Robert S. Astur

A characterization of performance by men and women in a virtual Morris water task:: A large and reliable sex difference

In many mammalian species, it is known that males and females differ in place learning ability. The performance by men and women is commonly reported to also differ, despite a large amount of variability and ambiguity in measuring spatial abilities. In the non-human literature, the gold standard for measuring place learning ability in mammals is the Morris water task. This task requires subjects to use the spatial arrangement of cues outside of a circular pool to swim to a hidden goal platform located in a fixed location. We used a computerized version of the Morris water task to assess whether this task will generalize into the human domain and to examine whether sex differences exist in this domain of topographical learning and memory. Across three separate experiments, varying in attempts to maximize spatial performance, we consistently found males navigate to the hidden platform better than females across a variety of measures. The effect sizes of these differences are some of the largest ever reported and are robust and replicable across experiments. These results are the first to demonstrate the effectiveness and utility of the virtual Morris water task for humans and show a robust sex difference in virtual place learning.

Humans with hippocampus damage display severe spatial memory impairments in a virtual Morris water task

For nonhumans, it has been shown that the hippocampus (HPC) is critical for spatial memory. We tested patients with unilateral HPC resections on a virtual analogue of a classic spatial task to assess HPC functioning in nonhumans: the Morris water task. We found that when humans are required to use spatial cues to navigate to a hidden escape platform in a pool, patients with HPC resections display severe impairments in spatial navigation relative to age-matched controls and age-matched patients who have had extra-HPC resections. This effect occurred for every patient tested and was evident regardless of side of surgery. Hence, it is apparent across species and irrespective of which hemisphere is damaged that the human HPC is critical for spatial/relational memory.

Sex differences and correlations in a virtual Morris water task, a virtual radial arm maze, and mental rotation

Different tasks are often used to assess spatial memory in humans compared to nonhumans. In order to bridge this paradigmatic gap, we used a within-subject design to test 61 undergraduates on three spatial memory tasks. One of these tasks, the Vanderberg 3D mental rotation task, is classically used to assess spatial memory in humans. The other two tests are virtual analogues of two tasks used classically to assess spatial memory in rodents: the Morris water task and an eight-arm radial maze. We find that males perform significantly better than females on the mental rotation task and in finding a hidden platform in the virtual Morris water task. Moreover, during a probe trial, males spend significantly more distance of their swim in the training quadrant, but males and females do not differ in navigating to a visible platform. However, for the virtual eight-arm radial maze, there is no sex difference in working memory errors, reference memory errors, or distance to find the rewards. Surprisingly, an examination of the correlations among the three tasks indicates that only mental rotation ability and Morris water task probe trial performance correlate significantly among the three tasks (i.e. there are no significant correlations with traditional measures the tasks, e.g. time or distance to completion). Hence, the Morris water task and the eight-arm radial maze do not assess spatial memory in the same manner, and even after equating factors such as motivation, stress, and motor demands, there still are procedural demands of the tasks that reinforce differential strategy selection during spatial memory. This suggests that caution should be taken when utilizing these two tasks interchangeable as tests of spatial memory.

Retrograde amnesia after hippocampal damage: Recent vs. remote memories in two tasks

We review evidence from experiments conducted in our laboratory on retrograde amnesia in rats with damage to the hippocampal formation. In a new experiment reported here, we show that N‐methyl‐D‐aspartate (NMDA)‐induced hippocampal damage produced retrograde amnesia for both hidden platform and two‐choice visible platform discriminations in the Morris water task. For both problems there was a significant trend for longer training‐surgery intervals to be associated with worse retention performance. Little support is offered by our work for the concept that there is a process involving hippocampal‐dependent consolidation of memories in extrahippocampal permanent storage sites. Long‐term memory consolidation may take place within the hippocampus. The hippocampus may be involved permanently in storage and/or retrieval of a variety of relational and nonrelational memories if it was intact at the time of learning, even involving information which is definitely not affected in anterograde amnesia after hippocampal damage. Hippocampus 2001;11:27–42.

Retrograde amnesia and selective damage to the hippocampal formation: memory for places and object discriminations

Using a within-subjects design, rats were trained on two place-memory problems and five object-discrimination problems at different intervals prior to receiving either ibotenate lesions of the hippocampal formation or sham surgery. Places # 1 and 2 were fixed-platform water-maze tasks that were run in different rooms and they were learned during the 14th and 2nd week before surgery, respectively. Object-discrimination problems # 1-5 were learned during the 13th, 10th, 7th, 4th, and 1st week before surgery, respectively. Rats with hippocampal lesions displayed impaired retention of both Place problems with no evidence of a temporal gradient to the impairment. In contrast to their retrograde place-memory deficits, the hippocampal rats displayed normal retention of the five object-discriminations that were learned before surgery. Hippocampal lesions had similar consequences for anterograde learning, as the lesioned rats were impaired in acquisition of a new water-maze problem that was run in a third room (Place #3), whereas they showed normal acquisition of two new object-discriminations. The findings indicate that the hippocampal formation is not required for long-term consolidation of information underlying accurate performance of object-discriminations, and that its critical role in memory for places persists for at least 14 weeks, and probably for as long as those memories exist.

Selective Cognitive Impairments Associated with NMDA Receptor Blockade in Humans

Hypofunction of the N-methyl-D-aspartate receptor (NMDAR) may be involved in the pathophysiology of schizophrenia. NMDAR antagonists like ketamine induce schizophrenia-like features in humans. In rodent studies, NMDAR antagonism impairs learning by disrupting long-term potentiation (LTP) in the hippocampus. This study investigated the effects of ketamine on spatial learning (acquisition) vs retrieval in a virtual Morris water task in humans. Verbal fluency, working memory, and learning and memory of verbal information were also assessed. Healthy human subjects participated in this double-blinded, placebo-controlled study. On two separate occasions, ketamine/placebo was administered and cognitive tasks were assessed in association with behavioral ratings. Ketamine impaired learning of spatial and verbal information but retrieval of information learned prior to drug administration was preserved. Schizophrenia-like symptoms were significantly related to spatial and verbal learning performance. Ketamine did not significantly impair attention, verbal fluency, or verbal working memory task performance. Spatial working memory was slightly impaired. In conclusion, these results provide evidence for ketamines differential impairment of verbal and spatial learning vs retrieval. By using the Morris water task, which is hippocampal-dependent, this study helps bridge the gap between nonhuman animal and human NMDAR antagonism research. Impaired cognition is a core feature of schizophrenia. A better understanding of NMDA antagonism, its physiological and cognitive consequences, may provide improved models of psychosis and cognitive therapeutics.

Men and Women Differ in Object Memory but Not Performance of a Virtual Radial Maze.

The present study examined sex differences in object memory by using 2-dimensional object arrays and in spatial memory by using a computerized virtual 12-arm radial maze. Virtual T-maze and water maze tasks were also used to examine sex differences in the use of spatial and nonspatial strategies during navigation. Women significantly outperformed men in recalling the locations and identities of objects. However, the sexes did not differ in the commission of working memory and reference memory errors in the radial maze or in the use of particular navigational strategies. Because arms in the radial maze may become associated with specific extramaze cues, the superior object memory demonstrated by women may have eliminated the typical male advantage found in spatial navigation tasks.

A method for multitask fMRI data fusion applied to schizophrenia

It is becoming common to collect data from multiple functional magnetic resonance imaging (fMRI) paradigms on a single individual. The data from these experiments are typically analyzed separately and sometimes directly subtracted from one another on a voxel‐by‐voxel basis. These comparative approaches, although useful, do not directly attempt to examine potential commonalities between tasks and between voxels. To remedy this we propose a method to extract maximally spatially independent maps for each task that are “coupled” together by a shared loading parameter. We first compute an activation map for each task and each individual as “features,” which are then used to perform joint independent component analysis (jICA) on the group data. We demonstrate our approach on a data set derived from healthy controls and schizophrenia patients, each of which carried out an auditory oddball task and a Sternberg working memory task. Our analysis approach revealed two interesting findings in the data that were missed with traditional analyses. First, consistent with our hypotheses, schizophrenia patients demonstrate “decreased” connectivity in a joint network including portions of regions implicated in two prevalent models of schizophrenia. A second finding is that for the voxels identified by the jICA analysis, the correlation between the two tasks was significantly higher in patients than in controls. This finding suggests that schizophrenia patients activate “more similarly” for both tasks than do controls. A possible synthesis of both findings is that patients are activating less, but also activating with a less‐unique set of regions for these very different tasks. Both of the findings described support the claim that examination of joint activation across multiple tasks can enable new questions to be posed about fMRI data. Our approach can also be applied to data using more than two tasks. It thus provides a way to integrate and probe brain networks using a variety of tasks and may increase our understanding of coordinated brain networks and the impact of pathology upon them. Hum Brain Mapp, 2005.

Hippocampus function predicts severity of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is often accompanied by memory problems and abnormal brain structure, particularly within the hippocampus. We implemented a cross-species, hippocampal-dependent task--the virtual Morris Water task--to assess hippocampal function in people with PTSD and age-matched controls during functional magnetic resonance imaging (fMRI). Performance on the task was equivalent between the groups. However, when correlating fMRI-derived hippocampal activity during this task with PTSD severity, we observe a -0.84 correlation, indicating that those with reduced hippocampal activity show more severe PTSD symptoms. This correlation is not explained by differences in task performance, IQ, duration since trauma, nor time with PTSD. Hence, PTSD severity is predicted by functionally assessing the hippocampus using the virtual Morris water task, suggesting that this task may be used to identify those at risk for developing PTSD following a trauma.

Feature-based attentional set as a cause of traffic accidents

Voluntary and relatively involuntary subsystems of attention often compete. On one hand, people can intentionally “tune” attention for features that then receive visual priority; on the other hand, more reflexive attentional shifts can “short-circuit” top-down control in the face of urgent, behaviourally relevant stimuli. Thus, it is questionable whether voluntary attentional tuning (i.e., attentional set) can affect ones ability to respond to unexpected, urgent information in the real world. We show that the consequences of such tuning extend to a realistic, safety-relevant scenario. Participants drove in a first-person driving simulation where they searched at every intersection for either a yellow or blue arrow indicating which way to turn. At a critical intersection, a yellow or blue motorcycle—either matching or not matching drivers’ attentional set—suddenly veered into drivers’ paths and stopped in their way. Collision rates with the motorcycle were substantially greater when the motorcycle did not match drivers’ attentional sets.