Biomedical subjects

A Lacreuse

Publications and source records attributed to A Lacreuse.

11 recordsLinked to original sources

PubMed2005

Effects of ovarian hormones on cognitive function in nonhuman primates.

Several studies have suggested that estrogen benefits verbal memory and lowers the risk of Alzheimer's disease in women, and improves cognitive function in animal models. However, the negative outcome of the Women's Health Initiative Memory Study has challenged the rationale for using estrogen as a protective agent against age-related cognitive decline. In view of the limitations of the Women's Health Initiative Memory Study, it is clear that our understanding of estrogen effects would greatly benefit from further interactions between clinical and basic science. Animal models of menopause can provide crucial information regarding the consequences of estrogen loss and replacement on several systems, including cognition. In this paper, I review the evidence that nonhuman primates, who share numerous cognitive and physiological characteristics with humans, can substantially contribute to our understanding of estrogen influences on the brain and cognition. Studies in young adult females suggest that some aspects of cognition fluctuate with the menstrual cycle, but that ovariectomy and estrogen replacement have only modest effects on cognitive function. In contrast, data in aged, naturally or surgically menopausal monkeys indicate that estrogen modulates a broad range of cognitive domains. Neurobiological data are consistent with the cognitive findings and demonstrate an array of morphological and physiological changes in brain areas important for cognition following ovariectomy and/or estrogen replacement. It is concluded that nonhuman primates, by providing a bridge between rodent and human data, constitute invaluable models to further our understanding of hormonal actions on the brain and cognition and to develop effective hormonal interventions against brain and cognitive aging.

Adult↗

PubMed2004

Executive function is less sensitive to estradiol than spatial memory: performance on an analog of the card sorting test in ovariectomized aged rhesus monkeys.

Functions supported by the frontal lobes are particularly sensitive to the detrimental effects of aging. Recent studies on postmenopausal women find that estrogen replacement therapy benefits performance on tasks dependent on the frontal lobes. To determine whether estrogen has a similar influence in a rhesus monkey model of menopause, we tested five aged, long-term ovariectomized rhesus monkeys in a modified version of the Wisconsin Card Sort test which had been adapted to the nonhuman primate. In this test, monkeys had to select 3-D objects based either on color (blue, red, yellow) or shape (block, tube, cup) and had to be able to switch their response as a function of reinforcement contingencies. The monkeys were treated with placebo and ethinyl estradiol (EE2, 450 ng/kg/day) in alternation with each successive test. Contrary to our hypothesis, estradiol treatment did not affect performance. Because previous studies in the same monkeys [Neurobiol. Aging 23 (2002) 589] had shown that EE2 improves performance on a spatial memory task dependent on the hippocampus, but not on another task dependent upon the frontal lobes (the delayed response), we conclude that executive processes may be less sensitive to the effects of estradiol than hippocampal-dependent tasks.

Age Factors↗

PubMed2003

Estradiol selectively affects processing of conspecifics' faces in female rhesus monkeys.

Estrogen deficiency following ovariectomy or menopause increases the risk of developing diseases such as osteoporosis and may also lead to memory impairment. Although estrogen replacement therapy (ERT) alleviates many symptoms associated with estrogen loss, it is not clear whether it also benefits cognitive function. The effect of estrogens upon cognition can best be studied in an animal model of human menopause, in which estrogen levels can be experimentally manipulated. Six young ovariectomized female rhesus monkeys (6-9 years old) were tested on a battery of touchscreen-based cognitive tasks, including the Matching-to-Sample (MTS) task with mixed delays and the spatial, object, and face conditions of the Delayed Recognition Span Test (DRST). Monkeys were tested 5 days a week, one task per week, for a total of 8 months, while undergoing treatments with placebo and ethinyl estradiol (EE2) in alternating 28-days blocks. Blood samples were collected to verify EE2 levels. We also observed the monkeys by video monitor during test sessions and recorded locomotor activity and response topology. Performance on the face-DRST, a task that involved selecting the new face in an increasing array of rhesus monkey faces, was impaired by EE2 treatment, as compared to placebo. Other tasks were unaffected by EE2. There was no clear evidence of EE2 effects upon motor activity or anxiety. In order to test the reliability of our findings, we conducted an additional experiment in which the monkeys were again given the face-DRST with different categories of face stimuli for 4 months, while receiving placebo and EE2 in alternating 7-days blocks. They performed each task 4-5 days/week for 4 weeks with (1) the same rhesus monkey faces as in the first experiment, (2) human faces, (3) chimpanzee faces, and (4) novel rhesus monkey faces. Face-DRST performance did not vary as a function of treatment when human or chimpanzee faces were used as stimuli. In contrast, periods of EE2 treatment were associated with a lower performance for both sets of rhesus monkey faces. These findings suggest that EE2 treatment has a detrimental effect on processing faces of conspecifics by female rhesus monkeys. We speculate that estrogens may produce this effect by enhancing emotional reactivity to socially relevant stimuli.

Animals↗

PubMed2001

Fluctuations in spatial recognition memory across the menstrual cycle in female rhesus monkeys.

Findings are inconsistent regarding whether women's cognitive performance fluctuates across phases of the menstrual cycle, but differences in methodology and the use of reported cycle phase rather than precise hormonal measures may underlie these disparities. Studies in monkeys may help resolve these discrepant findings, since hormonal status can be reliably determined. We tested four young (5-7 years old) female rhesus monkeys daily during one entire menstrual cycle on three cognitive tasks displayed on a computerized touch-screen system: a Matching to Sample task with a 30 s delay (MTS-30s), a Matching to Sample task without delay (MTS-no delay) and the spatial condition of the Delayed Recognition Span Test (spatial-DRST). Blood samples were collected at specific time intervals throughout the cycle and assayed for estradiol and progesterone in order to identify hormonal status. There was a nonsignificant trend for the MTS-30s scores to be better during the follicular and luteal phases, when estradiol levels were low, than during the peri-ovulatory phase, when estradiol levels were at their highest. MTS-no delay performance did not vary as a function of hormonal status. Spatial-DRST scores were significantly better during the follicular and luteal phases than during the peri-ovulatory phase of the cycle. These data in the female rhesus monkey support the hypothesis that spatial memory performance is sensitive to estradiol variations across the menstrual cycle, with better performance associated with low estradiol levels.

Animals↗

PubMed2000

Cognitive function in aged ovariectomized female rhesus monkeys.

To determine whether ovariectomy exacerbates age-related cognitive decline, the performance of 6 aged monkeys that had been ovariectomized early in life (OVX-Aged) was compared to that of 8 age-matched controls with intact ovaries (INT-Aged) and that of 5 young controls with intact ovaries (INT-Young) in tasks of visual recognition memory, object and spatial memory, and executive function. The OVX-Aged monkeys were marginally more impaired than the INT-Aged monkeys on the delayed nonmatching-to-sample with a 600-s delay. In contrast, they performed significantly better than the INT-Aged controls on the spatial condition of the delayed recognition span test. The hypothesis that prolonged estrogenic deprivation may exaggerate the age-related decline in visual recognition memory will require additional support. However, the findings suggest that long-term ovariectomy may protect against the development with aging of spatial memory deficits.

Aging↗

PubMed1999

Age-related decline in DHEAS is not related to cognitive impairment in aged monkeys.

To determine whether endogenous DHEAS level is related to cognitive performance in the rhesus monkey, we tested 9 young and 14 old monkeys on the acquisition and the 120 s delay condition of the delayed non-matching to sample and on the spatial delayed recognition span test. A single summary measure of cognitive ability, the cognitive performance index (CPI), was derived from these three tests. As expected, the mean level of DHEAS as well as the CPI declined with age. DHEAS level, however, was not significantly correlated with CPI, after controlling for the relationship of age to these two variables. Further, impaired and unimpaired aged monkeys did not differ in DHEAS level. These findings suggest that DHEAS is not independently associated with age-related cognitive decline in the rhesus monkey.

Aging↗

PubMed1999

Spatial cognition in rhesus monkeys: male superiority declines with age.

Twelve young (4-7 years of age) and 14 old (20-27 years of age) male and female rhesus monkeys were tested on seven cognitive tasks. Males and females performed similarly on tasks of object memory and executive function, but young males outperformed young females on a spatial memory task (Delayed Recognition Span Test) that requires the identification of a new stimulus among an increasing array of serially presented stimuli. This superior level of spatial ability in young males declined sharply with age, so that old males did not perform significantly better than old females. These findings in the nonhuman primate suggest that biological rather than sociocultural factors underlie the sex differences in cognition and their diminution with age.

Aging↗

PubMed1999

Left hand preferences in capuchins (Cebus apella): role of spatial demands in manual activity.

Sixteen capuchins (Cebus apella) participated in four tasks that differed in their exploration demands and availability of visual cues. The two explorative tasks required the monkeys to discover sunflower seeds hidden in crevices in objects of various shapes, with vision (Haptic-Visual task) or without vision (Haptic task). Two other tasks required the capuchins to grasp sunflower seeds directly on a flat support, with vision (Visual reaching) or without vision (Tactual reaching). The presence or absence of exploration demands had a significant effect on the direction of hand preferences. The group displayed greater left hand preferences for the Haptic and Haptic-Visual tasks than for the two reaching tasks. The strength of manual preferences did not differ significantly among the four tasks. These findings suggest that the manipulo-spatial demands of a task are of particular importance for the expression of left hand bias in a population of capuchins. It is argued that left hand preferences for the haptic tasks may reflect a right hemisphere specialisation to integrate the spatial and motor components of action.

Journal Article↗

PubMed1997

Manual exploratory procedures and asymmetries for a haptic search task: a comparison between capuchins (Cebus apella) and humans.

Left-hand preferences in monkeys (capuchins, macaques) for haptic discriminations have been taken to indicate that the right hemisphere is more involved than the left hemisphere in solving these tasks. We confirmed this left-hand bias in a group of 21 capuchins haptically searching for sunflower seeds located in crevices in 12 different objects (Lacreuse & Fragaszy, 1996). In an attempt to specify the relations of the left-hand bias to hand performance and hemispheric lateralisation, we analysed the manual exploratory procedures used by the subjects when exploring the objects, and compared them to those of humans confronted with the same task. All the hand-movement patterns displayed by humans were also observed in capuchins, but humans performed exhaustive explorations, whereas capuchins restricted their haptic investigations to limited portions of the objects. Both species adopted several ''exploratory procedures'' to investigate particular objects. Although capuchins showed a left-hand preference to perform the task, finer analyses of haptic exploratory procedures revealed no difference in the way the left and right hands explored the objects, nor in the efficiency with which each hand solved the task. Nor was any measurable difference in manual exploratory procedure and efficiency found in humans. The discussion emphasises the need to complement measures of manual preference with finer indices of hemispheric lateralisation, for a better understanding of functional asymmetries in primates.

Journal Article↗

PubMed1994

Hand-movement profiles in a tactual-tactual matching task: effects of spatial factors and laterality.

We examined the effect of spatial factors and hemispheric lateralization upon hand-scanning strategies in 14 right-handed men tested in a tactual-tactual matching task. The experiment involved comparisons (judgments of same or different) between two objects sequentially touched by the fingertips of the left or right hand. Stimuli were made of smoothly joined cubes whose junctions were not haptically discernible. Exploratory strategies were inferred from the durations and locations of hand contacts with any of the cubes composing the stimuli. Accuracy was greater when the same stimulus was touched twice by the same hand than when different hands were used to feel it. With regard to strategies, both hands touched the upper parts of the object longer than the lower parts. Subjects also inspected more portions of the objects ipsilateral to the hand used. Overall differences in time spent touching cubes were greater for the right hand than for the left hand, showing that touch times were less evenly distributed on object parts for the former than for the latter. In this study, the process of information gathering by touch appears to be determined by the intertwining integration of contextual factors (e.g., stimulus position in space), biomechanical constraints on hand movements, and such cognitive factors as hemispheric differences on the ability to encode spatial pattern information.

Adult↗

PubMed1993

Haptic discrimination of nonsense shapes: hand exploratory strategies but not accuracy reveal laterality effects.

Studies on haptic processing show inconsistent results concerning sex and hand differences. We present a novel approach in which manual exploratory strategies were examined. Twenty-four right-handed adults of both sexes had to monohaptically explore unseen meaningless stimuli and then to recognize their visually presented outline drawings among drawings of different stimuli. Tactual stimuli were composed of eight smoothly joined cubes whose junctions were not haptically discernible. The computer recorded number and duration of hand contacts on each cube. Analyses included the accuracy of the recognition phase, the number and duration of exhaustive explorations of the stimulus, and the number of cubes simultaneously touched. Neither hand nor sex differences were found for the accuracy measurement. The number and duration of exhaustive explorations also provide no evidence of hand differences. However, the left hand touched simultaneously more cubes than the right and this asymmetry was more pronounced in males than in females. Such an asymmetry was apparent in the very first contact of the hand with the shape. It is suggested that exploratory strategies may be more sensitive measures in revealing hand lateralization than the accuracy measurement.

Adult↗