Landmark-dependent Navigation Strategy Declines across the Human Life-Span: Evidence from Over 37,000 Participants.

Humans show a remarkable capacity to navigate various environments using different navigation strategies, and we know that strategy changes across the life span. However, this observation has been based on studies of small sample sizes. To this end, we used a mobile app-based video game (Sea Hero Quest) to test virtual navigation strategies and memory performance within a distinct radial arm maze level in over 37,000 participants. Players were presented with six pathways (three open and three closed) and were required to navigate to the three open pathways to collect a target. Next, all six pathways were made available and the player was required to visit the pathways that were previously unavailable. Both reference memory and working memory errors were calculated. Crucially, at the end of the level, the player was asked a multiple-choice question about how they found the targets (i.e., a counting-dependent strategy vs. a landmark-dependent strategy). As predicted from previous laboratory studies, we found the use of landmarks declined linearly with age. Those using landmark-based strategies also performed better on reference memory than those using a counting-based strategy. These results extend previous observations in the laboratory showing a decreased use of landmark-dependent strategies with age.

The BDNF val66met polymorphism is associated with decreased use of landmarks and decreased fMRI activity in the hippocampus during virtual navigation.

People can navigate in a new environment using multiple strategies dependent on different memory systems. A series of studies have dissociated between hippocampus-dependent 'spatial' navigation and habit-based 'response' learning mediated by the caudate nucleus. The val66met polymorphism of the brain-derived neurotrophic factor (BDNF) gene leads to decreased secretion of BDNF in the brain, including the hippocampus. Here, we aim to investigate the role of the BDNF val66met polymorphism on virtual navigation behaviour and brain activity in healthy older adults. A total of 139 healthy older adult participants (mean age = 65.8 ± 4.4 years) were tested in this study. Blood samples were collected, and BDNF val66met genotyping was performed. Participants were divided into two genotype groups: val homozygotes and met carriers. Participants were tested on virtual dual-solution navigation tasks in which they could use either a hippocampus-dependent spatial strategy or a caudate nucleus-dependent response strategy to solve the task. A subset of the participants (n = 66) were then scanned in a 3T functional magnetic resonance imaging (fMRI) scanner while engaging in another dual-solution navigation task. BDNF val/val individuals and met carriers did not differ in learning performance. However, the two BDNF groups differed in learning strategy. BDNF val/val individuals relied more on landmarks to remember target locations (i.e., increased use of flexible spatial learning), while met carriers relied more on sequences and patterns to remember target locations (i.e., increased use of inflexible response learning). Additionally, BDNF val/val individuals had more fMRI activity in the hippocampus compared with BDNF met carriers during performance on the navigation task. This is the first study to show in older adults that BDNF met carriers use alternate learning strategies from val/val individuals and to identify differential brain activation of this behavioural difference between the two groups.

Negative correlation between grey matter in the hippocampus and caudate nucleus in healthy aging.

Neurobiological changes that occur with aging include a reduction in function and volume of the hippocampus. These changes were associated with corresponding memory deficits in navigation tasks. However, navigation can involve different strategies that are dependent on the hippocampus and caudate nucleus. The proportion of people using hippocampus-dependent spatial strategies decreases across the lifespan. As such, the decrease in spatial strategies, and corresponding increase in caudate nucleus-dependent response strategies with age, may play a role in the observed neurobiological changes in the hippocampus. Furthermore, we previously showed a negative correlation between grey matter in the hippocampus and caudate nucleus/striatum in mice, young adults, and in individuals diagnosed with Alzheimer's disease. As such, we hypothesized that this negative relationship between the two structures would be present during normal aging. The aim of the current study was to investigate this gap in the literature by studying the relationship between grey matter in the hippocampus and caudate nucleus of the striatum, in relation to each other and to navigation strategies, during healthy aging. Healthy older adults (N = 39) were tested on the Concurrent Spatial Discrimination Learning Task (CSDLT), a virtual radial task that dissociates between spatial and response strategies. A regression of strategies against structural MRIs showed for the first time in older adults that the response strategy was associated with higher amounts of grey matter in the caudate nucleus. As expected, the spatial strategy correlated with grey matter in the hippocampus, which was negatively correlated with grey matter in the caudate nucleus. Interestingly, a sex difference emerged showing that among older adult response learners, women have the least amount of grey matter in the hippocampus, which is a known risk for Alzheimer's disease. This difference was absent among spatial learners. These results are discussed in the context of the putative protective role of spatial memory against grey matter loss in the hippocampus, especially in women.

Opposing effects of cortisol on learning and memory in children using spatial versus response-dependent navigation strategies.

Previous studies showed that healthy young adults who spontaneously use caudate nucleus-dependent strategies on a virtual navigation task, have significantly lower basal levels of cortisol compared with adults who use hippocampus-dependent spatial navigation strategies. In the current paper, we assessed the relation between basal cortisol levels and learning using a virtual navigation task in children. We show that basal cortisol level has a differential effect on learning and memory between children using spatial and response navigation strategies. Specifically, cortisol was found to be beneficial for learning performance in children using spatial strategies, such that higher levels of cortisol were associated with more efficient learning in a virtual maze. In contrast, cortisol had a deleterious effect on learning the virtual maze in children using response strategies, such that higher cortisol levels were associated with increased spatial working memory errors. Based on these results, individual differences in navigation strategy could help explain contradictory results in the literature showing that cortisol can have either a positive or negative association with learning and memory performance.

Caudate nucleus-dependent navigation strategies are associated with increased risk-taking and set-shifting behavior.

When people navigate, they use strategies dependent on one of two memory systems. The hippocampus-based spatial strategy consists of using multiple landmarks to create a cognitive map of the environment. In contrast, the caudate nucleus-based response strategy is based on the memorization of a series of turns. Importantly, response learners display more gray matter and functional activity in the caudate nucleus and less gray matter in the hippocampus. In parallel, the caudate nucleus is involved in decision-making by mediating attention toward rewards and in set-shifting by mediating preparatory actions. The present study, therefore, examined the link between navigational strategy use, that are associated with gray matter differences in the caudate nucleus and hippocampus, and decision-making and set-shifting performance. Fifty-three participants completed the 4 on 8 virtual maze, the Iowa Gambling Task (IGT), the Wisconsin Card Sorting Test-64 (WCST-64), and a task-switching test. The results revealed that people who use response strategies displayed increased risk-taking behavior in the IGT compared to the people using hippocampus-dependent spatial strategies. Response strategy was also associated with enhanced set-shifting performance in the WCST-64 and task-switching test. These results confirm that risk-taking and set-shifting behavior, that are differentially impacted by the caudate nucleus and hippocampus memory systems, can be predicted by navigational strategy.

Electrophysiological evidence for enhanced attentional deployment in spatial learners.

Visual spatial attention is important during navigation processes that rely on a cognitive map, because spatial relationships between environmental landmarks need to be selected, encoded, and learned. People who navigate using this strategy are spatial learners, and this process relies on the hippocampus. Conversely, response learners memorize a series of actions to navigate, which relies on the caudate nucleus. Response learning, which is more efficient, is thought to involve less demanding cognitive operations, and is related to reduced grey matter in the hippocampus. To test if navigational strategy can impact visual attention performance, we investigated if spatial and response learners showed differences in attentional engagement used during a visual spatial task. We tested 40 response learners and 39 spatial learners, as determined by the 4-on-8 Virtual Maze (4/8 VM), on a target detection task designed to elicit an N2pc component (an index visual spatial attention). Spatial learners produced a larger N2pc amplitude during target detection compared to response learners. This relationship might represent an increase in goal-directed attention towards target stimuli or a more global increase in cognitive function that has been previously observed in spatial learners.

Habitual action video game playing is associated with caudate nucleus-dependent navigational strategies.

The habitual playing of video games is associated with increased grey matter and activity in the striatum. Studies in humans and rodents have shown an inverse relationship between grey matter in the striatum and hippocampus. We investigated whether action video game playing is also associated with increased use of response learning strategies during navigation, known to be dependent on the caudate nucleus of the striatum, when presented in a dual solution task. We tested 26 action video game players (actionVGPs) and 33 non-action video game players (nonVGPs) on the 4-on-8 virtual maze and a visual attention event-related potential (ERP) task, which elicits a robust N-2-posterior-controlateral (N2pc) component. We found that actionVGPs had a significantly higher likelihood of using a response learning strategy (80.76%) compared to nonVGPs (42.42%). Consistent with previous evidence, actionVGPs and nonVGPs differed in the way they deployed visual attention to central and peripheral targets as observed in the elicited N2pc component during an ERP visual attention task. Increased use of the response strategy in actionVGPs is consistent with previously observed increases in striatal volume in video game players (VGPs). Using response strategies is associated with decreased grey matter in the hippocampus. Previous studies have shown that decreased volume in the hippocampus precedes the onset of many neurological and psychiatric disorders. If actionVGPs have lower grey matter in the hippocampus, as response learners normally do, then these individuals could be at increased risk of developing neurological and psychiatric disorders during their lifetime.

Dissociable contributions of the prefrontal cortex to hippocampus- and caudate nucleus-dependent virtual navigation strategies.

The hippocampus and the caudate nucleus are critical to spatial- and stimulus-response-based navigation strategies, respectively. The hippocampus and caudate nucleus are also known to be anatomically connected to various areas of the prefrontal cortex. However, little is known about the involvement of the prefrontal cortex in these processes. In the current study, we sought to identify the prefrontal areas involved in spatial and response learning. We used functional magnetic resonance imaging (fMRI) and voxel-based morphometry to compare the neural activity and grey matter density of spatial and response strategy users. Twenty-three healthy young adults were scanned in a 1.5 T MRI scanner while they engaged in the Concurrent Spatial Discrimination Learning Task, a virtual navigation task in which either a spatial or response strategy can be used. In addition to increased BOLD activity in the hippocampus, spatial strategy users showed increased BOLD activity and grey matter density in the ventral area of the medial prefrontal cortex, especially in the orbitofrontal cortex. On the other hand, response strategy users exhibited increased BOLD activity and grey matter density in the dorsal area of the medial prefrontal cortex. Given the prefrontal cortex's role in reward-guided decision-making, we discuss the possibility that the ventromedial prefrontal cortex, including the orbitofrontal cortex, supports spatial learning by encoding stimulus-reward associations, while the dorsomedial prefrontal cortex supports response learning by encoding action-reward associations.

The relationship between object-based spatial ability and virtual navigation performance.

Spatial navigation is a multi-faceted behaviour drawing on many different aspects of cognition. Visuospatial abilities, such as mental rotation and visuospatial working memory, in particular, may be key factors. A range of tests have been developed to assess visuospatial processing and memory, but how such tests relate to navigation ability remains unclear. This understanding is important to advance tests of navigation for disease monitoring in various disorders (e.g., Alzheimer's disease) where spatial impairment is an early symptom. Here, we report the use of an established mobile gaming app, Sea Hero Quest (SHQ), as a measure of navigation ability in a sample of young, predominantly female university students (N = 78; 20; female = 74.3%; mean age = 20.33 years). We used three separate tests of navigation embedded in SHQ: wayfinding, path integration and spatial memory in a radial arm maze. In the same participants, we also collected measures of mental rotation (Mental Rotation Test), visuospatial processing (Design Organization Test) and visuospatial working memory (Digital Corsi). We found few strong correlations across our measures. Being good at wayfinding in a virtual navigation test does not mean an individual will also be good at path integration, have a superior memory in a radial arm maze, or rate themself as having a strong sense of direction. However, we observed that participants who were good in the wayfinding task of SHQ tended to perform well on the three visuospatial tasks examined here, and to also use a landmark strategy in the radial maze task. These findings help clarify the associations between different abilities involved in spatial navigation.

Caudate nucleus-dependent navigational strategies are associated with increased use of addictive drugs.

This study aimed to investigate the relationship between navigational strategies and the use of abused substances in a sample of healthy young adults. Navigational strategies were assessed with the 4-on-8 virtual maze (4/8VM), a task previously shown to dissociate between hippocampal-dependent spatial navigational strategies and caudate nucleus-dependent stimulus-response navigational strategies. Spatial strategies involve learning the spatial relationships between the landmarks in an environment, while response learning strategies involve learning a rigid set of stimulus-response type associations, e.g., see the tree, turn left. We have shown that spatial learners have increased gray matter and fMRI activity in the hippocampus compared with response learners, while response learners have increased gray matter and fMRI activity in the caudate nucleus. We were interested in the prevalence of use of substances of abuse in spatial and response learners because of the evidence that people who score high on traits such as novelty seeking, sensation seeking, reward seeking, and impulsivity, are more cue-responsive and more likely to use substances of abuse. Since response learners show increased activity and gray matter in the caudate nucleus of the striatum, which is a brain area involved in addiction, we hypothesized that response learners would have a greater use of abused substances than spatial learners. Fifty-five young adults were tested on the 4/8VM and completed a time-line follow-back assessment of drug and alcohol use. We found that response learners had smoked a significantly greater number of cigarettes in their lifetime than spatial learners, were more likely to have used cannabis, and had double the lifetime alcohol consumption. We discuss the possible relationship between substance abuse and response strategies as well as the implications for the hippocampus, risks of neurological and psychiatric disorders, and healthy cognition.

Decreased functional magnetic resonance imaging activity in the hippocampus in favor of the caudate nucleus in older adults tested in a virtual navigation task.

The neuroimaging literature has shown consistent decreases in functional magnetic resonance imaging (fMRI) activity in the hippocampus of healthy older adults engaged in a navigation task. However, navigation in a virtual maze relies on spatial or response strategies known to depend on the hippocampus and caudate nucleus, respectively. Therefore, since the proportion of people using spatial strategies decreases with normal aging, we hypothesized that it was responsible for the observed decreases in fMRI activity in the hippocampus reported in the literature. The aim of this study was to examine the effects of aging on the hippocampus and caudate nucleus during navigation while taking into account individual navigational strategies. Young (N = 23) and older adults (N = 29) were tested using fMRI on the Concurrent Spatial Discrimination Learning Task, a radial task that dissociates between spatial and response strategies (in Stage 2) after participants reached criteria (in Stage 1). Success on Stage 2 requires that participants have encoded the spatial relationship between the target object and environmental landmarks, that is, the spatial strategy. While older adults required more trials, all participants reached criterion. fMRI results showed that, as a group, young adults had significant activity in the hippocampus as opposed to older adults who instead had significant activity in the caudate nucleus. Importantly, individual differences showed that the older participants who used a spatial strategy to solve the task had significant activity in the hippocampus. These findings suggest that the aging process involves a shift from using the hippocampus toward the caudate nucleus during navigation but that activity in the hippocampus is sustained in a subset of healthy older adults engaged in spatial strategies.

Selective deficit in spatial memory strategies contrast to intact response strategies in patients with schizophrenia spectrum disorders tested in a virtual navigation task.

Spatial memory is impaired among persons with schizophrenia (SCZ). However, different strategies may be used to solve most spatial memory and navigation tasks. This study investigated the hypothesis that participants with schizophrenia-spectrum disorders (SSD) would demonstrate differential impairment during acquisition and retrieval of target locations when using a hippocampal-dependent spatial strategy, but not a response strategy, which is more associated with caudate function. Healthy control (CON) and SSD participants were tested using the 4-on-8 virtual maze (4/8VM), a virtual navigation task designed to differentiate between participants' use of spatial and response strategies. Consistent with our predictions, SSD participants demonstrated a differential deficit such that those who navigated using a spatial strategy made more errors and took longer to locate targets. In contrast, SSD participants who spontaneously used a response strategy performed as well as CON participants. The differential pattern of spatial-memory impairment in SSD provides only indirect support for underlying hippocampal dysfunction. These findings emphasize the importance of considering individual strategies when investigating SSD-related memory and navigation performance. Future cognitive intervention protocols may harness SSD participants' intact ability to navigate using a response strategy and/or train the deficient ability to navigate using a spatial strategy to improve navigation and memory abilities in participants with SSD.

Prenatal stress changes learning strategies in adulthood.

It is well known that stressful experiences may shape hippocampus-dependent learning and memory processes. However, although most studies focused on the impact of stress at the time of learning or memory testing, very little is known about how stress during critical periods of brain development affects learning and memory later in life. In this study, we asked whether prenatal stress exposure may influence the engagement of hippocampus-dependent spatial learning strategies and caudate nucleus-dependent response learning strategies in later life. To this end, we tested healthy participants whose mothers had experienced major negative life events during their pregnancy in a virtual navigation task that can be solved by spatial and response strategies. We found that young adults with prenatal stress used rigid response learning strategies more often than flexible spatial learning strategies compared with participants whose mothers did not experience major negative life events during pregnancy. Individual differences in acute or chronic stress do not account for these findings. Our data suggest that the engagement of hippocampal and nonhippocampal learning strategies may be influenced by stress very early in life.

Evidence for a virtual human analog of a rodent relational memory task: a study of aging and fMRI in young adults.

A radial maze concurrent spatial discrimination learning paradigm consisting of two stages was previously designed to assess the flexibility property of relational memory in mice, as a model of human declarative memory. Aged mice and young adult mice with damage to the hippocampus, learned accurately Stage 1 of the task which required them to learn a constant reward location in a specific set of arms (i.e., learning phase). In contrast, they were impaired relative to healthy young adult mice in a second stage when faced with rearrangements of the same arms (i.e., flexibility probes). This mnemonic inflexibility in Stage 2 is thought to derive from insufficient relational processing by the hippocampus during initial learning (Stage 1) which favors stimulus-response learning, a form of procedural learning. This was proposed as a model of the selective declarative and relational memory decline classically described in elderly people. As a first step to examine the validity of this model, we adapted this protocol to humans using a virtual radial-maze. (1) We showed that performance in the flexibility probes in young and older adults positively correlated with performance in a wayfinding task, suggesting that our paradigm assesses relational memory. (2) We demonstrated that older healthy participants displayed a deficit in the performance of the flexibility probes (Stage 2), similar to the one previously seen in aged mice. This was associated with a decline in the wayfinding task. (3) Our fMRI data in young adults confirmed that hippocampal activation during early discrimination learning in Stage 1 correlated with memory flexibility in Stage 2, whereas caudate nucleus activation in Stage 1 negatively correlated with subsequent flexibility. By enabling relational memory assessment in mice and humans, our radial-maze paradigm provides a valuable tool for translational research.

Eye tracking, strategies, and sex differences in virtual navigation.

Reports of sex differences in wayfinding have typically used paradigms sensitive to the female advantage (navigation by landmarks) or sensitive to the male advantage (navigation by cardinal directions, Euclidian coordinates, environmental geometry, and absolute distances). The current virtual navigation paradigm allowed both men and women an equal advantage. We studied sex differences by systematically varying the number of landmarks. Eye tracking was used to quantify sex differences in landmark utilisation as participants solved an eight-arm radial maze task within different virtual environments. To solve the task, participants were required to remember the locations of target objects within environments containing 0, 2, 4, 6, or 8 landmarks. We found that, as the number of landmarks available in the environment increases, the proportion of time men and women spend looking at landmarks and the number of landmarks they use to find their way increases. Eye tracking confirmed that women rely more on landmarks to navigate, although landmark fixations were also associated with an increase in task completion time. Sex differences in navigational behaviour occurred only in environments devoid of landmarks and disappeared in environments containing multiple landmarks. Moreover, women showed sustained landmark-oriented gaze, while men's decreased over time. Finally, we found that men and women use spatial and response strategies to the same extent. Together, these results shed new light on the discrepancy in landmark utilisation between men and women and help explain the differences in navigational behaviour previously reported.

Wayfinding: the effects of large displays and 3-D perception.

Large displays and stereopsis have been shown to improve performance in several virtual navigation tasks. In the present research, we sought to determine whether wayfinding could benefit from these factors. Participants were tested in a virtual town. There were three viewing conditions: a desktop, a large screen, and a large screen on which the virtual environment was viewed in three dimensions (3-D) using polarized glasses. Participants explored the town and had to remember the location of several landmarks. Their memory of the layout of the town was tested by asking them to navigate from one landmark to another, taking the shortest route possible. All groups performed equally well in terms of the distance traveled to target locations. From this result, we concluded that large displays and 3-D perception do not significantly contribute to wayfinding. Thus, experimental paradigms and training programs that utilize wayfinding are as valuable when administered on standard desktops as on more sophisticated and costly equipment and do not induce simulator sickness as large displays tend to do.

Associations Between Video Game Engagement and ADHD Symptoms in Early Adolescence.

OBJECTIVE: We aim to investigate the direction of causality of the association between adolescent video game playing and later development of ADHD symptoms using a population-based sample of Canadian Youth. METHOD: The present study is based on longitudinal cohort data (N = 1,467). Youth self-reported weekly hours of video game playing as well as ADHD symptoms at both 12 and 13 years of age. RESULTS: Cross-lagged panel model were estimated to examine how adolescent video game playing prospectively contributes to ADHD symptoms while simultaneously considering how adolescent ADHD symptoms may prospectively contribute to videogame playing. Analyses revealed a significant positive association between adolescent video games playing at age 12 and ADHD symptoms at age 13. Youth ADHD symptoms at age 12 did not predict video game use at age 13. CONCLUSION: Our results help clarify the direction of causality of the association between video game playing and ADHD symptoms and provide evidence that video game playing can represent a risk factor for the development of attention problems in early adolescence.

Maze training in mice induces MRI-detectable brain shape changes specific to the type of learning.

Multiple recent human imaging studies have suggested that the structure of the brain can change with learning. To investigate the mechanism behind such structural plasticity, we sought to determine whether maze learning in mice induces brain shape changes that are detectable by MRI and whether such changes are specific to the type of learning. Here we trained inbred mice for 5 days on one of three different versions of the Morris water maze and, using high-resolution MRI, revealed specific growth in the hippocampus of mice trained on a spatial variant of the maze, whereas mice trained on the cued version were found to have growth in the striatum. The structure-specific growth found furthermore correlated with GAP-43 staining, a marker of neuronal process remodelling, but not with neurogenesis nor neuron or astrocyte numbers or sizes. Our findings provide evidence that brain morphology changes rapidly at a scale detectable by MRI and furthermore demonstrate that specific brain regions grow or shrink in response to the changing environmental demands. The data presented herein have implications for both human imaging as well as rodent structural plasticity research, in that it provides a tool to screen for neuronal plasticity across the whole brain in the mouse while also providing a direct link between human and mouse studies.

The brain-derived neurotrophic factor Val66Met polymorphism is associated with reduced functional magnetic resonance imaging activity in the hippocampus and increased use of caudate nucleus-dependent strategies in a human virtual navigation task.

Multiple memory systems are involved in parallel processing of spatial information during navigation. A series of studies have distinguished between hippocampus-dependent 'spatial' navigation, which relies on knowledge of the relationship between landmarks in one's environment to build a cognitive map, and habit-based 'response' learning, which requires the memorization of a series of actions and is mediated by the caudate nucleus. Studies have demonstrated that people spontaneously use one of these two alternative navigational strategies with almost equal frequency to solve a given navigation task, and that strategy correlates with functional magnetic resonance imaging (fMRI) activity and grey matter density. Although there is evidence for experience modulating grey matter in the hippocampus, genetic contributions may also play an important role in the hippocampus and caudate nucleus. Recently, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene has emerged as a possible inhibitor of hippocampal function. We have investigated the role of the BDNF Val66Met polymorphism on virtual navigation behaviour and brain activation during an fMRI navigation task. Our results demonstrate a genetic contribution to spontaneous strategies, where 'Met' carriers use a response strategy more frequently than individuals homozygous for the 'Val' allele. Additionally, we found increased hippocampal activation in the Val group relative to the Met group during performance of a virtual navigation task. Our results support the idea that the BDNF gene with the Val66Met polymorphism is a novel candidate gene involved in determining spontaneous strategies during navigation behaviour.

Caudate nucleus-dependent response strategies in a virtual navigation task are associated with lower basal cortisol and impaired episodic memory.

The present research examined the relationship between endogenous glucocorticoids, navigational strategies in a virtual navigation task, and performance on standard neuropsychological assessments of memory. Healthy young adult participants (N=66, mean age: 21.7) were tested on the 4 on 8 virtual maze (4/8 VM) and standard neuropsychological tests such as the Rey-Osterrieth Complex Figure (RO) and the Rey Auditory Verbal Learning Task (RAVLT), which measure episodic memory. The 4/8 VM differentiates between navigational strategies, where participants either use a hippocampal-dependent spatial strategy by building relationships between landmarks, or a caudate nucleus-dependent stimulus-response strategy by automatizing a pattern of open and closed arms to learn the location of objects within the maze. Degree of stress was assessed by administering the Perceived Stress Scale (PSS) questionnaire. Cortisol samples were taken on two consecutive days upon waking, 30 min after waking, at 11 am, 4 pm, and 9 pm. There was a significant difference in basal levels of cortisol between spatial and response learners. Interestingly, response learners had significantly lower cortisol levels throughout the day. The two groups did not differ in terms of perceived stress as measured with the PSS questionnaire. Moreover, there was no significant correlation between PSS scores and salivary cortisol levels, indicating that the higher cortisol levels in the spatial group were not associated with greater perceived stress. In addition, participants who spontaneously used a spatial strategy performed significantly better on the RAVLT and RO. These data indicate that the cortisol levels in the spatial group may be optimal in terms of episodic memory performance whereas the cortisol levels in the response group may be associated with poorer memory. These results are suggestive of an inverted U-shaped curve describing the effects of basal levels of circulating cortisol on memory in young adults.