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

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.

[1]  T. Shors,et al.  Glucocorticoids are necessary for enhancing the acquisition of associative memories after acute stressful experience , 2003, Hormones and Behavior.

[2]  Oliver T. Wolf,et al.  Endogenous Estradiol and Testosterone Levels Are Associated with Cognitive Performance in Older Women and Men , 2002, Hormones and Behavior.

[3]  S. Huettel,et al.  Males and females use different distal cues in a virtual environment navigation task. , 1998, Brain research. Cognitive brain research.

[4]  R. Astur,et al.  Sex differences and correlations in a virtual Morris water task, a virtual radial arm maze, and mental rotation , 2004, Behavioural Brain Research.

[5]  Marion Perlmutter,et al.  Spatial and Temporal Memory in 20 and 60 Year Olds , 1981 .

[6]  Bryan Kolb,et al.  Spatial mapping: definitive disruption by hippocampal or medial frontal cortical damage in the rat , 1982, Neuroscience Letters.

[7]  Piyadasa Kodituwakku,et al.  Children with Fetal Alcohol Syndrome are impaired at place learning but not cued-navigation in a virtual Morris water task , 2003, Behavioural Brain Research.

[8]  J. Janowsky,et al.  Testosterone influences spatial cognition in older men. , 1994, Behavioral neuroscience.

[9]  R. Shepard,et al.  Transformational studies of the internal representation of three-dimensional objects. , 1974 .

[10]  S. G. Vandenberg,et al.  Sex Differences in Cognition: Evidence from the Hawaii Family Study , 1978 .

[11]  L. Squire,et al.  Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[12]  B. McEwen,et al.  Chronic stress impairs rat spatial memory on the Y maze, and this effect is blocked by tianeptine pretreatment. , 1996, Behavioral neuroscience.

[13]  H. W. Gordon,et al.  A relationship between gonadotropins and visuospatial function , 1986, Neuropsychologia.

[14]  D. McCloskey,et al.  Chronic administration of corticosterone impairs spatial reference memory before spatial working memory in rats , 2003, Neurobiology of Learning and Memory.

[15]  B. Vellas,et al.  Longitudinal study of dietary intakes and plasma lipids in healthy elderly men and women. , 1992, The American journal of clinical nutrition.

[16]  Neil Burgess,et al.  Human spatial navigation: cognitive maps, sexual dimorphism, and neural substrates , 1999, Current Opinion in Neurobiology.

[17]  M. Leon,et al.  Hippocampal atrophy in normal aging. An association with recent memory impairment. , 1993, Archives of neurology.

[18]  K. Christiansen,et al.  Sex hormones and cognitive functioning in men. , 1987, Neuropsychobiology.

[19]  R. Morris,et al.  Place navigation impaired in rats with hippocampal lesions , 1982, Nature.

[20]  M. Gallagher,et al.  An evaluation of spatial information processing in aged rats. , 1987, Behavioral neuroscience.

[21]  Irwin Silverman,et al.  Effects of estrogen changes during the menstrual cycle on spatial performance , 1993 .

[22]  I. Silverman,et al.  The relationship between testosterone and route-learning strategies in humans , 2002, Brain and Cognition.

[23]  S. Berent,et al.  Elevated Cortisol Levels in Cushing’s Disease Are Associated With Cognitive Decrements , 2001, Psychosomatic medicine.

[24]  R. Passingham The hippocampus as a cognitive map J. O'Keefe & L. Nadel, Oxford University Press, Oxford (1978). 570 pp., £25.00 , 1979, Neuroscience.

[25]  R. Sutherland,et al.  Human place learning in a virtual Morris water task: some important constraints on the flexibility of place navigation , 2002, Behavioural Brain Research.

[26]  Raymond M. Klein,et al.  Of mice and men: Virtual Hebb—Williams mazes permit comparison of spatial learning across species , 2001, Cognitive, affective & behavioral neuroscience.

[27]  L. Nadel,et al.  The Hippocampus as a Cognitive Map , 1978 .

[28]  B. McEwen,et al.  Restraint stress reversibly enhances spatial memory performance , 1996, Physiology & Behavior.

[29]  W H Meck,et al.  Organizational effects of early gonadal secretions on sexual differentiation in spatial memory. , 1990, Behavioral neuroscience.

[30]  Derek A. Hamilton,et al.  Blocking in human place learning: Evidence from virtual navigation , 1999, Psychobiology.

[31]  R. Sutherland,et al.  The aging hippocampus: cognitive, biochemical and structural findings. , 2003, Cerebral cortex.

[32]  G. A. Press Hippocampal abnormalities in amnesic patients revealed by high-resolution magnetic resonance imaging , 1996 .

[33]  Kristine Yaffe,et al.  Sex Hormones and Cognitive Function in Older Men , 2002, Journal of the American Geriatrics Society.

[34]  M. Gallagher,et al.  The use of animal models to study the effects of aging on cognition. , 1997, Annual review of psychology.

[35]  W. Meck,et al.  The organizational effects of gonadal steroids on sexually dimorphic spatial ability , 1991, Psychoneuroendocrinology.

[36]  T. Shors,et al.  Stress impedes exploration and the acquisition of spatial information in the eight-arm radial maze , 1992, Psychobiology.

[37]  S. Asthana,et al.  Testosterone supplementation improves spatial and verbal memory in healthy older men , 2001, Neurology.

[38]  M Perlmutter,et al.  Spatial and temporal memory in 20 to 60 year olds. , 1981, Journal of gerontology.

[39]  R. Morris Spatial Localization Does Not Require the Presence of Local Cues , 1981 .

[40]  B. Kudielka,et al.  Testosterone and cognition in elderly men: a single testosterone injection blocks the practice effect in verbal fluency, but has no effect on spatial or verbal memory , 2000, Biological Psychiatry.

[41]  J L Dawson,et al.  Effects of sex hormones on cognitive style in rats and men , 1972, Behavior genetics.

[42]  Doreen Kimura,et al.  Sex hormones influence human cognitive pattern. , 2002, Neuro endocrinology letters.

[43]  R Shayna Rosenbaum,et al.  Implicit memory varies across the menstrual cycle: estrogen effects in young women , 2002, Neuropsychologia.

[44]  S. Moffat,et al.  Navigation in a “Virtual” Maze: Sex Differences and Correlation With Psychometric Measures of Spatial Ability in Humans , 1998 .

[45]  M. Linn,et al.  Emergence and characterization of sex differences in spatial ability: a meta-analysis. , 1985, Child development.

[46]  N. Neave,et al.  Sex Differences in Cognition: The Role of Testosterone and Sexual Orientation , 1999, Brain and Cognition.

[47]  F. Morrell,et al.  Hippocampal markers of age-related memory dysfunction: Behavioral, electrophysiological and morphological perspectives , 1995, Progress in Neurobiology.

[48]  Stephen M Kosslyn,et al.  The relationship of male testosterone to components of mental rotation , 2004, Neuropsychologia.

[49]  M. Meaney,et al.  Enduring effects of chronic corticosterone treatment on spatial learning, synaptic plasticity, and hippocampal neuropathology in young and mid-aged rats , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[50]  M. S. Masters,et al.  Is the gender difference in mental rotation disappearing? , 1993, Behavior genetics.

[51]  S. Vandenberg,et al.  Mental Rotations, a Group Test of Three-Dimensional Spatial Visualization , 1978, Perceptual and motor skills.

[52]  S. Resnick,et al.  Age differences in spatial memory in a virtual environment navigation task , 2001, Neurobiology of Aging.

[53]  M. S. Moody Changes in Scores on the Mental Rotations Test during the Menstrual Cycle , 1997, Perceptual and motor skills.

[54]  C. McCormick,et al.  Menstrual Cycle Variation in Spatial Ability: Relation to Salivary Cortisol Levels , 2001, Hormones and Behavior.

[55]  B Sanders,et al.  The sex difference on one test of spatial visualization: a nontrivial difference. , 1982, Child development.

[56]  M. Gallagher,et al.  Spatial learning impairments in aged rats trained with a salient configuration of stimuli , 1987, Psychobiology.

[57]  R. Morris Developments of a water-maze procedure for studying spatial learning in the rat , 1984, Journal of Neuroscience Methods.

[58]  M. Kavaliers,et al.  Sex differences in performance in the Morris water maze and the effects of initial nonstationary hidden platform training. , 1996, Behavioral neuroscience.

[59]  M. Albert,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1997 by The Endocrine Society Increase in Urinary Cortisol Excretion and Memory Declines: MacArthur Studies of Successful Aging* , 2022 .

[60]  C. Barnes,et al.  Impact of aging on hippocampal function: plasticity, network dynamics, and cognition , 2003, Progress in Neurobiology.

[61]  I. Silverman,et al.  Testosterone levels and spatial ability in men , 1999, Psychoneuroendocrinology.

[62]  R. Sutherland,et al.  A characterization of performance by men and women in a virtual Morris water task: A large and reliable sex difference , 1998, Behavioural Brain Research.

[63]  D. Kausler Learning and memory in normal aging , 1994 .

[64]  A. Convit,et al.  Cortisol levels during human aging predict hippocampal atrophy and memory deficits , 1998, Nature Neuroscience.

[65]  G. Lindzey,et al.  Genetic aspects of negative geotaxis in mice , 1970, Behavior genetics.

[66]  S. Resnick,et al.  Effects of age on virtual environment place navigation and allocentric cognitive mapping. , 2002, Behavioral neuroscience.

[67]  A. Kenny,et al.  Effects of transdermal testosterone on cognitive function and health perception in older men with low bioavailable testosterone levels. , 2002, The journals of gerontology. Series A, Biological sciences and medical sciences.

[68]  E. Maccoby,et al.  The Psychology of Sex Differences , 1974 .