Theory of mind and executive function: working-memory capacity and inhibitory control as predictors of false-belief task performance

This study of the relationship between theory of mind and executive function examined whether on the false-belief task age differences between 3 and 5 ears of age are related to development of working-memory capacity and inhibitory processes. 72 children completed tasks measuring false belief, working memory, and inhibition. Significant age effects were observed for false-belief and working-memory performance, as well as for the false-alarm and perseveration measures of inhibition. A simultaneous multiple linear regression specified the contribution of age, inhibition, and working memory to the prediction of false-belief performance. This model was significant, explaining a total of 36% of the variance. To examine the independent contributions of the working-memory and inhibition variables, after controlling for age, two hierarchical multiple linear regressions were conducted. These multiple regression analyses indicate that working memory and inhibition make small, overlapping contributions to false-belief performance after accounting for age, but that working memory, as measured in this study, is a somewhat better predictor of false-belief understanding than is inhibition.     

Putting things into perspective: individual differences in working-memory span and the integration of information

An important function of working memory is the integration of incoming information into an appropriate model of the contextual situation. We hypothesized that individual variability in working-memory function (estimated using Engle's operation-span measure) may lead to differential reactivity to a changing context. We recorded event-related brain potentials (ERPs) and reaction-time measures to stimuli embedded in long stimulus series (two auditory discrimination tasks), and examined the participants' responses in relation to how the current stimuli fit with the context generated by the previous stimuli. In both tasks, participants with low working-memory span scores showed larger brain responses as a function of variations in the local stimulus sequence than participants with high span scores. These data suggest that the low working-memory span group is more affected by the local stimulus sequence than the high span group, possibly because they are more easily swayed by ongoing changes and are therefore less capable of maintaining their attention on the overall sequence.     

Effects of adult age and working memory on reasoning and spatial abilities

Three predictions were derived from the hypothesis that adult age differences in certain measures of cognitive functioning are attributable to age-related reductions in a processing resource such as working-memory capacity. Each prediction received at least some degree of empirical support in a study involving 120 males ranging between 20 and 79 years of age. First, older adults exhibited greater impairments of performance than did young adults when task complexity increased and more demands were placed on the limited processing resources; second, the magnitudes of these complexity effects were highly correlated across verbal (reasoning) and spatial (paper folding) tasks. Finally, statistical control of an index of a working-memory processing resource attenuated the effects of age on the measures of cognitive performance. It was concluded that further progress in understanding the mechanisms of the relation between age and cognitive functioning will require improved conceptualizations of the nature of working memory or other hypothesized mediating constructs.     

Sex-dependent effects of neonatally administered morphiceptin and D-ala-D-leu-enkephalin on maze learning in rats

Newborn rats were injected (ip) with morphiceptin [72.7 micrograms/kg (a mu-type opioid receptor agonist)], D-alanine2-D-leucine5-enkephalin [79.4 micrograms/kg (a delta-receptor agonist)], or saline for 7 days after birth. Testing on a complex maze on Day 25 revealed a significant sex-dependent facilitation of performance by the opioid peptides. Peptide-treated females performed better than the males on the first day of training as measured by errors. Opioid treatment increased mortality, as three times as many peptide-treated animals died in comparison to the saline control group. Peptide treatment did not affect locomotor activity measured in an open field. Weight at Day 24 was also affected by the peptide treatment, females and males injected with the opioids being lighter and heavier, respectively, than the control group.     

Validating the Electric Maze Task as a Measure of Planning

The Electric Maze Task (EMT) is a novel planning task designed to allow flexible testing of planning abilities across a broad age range and to incorporate manipulations to test underlying planning abilities, such as working-memory and inhibitory control skills. The EMT was tested in a group of 63 typically developing 7- to 12-year-olds. Participants completed 4 mazes designed to alter working-memory demands (by increasing the number of steps required from 6 to 8) and inhibitory control demands (by using a modified Dimensional Change Card Sort task) and 3 standardized measures using the Cambridge Neuropsychological Test Automated Battery. The EMT was found to correlate with measures of visual memory, working memory, and planning. The 6-step mazes were simpler for participants to solve and mapped on to performance on the visual memory task. The 8-step mazes were more difficult and mapped on to performance on the spatial working-memory and planning tasks. Children who were 10 to 12 years old were also better than 7- to 9-year-olds at solving all mazes, as evidenced by fewer errors and fewer errors later in solving the mazes. Younger children also struggled more than older children after a rule switch. Performance on the maze task differentiated 7- to 12-year-old children with better planning skills, and manipulations of the maze task were successful in altering the working-memory and inhibitory control demands.     

Intraseptal Flumazenil Enhances, while Diazepam Binding Inhibitor Impairs, Performance in a Working Memory Task

GABA_A/benzodiazepine receptors in the medial septum modulate the activity of cholinergic neurons that innervate the hippocampus. Injection of benzodiazepine (BDZ) agonists into the medial septum impairs working memory performance and decreases high-affinity choline transport (HAChT) in the hippocampus. In contrast, intraseptal injection of the BDZ antagonist flumazenil increases HAChT and prevents the memory deficits induced by systemic BDZs. The present studies attempted to further characterize the behavioral effects of medial septal injections of flumazenil to an endogenous negative modulator of the GABA_A/BDZ receptor complex, diazepam binding inhibitor (DBI). Male Sprague–Dawley rats were cannulated to study the effects of intraseptal injections of these BDZ ligands on spatial working memory, anxiety-related behaviors in the elevated plus maze, and on general locomotor activity. Intraseptal flumazenil (10 nmol/0.5 μl) produced a delay-dependent enhancement of DNMTS performance after an 8-h, but not a 4-h, delay interval. This promnestic dose of flumazenil had no effect on locomotor activity and did not produce changes in measures of anxiety on the plus maze. Intraseptal injection of DBI had no effect (8 nmol/0.5 μl) or slightly impaired (4 nmol/0.5 μl) DNMTS radial maze performance following an 8-h delay, without producing changes in locomotion or plus maze behavior. These data demonstrate that flumazenil has a unique profile of activity in enhancing working memory following intraseptal injection.     

Short forms of the "reference-" and "working-memory" Morris water maze for assessing age-related deficits.

Short forms of the reference- and working-memory versions of the Morris water maze, each limited to 10 trials, were examined for their reliability and sensitivity to age-related deficits in 16- and 24-month F-344 rats, relative to 2- to 2.5-month young controls. The reference-memory task used long intertrial intervals of 23 h, but required learning only one target location, while the working-memory task used shorter intertrial intervals of 60 min but required learning many different target locations. The reference-memory task was very reliable, revealed large age-related deficits, and correctly identified almost all aged rats as impaired relative to young controls. The working-memory task was less reliable, revealed smaller deficits than the reference memory task at 24 months, and did not discriminate as well between 2.5- and 24-month rats. Furthermore, in the working-memory task 16- and 24-month rats had longer swim paths than 2- to 2.5-month rats on the first trial of each trial pair, which is suggestive of a deficit in processing spatial information and raises questions about the validity of this test as a specific test of working memory. Although the working-memory procedures may be preferable under certain conditions, perhaps as a measure specific to hippocampal dysfunction, the reference-memory task seems more sensitive to age-related deficits and more accurately identifies older rats as impaired. These results are consistent with previous reports that age-related deficits in acquiring spatial learning tasks are common and that the magnitude of the deficit increases as the length of the retention interval increases.     

Performance dissociation during verbal and spatial working memory tasks

Past research has inconsistently distinguished the neural substrates of various types of working memory. Task design and individual performance differences are known to alter patterns of brain response during working-memory tasks. These task and individual differences may have produced discrepancies in imaging findings. This study of 50 healthy adults (M(age) = 19.6 yr., SD = .8) examined performance during various parametric manipulations of a verbal and spatial n-back working-memory task. Performance systematically dissociated on the basis of working-memory load, working memory type, and stimulus difficulty, with participants having greater accuracy but slower response time during conditions requiring verbal versus spatial working memory. These findings hold implications for cognitive and neuroimaging studies of verbal and spatial working memory and highlight the importance of considering both task design and individual behavior.     

东莨菪碱对吗啡诱导的大鼠行为敏感化的影响

药物重复处理导致的行为敏感化与成瘾过程密切相关。本实验检验东莨菪碱对吗啡诱导的大鼠行为敏感化发展和转化的影响。实验一动物分为3组,分别进行生理盐水（对照组）、吗啡（10mg/kg,吗啡组）、吗啡（10mg/kg）＋东莨菪碱（3mg/kg,吗啡-东莨菪碱组）前处理,36小时腹腔注射4次（第1~2天）。自然戒断7天（第3~9天）。第10天,所有动物均使用吗啡（4mg/kg）激发,记录动物的自发活动量;第24天,吗啡组和吗啡-东莨菪碱组动物重复第10天的操作。实验二动物分为3组,分别接受生理盐水（对照组）、吗啡（10mg/kg,吗啡组）、吗啡（10mg/kg,吗啡-东莨菪碱组）处理,36小时腹腔注射4次（第1~3天）;间隔12小时后,3组动物分别接受生理盐水、生理盐水和东莨菪碱（3mg/kg）处理,仍为36小时腹腔注射4次（第3 ~5天）。第6~9天不进行药物处理。第10天和第17天,分别使用吗啡（4mg/kg）激发,记录动物的活动量。记录时间均为两小时(10分钟为一个记录单元)。结果表明,东莨菪碱能够抑制吗啡诱导的行为敏感化的发展,一定程度上也能够延缓行为敏感化的转化但没有阻断这种转化     

Sex differences in spatial and non-spatial Y-maze performance after chronic stress

Chronic restraint is known to alter hippocampal CA3 dendritic morphology and spatial memory in male rats. The present study examined whether female rats, which exhibit different anatomical adaptations to chronic stress than those of males, would also show spatial memory impairments. Male and female Sprague-Dawley rats were restrained for 6 h/day for 21 days, a time frame previously demonstrated to cause hippocampal CA3 dendritic atrophy. The day after the last restraint session, rats were tested on a Y-maze, a habituation task that can be used to assess spatial memory. Chronic stress impaired Y-maze performance in both sexes without affecting levels of locomotion as measured by total arm entries in the first minute. However, Y-maze performance of stressed females improved in 2-5 min when chronically stressed males continued to show poor Y-maze performance. The enhanced Y-maze performance of chronically stressed females occurred when total arm entries were higher compared to the entries made by males. Therefore, correlations were performed between total arm entries and spatial memory in 1 and 2-5 min. In the first minute when control females demonstrated functional spatial memory, female controls with the lowest locomotor levels exhibited the best performance. The correlations for stressed females were not significant, and neither were the correlations for any group in 2-5 min. Overall, these results show important sex differences in response to chronic stress with females exhibiting an ability to recover quickly from deficits in Y-maze performance.     

The behavioral effects of enriched housing are not altered by serotonin depletion but enrichment alters hippocampal neurochemistry

To assess a possible role for serotonin in the mediation of the behavioral changes induced by enriched housing conditions (EC), adult female Long-Evans rats sustaining a serotonin depletion (150 microg of 5,7-dihydroxytryptamine, icv) and sham-operated rats were housed postoperatively for 30 days in enriched (12 rats/large cage containing various objects) or standard housing conditions (2 rats/standard laboratory cage). Thereafter, anxiety responses (elevated plus-maze), locomotor activity (in the home-cage), sensori-motor capabilities (beam-walking task), and spatial memory (eight-arm radial maze) were assessed. Monoamine levels were subsequently measured in the frontoparietal cortex and the hippocampus. Overall, EC reduced anxiety-related responses, enhanced sensori-motor performance and improved the memory span in the initial stage of the spatial memory task. Despite a substantial reduction of serotonergic markers in the hippocampus (82%) and the cortex (74%), these positive effects of EC were not altered by the lesion. EC reduced the serotonin levels in the ventral hippocampus (particularly in unlesioned rats: -23%), increased serotonin turnover in the entire hippocampus (particularly in lesioned rats: +36%) and augmented the norepinephrine levels in the dorsal hippocampus (+68% in unlesioned and +49% in lesioned rats); no such alterations were found in the frontoparietal cortex. Our data suggest that an intact serotonergic system is not a prerequisite for the induction of positive behavioral effects by EC. The neurochemical changes found in the hippocampus of EC rats, however, show that the monoaminergic innervation of the hippocampus is a target of EC.     

Age-related changes in antisaccade task performance: inhibitory control or working-memory engagement?

In antisaccade tasks, subjects are required to generate a saccade in the direction opposite to the location of a sudden-onset target stimulus. Compared to young adults, older adults tend to make more reflex-like eye movements towards the target, and/or show longer saccadic onset latencies on correct direct antisaccades. To better understand the nature of these effects of aging on antisaccade performance, we examined the role of age-related deficiencies in inhibitory control vis-a-vis age changes in the engagement of working memory. Inhibitory demands were manipulated using fixation-offset conditions, while working-memory demands were manipulated by varying memory-updating requirements. The results indicate that inhibitory oculomotor functions remain largely intact with advancing age; older adults' performance breaks down only when their limited working-memory capacity is taxed by increasing updating demands.     

Paradoxical sleep deprivation impairs acquisition, consolidation, and retrieval of a discriminative avoidance task in rats

The aim of the present study was to investigate the effects of paradoxical sleep deprivation (PSD) for 96 h on the learning/memory processes in rats submitted to the plus-maze discriminative avoidance task (PM-DAT), which simultaneously evaluates learning, memory, anxiety and motor function. Four experiments were performed in which rats were submitted to: (1) post-training and pre-test PSD; (2) post-training or pre-test PSD; (3) pre-training PSD or pre-training paradoxical sleep (PS) rebound (24 h) and (4) pre-test PSD rebound. Concerning Experiment I, post-training and pre-test PSD induced memory deficits, an anxiolytic-like behavior and an increase in locomotor activity. In Experiment II, both post-training PS-deprived and pre-test PS-deprived groups showed memory deficits per se. However, only the pre-test PS-deprived animals presented anxiolytic-like behavior and increased locomotor activity. In Experiment III, pre-training PS-deprived rats showed learning and memory deficits, anxiolytic-like behavior and increased locomotor activity. A 24h-sleep recovery period after the PSD abolished the learning and memory deficits but not anxiety and locomotor alterations. Finally, sleep rebound did not modify acquisition (Experiment III) and retrieval (Experiment IV). This study strengthened the critical role of paradoxical sleep (but not sleep rebound) in all the phases of learning and memory formation. In addition, it suggests that PSD effects on acquisition and consolidation do not seem to be related to other behavioral alterations induced by this procedure.     

Working memory and strategies in syllogistic-reasoning tasks

It has often been asserted that working-memory limitations are a major factor contributing to problem difficulty; for example, Johnson-Laird’s (1983) mental-models theory appeals to working memory limitations to explain the difficulty of syllogistic reasoning. However, few studies have directly explored working memory in problem solving in general or syllogistic reasoning in particular. This paper reports two studies. In the first, working-memory load was varied by presenting syllogistic tasks either verbally or visually (so that the premises were continuous1y avai1ab1e for inspection). A significant effect of memory load was obtained. In the second study, premises were presented visually for a subject-determined time. Dual-task methods were used to assess the role of working-memory components, as identified in Baddeley’s (1986) model. Syllogistic performance was disrupted by concurrent random-number generation but not by concurrent articulatory suppression or by concurrent tapping in a preset pattern. Furthermore, the concurrent syllogism task interfered with random generation and to a lesser extent with articulatory suppression, but not with tapping. We conclude that while the central-executive component of working memory played a major role in the syllogistic-task performance reported here, the articulatory loop had a lesser role, and the visuospatial scratch pad was not involved.     

Binding facilitates attention switching within working memory

The authors investigated the units of selective attention within working memory. In Experiment 1, a group of participants kept 1 count and 1 location in working memory and updated them repeatedly in random order. Another group of participants were instructed to achieve the same goal by memorizing the verbal and spatial information in an integrative way as a moving digit. The behavioral data showed that switching attention between properties of an integrated working-memory item was faster than switching between respective properties of different items. Experiment 2 demonstrated that this switching facilitation cannot be simply ascribed to the different amount of working-memory items maintained by the two groups of participants. Finally, by adopting a pure verbal task in Experiment 3, the authors observed the same binding facilitation, with the possibility of "location-based selection" excluded. They summarize the observations of all 3 experiments in the study and suggest both a location- and object-based mechanism for attention selection in working memory.     

Independence of blood pressure and locomotor hyperactivity in normotensive and genetically hypertensive rat

The spontaneously hypertensive rat (SHR) exhibits locomotor hyperactivity in comparison to its normotensive progenitor Wistar-Kyoto (WKY) strain. We asked whether the hyperactive behavior was a direct consequence of elevated blood pressure in the hypertensive rat. Three experimental protocols were used to chronically alter blood pressure. In the first protocol, a group of adult SHRs was given hydralazine (20 mg/kg/day) in their drinking water to lower blood pressure. These animals exhibited a significant decrease in blood pressure, but no change in locomotor activity. In the second protocol, young SHRs (4 weeks of age) were treated with the same dosage of hydralazine until 16 weeks of age. Blood pressure was significantly decreased in these animals with no change in locomotor activity. In the third protocol, normotensive WKY and Sprague-Dawley (SD) rats were made hypertensive with unilateral renal clips. The resulting increase in blood pressure in these animals did not alter locomotor activity. These results suggest that locomotor hyperactivity is an inherent property of the SHR and is independent of blood pressure.     

Sex differences and estropausal phase effects on water maze performance in aged rats

An age-related decline in memory has been reported in male rats; however, there are few studies that have addressed these changes in aged female rats. In young female rats, hormonal cycles influence behavior. By the age of 22 months most female rats have not had regular hormonal cycles for at least 9 months. In the current study we examined how the hormonal status (persistent estrus and pseudo-pregnant) of the aged (22-24 months) female rat (Long Evans) influenced performance on a spatial version of the Morris water maze and compared this to aged male rats. Aged females in persistent estrus showed better performance on the water maze than both aged females that were pseudopregnant and aged males. Thus, postestropausal hormonal status may influence the course of aging in females.     

Interference in memory for tonal pitch: Implications for a working-memory model

The degree of interference caused by different kinds of stimuli on memory for tonal pitch was studied. Musically trained and untrained subjects heard a sequence of two tones separated by an interval of 5 sec. The tones were either identical in pitch or differed by a semitone. Subjects had to decide whether the tones were identical or not. The interval was filled with tonal, verbal, or visual material under attended and unattended conditions. The results revealed clear group differences. Musically trained subjects' retention of the first test tone was only affected by the interposition of other tones. In contrast, the performance of musically untrained subjects was also affected by verbal and visual items. The findings are discussed in the framework of Baddeley's (1986) working-memory model.     

Early and late stages of working-memory maintenance contribute differentially to long-term memory formation

The present paper investigated the role of early and late stages of working-memory maintenance, which have been suggested to differentially contribute to long-term memory formation. In experiment 1, we administered a delayed-match-to-sample task, requiring participants to remember line drawings of non-sense three-dimensional stimuli. In the delay phase, participants were either presented with a fixation cross (for 2 or 9 s) or with one of two different interference tasks, varying in visual overlap with the target. The interference task was presented 1.5, 4.5 or 7.5 s after target offset. Early interfering and early probing disproportionately affected performance on an unexpected subsequent recognition-memory task compared to later interference or probing. This was not modulated by the type of interference task. In Experiment 2, we examined whether the formation of a holistic internal code of the target may be a gradual process. An analogous delayed-match-to-sample task was administered, with interference after 0.5, 2.5 or 4.5 s after target offset. The early and middle interference condition similarly disproportionately affected performance compared to later interference. Hence, the present results support the view of a functional dissociation between early and late stages of working-memory maintenance and that early working-memory processes contribute particularly to long-term memory formation.     

Spatial memory and visual evoked potentials in young and old rats after housing in an enriched environment

The effects of aging and of housing in an enriched environment on performance in an 8-arm radial maze were evaluated in young adult (7-8 months) and old (30-33 months) male Brown-Norway rats, using a procedure in which the rats were confined for 8 s to the central platform of the maze between consecutive choices. Although the old rats attained a level of performance which was clearly above change, they were shown to perform worse than the young rats. No performance differences were found between differentially housed rats of the same age group. In a second experiment recovery cycles of visual evoked potentials were determined in the same rats by using paired flashes with an interstimulus time of 400, 300, 200, or 100 ms. Recovery was consistently smaller in the old rats as compared to the young ones. No correlation could be demonstrated, however, between radial maze performance or housing condition and recovery functions of the visual evoked potentials. This finding indicates that a decline in visual sensitivity cannot readily explain the impaired radial maze performance of old rats. Evidence which suggests that age-related hippocampal changes play a major role in the radial maze performance deficit is discussed.