Elsevier

Hormones and Behavior

Volume 47, Issue 3, March 2005, Pages 326-335
Hormones and Behavior

Virtual navigation in humans: the impact of age, sex, and hormones on place learning

https://doi.org/10.1016/j.yhbeh.2004.11.013Get rights and content

Abstract

Certain cognitive processes, including spatial ability, decline with normal aging. Spatial ability is also a cognitive domain with robust sex differences typically favoring males. However, tests of spatial ability do not seem to measure a homogeneous class of processes. For many, mentally matching rotated three-dimensional images is the gold standard for measuring spatial cognition in humans, while the Morris water task (MWT) is a preferred method in the domain of nonhuman animal research. The MWT is sensitive to hippocampal damage, a structure critical for normal learning and memory and often implicated in age-related cognitive decline. A computerized (virtual) version of the MWT (VMWT) appears to require and engage human hippocampal circuitry, and has proven useful in studying sex differences and testing spatial learning theories. In Experiment 1, we tested participants (20–90 years of age) in the VMWT and compared their performance to that on the Vandenberg Mental Rotation Test. We report an age-related deficit in performance on both tasks. In Experiment 2, we tested young (age 20–39) and elderly (age >60) participants in the VMWT and correlated their performance to the circulating levels of testosterone and cortisol. Our findings indicate that the persistence of male spatial advantage may be related to circulating testosterone, but not cortisol levels, and independent of generalized age-related cognitive decline.

Introduction

Contemporary studies of cognitive aging attempt to understand the changing cognitive abilities as a normal developmental progression. Processes involving verbal skills, priming, implicit learning, and semantic memory seem to be largely spared. However, normal aging is associated with declines in numerous cognitive processes including episodic memory, attention, working memory, and spatial learning (Kausler, 1994). It is often assumed that the neural circuitry underlying different cognitive processes varies in terms of susceptibility to age-related degeneration. The hippocampal formation is often implicated in age-related cognitive decline and is critical for certain forms of learning and memory (O’Keefe and Nadel, 1978, Sutherland et al., 1982). Many cognitive deficits exhibited during normal aging are said to resemble impairments following bilateral damage to the hippocampus (Geinisman et al., 1995, Press et al., 1989, Zola-Morgan et al., 1986).

Nonhuman animal research provides a wealth of knowledge regarding tasks that are sensitive to hippocampal damage. The Morris water task (MWT; Morris, 1981, Morris, 1984) is dependent upon hippocampal integrity (Morris et al., 1982, Sutherland et al., 1982) and has been extensively employed in studying the relationship between hippocampal function, aging, and spatial learning and memory in rodents (for reviews, see Gallagher and Rapp, 1997, Geinisman et al., 1995, Rosenzweig and Barnes, 2003). In the MWT, animals are trained to locate an escape platform hidden in a featureless pool of opaque water based upon its fixed spatial relationship to a configuration of visual cues in the distal environment. Deficits similar to those seen in hippocampectomized animals have been previously reported in studies of aged animals (Geinisman et al., 1995, Pelleymounter et al., 1987, Rapp et al., 1987). Deficits in tasks requiring spatial information processing have also been reported in aged humans (Golomb et al., 1993, Kirasic and Allen, 1985, Perlmutter et al., 1981). It is not clear however whether spatial cognition documented in humans is homologous to that studied in nonhuman animals because the tasks used to assess spatial ability in respective species, while spatial in nature, are not analogous.

Recently, a computerized (virtual) version of the Morris water task (VMWT) has been developed for laboratory testing of human spatial ability (Astur et al., 1998, Hamilton and Sutherland, 1999, Hamilton et al., 2002). The research design was carried over from nonhuman work into a virtual domain, showing that many psychological functions engaged by the task in rats are similarly engaged in humans (Hamilton and Sutherland, 1999, Hamilton et al., 2002). In addition, the VMWT has proven useful in studying spatial learning theories (Hamilton and Sutherland, 1999, Hamilton et al., 2002), Fetal Alcohol Syndrome (Hamilton et al., 2003), aging (Driscoll et al., 2003), and sex differences in human spatial ability (Astur et al., 1998, Driscoll et al., 2003). The robust sex difference in spatial navigation reported in studies conducted in the virtual domain, where men are more successful than women (Astur et al., 1998, Driscoll et al., 2003, Hamilton and Sutherland, 1999, Moffat and Resnick, 2002, Moffat et al., 1998, Shore et al., 2001, Sandstrom et al., 1998), is of particular interest. Recently, we reported that sex differences persisted in a sample of healthy elderly compared to college-aged participants, such that males performed better than females despite deficits in the VMWT learning and memory, and despite age-related structural and biochemical changes in the hippocampus that may underlie observed cognitive deficits in performance (Driscoll et al., 2003). The male advantage in spatial ability has been reported in other mammalian species as well (Dawson, 1972, Williams and Meck, 1991, Williams et al., 1990). Despite numerous reports of male advantage in spatial performance of both rats and humans, the cause of sex differences in certain cognitive domains remains a matter of debate.

The inquiry into sex differences in spatial cognition has prompted questions regarding the biological bases of sexually dimorphic spatial behavior. Difference in the levels of circulating hormones represents one obvious possibility. Sex-specific patterns of relationships between circulating testosterone and spatial performance have been previously reported in both rodents (Gordon and Lee, 1986, Neave et al., 1999) and humans (Choi and Silverman, 2002, Christiansen and Knussmann, 1987, Silverman et al., 1999). Levels of total and bioavailable testosterone also gradually decrease with age and are associated with changes in cognition (Cherrier et al., 2001). There are emerging reports suggesting enhancement of cognitive function in healthy elderly men that received testosterone (Cherrier et al., 2001, Janowsky et al., 1994, Kenny et al., 2002, Yaffe et al., 2002), including improvements in spatial cognition (Cherrier, 1999). On a similar note, chronically elevated levels of glucocorticoids have deleterious effects on particular domains of cognition, and cognitive deficits due to elevated levels of cortisol are clearly apparent in Cushing's disease patients (Seeman et al., 1997, Starkman et al., 2001). Associations between cortisol and poor memory have been reported in both rodents (Shors and Dryver, 1992) and humans (Lupien et al., 1998) in response to increased stress.

As we previously alluded, a variety of tasks have been used to assess human spatial cognition showing superior male spatial ability. For example, mental rotation, spatial orientation, route learning, map learning, pointing to places, throwing to targets, intercepting projectiles, and measuring water levels have all been employed to measure spatial ability (see Kimura, 2002). For many, the mental rotation task originally described by Metzler and Sheperd (1974) is the gold standard for measuring spatial cognition in humans, and several studies have reported male advantage in mentally rotating images (Linn and Petersen, 1985, Masters and Sanders, 1993, Sanders et al., 1982, Wilson and Vandenberg, 1978). Men outperform women by as much as one standard deviation on this test, making this one of the largest cognitive sex differences, second only to that observed in the VMWT (Astur et al., 1998).

As it can be gathered from the literature, there have been numerous attempts to explain what underlies sex differences in certain domains of cognition, from hormonal factors (Silverman et al., 1999) to socialization practices (Maccoby and Jacklin, 1974). The recent development of virtual navigation tasks allows researchers to connect with the wealth of information concerning the neurobiology of spatial learning and memory in nonhuman animals, and facilitates comparison of human and nonhuman spatial behavior in analogous tasks. In the current study, we employ the VMWT to address two questions in Experiment 1: (1) does the sexual dimorphism previously reported in this task vary as a function of age, and (2) is there a relationship between behavior in the virtual Morris water task and a more traditional measure of spatial ability, the Vandenberg Mental Rotation Test. In Experiment 2, we attempt to relate the spatial ability to circulating salivary testosterone and cortisol levels.

Section snippets

Participants

A total of 70 volunteers participated in the study. Participants were divided into 3 groups: Young (age 20–39), Middle (age 40–59), and Old (>60). The sex and age distribution of the sample is presented in Table 1. Young participants were University of New Mexico undergraduates who received research credit for a psychology course. Older and middle-aged participants were generally healthy, community-dwelling volunteers who responded to advertisements requesting participants and received no

Experiment 1

We report analyses of three performance measures on the VMWT: (1) latency to locate the platform, (2) percentage of time spent in correct quadrant of the pool on the no-platform probe trial, and (3) percentage of distance in correct quadrant of the pool on the no-platform probe trial. Performance on the MRT was assessed by the score for the timed portion of the task (5 min), as well as the total number of correct responses.

General discussion

The broad aim of this study was to evaluate behavioral changes in human spatial cognition associated with normal aging. We employed the Vandenberg Mental Rotation Test in order to assess performance of our participants on this commonly used test of human spatial cognition and to allow comparison with the virtual Morris water task, a human analog of the test commonly used for measuring spatial ability in nonhuman animals. Our findings indicate a significant age-related deficit on both tests of

Acknowledgments

We would like to thank Dr. Richard Baumgartner, Lori Bachert, the staff, and participants of the NMPAS for their time and support. This material is based upon work supported under a National Science Foundation Graduate Research Fellowship to ID and in part by grants from the State of New Mexico, the National Institute of Health (NS35708, NS39123, HD41237, RR15363, AG16418), and from the MIND Institute (D.O.E. DE-FG03-99ER62764-A000) to WMB.

References (68)

  • V. Luine et al.

    Restraint stress reversibly enhances spatial memory performance

    Physiol. Behav.

    (1996)
  • E.A. Maguire et al.

    Human spatial navigation: cognitive maps, sexual dimorphism, and neural substrates

    Curr. Opin. Neurobiol.

    (1999)
  • P.M. Maki et al.

    Implicit memory varies across the menstrual cycle: estrogen effects in young women

    Neuropsychologia

    (2002)
  • C.M. McCormick et al.

    Menstrual cycle variation in spatial ability: relation to salivary cortisol levels

    Hormon. Behav.

    (2001)
  • S. Moffat et al.

    Navigation in a “virtual” maze: sex differences and correlation with psychometric measures of spatial ability in humans

    Evol. Human. Behav.

    (1998)
  • S.D. Moffat et al.

    Age differences in spatial memory in a virtual environment navigation task

    Neurobiol. Aging

    (2001)
  • R.G.M. Morris

    Spatial localization does not require the presence of local cues

    Learn. Motiv.

    (1981)
  • R.G.M. Morris

    Developments of a water-maze procedure for studying spatial-learning in the rat

    J. Neurosci. Methods

    (1984)
  • N. Neave et al.

    Sex differences in cognition: the role of testosterone in and sexual orientation

    Brain Cogn.

    (1999)
  • E.S. Rosenzweig et al.

    Impact of aging on hippocampal function: plasticity, network dynamics, and cognition

    Prog. Neurobiol.

    (2003)
  • N.J. Sandstrom et al.

    Males and females use different distal cues in a virtual environment navigation task

    Cognit. Brain Res.

    (1998)
  • I. Silverman et al.

    Testosterone levels and spatial ability in men

    Psychoneuroendocrinology

    (1999)
  • R.J. Sutherland et al.

    Spatial mapping: definitive disruption by hippocampal or medial frontal cortical damage in the rat

    Neurosci. Lett.

    (1982)
  • C.L. Williams et al.

    The organizational effects of gonadal steroids on sexually dimorphic spatial ability

    Psychoneuroendocrinology

    (1991)
  • O.T. Wolf et al.

    Endogenous estradiol and testosterone levels are associated with cognitive performance in older women and men

    Hormon. Behav.

    (2002)
  • O.T. Wolf et al.

    Testosterone and cognition in older men: a single testosterone injection blocks the practice effect in verbal fluency, but has no effect on spatial and verbal memory

    Biol. Psychiatry

    (2000)
  • S.R. Bodnoff et al.

    Enduring effects of chronic corticosterone treatment on spatial learning, synaptic plasticity, and hippocampal neuropathology in young and mid-aged rats

    J. Neurosci.

    (1995)
  • M.M. Cherrier

    Androgens, ageing, behavior and cognition: complex interactions and novel areas of inquiry

    N. Z. J. Psychol.

    (1999)
  • M.M. Cherrier et al.

    Testosterone supplementation improves spatial and verbal memory in healthy older men

    Neurology

    (2001)
  • K. Christiansen et al.

    Sex hormones and cognitive functioning in men

    Neuropsychobiology

    (1987)
  • C.D. Conrad et al.

    Chronic stress impairs rat spatial memory on the Y maze, and this effect is blocked by tianeptine pretreatment

    Behav. Neurosci.

    (1996)
  • J.L.M. Dawson

    Effects of sex hormones on cognitive style in rats and men

    Behav. Genet.

    (1972)
  • I. Driscoll et al.

    The aging hippocampus: cognitive, biochemical and structural findings

    Cereb. Cortex

    (2003)
  • M. Gallagher et al.

    The use of animal models to study the effects of aging on cognition

    Annu. Rev. Psychol.

    (1997)
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