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Fluoxetine disrupts the integration of anxiety and aversive memories.

Anxiety disorders may result from an overexpression of aversive memories. Evidence suggests that the hippocampal cholinergic system could be the point of convergence of anxiety and memory. We propose that clinically effective anxiolytics may exert their effect by interfering with this integration mechanism. To assess anxiety and aversive memory, we used the shock-probe burying test. A reduction in anxiety in this test is indicated by decreased burying, whereas impaired cognition is reflected by an increased number of probe-contacts and/or reduced retention latency. Both an aversive stimulus and the memory of that stimulus significantly increased hippocampal acetylcholine (ACh) levels (Experiment 1). In fact, the memory of the event seemed to be more important than the event itself since the aversive memory induced a greater increase in hippocampal ACh. Injections (i.p.) of fluoxetine (Prozac) reduced burying behavior, while not affecting probe contacts or retention latency (Experiment 2). Although injections of fluoxetine did not affect basal hippocampal ACh efflux (Experiment 3), fluoxetine abolished the increase in ACh induced by the aversive stimulus and the memory of that stimulus (Experiment 4), emphasizing the significance of aversive memories in anxiety disorders. These actions may be mediated by a decrease in the event-related enhancement in cholinergic neurotransmission through M1 cholinergic receptors (Experiment 5). Therefore, anxiety disorders may stem from an unopposed formation of aversive memories and clinically effective anxiolytics hinder the association between emotional and cognitive processing. This reduces the emotional impact of aversive memories, thereby opposing consequent anxiety.

Acetylcholine↗

Higher-order associative processing in Hermissenda suggests multiple sites of neuronal modulation.

Two important features of modern accounts of associative learning are (1) the capacity for contextual stimuli to serve as a signal for an unconditioned stimulus (US) and (2) the capacity for a previously conditioned (excitatory) stimulus to "block" learning about a redundant stimulus when both stimuli serve as a signal for the same US. Here, we examined the process of blocking, thought by some to reflect a cognitive aspect of classical conditioning, and its underlying mechanisms in the marine mollusc Hermissenda. In two behavioral experiments, a context defined by chemosensory stimuli was made excitatory by presenting unsignalled USs (rotation) in that context. The excitatory context subsequently blocked overt learning about a discrete conditioned stimulus (CS; light) paired with the US in that context. In a third experiment, the excitability of the B photoreceptors in the Hermissenda eye, which typically increases following light-rotation pairings, was examined in behaviorally blocked animals, as well as in animals that had acquired a normal CS-US association or animals that had been exposed to the CS and US unpaired. Both the behaviorally blocked and the "normal" learning groups exhibited increases in neuronal excitability relative to unpaired animals. However, light-induced multiunit activity in pedal nerves was suppressed following normal conditioning but not in blocked or unpaired control animals, suggesting that the expression of blocking is mediated by neuronal modifications not directly reflected in B-cell excitability, possibly within an extensive network of central light-responsive interneurons.

Animals↗

Final-year nursing students' clinical practice experiences: a reflection study.

OBJECTIVES: This study aimed to explore the most impactful clinical practice experiences of final-year nursing students and the future-oriented actions developed in response to these experiences. METHODS: A retrospective descriptive qualitative design was used. Following reflection training in the internship practice course, 134 final-year nursing students were asked to describe the experience that affected them most during clinical practice. A total of 123 written reflections were analyzed using content analysis. RESULTS: Three themes emerged: near-miss events, incivility behaviors, and positive preceptoring roles. Negative experiences were mainly related to patients, relatives, and nurses and often led students to feel fear and inadequacy. Students reported action plans focused on effective communication, safe patient care, and becoming positive role models. CONCLUSIONS: These findings highlight the importance of supportive clinical learning environments and positive professional socialization during the transition from student to nurse. IMPLICATIONS FOR INTERNATIONAL AUDIENCE: Nursing students worldwide may encounter incivility and near-miss events during clinical practice, potentially adversely affecting their learning experiences and professional development.

Humans↗

Autonomic responses correlate to motor anticipation.

New findings have stated that autonomic nervous system (ANS) functioning may reflect some cognitive processes observed in real time analysis. Four ANS variables plus instantaneous heart rate and respiratory frequency were quantified by original techniques and indices on 11 subjects during a coincidence-anticipation task, performed on a computer screen under six different, randomly-presented modalities (3 modalities describing the spot moving along a parabola at 2 speeds). Tonic levels and phasic responses corresponding to each trial were recorded continuously. Results showed that skin resistance tonic level evolution gave evidence of vigilance changes. Thus, performance can be related to subjects' vigilance. An autonomic response was always observed during performance of an anticipation task. The six task modalities were distinguished by performance values. Simultaneously recorded ANS responses fully differentiated these same modalities for 10 subjects out of 11. These ANS responses were furthermore related to performance. Ten subjects out of 11 possess at least one Autonomic variable which can differentiate the six task modalities, confirming Lacey's hypothesis on ANS preferential response, and suggesting ANS specificity. ANS functioning may reveal some brain functions through a specific autonomic channel, characterizing each subject. The behavioral output of an individual may thus be reflected by such a functioning.

Adolescent↗

"Brain-specific" nutrients: a memory cure?

OBJECTIVE: We review the experimental evaluations of several widely marketed nonprescription compounds claimed to be memory enhancers and treatments for age-related memory decline. We generally limit our review to double-blind placebo-controlled studies. The compounds examined are phosphatidylserine (PS), phosphatidylcholine (PC), citicoline, piracetam, vinpocetine, acetyl-L-carnitine (ALC), and antioxidants (particularly vitamin E). RESULTS: In animals, PS has been shown to attenuate many neuronal effects of aging, and to restore normal memory on a variety of tasks. Preliminary findings with humans, though, are limited. For older adults with probable Alzheimer's disease, a single study failed to demonstrate positive effects of PS on memory performance. For older adults with moderate cognitive impairment, PS has produced consistently modest increases in recall of word lists. Positive effects have not been as consistently reported for other memory tests. There is one report of consistent benefits across a number of memory tests for a subset of normal adults who performed more poorly than their peers at baseline. The choline compounds PC and citicoline are thought to promote synthesis and transmission of neurotransmitters important to memory. PC has not proven effective for improving memory in patients with probable Alzheimer's disease. The issue remains open for older adults without serious degenerative neural disease. Research on citicoline is practically nonexistent, but one study reported a robust improvement in story recall for a small sample of normally aging older adults who scored lower than their peers in baseline testing. Animal studies suggest that piracetam may improve neuronal efficiency, facilitate activity in neurotransmitter systems, and combat the age-related decrease in receptors on the neuronal membrane. However, for patients with probable Alzheimer's disease, as well as for adults with age-associated memory impairment, there is no clear-cut support for a mnemonic benefit of piracetam. Vinpocetine increases blood circulation and metabolism in the brain. Animal studies have shown that vinpocetine can reduce the loss of neurons due to decreased blood flow. In three studies of older adults with memory problems associated with poor brain circulation or dementia-related disease, vinpocetine produced significantly more improvement than a placebo in performance on global cognitive tests reflecting attention, concentration, and memory. Effects on episodic memory per se have been tested minimally, if at all. ALC participates in cellular energy production, a process especially important in neurons, and in removal of toxic accumulation of fatty acids. Animal studies show that ALC reverses the age-related decline in the number of neuron membrane receptors. Studies of patients with probable Alzheimer's disease have reported nominal advantages over a range of memory tests for ALC-treated patients relative to placebo groups. Significant differences have been reported rarely, however. Whether ALC would have mnemonic benefits for aging adults without brain disease is untested as far as we know. Antioxidants help neutralize tissue-damaging free radicals, which become more prevalent as organisms age. It is hypothesized that increasing antioxidant levels in the organism might retard or reverse the damaging effects of free radicals on neurons. Thus far, however, studies have found that vitamin E does not significantly slow down memory decline for Alzheimer's patients and does not produce significant memory benefits among early Parkinson's patients. Neither did a combination of vitamins E and C significantly improve college students' performance on several cognitive tasks. CONCLUSIONS: In sum, for most of the "brain-specific" nutrients we review, some mildly suggestive effects have been found in preliminary controlled studies using standard psychometric memory assessments or more general tests designed to reveal cognitive impairment. We suggest that future evaluations of the possible memory benefits of these supplements might fruitfully focus on memory processes rather than on memory tests per se.

Acetylcarnitine↗

New learning and remote memory in atypical Alzheimer's disease.

This paper presents the case of BB, an individual with an atypical posterior cortical presentation of Alzheimer's disease (AD). The severity of BB's visuo-spatial impairment far outweighed impairment of other cognitive functions. BB's case is also unusual in that despite a long history of progressive impairment, his cognitive symptoms remain relatively circumscribed. More specifically, BB's pattern of memory impairment was striking, since his impairment on formal psychometric tests of memory contrasted with his performance at clinical interview, where he talked lucidly about events in his past, and displayed remarkably well-preserved general semantic knowledge. On the basis of BB's clinical profile, it was hypothesised that his pattern of cognitive performance reflected an impairment of anterograde memory in the context of relative preservation of remote memory. Further investigations revealed that while BB's anterograde memory function was comparable to that of other AD patients, his remote memory was well preserved relative to other AD 'controls'. These findings are discussed in terms of typical and atypical presentations of Alzheimer's disease, and in terms of the possible fractionation of different aspects of long-term memory. The implications of these findings for our understanding of the neural bases of different types of retrograde memory (i.e. 'old' versus 'recent') are considered, with particular reference to the contrasting theoretical frameworks that have recently been advanced by Squire and Moscovitch.

Aged↗

Relating personnel costs in special care units and in traditional care units to resident characteristics.

BACKGROUND: There are over 16 000 nursing homes in the United States (US), among which approximately 70% of residents are cognitively impaired. Reflecting this, approximately 20% of US nursing homes maintain Special Dementia Care Units (SCUs). SCUs supposedly provide more staff time and more specialized staff assignments to residents than do traditional care units. AIMS OF THE STUDY: This paper addresses the issues of staff time and assignment: do the costs of personal care inputs differ according to whether they are provided by SCUs or in traditional care settings? Related to this, are differences associated with the different settings, or are they accounted for by resident characteristics within the settings? METHODS: Given the bias generally associated with collection of staff time data, the author developed (supported by the Health Care Financing Administration and the National Institute on Aging) and used in this study a barcode-based system ('InfoAide'). Using InfoAide, each provider automatically recorded task- and resident-specific time expenditure data which were subsequently monetized, using prevailing local wage rates. Individual resident personal characteristics and status data were provided by another simultaneous study of SCU impacts among the same residents. Regression analysis (MANCOVA for significantly correlated dependent variables) was used to examine the relationships between cost and SCU/traditional status, and individual resident characteristics, separately for each category of provider. RESULTS: Controlling for resident characteristics, the cost of aide care is significantly (positively) related (p <=0.01) to SCU status. Cognitive impairment, ADL impairment and being restrained are also related to higher aide care cost (p <=0.05, p <=0.01, and p <=0.05, respectively). The same is generally true of Speech Therapy, Social Service and care by licensed practical nurses, although the differences between SCU and traditional care units are essentially trivial - and there are no SCU/traditional care differences for registered nurses. DISCUSSION: SCU/traditional unit status, even when combined with the central resident covariates, explains very little variance in service costs, other than among nursing aides; in separate MR analyses in which monetized service time was the dependent variable, the cumulative adjusted R2 among aides was 0.37; for each of the other categories of service provider, the adjusted R2 was less than 0.10. There were differences (particularly in cognitive and ADL impairment) between SCU and non-SCU residents; these differences were related to differences in basic services which were, in turn, provided primarily by aides. The increased level of care provided in SCUs is attributable primarily to nursing aides. However, there is relatively little (albeit statistically significant) variation in more 'elective'services according to individual characteristics or to SCU versus traditional unit placement. This discussion is limited by the absence of analyses of possible interactions among variables, and by the cross-sectional nature of the data presented here. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: This absence of a substantial relationship between SCU/traditional status suggests that dichotomization between SCU and traditional care is misplaced, and that more attention should perhaps be given to the targeting and tailoring of services related to individual gradations of impairment and need. IMPLICATIONS FOR HEALTH POLICY FORMULATIONS: A very considerable literature has developed recently pertaining to Special versus Traditional care for persons with dementing illness. These data suggest that this is not a fruitful distinction, and that more effort should be devoted to defining and quantifying the elements and quality of care provided to nursing home residents. IMPLICATIONS FOR FURTHER RESEARCH: Further research is needed into the components of optimal quality care for demented nursing home residents, and into the interaction among these components as they relate to resident outcomes.

Journal Article↗

Uncoupling learning from initial recall: the relationship between speed and memory deficits in old age.

Nettelbeck & Rabbitt (1992) found that measures of speed of performance with low knowledge requirements (four-choice reaction time, inspection time and coding-substitution) accounted substantially for age-related changes among 104 persons aged from 54 to 85 years in a number of more complex cognitive measures reflecting general fluid ability. However, the numbers of words recalled from a list after either a single brief viewing of each word, or following a cumulative learning procedure across four trials, provided an exception to this general trend, leading to the conclusion that some aspects of memory may be independent of mental speed. A follow-up of 82 of the same people 18-20 months later was designed to partition performance in a similar cumulative learning procedure into an initial first recall component and a subsequent learning component. This was accomplished by fitting individual cumulative learning data with a hyperbolic power function which met the theoretical requirement of defining separate initial recall and learning parameters. These parameters were found to be independent and it was concluded that learning involved rehearsal, whereas first recall did not. The hyperbolic power function provided a good account for 92 per cent of individual cases. Analyses which combined Nettelbeck & Rabbitt's (1992) data with new measures confirmed the reliability of these authors' results. Furthermore, it was found that first recall, but not learning, was mediated by processing speed. Learning was relatively unaffected by age-related slowing in mental speed, suggesting that Nettelbeck & Rabbitt's results were the consequence of a strong rehearsal component in their memory tasks. Thus, while mental slowing is clearly one important aspect of cognitive decline during old age, it does not constitute a sufficient explanation for changes in all areas of cognitive functioning. Specifically, age-decline in rate of learning with rehearsal appeared to be independent of slowing in speed of information processing.

Aged↗

Event related evoked potentials in dementia: role of vitamin E.

Dementia is a common cognitive syndrome reflecting a wide spread chronic progressive disease as an extension to normal aging process. Oxidative stress has been implicated in dementia and antioxidants have become attractive therapeutic agents. Among the antioxidants vitamin E is the most potent in the treatment of dementia. Study was conducted in 20 patients suffering from dementia in the age group of 66-74 and in 20 age and sex matched controls. Latency of the P3 component of event related evoked potential (ERP) showed an increase from 338.65 +/- 42.22 msec in control group to 348.9 +/- 46.38 msec in patients of dementia. In control group P3 latency decreased from 338.65 +/- 42.22 msec to 331.6 +/- 38.75 msec after Vitamin E therapy. In patients of dementia latency decreased significantly from 348.9 +/- 46.38 msec to 324.62 +/- 44.25 msec after vitamin therapy for one month. P3 amplitude in controls and demented was 7.2 +/- 3.62 mu v and 7.07 +/- 3.73 mu v respectively. After vitamin E therapy a statistically significant increase in amplitude (P < 0.05) was observed in controls (9.34 +/- 5.04 mu v) and in patients of dementia (9.58 +/- 5.24 mu v). The study suggests that the latency and amplitude of P3 were not significantly different in control and dementia patients, while vitamin E supplementation (oral 800 mg per day for 30 days) decreased the latency and increased the P3 amplitude in both the control and dementia patients. Our study further supports that Vitamin E supplementation, because of its antioxidant property might be decreasing oxidative stress, which may lead to improvement in cognitive pool of generator neurons of P3.

Aged↗

If it changes it must be a process: study of emotion and coping during three stages of a college examination.

This natural experiment provides substantial evidence for the following major themes, which are based on a cognitively oriented, process-centered theory of stress and coping: First, a stressful encounter should be viewed as a dynamic, unfolding process, not as a static, unitary event. Emotion and coping (including the use of social support) were assessed at three stages of a midterm examination: the anticipation stage before the exam, the waiting stage after the exam and before grades were announced, and after grades were posted. For the group as a whole there were significant changes in emotions and coping (including the use of social support) across the three stages. Second, people experience seemingly contradictory emotions and states of mind during every stage of an encounter. In this study, for example, subjects experienced both threat emotions and challege emotions. The complexity of emotions and their cognitive appraisals reflects ambiguity regarding the multifaceted nature of the exam and its meanings, especially during the anticipation stage. Third, coping is a complex process. On the average, subjects used combinations of most of the available forms of problem-focused coping and emotion-focused coping at every stage of the exam. Different forms of coping were salient during the anticipation and waiting stages. Problem-focused coping and emphasizing the positive were more prominent during the former, and distancing more prominent during the latter. Finally, despite normatively shared emotional reactions at each stage, substantial individual differences remained. Using selected appraisal and coping variables, and taking grade point averages (GPA) into account, approximately 48% of the variances in threat and challenge emotions at the anticipation stage was explained. Controlling for variance due to the grade received, appraisal, and coping variables accounted for 28% of the variance in positive and negative emotions at the outcome stage. Including grade, 57% of the variance in positive emotions at outcome and 61% of the negative emotions at outcome were explained.

Adaptation, Psychological↗

Mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS): clinical, radiological, pathological, and genetic observations.

We reviewed 10 patients (5 males, 5 females) with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. The age of symptom onset ranged from 3 months to 12 years. All had lactic acidosis, multiple stroke-like events with secondary neurological deficits, radiological changes of progressive brain infarction, and muscle biopsy showing ragged-red fibers. In patients with earlier onset of symptoms (< 2 yr), involvement tended to be more diffuse, with failure to thrive and early onset of delayed development. Patients whose symptoms appeared later tended to have focal neurological deficits with migraine-like headache, and a rate of cognitive regression reflecting the rapidity of disease progression. Radiological changes included multiple areas of infarction with initial predilection for parietal occipital areas, progressing to generalized atrophy. Pathological findings in muscle biopsies included type 1 fiber predominance, ragged-red fibers, increased intermyofibrillar lipid deposition, and abnormal mitochondria. Four patients showed mitochondrial DNA tRNA mutation at position 3,243. No difference was noted in clinical, radiological, or pathological findings in patients with and without this mutation, suggesting that multiple sites of point mutation may give rise to mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes.

Base Sequence↗

Verbal fluency facilitated by the cholinergic blocker, scopolamine.

This study was designed to explore putative facilitatory effects of low doses of scopolamine (SP) on phonemic (letter) and semantic (category) verbal fluency. A double-blind, parallel-group design was used with 36 subjects who completed a test battery before and 2 h after 0.6 mg or 1.2 mg of SP or placebo. Fluency measures included total number of words generated, clustering (the production of words within semantic or phonemic subcategories) and switching (the ability to shift efficiently to new subcategories). Low doses of scopolamine increased phonemic fluency, as has been shown previously. Semantic fluency was not increased by SP, although subjects treated with 1.2 mg of SP generated higher-frequency words. SP did not affect clustering or switching. It is suggested that phonemic and semantic fluency reflect distinct cognitive processes.

Adolescent↗

Topographic organization of nonlinear interdependence in multichannel human EEG.

This paper investigates the spatial organization of nonlinear interactions between different brain regions in healthy human subjects. This is achieved by studying the topography of nonlinear interdependence in multichannel EEG data, acquired from 40 healthy human subjects at rest. An algorithm for the detection and quantification of nonlinear interdependence is applied to four pairs of bipolar electrode derivations to detect posterior and anterior interhemispheric and left and right intrahemispheric interdependences. Multivariate surrogate data sets are constructed to control for linear coherence and finite sample size. Nonlinear interdependence is shown to occur in a small but statistically robust number of epochs. The occurrence of nonlinear interdependence in any region is correlated with the concurrent presence of nonlinear interdependence in other regions at high levels of significance. The strength, direction and topography of the interdependences are also correlated. For example, posterior interhemispheric interdependence from right-to-left is strongly correlated with right intrahemispheric interdependence from back-to-front. There is a subtle change in these correlations when subjects open their eyes. These results suggest that nonlinear interdependence in the human brain has a specific topographic organization which reflects simple cognitive changes. It sometimes occurs as an isolated phenomenon between two brain regions, but often involves concurrent interdependences between multiple brain regions.

Brain↗

Neural correlates of artificial grammar learning.

Artificial grammar learning (AGL) is a form of nondeclarative memory that involves the nonconscious acquisition of abstract rules. While data from amnesic patients indicate that AGL does not depend on the medial temporal lobe, the neural basis of this type of memory is unknown and was therefore examined using event-related fMRI. Prior to scanning, participants studied letter strings constructed according to an artificial grammar. Participants then made grammaticality judgments about novel grammatical and nongrammatical strings while fMRI data were collected. The participants successfully acquired knowledge of the grammar, as evidenced by correct identification of the grammatical letter strings (57.4% correct; SE 1.9). During grammaticality judgments, widespread increases in activity were observed throughout the occipital, posterior temporal, parietal, and prefrontal cortical areas, reflecting the cognitive demands of the task. More specific analyses contrasting grammatical and nongrammatical strings identified greater activity in left superior occipital cortex and the right fusiform gyrus for grammatical stimuli. Increased activity was also observed in the left superior occipital and left angular gyrus for correct responses compared to incorrect. Comparing activity during grammaticality judgments versus a matched recognition control task again identified greater activation in the left angular gyrus. The network of areas exhibiting increased activity for grammatical stimuli appears to have more in common with studies examining word-form processing or mental calculation than the fluency effects previously reported for nondeclarative memory tasks such as priming and visual categorization. These results suggest that a novel nondeclarative memory mechanism supporting AGL exists in the left superior occipital and inferior parietal cortex.

Adult↗

Neural basis of temporal context memory: a functional MRI study.

Temporal context information is crucial to understanding human episodic memory. Human lesion and neuroimaging data indicate that prefrontal regions are important for retrieving temporal context memory, although the exact nature of their involvement is still unclear. We employed functional magnetic resonance imaging (fMRI) to elucidate the neural basis of two kinds of temporal context memory: the temporal order of items between lists and within a list. On the day of the fMRI experiment, subjects memorized a list of 30 pictures in the morning and another list of 30 pictures in the afternoon. During the scanning session, the subjects performed three tasks. In a between-lists task, they were asked to judge the temporal order between two items that had been presented in different lists. In a within-list task, they were asked to judge the temporal order between two items that had been presented in a single list. We found bilateral prefrontal activities during these two temporal context memory tasks compared with a simple item-recognition task. Furthermore, in direct comparison between these two tasks, we found differential prefrontal activities. Thus, right prefrontal activity was associated with temporal order judgment of items between lists, whereas left prefrontal activity was related to temporal order judgment of items within a list. These results indicate that retrieval processes of two kinds of temporal context memory are supported by different, but overlapping, sets of cerebral regions. We speculate that this reflects different cognitive processes for retrieving temporal context memory between separate episodes and within a single episode.

Adult↗

Learning behavior, escape behavior, and depression in an ulcer susceptible rat strain.

The aim of the present study was to explore the relationship between depression (helpless withdrawal behavior) and susceptibility to stress ulcer in rats. The WKY genetic strain of rats has been described as highly susceptible to stomach ulcer development during water restraint, i.e., when placed in a jar of water and forced to swim to keep their head above water, a setting in which Richter identified "giving up" behavior akin to hopelessness (Richter, 1957). Since WKY rats tended to float in the water instead of swimming in an attempt to escape, and were also found to be relatively inactive in open field tests, a series of experiments were performed to ascertain whether their diminished activity and their failure to swim reflected slowness, cognitive impairment, or something actually akin to depression. The latter interpretation was supported by evidence from tests of shock avoidance behavior, of capacity to learn discrimination in an operant setting, and by the capacity of an antidepressive drug to lessen floating time in the forced swim test and also to reduce the incidence of stomach ulcers.

Animals↗

Effect of zopiclone and temazepam on sleep EEG parameters, psychomotor and memory functions in healthy elderly volunteers.

RATIONALE: The increased prevalence of sleep disturbance in old age is accompanied by a higher prescription rate of hypnotics, predominantly benzodiazepines in the elderly. In young volunteers zopiclone exerts a beneficial effect on sleep continuity without suppression of SWS and REM sleep; psychomotor performance and vigilance seemed to be less impaired than under classical benzoediazepines. OBJECTIVE: The present study investigates the effects of zopiclone on sleep EEG and cognitive performance in comparison to temazepam and placebo in the elderly population. METHODS: Single oral doses of zopiclone (7.5 mg), temazepam (20 mg) and placebo were administered in a randomized double-blind, completely counterbalanced cross-over design to 12 healthy elderly men and women (65.9 +/- 3.6 years, range 60-70 years). On each of the 3 study nights a sleep EEG was registered from 10 p.m. to 6.30 a.m. and cognitive performance tests were applied at 8 p.m., 2 a.m. (when subjects were awake for 30 min), 7 a.m. and 9 a.m. RESULTS: After zopiclone treatment, sleep continuity had significantly improved and sleep stage 4 was increased compared to temazepam and placebo. In addition, both active substances significantly reduced REM density. Neither active compound substantially altered psychomotor and memory performance. CONCLUSIONS: Zopiclone and temazepam can be considered as effective hypnotics in elderly subjects when administered in that dosage. The superiority of zopiclone on sleep architecture may be related to a more specific action of zopiclone at the GABA-A benzodiazepine receptor complex. The suppression of REM density by both compounds and their subtle effects on cognition may reflect a GABAergic mediated reduction of cholinergic neuro-transmission.

Aged↗

The effects of increasing memory load on the directional accuracy of pointing movements to remembered targets.

The directional accuracy of pointing arm movements to remembered targets in conditions of increasing memory load was investigated using a modified version of the Sternberg's context-recall memory-scanning task. Series of 2, 3 or 4 targets (chosen randomly from a set of 16 targets around a central starting point in 2D space) were presented sequentially, followed by a cue target randomly selected from the series excluding the last one. The subject had to move to the location of the next target in the series. Correct movements were those that ended closer to the instructed target than any other target in the series while all other movements were considered as serial order errors. Increasing memory load resulted in a large decrease in the directional accuracy or equivalently in the directional information transmitted by the motor system. The constant directional error varied with target direction in a systematic fashion reproducing previous results and suggesting the same systematic distortion of the representation of direction in different memory delay tasks. The constant directional error was not altered by increasing memory load, contradicting our hypothesis that it might reflect a cognitive strategy for better remembering spatial locations in conditions of increasing uncertainty. Increasing memory load resulted in a linear increase of mean response time and variable directional error and a non-linear increase in the percentage of serial order errors. Also the percentage of serial order errors for the last presented target in the series was smaller (recency effect). The difference between serial order and directional spatial accuracy is supported by neurophysiological and functional anatomical evidence of working memory subsystems in the prefrontal cortex.

Adult↗