Virtual Radial Arm Maze Research Articles

Application of Real and Virtual Radial Arm Maze Task in Human.

Virtual Reality (VR) emerges as a promising technology capable of creating different scenarios in which the body, environment, and brain are closely related, proving enhancements in the diagnosis and treatment of several spatial memory deficits. In recent years, human spatial navigation has increasingly been studied in interactive virtual environments. However, navigational tasks are still not completely adapted in immersive 3D VR systems. We stipulate that an immersive Radial Arm Maze (RAM) is an excellent instrument, allowing the participants to be physically active within the maze exactly as in the walking RAM version in reality modality. RAM is a behavioral ecological task that allows the analyses of different facets of spatial memory, distinguishing declarative components from procedural ones. In addition to describing the characteristics of RAM, we will also analyze studies in which RAM has been used in virtual modality to provide suggestions into RAM building in immersive modality.

Estradiol effects on spatial memory in women

To examine the role of estradiol in hippocampal-dependent spatial memory in women, 86 female undergraduates were tested in a virtual Morris water task (VMWT), a virtual radial arm maze (VRAM), and a mental rotation task (MRT) within a single daily session. The VMWT and RAM were also administered 24 h later to examine the effects of estradiol on memory consolidation. Women on oral contraceptives (OCs) or those who were naturally cycling and exhibited low estradiol (LE) or high estradiol (HE), as determined by salivary assays, were included. At the start of day two, the HE group showed superior spatial reference memory on the VMWT relative to the LE group, as evidenced by significantly shorter distances navigating to the hidden platform. The LE group also had the poorest probe trial performance at the start of day two compared to both other groups. There were no group differences in performance on the RAM or MRT. These results provide support for estradiol’s role in the consolidation of spatial reference memory in women, and emphasize the differential sensitivities of various virtual memory tasks in assessing spatial memory function in women.

The art gallery maze: a novel tool to assess human navigational abilities.

Humans differ widely in their ability to navigate effectively through the environment and in spatial memory skills. Navigation in the environment requires the analysis of many spatial cues, the construction of internal representations, and the use of various strategies. We present a novel tool to assess individual differences in human navigation, consisting of a virtual radial-arm maze presented as an art gallery to explore whether different sets of instructions (intentional or incidental) affect subjects' navigation performance. We furthermore tested the effect of the instructions on exploration strategies during both place learning and recall. We evaluated way-finding ability in 42 subjects, and individual differences in navigation were assessed through the analysis of navigational paths, which permitted the isolation and definition of a few strategies adopted by the incidental and intentional instructions groups. Our results showed that the intentional instruction group performed better than the other group: these subjects correctly paired each central statue and the two paintings in the adjacent arms, and they made less working and reference memory errors. Our analysis of path lengths showed that the intentional instruction group spent more time in the maze (thus being slower), specifically in the central hall, and covered more distance; the time spent in the main hall was, therefore, indicative of the quality of the following performance. Studying how environmental representations and the relative navigational strategies vary among "intentional" and "incidental" groups provides a new window into the acknowledgment of possible strategies to help subjects construct more efficient approaches in human navigation.

Sex-specific associations between co-exposure to multiple metals and visuospatial learning in early adolescence

The predisposition, severity, and progression of many diseases differ between males and females. Sex-related differences in susceptibility to neurotoxicant exposures may provide insight into the cause of the observed discrepancy. Early adolescence, a period of substantial structural and functional brain changes, may present a critical window of vulnerability to environmental exposures. This study aimed to examine sex-specific associations between co-exposure to multiple metals and visuospatial memory in early adolescence. Manganese (Mn), lead (Pb), chromium (Cr), and copper (Cu) were measured in blood, urine, hair, nails, and saliva of 188 participants (88 girls; 10–14 years of age). Visuospatial memory skills were assessed using a computerized maze task, the virtual radial arm maze (VRAM). Using generalized weighted quantile sum regression, we investigated sex-specific associations between the combined effect of exposure to the metal mixture and visuospatial working memory and determined the contribution of each component to the outcome. The results suggest that sex moderates the association between the metal mixture and visuospatial learning for all outcomes measured. In girls, exposure was associated with slower visuospatial learning and driven by Mn and Cu. In boys, exposure was associated with faster visuospatial learning, and driven by Cr. These results suggest that (a) the effect of metal co-exposure on learning differs in magnitude, and in the direction between sexes, and (b) early adolescence may be a sensitive developmental period for metal exposure.

Sex-specific associations between exposure to multiple metals and visuospatial memory skills in adolescents

OPS 40: Metals: neurological effects, Room 412, Floor 4, August 28, 2019, 10:30 AM - 12:00 PM Background/Aim: In rodents, visuospatial memory deficits following metal exposure have been measured with the radial arm maze (RAM) task. In humans, the virtual radial arm maze (VRAM), is the computerized analogue developed to assess visuospatial memory in children. The goal of this study was to examine associations between exposure to metals and performance on the VRAM among adolecents that can be utilized to plan future translational studies using RAM. Methods: Manganese (Mn), lead (Pb), chromium (Cr) and copper (Cu) were measured in blood, urine, hair, nails and saliva of 184 participants (84 girls; 11-15 years of age) enrolled in the PHIME study (Public Health Impact of Manganese Exposure) who resided near a ferroalloy plant in Italy. VRAM performance was assessed as the time required to complete the task. Using generalized weighted quartile sum (gWQS) regression, we investigated associations between a mixture of four metals in all matrices and VRAM performance, controlling for covariates. We estimated metal mixture weights and effects for the whole cohort and for each sex individually. Results: A higher metal mixture index was associated with poorer VRAM performance (β: 0.28; p=0.02). Upon stratification, this association was observed in girls (β: 0.65; p<0.001) and not boys. Urine Mn and blood Cu contributed 27% and 13% respectively to the overall mixture effect. Mn in all 5 matrices combined contributed to 54% to the overall mixture effect. In post-hoc analyses, no associations were observed between exposure to each metal separately and VRAM performance. Conclusions: Exposure to this metal mixture during adolescence may disrupt visuospatial skill acquisition in females. Our results can inform translational research that may address underlying neurotoxic mechanisms and guide additional studies on which metals to focus in future research.

Manganese in teeth and neurobehavior: Sex-specific windows of susceptibility

BackgroundManganese (Mn) is an essential element required for growth and development, but higher body burdens have been associated with neurobehavioral decrements in children. ObjectivesWe examined whether prenatal or postnatal Mn measured in deciduous teeth was associated with scores on a test of visuospatial learning and memory. MethodsDeciduous teeth were collected from 142 participants (ages 10–14years) residing near varied ferro‑manganese industry in Italy. Mn concentrations were measured in prenatal and postnatal tooth regions by laser ablation inductively coupled plasma mass spectrometry (ICP-MS). The Virtual Radial Arm Maze (VRAM), an animal-human analogue task, was used to assess visuospatial learning and memory. We used generalized additive, linear and zero-inflated Poisson mixed regression models to estimate associations between prenatal or postnatal Mn concentrations and repeated measures of all four VRAM outcomes: time, distance, working and reference memory errors. Effect measure modification by sex was examined in stratified models. ResultsU-shaped associations between prenatal Mn and VRAM outcomes were observed among girls only (pGAMM=0.001 to 0.02 in stratified models). Compared to the mid-tertile of prenatal Mn, girls in the highest tertile took 7.7s [95% CI: −6.1, 21.5] longer to complete the task, traveled 2.3 maze units [0.1, 4.4] farther, and committed more working and reference memory errors (β for count ratio=1.33 [1.01, 1.83]; 1.10 [0.98, 1.24], respectively). This association was not observed among boys. In contrast, for postnatal Mn, no significant associations were found, and patterns were similar for boys and girls. ConclusionsThe prenatal period may be a critical window for the impact of environmental Mn on visuospatial ability and executive function, especially for females.

Tooth manganese and neurobehavior in Italian children: sex-specific windows of susceptibility

Introduction: Manganese (Mn) exposure can now be quantified using teeth, which can determine dose and exposure timing. Translation of epidemiologic research can be further facilitated by employing behavioral tasks that parallel animal studies, which in turn have access to neurologic tissue for mechanistic research. We examined associations of Mn exposure among Italian adolescents living near a ferromanganese plant with visuospatial learning assessed using the virtual radial arm maze (VRAM). Methods: We analyzed deciduous teeth from 137 children ages 10-15 years by laser ablation inductively coupled plasma mass spectrometry. Mn levels were measured in prenatal and postnatal exposure periods. We assessed performance on the VRAM, a computerized version of the rodent task, estimating latency, distance, working and reference memory errors. Linear mixed regression and generalized additive mixed regression were used to model associations between tooth Mn and VRAM performance and to assess interactions with sex. Results are compared to rodent research. Results: Adjusting for age, socioeconomic status, video game use, childhood blood lead, and tooth type, we observed sex-specific associations of tooth Mn with VRAM performance: among girls, there was a U-shaped association between prenatal Mn and latency, distance and working memory errors (pGAM=0.009-0.02). This result suggest both lower and higher prenatal tooth Mn predict worse performance among girls. Among boys, no association was observed in the prenatal period, but postnatal Mn was associated with latency, distance and reference memory in a non-linear manner (pGAM=0.004-0.08), which is consistent with a rodent study of Mn that also used a radial arm maze. Conclusions: Our sex specific results parallel a rodent study of postnatal Mn exposure demonstrating the utility of employing parallel phenotyping methods for translational research. Sensitive exposure windows appeared to be sex-specific.

Stop and look! Evidence for a bias towards virtual navigation response strategies in children with ADHD symptoms

Studies in children show that the development of spatial competence emerges between seven and eight years of age. Multiple memory systems (hippocampus-dependent spatial and caudate nucleus-dependent response learning) are involved in parallel processing of information during navigation. As a hippocampus-dependent spatial strategy also relies on frontoparietal executive control and working memory networks that are impaired in ADHD, we predicted that children will be more likely to adopt a response strategy as they exhibit ADHD symptoms. We tested 285 healthy children on a virtual radial-arm maze paradigm in order to test this hypothesis. We found that children displaying at least one ADHD symptom were more likely to have a perfect performance on a probe trial, which suggests that they did not rely on environmental landmarks. Children with ADHD symptoms may primarily rely on caudate nucleus-dependent response learning strategies at the expense of hippocampus-dependent spatial strategies. Repetition and reward based learning strategies, which are hallmarks of response learning, may be most effective in children exhibiting ADHD symptoms.

Spatial memory impairments in amnestic mild cognitive impairment in a virtual radial arm maze.

ObjectiveThis study aims to apply the virtual radial arm maze (VRAM) task to find spatial working memory and reference memory impairments in patients of amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). Spatial memory functions between aMCI converters and nonconverters are also compared using VRAM results.MethodsWe assessed the spatial memory in 20 normal controls, 20 aMCI, and 20 mild AD subjects using VRAM. The Mini-Mental State Examination, Clinical Dementia Rating scale, and other neuropsychological tests were given to the subjects in conjunction with the VRAM test. Scores in working memory errors and reference memory errors were compared among the three groups using repeated measures analysis of variance. In addition, aMCI patients were followed-up after 5 years and surveyed for AD conversion rate.ResultsIn AD patients, both spatial working and reference memory were impaired. However, in aMCI subjects, only spatial reference memory was impaired. Significant spatial reference memory impairment was found in the aMCI converter group when compared to the nonconverter group.ConclusionSpatial working memory is less impaired in aMCI while reference memory is similarly damaged in AD. In aMCI patients, more severe spatial reference memory deficit is a neuropsychological marker for AD conversion. VRAM may be well utilized in humans to assess spatial memory in normal aging, in aMCI, and in AD.

Predictors of virtual radial arm maze performance in adolescent Italian children

BackgroundComparisons between animal and human neurotoxicology studies are a foundation of risk assessment, but are hindered by differences in measured behaviors. The radial arm maze (RAM), a rodent visuospatial learning and memory task, has a computerized version for use in children, which may help improve comparisons between animal and human studies. ObjectiveTo describe the characteristics and correlates of the virtual radial arm maze (VRAM) in 255 children age 10–15 years from Italy. MethodsWe administered the VRAM using a laptop computer and measured children's performance using the latency, distance, and working/reference memory errors during eight trials. Using generalized linear mixed models, we described VRAM performance in relation to demographic factors, child activities, and several standard neuropsychologic tests (Italian translations), including the Conners Parent Rating Scales-Short Version (CPRS), California Verbal Learning Test (CVLT), Wechsler Intelligence Scales for Children, finger tapping speed, reaction time, and motor skills. ResultsChildren's VRAM performance tended to improve between trials 1 and 6 and then plateaued between trials 6 and 8. Males finished the task 14s faster (95% confidence interval [CI]: −20, −9) than females. Children who played 2+h of video games per day finished 16s faster (CI: −26, −6) and with 34% (CI: 5, 54%) fewer working memory errors than children who reported not playing video games. Higher IQ and better CVLT scores were associated with better VRAM performance. Higher cognitive/inattention CPRS scores were associated with more working (11%; CI: 1, 22) and reference memory errors (7%; CI: 1, 12). ConclusionsConsistent with animal studies, VRAM performance improved over the course of test trials and males performed better than females. Better VRAM performance was related to higher IQ, fewer inattentive behaviors, and better verbal memory. The VRAM may help to improve the integration and comparison between animal and epidemiological studies of environmental neurotoxicants.

A Virtual Radial Arm Maze for the Study of Multiple Memory Systems in a Functional Magnetic Resonance Imaging Environment

An increasing number of functional brain imaging studies are employing computer-based virtual reality (VR) to study changes in brain activity during the performance of high-level psychological and cognitive tasks. We report the development of a VR radial arm maze that adapts for human use in a scanning environment with the same general experimental design of behavioral tasks as that has been used with remarkable effectiveness for the study of multiple memory systems in rodents. The software platform is independent of specific computer hardware and operating systems, as we aim to provide shared access to this technology by the research community. We hope that doing so will provide greater standardization of software platform and study paradigm that will reduce variability and improve the comparability of findings across studies. We report the details of the design and implementation of this platform and provide information for downloading of the system for demonstration and research applications.

Spatial memory deficits in a virtual reality eight-arm radial maze in schizophrenia

Learning and memory impairments are present in schizophrenia (SZ) throughout the illness course and predict psychosocial function. Abnormalities in prefrontal and hippocampal function are thought to contribute to SZ deficits. The radial arm maze (RAM) is a test of spatial learning and memory in rodents that relies on intact prefrontal and hippocampal function. The goal of the present study was to investigate spatial learning in SZ using a virtual RAM. Thirty-three subjects with SZ and thirty-nine healthy controls (HC) performed ten trials of a virtual RAM task. Subjects attempted to learn to retrieve four rewards each located in separate arms. As expected, subjects with SZ used more time and traveled more distance to retrieve rewards, made more reference (RM) and working memory (WM) errors, and retrieved fewer rewards than HC. It is important to note that the SZ group did learn but did not reach the level of HC. Whereas RM errors decreased across trials in the SZ group, WM errors did not. There were no significant relationships between psychiatric symptom severity and maze performance. To our knowledge, use of a virtual 8-arm radial maze task in SZ to assess spatial learning is novel. Impaired virtual RAM performance in SZ is consistent with studies that examined RAM performance in animal models of SZ. Results provide further support for compromised prefrontal and hippocampal function underlying WM and RM deficits in SZ. The virtual RAM task could help bridge preclinical and clinical research for testing novel drug treatments of SZ.

Spatial memory deficits in a virtual radial arm maze in amnesic participants with hippocampal damage.

Extensive research with laboratory animals indicates that the hippocampus is crucial for the formation and use of spatial memory. Hippocampal lesions in rodents impair spatial memory on radial arm maze tasks. It is unknown whether amnesic patients with hippocampal damage would exhibit similar impairments on a virtual version of a radial arm maze. To evaluate the importance of the hippocampus in spatial learning and memory, we tested amnesic participants with hippocampal damage in a virtual radial arm maze environment. The virtual radial arm maze required participants to learn and remember 4 rewarded arms of 8 total arms. Spatial learning and memory were assessed using the participants' ability to use salient distal cues in the virtual room to remember the 4 rewarded arms. Amnesic participants' latencies were longer and distance traveled was greater to the rewarded arms compared with nonamnesic participants. Amnesic participants made more errors than nonamnesic participants by either entering nonrewarded arms or by revisiting previously entered arms. These data are analogous to previous animal research. Overall, the human hippocampus is necessary for spatial memory and navigation in a virtual radial arm maze task.

Spatial memory: A Rosetta stone for rat and human hippocampal discourse: Theoretical comment on Goodrich-Hunsaker and Hopkins (2010).

The article by Goodrich-Hunsaker and Hopkins (2010, this issue) takes up an important place among in the recent contributions on the role of the hippocampus in memory. They evaluate the effect of bilateral damage to the hippocampus on performance by human participants in a virtual 8-arm radial maze. The hippocampal damage appears to be highly selective and nearly complete. Exactly as with selective hippocampal damage in rats, the human participants showed a deficit in accurately choosing rewarded versus never-rewarded arms and a deficit in avoiding reentering recently visited arms. The results are triply significant: (1) They provide good support for the idea that the wealth of neurobiological information, from network to synapse to gene, on spatial memory in the rat may apply as a whole to the human hippocampal memory system; (2) They affirm the utility of human virtual task models of rat spatial memory tasks; (3) They support one interpretation of the dampening of the hippocampal functional MRI (fMRI) blood oxygen level-dependent (BOLD) signal during performance of the virtual radial arm maze observed by Astur et al. (2005).

FMRI Hippocampal Activity During a VirtualRadial Arm Maze

Numerous studies have shown that the hippocampus is critical for spatial memory. Within nonhuman research, a task often used to assess spatial memory is the radial arm maze. Because of the spatial nature of this task, this maze is often used to assess the function of the hippocampus. Our goal was to extrapolate this task to humans and examine whether healthy undergraduates utilize their hippocampus while performing a virtual reality version of the radial arm maze task. Thirteen undergraduates performed a virtual radial arm maze during functional magnetic resonance imaging. The brain maps of activity reveal bilateral hippocampal BOLD signal changes during the performance of this task. However, paradoxically, this BOLD signal change decreases during the spatial memory component of the task. Additionally, we note frontal cortex activity reflective of working memory circuits. These data reveal that, as predicted by the rodent literature, the hippocampus is involved in performing the virtual radial arm maze in humans. Hence, this virtual reality version may be used to assess the integrity of hippocampus so as to predict risk or severity in a variety of psychiatric disorders.

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.