent, reserpine, dramatically reduced performance on the delayed response task, a test of spatial working memory that depends upon the integrity of the prefrontal cortex. Delayed response performance fell from an average of 27.2/30 trials correct before reserpine treatment to an average of 20.4/30 trials correct after repeated reserpine administration. Injection of the alpha 2-adrenergic agonist, clonidine (0.0001-0.05 mg/kg), to chronic reserpine-treated monkeys significantly restored performance on the delayed response task; performance after an optimal dose averaged 27.8/30 trials correct. Clonidine's beneficial effects on delayed response performance were longlasting; monkeys remained improved for more than 24 h after a single clonidine injection. The finding that clonidine is efficacious in reserpinized animals supports the hypothesis that alpha 2-adrenergic agonists improve cognitive function through actions at postsynaptic, alpha 2-adrenergic receptors on non-adrenergic cells. In contrast to the delayed response task, reserpine had little effect on performance of a visual discrimination task, a reference memory task which does not depend on the prefrontal cortex. These results emphasize the importance of postsynaptic, alpha 2-adrenergic mechanisms in the regulation of working memory.

Adrenergic alpha-Agonists↗
PubMed2004

Dissociative style and individual differences in verbal working memory span.

Dissociative style is mostly studied as a risk factor for dissociative pathology, but it may also reflect a fundamental characteristic of healthy information processing. Due to the close link between attention and working memory and the previous finding of enhanced attentional abilities with a high dissociative style, a positive relationship was also expected between dissociative style and verbal working memory span. In a sample of 119 psychology students, it was found that the verbal span of the high-dissociative group was about half a word larger than of the medium and low-dissociative groups. It is suggested that dissociative style may be one of only very few individual differences that is directly relevant to consciousness research.

Adolescent↗
PubMed2000

Working memory control in patients with schizophrenia: a PET study during a random number generation task.

OBJECTIVE: The authors' goal was to investigate brain regions involved in the deficiency of working memory control processes in patients with schizophrenia. METHOD: Regional cerebral blood flow was measured with positron emission tomography in eight men with stabilized schizophrenia and eight healthy men while they were performing a graded random number generation task. Twelve scans were made for each subject. Covariations between randomness of responses and regional activation were analyzed. RESULTS: The pattern of covariation between randomness of responses and activation in the anterior cingulate and superior parietal regions differed between patients and healthy subjects. CONCLUSIONS: These results suggest a cinguloparietal dysfunction underlying the impairment of working memory control processes during a random number generation task in patients with schizophrenia.

Adult↗
PubMed1996

Bilateral simultaneous transcranial Doppler monitoring of flow velocity changes during visuospatial and verbal working memory tasks.

Twenty-two normal volunteers were studied by simultaneous bilateral transcranial Doppler (TCD) monitoring of flow velocity changes in the middle cerebral arteries during visuospatial and verbal working memory tasks. All tasks were visually presented material; they required full engagement of subjects during the study, similar attention demands and a manual response when the appropriate target was recognized. Stimuli were presented tachistoscopically. Each task produced significant and distinct effects on flow velocity with respect to baseline values. When side-to-side comparisons were performed, a significantly higher increase in flow velocity was observed in the right middle cerebral artery (MCA) compared with the left one during the visuospatial task (P < 0.005). Our findings agree with results of recent studies using PET which show lateralized activation during working memory tasks. The high temporal resolution of this technique suggests that further application in cerebral flow change monitoring during neuropsychological studies could be promising.

Adult↗
PubMed2004

Verbal working memory deficits in current and previous users of MDMA.

Previous research suggests that MDMA users are impaired in various aspects of cognitive functioning, however, it remains unclear whether they might experience deficits in established measures of verbal working memory functioning. In the present study current and previous MDMA users were compared with non-users on verbal working memory measures including reading and computation span. Both user groups were found to be impaired on the computation span measure while current users also exhibited impairment in reading span. The MDMA-related deficit on the computation span measure remained significant following the introduction of statistical controls for the potentially confounding effects of cannabis and other drugs. The results are discussed in the context of recent research on executive processes. It is suggested that MDMA may produce differential effects on specific components within a fractionated executive system.

Adult↗
PubMed2000

Network analysis of brain activations in working memory: behavior and age relationships.

Forty-six middle-aged female subjects were scanned using functional Magnetic Resonance Imaging (fMRI) during performance of three distinct stages of a working memory task-encoding, rehearsal, and recognition-for both printed pseudowords and visual forms. An expanse of areas, involving the inferior frontal, parietal, and extrastriate cortex, was active in response to stimuli during both the encoding and recognition periods. Additional increases during memory recognition were seen in right prefrontal regions, replicating a now-common finding [for reviews, see Fletcher et al. (1997) Trends Neurosci 20:213-218; MacLeod et al. (1998) NeuroImage 7:41-48], and broadly supporting the Hemispheric Encoding/Retrieval Asymmetry hypothesis [Tulving et al. (1994) Proc Natl Acad Sci USA 91:2016-2020]. Notably, this asymmetry was not qualified by the type of material being processed. A few sites demonstrated higher activity levels during the rehearsal period, in the absence of any new stimuli, including the medial extrastriate, precuneus, and the medial temporal lobe. Further analyses examined relationships among subjects' brain activations, age, and behavioral scores on working memory tests, acquired outside the scanner. Correlations between brain scores and behavior scores indicated that activations in a number of areas, mainly frontal, were associated with performance. A multivariate analysis, Partial Least Squares [McIntosh et al. (1996) NeuroImage 3:143-157, (1997) Hum Brain Map 5:323-327], was then used to extract component effects from this large set of univariate correlations. Results indicated that better memory performance outside the scanner was associated with higher activity at specific sites within the frontal and, additionally, the medial temporal lobes. Analysis of age effects revealed that younger subjects tended to activate more than older subjects in areas of extrastriate cortex, medial frontal cortex, and the right medial temporal lobe; older subjects tended to activate more than younger subjects in the insular cortex, right inferior temporal lobe, and right inferior frontal gyrus. These results extend recent reports indicating that these regions are specifically involved in the memory impairments seen with aging.

Adult↗
PubMed2005

Working memory and learning in early Alzheimer's disease.

Cognitive deficits associated with early Alzheimer's disease (AD) have been recently operationalised in terms of an acquisition deficit and the research supporting this view is presented. However, there is still debate concerning the nature of this deficit and how underlying cognitive processes may be detrimentally affecting the ability to acquire new information in early AD. This review argues that the pattern of cognitive deficits contributing to the acquisition impairment in early AD patients may be readily interpreted within the context of a working memory model. Isolating the component processes of working memory that underlie the acquisition deficit in early AD patients will aid in the design of clinical applications that are focussed at enhancing the ability to acquire new information in everyday life.

Alzheimer Disease↗
PubMed2000

Verbal working memory and solvent exposure: a positron emission tomography study.

Neuropsychological studies have documented frontal dysfunction in patients with a history of exposure to organic solvents. The deficits typically observed in these patients appear to be related to working memory (WM). This study used [15O] water positron emission tomography (PET) to examine the pattern of neural activation during verbal working memory in patients with a history of exposure to solvents. Six individuals with solvent exposure were compared with 6 age- and education-matched controls. On the 2 WM tasks examined with PET, with equivalent task performance, participants with solvent exposure demonstrated frontal peaks that were atypical for the tasks, whereas the posterior peaks were typical for the tasks. The results support frontal dysfunction and compensatory use within anterior regions of the WM system in patients with solvent exposure.

Brain↗
PubMed1990

Prenatal protein malnutrition and working memory performance in adult rats.

The performance of prenatally protein malnourished rats was examined in 2 different tasks of learning and memory beginning at 90 or 160 days of age. In Experiment 1, a rewarded alternation task, run as a spatial working memory procedure on an elevated T-maze, revealed no differences between the formerly malnourished (6/25) and control (25/25) rats when either a minimal or a 20-s inter-trial delay was used. Neither was there a difference when an additional, and conflicting, 'information' run was given to provide a source of proactive interference. In extinction, the 6/25 rats required significantly more sessions to abolish their learned alternation response than the controls. In Experiment 2, an operant equivalent of the T-maze task was applied which allowed greater control over the delay interval and task difficulty. Each trial consisted of a forced information response, for which a randomly selected lever was presented, followed by a free-choice stage, when both levers were presented. The rats were rewarded for pressing the lever not presented at the information stage. The inter-trial interval was always 30 s. When the information response requirement was 10 presses no group differences were found in acquisition of the alternation response or in task performance at delays of 5, 10, 15 or 30 s between information and choice stages. As task difficulty was increased, the performance of the 6/25 rats improved more than that of the 25/25 rats, such that they performed significantly better at the longest delay when the information response requirement was 2 presses. This superior performance of the experimental animals is discussed. No differences in reversal were detected. It was concluded that there is no straight-forward 'hippocampal syndrome' in prenatally malnourished adult rats. Working memory appears largely unaffected, whereas susceptibility to interference and extinction may be modified, depending upon the test parameters employed.

Animals↗
PubMed1990

Planning and spatial working memory following frontal lobe lesions in man.

Twenty-six patients with unilateral or bilateral frontal lobe excisions were compared with age and IQ matched controls on a computerized battery of tests of spatial working memory and planning. A computerized test of spatial short term memory capacity revealed no significant impairment in the patients' ability to execute a given sequence of visuo-spatial moves. In contrast, a paradigm designed to assess spatial working memory capacity, revealed significant impairments in the patient group in both possible types of search errors. Furthermore, additional analysis showed that the frontal lobe patients were less efficient than controls in their usage of a strategy for improving performance on this test. Higher level planning was also investigated using a test based on the "Tower of London" problem [SHALLICE, T. Phil. Trans. R. Soc. Lond. B. 298, 199-209, 1982]. Patients with frontal lobe damage required more moves to complete the problems and a yoked motor control condition revealed that movement times were significantly increased in this group. Taking both of these factors into consideration, initial thinking (planning) time was unimpaired in the patient group although the thinking time subsequent to the first move was significantly prolonged. These data are compared to previous findings from patients with idiopathic Parkinson's disease and are discussed in terms of an impairment of higher cognitive functioning following frontal lobe damage.

Attention↗
PubMed1999

Genetically dissociated components of working memory: evidence from Down's and Williams syndrome.

Wang and Bellugi [J clin exp Neuropsychol 1994;16:317 22] have suggested that Down's and Williams syndrome might be associated with specific and contrasting working memory deficits; with impaired verbal short-term memory in Down's syndrome, and a visuo-spatial short-term memory deficit in Williams syndrome. In two studies we examine whether these apparent deficits might simply be a consequence of the general pattern of learning difficulties associated with these disorders. Experiment 1 compared verbal and visuo-spatial short-term memory abilities in these groups, using analysis of covariance to control for mental age differences. In Experiment 2 individuals with Williams syndrome were matched to control groups for non-verbal mental age, and the short-term memory abilities of these matched groups were compared. The results of both experiments are broadly consistent with those reported by Wang and Bellugi, and support the view that working memory can be dissociated into separate subsystems.

Adolescent↗
PubMed2003

Impairments in working memory associated with naturalistic dieting in women: no relationship between task performance and urinary 5-HIAA levels.

The present study investigated the question of whether the previously observed impairments of working memory characteristic of dieting to lose weight can be explained in terms of preoccupying cognitions relating to body shape or to alterations in serotonergic function resulting from a low dietary intake of tryptophan. The population comprised female non-dieting, lower restrained eaters (N=23), non-dieting higher restrained eaters (N=11) and current dieters (N=19). Each participant completed three tasks, each of which selectively loaded on to a different sub-component of working memory. The tasks comprised the Tower of London task, a letter string recall task and a mental rotation task. In addition, all participants completed self-report measures of body shape concern and affective state. Serotonin turnover was assessed by means of 24 h urine sample collection for each participant on their day of testing. This was analysed (via HPLC) for levels of the main serotonin metabolite 5-HIAA.The results of the present study broadly replicated previous findings of a Central Executive and Phonological Loop (but not Visuo-Spatial Sketchpad) deficit in those subjects who reported themselves to be currently dieting. Tower of London task performance also significantly correlated with self-reported feelings of fatness and body shape disparagement. There were no group differences in 5-HIAA levels nor did 5-HIAA levels correlate with task performance. However, there was a significant negative correlation between 5-HIAA levels and self-reported depression. These results support the hypothesis that the variables mediating this deficit are preoccupying cognitions concerning body shape. They do not support the hypothesis that the serotonergic function of dieters is compromised, although this conclusion is tentative.

Adult↗
PubMed2006

Scopolamine and MK801-induced working memory deficits in rats are not reversed by CBD-rich cannabis extracts.

Smoking marijuana causes working and short-term memory deficits, an effect that is mediated by cannabinoid receptor (CB1) activation in the brain. While this may be due to the main psychoactive constituent Delta9-tetrahydrocannabinol (Delta9-THC), plant extracts also contain other cannabinoid and terpenoid compounds with unknown properties. Towards this end, we have recently shown that high concentrations of plant extracts rich in cannabidiol (CBD) can reverse working memory deficits induced by Delta9-THC which is a remaining contaminant of this extract [Fadda P, Robinson L, Fratta W, Pertwee RG, Riedel G. Differential effects of THC- and CBD-rich cannabis-extracts on working memory in rats. Neuropahrmacology 2004;47:1170-9]. Since this effect was dose-dependent and indicative of memory enhancing qualities of the CBD-rich extract, this prompted a wider investigation into the effects of CBD on other forms of amnesia in order to determine the mechanism of action and to reveal its potency against anticholinergic and antiglutamatergic agents. We employed a spatial delayed matching to position task in the open-field water maze. Both scopolamine (0.2 mg/kg i.p.) and dizocilpine (MK801: 0.1mg/kg i.p.) impaired working memory at delays of 30 s and 4 h. Two doses of CBD-rich extracts (5 and 10 mg/kg), which did not affect working memory when given alone, were unable to reverse these deficits when co-administered with scopolamine or MK801. These data suggest that reversal of working memory deficits by CBD-rich extracts are specific to the cannabinoid system and do not compensate for acutely induced cholinergic or glutamatergic receptor hypoactivity.

Analysis of Variance↗
PubMed1993

Working memory and the Self-Ordered Pointing Task: further evidence of early prefrontal decline in normal aging.

Two major lines of investigation are currently clarifying the nature of the impairment of working memory associated with normal aging. Cognitive psychology has formulated the problem in terms such as the balance of impairment of encoding, retrieval, storage and/or attention, whereas neuropsychology has formulated the problem in terms such as the balance of frontal (executive) versus temporal (mnemonic) degeneration. The findings of this study support the contention that the primary impairment of working memory in early normal aging is an active attentional executive processing deficit. Specifically, on the Self-Ordered Pointing Task, there is significantly ineffective exploitation of top-down clustering strategy as a function of aging. On this task, self-organization of encoding and retrieval must occur simultaneously with ongoing responding. The finding cannot be explained as an impairment of encoding, retrieval, storage, or build-up and/or release of proactive interference, since indexes of these did not discriminate young-adult from middle-aged samples.

Adult↗
PubMed1993

Medial septal lesions disrupt spatial, but not nonspatial, working memory in rats.

In Experiment 1, rats with small medial septal lesions were less able than were control rats to remember the location of the arm of a Y maze they had been forced to enter on the preceding sample run. Moreover, as the retention interval between the sample and choice runs on this spatial delayed nonmatching-to-sample (DNMTS) task was increased to 1 and 2 min, the magnitude of the deficit increased. In contrast, these same lesioned rats were not deficient in Experiment 2 in their ability to remember the object they had encountered in the straight alley on the sample run. In fact, when the retention interval was increased to 1 min on this nonspatial DNMTS task, the rats with medial septal lesions were more accurate than were the controls. This pattern of results did not appear to be due to task difficulty, recovery of function, or sequence of training. Rather, these results indicate that damage to the septohippocampal system disrupts spatial working memory more than it disrupts nonspatial working memory.

Animals↗
PubMed2000

What's working in working memory: a role for the Central Executive.

Two experiments are reported which seek to explore the nature of the Central Executive of Baddeley's (Baddeley and Hitch, 1974) model of working memory. Experiment 1 uses a dual task methodology to compare performance on two storage tasks, making use of the two slave systems, the Phonological Loop (PL) and the Visuo-Spatial Scratch Pad (VSSP). Results suggest that storage can be thought of as based on the use of slave system independent resources. Experiment 2 uses a similar approach to compare performance on 2 processing tasks, again one PL based, the other VSSP based. These results suggest that processing is based on a central, shared set of resources. The two experiments support both a multiple resources model of working memory and more specifically identify a role for the Central Executive.

Adolescent↗