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PubMed2006

Systemic and local administration of estradiol into the prefrontal cortex or hippocampus differentially alters working memory.

The influence of estradiol on learning and memory is dependent on a number of factors. The effects of physiological levels of estradiol on the acquisition of a spatial working memory task mediated by the prefrontal cortex (PFC) and the hippocampus were examined in Experiment 1. Ovariectomized Long-Evans rats received daily injections of estradiol or vehicle were tested on the win-shift version of the radial arm maze. A high dose of estradiol benzoate (5 microg) enhanced acquisition of the task, whereas a low dose of estradiol (0.3 microg) increased the number of errors committed over 17 days of testing. Experiment 2 was conducted to examine site-specific influences of estradiol on spatial working memory in well-trained rats. Saline and estradiol cyclodextrin (0.1 and 0.9 microg) were infused into the prelimbic region of the PFC or dorsal hippocampus 40 min prior to testing on the win-shift task. Infusions of estradiol into both brain areas attenuated saline-infusion disruptions in working memory. Specifically, the higher dose of estradiol facilitated working memory when infused into the PFC, whereas the lower dose of estradiol facilitated performance when infused into the dorsal hippocampus. Moreover, working memory was significantly impaired 24 h after infusions of estradiol into the dorsal hippocampus but not the PFC. These data provide further evidence for the notion that estradiol can dose-dependently alter memory processes and suggest that facilitation or disruptions of working memory by estradiol are site- and time-specific.

Analysis of Variance↗
PubMed2001

Medial temporal and prefrontal contributions to working memory tasks with novel and familiar stimuli.

Lesions of parahippocampal structures impair performance of delayed matching tasks in nonhuman primates, suggesting a role for these structures in the maintenance of items in working memory and short-term stimulus matching. However, most human functional imaging studies have not shown medial temporal activation during working memory tasks and have primarily focused on functional magnetic resonance imaging (fMRI) signal intensity changes in the prefrontal and posterior parietal cortex. The goal of this study was to test the hypothesis that the difference between the human and nonhuman primate data results from the use of highly familiar stimuli in human working memory studies and trial-unique stimuli in nonhuman primate studies. We used fMRI to examine prefrontal and temporal lobe activation during performance of a working memory (two-back) task, using blocks of novel and highly familiar complex pictures. Performance of the working memory task with novel complex pictures resulted in greater signal change within medial temporal lobe structures than performance of the task with familiar complex pictures. In contrast, the working memory task with highly familiar stimuli resulted in greater prefrontal activation. These results are consistent without hypothesis that the medial temporal lobe is recruited for the short-term maintenance of information that has no prior representation in the brain, whereas the prefrontal cortex is important for monitoring familiar stimuli that have a high degree of interference. A second set of tasks examined stimulus matching. Subjects performed a target-matching task, during which they identified a single target presented in blocks of novel or familiar stimuli. The results provide evidence of hippocampal and parahippocampal recruitment in the target-matching task with familiar stimuli. These results are consistent with prior animal studies and suggest that prefrontal regions may be important for the monitoring and matching of familiar stimuli which have a high potential for interference, whereas medial temporal regions may become proportionally more important for matching and maintenance of novel stimuli.

Adult↗
PubMed2001

A sex difference on a novel spatial working memory task in humans.

Neurophysiological and behavioral evidence suggests that the prefrontal cortex (PFC) may be sexually differentiated in nonhuman primates. The present study examined whether there are sex differences in working memory in humans that might reflect sexual differentiation of human PFC. Male and female undergraduates were administered a novel multitrial spatial working memory task (SPWM) and a verbal working memory task. In three experiments, females committed significantly fewer working memory errors and took significantly less time to reach criterion than males on the SPWM task. The female advantage was not accounted for by differences in general intellectual ability, attention, perceptual speed, incidental memory, or speed of verbal access. In Study 3, a sex difference was also observed on a measure of verbal working memory. The findings suggest that some prefrontal functions may be sexually differentiated in humans.

Adult↗
PubMed1992

Those cheating rats: male and female rats use odor trails in a water-escape "working memory" task.

Three-month-old Sprague-Dawley rats were trained on a working memory win-stay (spatial delayed matching-to-sample) water-escape task with the escape platform location the same for all subjects on a given trial, a procedure that maximizes the buildup of an odor trail to the escape platform. In subsequent tests during which the location of the escape platform varied randomly between subjects, the rats, especially the females, while continuing to perform above chance level, made increased errors. Varying the platform location between subjects eliminated odor trail as a nonambiguous cue for locating the escape platform. In a second experiment females performed better than males on a reference memory odor trail discrimination task which involved following the path of like-gender "pathmaker" rats to the escape platform. The relatively poor use of odor trails by the males was associated with a high frequency of choosing a preferred choice section or returning to the choice section selected first on the immediately preceding trial (perseveration). Collectively, the two experiments demonstrate that rats can use either working memory or odor trails to locate an escape platform in a water maze, and that they, especially females, will use odor trails in a working memory task if odor trails are available. Clearly, the location of the escape platform should be varied randomly between subjects in tests of working memory.

Analysis of Variance↗
PubMed1998

Sustained activity in the medial wall during working memory delays.

We have taken advantage of the temporal resolution afforded by functional magnetic resonance imaging (fMRI) to investigate the role played by medial wall areas in humans during working memory tasks. We demarcated the medial motor areas activated during simple manual movement, namely the supplementary motor area (SMA) and the cingulate motor area (CMA), and those activated during visually guided saccadic eye movements, namely the supplementary eye field (SEF). We determined the location of sustained activity over working memory delays in the medial wall in relation to these functional landmarks during both spatial and face working memory tasks. We identified two distinct areas, namely the pre-SMA and the caudal part of the anterior cingulate cortex (caudal-AC), that showed similar sustained activity during both spatial and face working memory delays. These areas were distinct from and anterior to the SMA, CMA, and SEF. Both the pre-SMA and caudal-AC activation were identified by a contrast between sustained activity during working memory delays as compared with sustained activity during control delays in which subjects were waiting for a cue to make a simple manual motor response. Thus, the present findings suggest that sustained activity during working memory delays in both the pre-SMA and caudal-AC does not reflect simple motor preparation but rather a state of preparedness for selecting a motor response based on the information held on-line.

Adult↗
PubMed1995

Low doses of ethanol impair spatial working memory and reduce hippocampal theta activity.

Low doses of ethanol can alter neural activity in the septohippocampal pathway, a pathway critical for spatial working memory. The present study was designed to determine whether acute ethanol induces impairments in working memory and disrupts septohippocampal function as measured by the hippocampal theta rhythm. Rats were preoperatively trained on delayed alternation. A within-subject design was used to evaluate the effects of ethanol (0.25, 0.5, 0.75 and 1.0 g/kg, intraperitoneally) on performance 10 min and 90 min after injection as compared with preinjection baseline. Ethanol produced dose-, delay-, and time-dependent impairments in working memory as indicated by a change in choice accuracy in the delayed alternation task. Ethanol did not affect performance time, the ability to complete the task, or response bias. Thus, the impairment does not appear to result from a decrement in general performance, but rather from an impairment in spatial working memory. Hippocampal theta activity was suppressed by ethanol at the same doses, 0.75 g/kg and 1.0 g/kg, that impaired working memory. The interaction of ethanol with functions of the septohippocampal pathway are discussed.

Animals↗
PubMed1999

Depression in multiple sclerosis: relationship to working memory capacity.

Recent research has shown that depression in multiple sclerosis (MS) is associated with deficits on cognitively demanding tasks. One explanation for this relationship is that depressed MS patients may have reduced working memory capacity. The present study was designed to test this hypothesis. Depressed MS patients were compared with nondepressed MS patients and nondepressed healthy controls on a task of working memory capacity (reading span) and a short-term memory task not taxing working memory capacity (word span). In support of the capacity-reduction model, compared with the nondepressed groups, depressed MS patients performed significantly worse on reading span (p<.001) but not on word span. Additionally, reading span was significantly correlated with capacity-demanding tasks shown to be impaired in depressed MS patients in previous reports. Results suggest that depressed MS patients are characterized by limited working memory capacity and that the central executive component of the working memory system may be most affected.

Adult↗
PubMedDate not supplied

Verbal and visuospatial short-term and working memory in children: are they separable?

This study explored the structure of verbal and visuospatial short-term and working memory in children between ages 4 and 11 years. Multiple tasks measuring 4 different memory components were used to capture the cognitive processes underlying working memory. Confirmatory factor analyses indicated that the processing component of working memory tasks was supported by a common resource pool, while storage aspects depend on domain-specific verbal and visuospatial resources. This model is largely stable across this developmental period, although some evidence exists that the links between the domain-specific visuospatial construct and the domain-general processing construct were higher in the 4- to- 6-year age group. The data also suggest that all working memory components are in place by 4 years of age.

Child↗
PubMed2005

Neural correlates of spatial working memory in humans: a functional magnetic resonance imaging study comparing visual and tactile processes.

Recent studies of neural correlates of working memory components have identified both low-level perceptual processes and higher-order supramodal mechanisms through which sensory information can be integrated and manipulated. In addition to the primary sensory cortices, working memory relies on a widely distributed neural system of higher-order association areas that includes posterior parietal and occipital areas, and on prefrontal cortex for maintaining and manipulating information. The present study was designed to determine brain patterns of neural response to the same spatial working memory task presented either visually or in a tactile format, and to evaluate the relationship between spatial processing in the visual and tactile sensory modalities. Brain activity during visual and tactile spatial working memory tasks was measured in six young right-handed healthy male volunteers by using functional magnetic resonance imaging. Results indicated that similar fronto-parietal networks were recruited during spatial information processing across the two sensory modalities-specifically the posterior parietal cortex, the dorsolateral prefrontal cortex and the anterior cingulate cortex. These findings provide a neurobiological support to behavioral observations by indicating that common cerebral regions subserve generation of higher order mental representations involved in working memory independently from a specific sensory modality.

Adult↗
PubMed1996

Individual differences in children's working memory and writing skill.

The purpose of this research is to address (a) whether individual differences in working memory (WM) and writing are related to a general or process-specific system, (b) whether WM tasks operate independently of phonological short-term memory (STM) on measures of writing and reading, and (c) whether working memory predicts variance in writing beyond that predicted by reading alone. The present study correlated several WM and phonological STM measures with writing and reading measures. The study showed among the memory measures that a four-factor model reflecting phonological STM, verbal WM span, executive processing, and visual-spatial WM span best fit the multivariate data set. Working memory was correlated significantly with a number of writing measures, particularly those related to text generation. WM measures contributed unique variance to writing that was independent of reading skill, and STM measures best predicted transcription processes and reading recognition, whereas WM measures best predicted text generation and reading comprehension. Both verbal and visual-spatial working memory measures predicted reading comprehension, whereas only WM measures that reflect executive processing significantly predicted writing. In general, the results suggest that individual differences in children's writing reflect a specific capacity system, whereas reading comprehension draws upon a multiple capacity system.

Attention↗
PubMed1989

Visual and phonological components of working memory in children.

Previous studies have shown that young children's immediate memory for a short series of drawings of objects is mediated by a visual component of working memory, whereas older children rely chiefly upon a phonological component. Three experiments investigated the hypothesis that older children rely also, but to a lesser extent, on visual working memory. Experiment 1 confirmed previous evidence that 11-year-olds' memory is disrupted by phonemic similarity of object names, but is unaffected by visual similarity of the objects themselves. However, when articulatory suppression was used to prevent phonological coding, levels of recall were sensitive to visual rather than phonemic similarity. Experiment 2 compared the effects of interpolating an auditory-verbal or a visual postlist task on memory for drawings viewed either with or without suppression. The visual task had a clear disruptive effect only in the suppression condition, where it interfered selectively with recall of the most recent item. Experiment 3 compared the effects of interpolating an auditory-verbal or a mixed-modality (visual-auditory) postlist task when subjects were not required to suppress. There was greater interference from the mixed-modality task, and this effect was confined to the last item presented. These experiments are taken as confirming the presence of a small but reliable contribution from visual memory in 11-year-old children's recall. As in younger children, visual working memory in 11-year-olds is sensitive to visual similarity and is responsible for a final-item visual recency effect. The results also show that older children's use of visual working memory is usually masked by the more pervasive phonological component of recall. Some implications for the structure of working memory and its development are discussed.

Child↗
PubMed1999

Estradiol facilitates performance as working memory load increases.

A water-escape version of the radial-arm maze was used to assess rat spatial working memory performance. Intact females and ovariectomized females receiving a physiologically low dose, physiologically moderate dose or no estradiol replacement were studied. Subjects were given seven trials a day for 12 days. Females receiving moderate dose estradiol made fewer errors than the other three groups during the latter portion of testing. As trials progressed within a session, the elements of information to be remembered increased. Assessment of individual trials revealed that when the demand on an animal's working memory system was limited to one to four elements of information, the three groups with estrogen (including intact females) maintained successful performance, whereas the ovariectomized females made more errors. However, when the demand on an animal's working memory system was increased to six elements of information, only the moderate dose estradiol females maintained successful performance. These data suggest that, although moderate levels of estradiol replacement are the most beneficial for working memory function, even low-dose estradiol replacement can act to protect working memory systems from the decline seen with the removal of ovarian hormones.

Animals↗
PubMed1999

Measuring infant spatial working memory using a modified delayed-response procedure.

Infant spatial working memory was assessed in 96 nine-month-old human infants using a modification of the delayed-response procedure. A person was the hidden stimulus, gaze was used as the response modality, the response context was a naturalistic "peek-a-boo" game, and a salient cue (i.e. curtains opening to reveal two windows) was used to evoke responses. Infants responded on most trials and performed significantly above chance in delay conditions of 10 and 20 seconds. Reinforcement affected performance, but performance was above chance even in a 0% reinforcement condition. These procedural variations boost estimates of infant spatial working memory over previous estimates and enhance the usefulness of the delayed-response procedure as a marker task for infant spatial working memory.

Analysis of Variance↗
PubMed2001

Behavioural relevance modulates access to spatial working memory in humans.

Neurophysiological studies in monkeys suggest selective representation of behaviourally relevant information in working memory. So far, no behavioural evidence for this has been reported for humans. Here, we investigated the role of behavioural relevance for access to human visuospatial working memory by using delayed oculomotor response tasks. Subjects were presented two successive visual cues in different and unpredictable locations while fixating on a central fixation point. After a delay, an unpredictable auditory signal (one beep or two beeps) sounded and the central fixation point was turned off, initiating the oculomotor response (i.e. memory-guided saccade) phase. Two groups of 10 subjects each were studied in two conditions: in the 'relevant' condition, subjects were instructed to memorize both visual cues and to move the eyes to the remembered position of the first cue (one beep) or the second cue (two beeps). The same stimuli were used in the 'irrelevant' condition, but subjects were instructed to memorize and move the eyes to the position of the first cue only, regardless of the second cue and the auditory signal. In the 'relevant' condition, we found a significant increase in errors of memory-guided saccades to the first cue, when the second cue was located between central fixation point and first cue. This spatially selective interference effect disappeared in the 'irrelevant' condition, despite identical stimuli. On a behavioural level, these results show for the first time the significance of behavioural relevance for access to human spatial working memory. These findings complement recent single-neuron studies in monkeys, showing that the neuronal substrates of working memory selectively represent behaviourally relevant perceptual information.

Adult↗
PubMed2005

Alpha-2 adrenoceptor activation inhibits phencyclidine-induced deficits of spatial working memory in rats.

N-methyl-D-aspartate (NMDA)/glutamate receptor antagonists, such as phencyclidine (PCP), induce behavioral abnormalities (locomotor hyperactivity, sensorimotor gating deficits, impairments of cognition) in animals that are thought to model aspects of schizophrenia. The administration of PCP increases noradrenaline transmission in the rat prefrontal cortex, a brain structure required for normal cognitive processes. Noradrenaline, in turn, works through a set of receptors that have themselves been implicated directly in NMDA antagonist-induced deficits; we recently reported that the alpha-2 agonist, clonidine, is effective at preventing PCP-induced deficits of working memory and visual attention in rats. Here, we further investigated the role for alpha-2 adrenoreceptors in the effects of PCP on spatial working memory performance. The alpha-2 agonist clonidine (0.001-0.01 mg/kg, subcutaneously (s.c.)) produced a significant amelioration of PCP-induced working memory deficits; the effects of PCP (1.0 mg/kg, s.c.), but not clonidine, were reduced in noradrenaline-depleted rats. In addition, the alpha-2A-preferring agonist guanfacine (0.05-1.0 mg/kg, s.c.) dose-dependently prevented the deficits of spatial working memory performance produced by PCP. Although the highly selective alpha-2 receptor antagonist, atipamezole (ATI), failed to affect spatial working memory on its own, at the doses studied (0.1-0.5 mg/kg, s.c.), it dramatically enhanced the working memory deficit produced by PCP. These data indicate that alpha-2 adrenoreceptors tonically inhibit PCP-induced deficits of spatial working memory, suggesting an important role for these receptors in cognitive deficits associated with NMDA receptor hypofunction.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2006

Working memory and proverb comprehension in adolescents with traumatic brain injury: a preliminary investigation.

PRIMARY OBJECTIVE: This study investigated the relationship between working memory and comprehension of low-familiarity proverbs in adolescents with traumatic brain injury (TBI). METHODS AND PROCEDURES: Ten adolescents, aged 12-21 years who had suffered a TBI prior to the age of 10 years and 10 individually age-matched peers with typical development participated in the study. The participants listened to short paragraphs containing a proverb and interpreted the meaning of the proverb using a forced-choice task. In addition, participants engaged in a task that evaluated working memory ability. MAIN OUTCOMES AND RESULTS: Analysis revealed that individuals with TBI differed from their non-injured peers in their understanding of proverbs. In addition, working memory capacity influenced performance for all participants. CONCLUSIONS: The importance of considering working memory when evaluating figurative language comprehension in adolescents with TBI is highlighted. Implications for future research, particularly with regard to varying working memory and task demands, are considered.

Adolescent↗
PubMed2007

Propranolol blocks chronic risperidone treatment-induced enhancement of spatial working memory performance of rats in a delayed matching-to-place water maze task.

RATIONALE: Atypical antipsychotics improve cognitive function, including working memory, in schizophrenia. Some atypical antipsychotics have been reported to activate the locus coeruleus and induce beta-adrenoceptor antagonist sensitive c-Fos-like immunoreactivity in the prefrontal cortex. MATERIALS AND METHODS: The present study investigated the effects of chronic treatment of rats with risperidone (1 mg kg(-1) day(-1) s.c.), clozapine (10 mg kg(-1) day(-1) s.c.), or acidified saline vehicle control for 2, 4, or 8 weeks on spatial working memory performance in a delayed matching-to-place water maze task with a 60-s inter-trial retention interval with and without acute challenge with propranolol (10 mg/kg i.p.). RESULTS: Treatment with risperidone for 8 weeks, but not 2 or 4 weeks, significantly improved working memory performance. In contrast, treatment with clozapine for up to 8 weeks did not improve working memory. Acute challenge with propranolol blocked the improvement in working memory produced by chronic treatment with risperidone, but had no significant effect on performance in saline- or clozapine-treated animals. CONCLUSIONS: The delayed matching-to-place water maze task may prove valuable in the investigation of the behavioural pharmacology of the cognitive effects of antipsychotic drugs. These data suggest that beta adrenoceptors may contribute to the cognitive effects of chronic treatment with atypical antipsychotics.

Adrenergic beta-Antagonists↗
PubMed2001

Educational level and age influence spatial working memory and Wisconsin Card Sorting Test performance differently: a controlled study in schizophrenic patients.

The influence of educational level and age on executive function, as evaluated by the Wisconsin Card Sorting Test (WCST), and 'working memory,' as evaluated by means of a visual-manual delayed-response task, has been investigated in 25 schizophrenic patients and 35 healthy controls matched for age. Different patterns of correlations between educational level, age and cognitive variables were seen for the 'working memory' task but not for the WCST. No significant correlations between the WCST and the 'working memory' task indexes have been observed. Based on multivariate analyses, poor performance of schizophrenic patients on working memory and executive function tasks was observed; after covarying for the educational level, group differences were no longer significant for executive functions, but the difference in 'working memory' performance persisted. The implications of sociodemographic variables as well as the role of statistical manipulation are evaluated and their differential impact on 'working memory' and executive functions is proposed in further support of these neurocognitive constructs that may be dissociable.

Adolescent↗