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Effects of Acrophobic Fear and Trait Anxiety on Human Behavior in a Virtual Elevated Plus-Maze


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The Elevated Plus-Maze (EPM) is a well-established apparatus to measure anxiety in rodents, i.e., animals exhibiting an increased relative time spent in the closed vs. the open arms are considered anxious. To examine whether such anxiety-modulated behaviors are conserved in humans, we re-translated this paradigm to a human setting using virtual reality in a Cave Automatic Virtual Environment (CAVE) system. In two studies, we examined whether the EPM exploration behavior of humans is modulated by their trait anxiety and also assessed the individuals’ levels of acrophobia (fear of height), claustrophobia (fear of confined spaces), sensation seeking, and the reported anxiety when on the maze. First, we constructed an exact virtual copy of the animal EPM adjusted to human proportions. In analogy to animal EPM studies, participants (N = 30) freely explored the EPM for 5 min. In the second study (N = 61), we redesigned the EPM to make it more human-adapted and to differentiate influences of trait anxiety and acrophobia by introducing various floor textures and lower walls of closed arms to the height of standard handrails. In the first experiment, hierarchical regression analyses of exploration behavior revealed the expected association between open arm avoidance and Trait Anxiety, an even stronger association with acrophobic fear. In the second study, results revealed that acrophobia was associated with avoidance of open arms with mesh-floor texture, whereas for trait anxiety, claustrophobia, and sensation seeking, no effect was detected. Also, subjects’ fear rating was moderated by all psychometrics but trait anxiety. In sum, both studies consistently indicate that humans show no general open arm avoidance analogous to rodents and that human EPM behavior is modulated strongest by acrophobic fear, whereas trait anxiety plays a subordinate role. Thus, we conclude that the criteria for cross-species validity are met insufficiently in this case. Despite the exploratory nature, our studies provide in-depth insights into human exploration behavior on the virtual EPM.
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Effects of Acrophobic Fear and Trait
Anxiety on Human Behavior in a Virtual
Elevated Plus-Maze
Octavia Madeira
*, Daniel Gromer
, Marc Erich Latoschik
and Paul Pauli
Department of Psychology I, Biological Psychology, Clinical Psychology and Psychotherapy, University of Würzburg, Würzburg,
Department of Human-Computer-Interaction, University of Würzburg, Würzburg, Germany,
Center of Mental Health,
University of Würzburg, Würzburg, Germany
The Elevated Plus-Maze (EPM) is a well-established apparatus to measure anxiety in
rodents, i.e., animals exhibiting an increased relative time spent in the closed vs. the open
arms are considered anxious. To examine whether such anxiety-modulated behaviors are
conserved in humans, we re-translated this paradigm to a human setting using virtual
reality in a Cave Automatic Virtual Environment (CAVE) system. In two studies, we
examined whether the EPM exploration behavior of humans is modulated by their trait
anxiety and also assessed the individualslevels of acrophobia (fear of height),
claustrophobia (fear of conned spaces), sensation seeking, and the reported anxiety
when on the maze. First, we constructed an exact virtual copy of the animal EPM adjusted
to human proportions. In analogy to animal EPM studies, participants (N30) freely
explored the EPM for 5 min. In the second study (N61), we redesigned the EPM to make
it more human-adapted and to differentiate inuences of trait anxiety and acrophobia by
introducing various oor textures and lower walls of closed arms to the height of standard
handrails. In the rst experiment, hierarchical regression analyses of exploration behavior
revealed the expected association between open arm avoidance and Trait Anxiety, an
even stronger association with acrophobic fear. In the second study, results revealed that
acrophobia was associated with avoidance of open arms with mesh-oor texture, whereas
for trait anxiety, claustrophobia, and sensation seeking, no effect was detected. Also,
subjectsfear rating was moderated by all psychometrics but trait anxiety. In sum, both
studies consistently indicate that humans show no general open arm avoidance analogous
to rodents and that human EPM behavior is modulated strongest by acrophobic fear,
whereas trait anxiety plays a subordinate role. Thus, we conclude that the criteria for cross-
species validity are met insufciently in this case. Despite the exploratory nature, our
studies provide in-depth insights into human exploration behavior on the virtual EPM.
Keywords: elevated plus-maze, EPM, anxiety, virtual reality, translational neuroscience, acrophobia, trait anxiety
The Elevated Plus-Maze (EPM) is a widely used and well-accepted apparatus to measure anxiety in
rodents. Its advantage is that it assesses natural behavior and therefore does not require a previous
conditioning process or other preparations that might interfere with experimental variables
distorting behavioral outcomes. The EPM, with its open and closed arms, comprises a conict
Edited by:
Barbara Rothbaum,
Emory University, United States
Reviewed by:
Mark Steven Burton,
Emory University, United States
Brian Dixon,
New Zealand Psychological Society,
New Zealand
Katarzyna Wyka,
City University of New York,
United States
Octavia Madeira
Specialty section:
This article was submitted to
Virtual Reality in Medicine,
a section of the journal
Frontiers in Virtual Reality
Received: 29 November 2020
Accepted: 18 February 2021
Published: 20 April 2021
Madeira O, Gromer D, Latoschik ME
and Pauli P (2021) Effects of
Acrophobic Fear and Trait Anxiety on
Human Behavior in a Virtual
Elevated Plus-Maze.
Front. Virtual Real. 2:635048.
doi: 10.3389/frvir.2021.635048
Frontiers in Virtual Reality | April 2021 | Volume 2 | Article 6350481
published: 20 April 2021
doi: 10.3389/frvir.2021.635048
situation as rodents, on the one hand, prefer dark and enclosed
arms to avoid potential predators, but, on the other hand, are
naturally prone to engage actively in exploration behavior
towards novel stimuli (Barnett, 2017). Following-up a study of
Montgomery (1955),Pellow et al. (1985) developed an elevated
plus-shaped platform with two closed and two open arms. They
examined rats and observed that anxiolytic drugs (e.g., diazepam)
signicantly increased open arm entries and open arm
exploration time, whereas anxiogenic medication induced
opposite effects.
These seminal ndings strongly suggest that rodents
movement patterns in the EPM are reliable and valid
indicators of general anxiety. Based on these ndings and
numerous follow-up studies, the EPM is now considered a
standard test of anxiety in rodents and routinely used in
preclinical translational research, i.e., for drug or target gene
testing. For instance, the anxiolytic effect of benzodiazepines was
detected in rodents by using the EPM, and this is why diazepam is
now an established anxiolytic drug within the human clinical
setting until today.
One way to examine the translational validity of animal tests is
re-translation, i.e., the development of human analogs to animal
paradigms (Kirlic et al., 2017). Such re-translation proved to be
successful for several cognitive tasks, e.g., monetary- or
punishment-based conict paradigms. First attempts to re-
translate animal paradigms assessing anxiety-related behavior
proved to be successful too (Kirlic et al., 2017). An advantage
of such re-translational human tasks is that they assess both
behaviors analogous to animal paradigms and verbal responses
which may help to validate the paradigm. For instance, Aupperle
et al. (2011) re-translated an approach-avoidance conict task
frequently used in anxiety researches in animals to humans and
found that either conict or reward approach is associated with
certain aspects of anxiety sensitivity including gender. Walz et al.
(2016) re-translated the open eld test, which is frequently used
in rodents to measure anxiety. In rodents, increased thigmotaxis
during exploration of the open eld, i.e., staying close to the open
elds wall, is interpreted as an indicator of animal anxiety (Gould
et al., 2009). In analogy, Walz et al. asked their participants to
freely explore an open eld, i.e., a soccer eld surrounded by trees
and bushes (Walz et al., 2016). Results revealed that individuals
reporting agoraphobic fear or high levels of anxiety sensitivity, a
known risk factor for agoraphobia and panic disorder (Hofmann
et al., 2009), displayed an increased thigmotaxis, i.e., they moved
along the walls of the open eld more and avoided its center for a
longer time. These results validate the open eld animal studies
because they corroborate an association between reported level of
anxiety and open eld behavior (Grillon and Ernst, 2016).
Interestingly, these ndings also imply that characteristic
ethologic patterns in rodents are conserved in humans also
and seem to play a signicant role in human anxiety.
However, there still exists a scientic gap regarding the cross-
species translational validity of these anxiety models. It is often
criticized that they lack predicational clinical value (Grillon and
Ernst, 2016). As a result, there is a paucity in developing new
anxiolytic agents or even therapeutic approaches based on these
preclinical classictests (Griebel and Holmes, 2013;Grillon
et al., 2019). At the same time, the (re-) translation of
Pavlovian fear conditioning already provided numerous
insights to fear-related issues in humans while maintaining
methodological comparability and providing cross-species
validity for years by now (Lonsdorf et al., 2017;Haaker et al.,
2019). Consequently, closing this gap by testing cross-species
validity could similarly set new impulses in both human and
animal research.
Trait anxiety is an enduring and generalized predisposition to
react with fear in potentially threatening or ambiguous situations
(Spielberger, 1966;Spielberger, 2013). It was found that
individuals with high trait anxiety scores are prone to develop
an anxiety disorder over their lifetime (Hofmann et al., 2009;
Gallagher et al., 2014;Kindt and Soeter, 2014). On a behavioral
level, high trait anxiety manifests in harm avoidance,
i.e., avoidance behavior (Maner and Schmidt, 2006). From a
clinical point of view, ndings on emotional and behavioral
mechanisms of subthreshold anxiety disorders (i.e., not yet
pathologic but close to meet diagnostic criteria) imply that it
can be similarly impairing as a fully developed pathologic
condition (Carter et al., 2001;Karsten et al., 2011). In light of
this scientic paucity, the human virtual EPM might be a
promising tool to investigate behavioral movement patterns
associated with trait anxiety and contribute to a translational
understanding of anxiety mechanisms. Moreover, the insights on
movement behavior related to trait anxiety might complement
current research methods such as self-report data and
physiological measures.
Virtual reality (VR) offers promising advancement in the
development of human analogs to animal paradigms. VR is a
computer-generated environment simulating sensory input,
mostly visual and auditory, in which the participant is
immersed, feels present, and can behave and interact with the
environment (see Sanchez-Vives and Slater, 2005, for a discussion
of its use in animal and human research; Bohil et al., 2011). For
instance, Dobricki and Pauli (2016) used virtual reality to assess
body-environment interactions and emotions in a virtual height
scenario in humans, and Gromer et al. (2019) systematically
examined the emotional responses of humans confronted with
virtual heights.
Biedermann et al. (2017) adopted a mixed virtual reality design
to develop a human elevated plus-maze (EPM) paradigm (see also
Madeira et al., 2017). Their virtual EPM consisted of a real-world
wooden maze providing haptic feedback combined with a virtual
maze providing visual feedback presented with a head-mounted
display (HMD). The maze was placed on a virtual rocky
mountain surrounded by water with two opposite arms, and
the center of the maze was surrounded by rocks while the other
two arms reached out over the water at 55 m height. Results
revealed that participants avoided open arms and reported more
anxiety on these arms. Signicantly, open arm avoidance was
positively associated with acrophobic fear but not with anxious
temperament (STAI) or social anxiety and negatively associated
with sensation seeking. These opposing associations of
acrophobia and sensation seeking with open arm avoidance
behavior correspond with assumptions that both constructs
are related to opposing motivational systems (Boecker and
Frontiers in Virtual Reality | April 2021 | Volume 2 | Article 6350482
Madeira et al. Exploration in a Virtual EPM
Pauli, 2019). Finally, anxioselective drugs were found to decrease
and increase open arm avoidance as expected. While this study
has several strengths, it also has important limitations. First, walls
surround the closed arms of the rodent EPM, while the closed
arms of the designed human EPM had no walls. Instead, the
humans stood in both conditions on real wooden planks with
tangible borders that in one condition were perceived visually as
lying on rocky ground and in the other condition as high above
the water. Second, the used HMD caused a dissociation of haptic
from visual feedback as it precluded the perception of the own
body including the feet. In consequence, participantsmovement
on the maze might have been unnatural requiring increased
attention on the feet and oor, and this might have
exaggerated the height perception and in consequence feelings
of insecurity and arousal especially on the openarms. Finally,
the rodent EPM behavior was found to be independent of height
(Treit et al., 1993) and is therefore considered as a measure of
general anxiety, e.g., it correlates with other anxiety measures like
the open eld test or the dark-light box (Ramos et al., 2008). In
contrast, the observed human EPM behavior was related to fear of
height, but not trait anxiety. In sum, the authors conclusion that
the identical outcome parameters in the human and rodent EPM
facilitate translational research across species(Biedermann et al.,
2017 p8) might be premature.
Here, we examined the construct validity of a virtual EPM
to assess the anxiety in humans in two studies. However, in
contrast to Biedermann et al. (2017), we used a 5-sided Cave
Automatic Virtual Environment (CAVE) instead of an HMD
to present the virtual environment with the advantage that it
allows participants to see the own body while simultaneously
being able to walk naturally. In our opinion, this better allows
free exploration comparable to a rodent EPM. Moreover, a
CAVE system allows a bigger eld of view and triggers less
simulatorsicknessthananHMD(Rebenitsch and Owen,
2016), which might be a moderating variable for anxiety if
using VR scenarios with height situations. Also, we decided to
stick to the animal EPM design as close as possible and
maintain the experimental procedure. Thus, the typical
animal EPM (Komada et al., 2008)wasenlargedtohuman
proportions, and participants were asked to freely explore
this environment while their behavior was recorded. In
addition, we used ratings to assess anxiety at different
EPM locations, and questionnaires were used to evaluate
trait anxiety, acrophobic fear, and sensation seeking. Based
on the ndings in the rst study and on participants
feedback, we decided to modify the virtual EPM in a
second study and re-tested our hypotheses. Assuming that
a human EPM allows behavioral assessment of anxiety in
humans in analogy to rodent studies, we hypothesized that 1)
humans exhibit a general open arm avoidance and that 2)
their level of trait anxiety is positively associated with open
arm avoidance and fear ratings on open arms. Alternatively,
we speculated following Biedermann et al. (2017) that 3)
acrophobic fear is positively associated with open arm
avoidances and fear ratings on open arms and that 4)
sensation seeking is negatively associated with open arm
A total of 33 individuals, most of them students, were recruited
via email and yers and received either 12 EUR or course credit
for participation. Due to technical problems during data
recording, three participants were excluded from analysis
resulting in a nal sample of 30 individuals (10 males and 20
females) with a mean age of M21.93 (SD 2.85).
The study was carried out following the recommendations of the
Declaration of Helsinki and the Ethical Guidelines of the German
Psychological Society. The Ethics Committee of the Department of
Human-Computer-Interaction of the University of Würzburg
provided ethical approval for the protocol.
Assessments were conducted in the 5-sided 3D Multisensoric
PsyCave Laboratory of the Department of Psychology I of the
University of Würzburg sized 4 ×3×2.95 m. The visual
simulations on the ve canvases (4 walls plus oor) were
presented via six projectors (NW-7, BARCO, Kuurne, Belgium)
with a resolution of 1920 ×1,200 pixels each and connected to two
computers per projector (Intel Core i7-2600K; 8GB RAM; Nvidia
Geforce GTX 580; OCZ Vertex2 SSDs). Participants wore passively
color-ltering glasses (Intec Premium, Intec, Ulm, Germany) for
stereoscopic effect. Auditory instructions were given via a 7.1
surround sound system (CANTON, Weilrod, Germany).
Motion tracking was recorded with four LED infrared cameras
installed on top of the CAVE canvases (PhaseSpace Impulse,
PhaseSpace Inc, San Leandro, CA, United States). A wireless
Xbox 360 controller (Microsoft, Redmond, WA, United States)
was used for navigation over long distances. Walking by foot was
possible within the space of the CAVE.
The experimental virtual environment was set up with a self-
made modication of the rst-person shooter game, Half Life 2:
Deathmatch(Valve, Bellevue, Washington, United States) based
FIGURE 1 | Screenshot of the virtual Elevated Plus-Maze. Center area
marks the starting point of the exploration phase lasting for 5 min; starting
gaze direction was randomized across participants.
Frontiers in Virtual Reality | April 2021 | Volume 2 | Article 6350483
Madeira et al. Exploration in a Virtual EPM
on Source Engine 2007. The experimental procedure was
managed by the CS-Research 5.6 software (VTplus, Würzburg,
Germany; see for detailed information)
(cf. Kinateder et al., 2014).
Virtual Scenario
The virtual human EPM was identical to the animal EPM but
adjusted to human proportions. Thus, the plus-shaped platform
had a height of 10 m with four maze arms arranged orthogonally
to each other, each 11 m long and 3 m wide. To control for
environmental cues that might interfere with exploration
behavior and to exacerbate height estimation for participants,
platform pillars were surrounded by fog. All arms had a solid
ground texture. The two open arms were free of any visible
barrier, whereas the two closed arms had wooden-textured walls
of 3 m in height (see Figure 1). Please note that we were unaware
of Biedermann et al.s (2017) design as we conducted the study
prior to their publication (Madeira et al., 2017).
Tracking Data
The participantspositioning data within the virtual scenario
were tracked continuously with a sample rate of 60 Hz. Based on
this positioning data, we calculated the behavioral parameters
during the 5 min of exploration time: time spent on open and
closed arms, distance walked on open and closed arms, and total
walking distance. The center area was dened as a transition zone
and therefore excluded from analyses (Hogg, 1996).
Anxiety and Presence Ratings
After the free exploration and fading out of the virtual
environment, participants were teleported to the center area of
the maze again and asked to walk forward to a green footprint on
one of the arms and then rate the anxiety experienced on that
position with Subjective Units of Discomfort Scales (SUDS)
ranged from 0 to 100. Footprint markers were used to ensure
consistency in position for ratings across participants. These
ratings were assessed on one open and one closed arm
selected randomly. After the anxiety rating trial, the feeling of
presence was also assessed with the question To which extent do
you feel present in the VE, i.e., as if you were really there?on a
scale ranging from 0 to 100 (Bouchard et al., 2008).
Means and standard deviation of anxiety and presence ratings
are summarized in supplementary materials (Supplementary
Table S1).
Psychometric Questionnaires
The German version of the State-Trait-Anxiety Inventory (STAI;
Laux et al., 1981) is a self-report questionnaire assessing state
anxiety with 20 items (e.g., I am nervous.) rated on a scale from
1(not at all)to4(very much) and assessing trait anxiety with
20 items (e.g., I am happy.) rated on a scale from 1 (almost
never)to4(almost always). Sum scores range from 20 to 80.
The Acrophobia Questionnaire (AQ; Cohen, 1977) is a 40-item
self-report questionnaire measuring fear of heights (acrophobia)
on two subscales. The Anxiety subscale assesses fear towards
common height situations, e.g., take a ride on the Ferris wheel,
with seven-point Likert scales from 0 (not anxious at all)to7
(extremely anxious), resulting in a sum score range of 0120. The
Avoidance subscale asks to rate the same items on a three-point
Likert scale from 0 (would not avoid)to3(would not do it under
any circumstances), thus assessing behavioral avoidance in
response to height situations with a sum score ranging from 0
to 40. Hüweler et al. (2009) and Diemer et al. (2016) already applied
the AQ to test the acrophobic symptoms in virtual environments.
The German version of the Sensation-Seeking Scale
(Beauducel et al., 2003) assesses the individuals optimal levels
of stimulation and arousal with 40 items with a forced-choice
design. Participants are asked to choose one of two statements
that best reect their personal beliefs (e.g., I get bored seeing the
same old faces.vs. I like the comfortable familiarity of everyday
friends.). The SSS-V has four subscales measuring Thrill and
Adventure Seeking,”“Disinhibition,”“Experience Seeking,and
Boredom Susceptibility.The total score ranging from 0 to 40
represents the sum score of all subscales. Due to technical
problems, 18 participants were unable to answer the last ve
items of the SSS-V. To complete the data set, missing items were
estimated by means of other items on each subscale and then
The Igroup Presence Questionnaire (IPQ; Schubert et al., 2001)
consists of 14 items and evaluates the feeling of presence within the
VR scenario as a self-report. Spatial Presence (e.g., Somehow I felt,
that the virtual world surrounded me.), Involvement (e.g., Iwas
not aware of my real environment.), and Experienced Realism
(e.g., How real did the virtual world seem to you?) are measured
on a seven-point Likert Scale. Additionally, a general item assesses
the sense of being there.All subscale scores range from 0 to 6. The
IPQ has been validated for various types of virtual environments
(see for further details).
Questionnaire scores (means and standard deviations) are
displayed in the supplementary materials section
(Supplementary Table S1).
After signing the written informed consent, participants reported
sociodemographic data and then completed the questionnaires
(see above, except IPQ). Then, they entered the CAVE and
completed a virtual tutorial to adapt to navigation and audio
The actual experiment started by teleporting participants to
the center area of the EPM with the instruction to explore the
environment for a total of 5 min freely. Starting gaze in the
direction of one of the arms was randomized across participants.
After 5 min, anxiety and presence were assessed on an open arm
and a closed arm as described above. Finally, participants
completed a questionnaire evaluating the sensation of presence
throughout the VR exposure (IPQ).
Statistical Analyses
Statistical analyses were performed with R and SPSS (RCoreTeam,
2013;IBM Corp., 2016). Exploration behavior was rst analyzed
regarding differences between open vs. closed arms with dependent
samples t-tests. In addition, distance walked on the various maze
areas was analyzed via dependent samples t-test. Second,
associations between exploration behavior and psychometric
Frontiers in Virtual Reality | April 2021 | Volume 2 | Article 6350484
Madeira et al. Exploration in a Virtual EPM
questionnaires were analyzed with correlations; due to multiple
testing, Bonferroni corrections were applied. Third, hierarchical
regression analyses were performed to further evaluate the
inuences on open arm activity by those psychometric
measures found to correlate with open arms avoidance. Finally,
the difference in anxiety ratings between arms was analyzed with a
t-test, and correlations between anxiety ratings on open and closed
arms with psychometric measures were performed.
Exploration Behavior
Analyses of the motion tracking data revealed that participants
spent overall more time on the open (M151.52, SD 58.96)
compared to the closed (M60.54, SD 33.39) arms, t
6.36, p<0.001,d1.14 (see Figure 2). On average, subjects
walked a total of 191.72 m (SD 44.85) throughout the
exploration phase and 51.89 (SD 27.57) and 99.05 (SD
44.77) meters on the closed and open arms, respectively. The
difference of walking distance between the two arms was
signicant, t
−4.52, p<0.001, d−0.83, indicating that
subjects were more active on the open than on the closed arms.
Correlational analyses (see Table 1) revealed that both trait
anxiety and acrophobia (both subscales) were negatively
associated with the time spent on the open arms. In contrast,
the SSS-V Total score was positively correlated with time spent on
open arms. However, after applying Bonferroni correction due to
multiple testing (p0.0063), only the negative correlation
between AQ Anxiety and time on open arms (r
p0.005) and the negative correlation between the SSS-V and
time spent on closed arms (r
−0.54,p0.002) remained
signicant, suggesting that in humans, acrophobic fear is
associated with open arm avoidance, whereas proneness to
sensation seeking is linked to closed arm avoidance.
Correlation analyses of walking distances and psychometrics
revealed no effect (all pvalues >0.05).
A subsequent three-stage hierarchical multiple regression for
time spent on open arms as the dependent variable and trait
measures as predictors was conducted to evaluate the EPM
behavior further. Predictors were selected based on the results
of correlational analyses (see above), variables were added based
on our hypotheses and correlations with the dependent variable.
The test for multicollinearity indicated very low levels of
multicollinearity, and other assumptions for implementation of
regression models were not violated. In the rst step, trait anxiety
was included to test for our main hypothesis. In a second step, the
Anxiety subscale of the AQ was added; the AQ Avoidance
subscale was deliberately excluded due to the strong
correlation between both measures (r
0.86, p<0.001)
suggesting multicollinearity. In the third step, the total score
of the SSS-V was included.
Comparison of all models via adjusted R
score (see Table 2)
indicated the second model to be best t to explain time spent on
open arms, R
0.28; F
6.307, p0.006. In this model, fear
of heights (AQ Anxiety) but not trait anxiety (STAI) signicantly
FIGURE 2 | Heatmap of motion tracking data of study 1 using every fth
recorded data point during the exploration phase (N30). Areas with lighter
colors depict areas with greater activity. The center area is dened as
transition zone, thus excluded from analyses.
TABLE 1 | Results of correlation analyses of time spent on open or closed arms
and psychometrics.
Time spent on open
Time spent on closed
Trait 0.38 0.043 0.17 0.371
Anxiety 0.51* 0.005 0.27 0.163
Avoidance 0.42 0.020 0.38 0.037
Total 0.36 0.048 0.54* 0.002
Note: *Bonferroni-corrected to p <0.0063; AQ, Acrophobia Questionnaire; STAI, State-
Trait-Anxiety Inventory; SSS-V, Sensation Seeking Scale.
TABLE 2 | Summary of hierarchical regression analyses for psychometric
questionnaire scores predicting time spent on open arms of the virtual EPM in
study 1.
Step 1 0.13 319.96 0.033*
Intercept 264.64 53.03 <0.001**
STAI Trait 3.43 1.53 0.40 0.033*
Step 2 0.28 303.40 0.006*
Intercept 258.70 48.24 <0.001**
STAI Trait 2.37 1.45 0.28 0.114
AQ Anxiety 1.61 0.63 0.43 0.017*
Step 3 0.26 305.29 0.018*
Intercept 250.91 75.32 0.003*
STAI Trait 2.36 1.48 0.28 0.158
AQ Anxiety 1.54 0.80 0.42 0.066
SSS-V Total 0.28 6.38 0.03 0.892
Note: *p <0.05, **p <0.01; R
adjusted R
; AQ, Acrophobia Questionnaire; STAI,
State-Trait-Anxiety Inventory; SSS-V, Sensation Seeking Scale.
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Madeira et al. Exploration in a Virtual EPM
explained exploration behavior suggesting that, in humans,
avoidance of open arms is primarily motivated by fear of heights.
Anxiety Ratings
T-test for dependent samples revealed signicantly higher
anxietyratingonopen(M17.30, SD 20.38) vs. closed
arms (M4.77, SD 6.06), t
3.717, p<0.001. Further
analyses of correlations between psychometrically assessed
traits and anxiety ratings on open and closed arms revealed a
signicant positive correlation (p-value was Bonferroni-
corrected to 0.0063) between anxiety rating on open arms
with the AQ Anxiety (r
0.53, p 0.003) and avoidance
subscales (r
0.62, p<0.001) (see Table 3). Thus, anxiety
ratings on open arms increased in line with acrophobic anxiety
and avoidance, whereas trait anxiety, including sensation
seeking, did not seem to be notably linked to anxiety ratings
on the maze.
Correlation of Trait Anxiety Measures
STAI-Trait and AQ subscale scores were uncorrelated (Anxiety:
0.29,p0.139; Avoidance: r
0.21, p 0.268), while
both AQ subscales were signicantly negatively correlated with
the SSS-V score (all ps <0.05). Overview on questionnaire
intercorrelations is provided in supplementary materials
(Supplementary Table S2).
Contrary to our hypothesis, we found a general open arm
preference in this study. In line with our hypothesis, we found
that open arm avoidance is associated with trait anxiety.
However, our results revealed that avoidance of open arms
was best predicted by acrophobic fear. Additionally,
correlations between fear ratings on open arms and
acrophobic fear and acrophobic avoidance suggest that
participants with an increased trait of acrophobia experienced
more fear on the open arms and therefore exhibited increased
avoidance of them. The observed negative correlation between
acrophobic fear and sensation seeking may explain why we
also found some evidence that sensation seeking is associated
with decreased time spent on closed arms and less fear on open
arms, although not signicant. These ndings replicate the
associations found by Biedermann et al. (2017), who reported
similar relationships between open arm avoidance and
acrophobic fear including sensation seeking, which is
remarkable as the two virtual EPMs differed considerably in
design. These concordant results further validate that human
behavior in a virtual EPM measures anxiety, most likely
acrophobic fear.
Based on the ndings in study 1, we speculate that an association
between EPM behavior and trait anxiety might exist but was
overshadowed by a rather strong effect of acrophobic fear. Also,
we found no general open arm avoidance as observed in animal
studies. We think that this is due to the direct translation of the
rodent EPM with closed arms with rather high walls. This
restricted the view considerably and perhaps induced some
claustrophobic fear, as reported by some participants post-
experimentally, which might have reversed the effect and led
to closed arm avoidance. Therefore, we modied the virtual EPM
into a more human-adapted version and re-tested our
The nal sample of 61 participants (20 males, 41 females, mostly
students) had a mean age of M23.21 years (SD 3.74). Seven
examined participants were excluded due to technical problems
or premature completion of the experimental procedure.
Recruitment was performed via an online platform, yers, and
emails. Participation was either monetary rewarded (12)or
compensated with course credit.
Participants were selected via online screening. For this, we
extracted six items of the AQ and the Claustrophobia
Questionnaire (CLQ; Radomsky et al., 2001), respectively. To
assess subjectslevel of acrophobia, they were asked to rate their
level of fear when confronted with six typical height situations
(corresponds with AQ Anxiety) on a ve-point Likert scale and
the extent of avoidance behavior towards them (corresponds with
AQ avoidance) on a three-point Likert scale. For claustrophobic
fear, the six selected items were rated on a ve-point Likert scale.
On a scale of sum scores ranging from 6 to 24 for acrophobic fear
(but not avoidance) including claustrophobia, only participants
scoring 12 or less, respectively, were invited. To examine
agoraphobic fear, we asked whether the subject ever
experienced a panic attack. If yes, we wanted to know whether
one or more of the listed situations, e.g., wide-open places, pulled
from the diagnostical criteria of the ICD-10 (Dilling and
Freyberger, 2012), are avoided out of fear of experiencing
another panic attack. Participants were excluded if
agoraphobic tendencies were present.
Additionally, estimation of the STAI Trait score was
conducted via four items with a four-point Likert scale but not
considered for inclusion.
TABLE 3 | Results of correlation analyses of anxiety ratings with psychometric
Anxiety ratings on
open arms
Anxiety ratings on
closed arms
Trait 0.16 0.405 0.42 0.023
Anxiety 0.53* 0.003 0.32 0.095
Avoidance 0.62* <0.001 0.27 0.156
Total 0.45 0.013 0.20 0.298
Note: Bonferroni-corrected to p <0.0063; AQ, Acrophobia Questionnaire; STAI, State-
Trait-Anxiety Inventory; SSS-V, Sensation Seeking Scale.
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Madeira et al. Exploration in a Virtual EPM
The study was carried out per the recommendations of the
Declaration of Helsinki and the Ethical Guidelines of the German
Psychological Society. The protocol was approved by the Ethics
Committee of the Institute of Human-Computer-Interaction. All
participants gave written informed consent.
Apparatus and Virtual Scenario
The apparatus was similar to that of study 1. The virtual EPM
scenario was modied as follows. Closed arms came with
handrails instead of walls with a height of 1.3 m, referring to
the ofcial German standard for the height of handrails. The
arms width and length were reduced to 1.5 and 10 m,
respectively. Finally, we changed the arms oor with one open
and one closed arm having solid metal oors (as in study 1) and
one open and one closed arm having see-through metal grid
oors; the center area of the maze was divided diagonally and had
both surface textures (see Figure 3). Please note that we were
unaware of Biedermann et al.s (2017) design as we conducted the
study prior to their publication (Madeira et al., 2017).
Tracking Data
Similar to study 1, positioning data within the virtual scenario
were tracked continuously with a sample rate of 60 Hz. For this
study, we calculated spent time and walked distance on each arm
individually to take the various arm types (open/closed) and oor
textures (solid/grid) into account. Again, we calculated the total
walked distance. The center area was dened as a transition zone
and therefore excluded from analyses (Hogg, 1996).
Procedure and Questionnaires
The experimental procedure was mostly similar to that of study 1,
with two exceptions. First, the Claustrophobia Questionnaire was
added and completed before the experiment started. Second,
anxiety ratings after the exploration trial were registered on all
four arms in a randomized sequence.
The German version of the Claustrophobia Questionnaire
(CLQ; Radomsky et al., 2001) evaluates fear of conned spaces
with overall 26 items assessing fear of suffocation (SS; 14 items,
e.g., swimming with a nose clip) and fear of restriction (RS; 12
items, e.g., wear handcuffs for 15 min) with ve-point Likert
scales from 0 (not anxious at all)to4(extremely anxious).
Sum score of the SS scale ranges from 0 to 56, whereas sum score
of the RS vary between 0 and 48. The total questionnaire score
consists of the sum score of the two subscales and ranges from 0
to 104.
A summary of questionnaire scores, exploration, and rating
data are displayed in supplementary materials (see
Supplementary Table S3).
Statistical Analyses
First, differences between time spent and walking distances on
EPM arms were analyzed with a 2 ×2 repeated measure ANOVA
with the within-subject factor arm type (open vs. closed) and
oor texture (solid vs. grid). Second, associations between
exploration behavior and psychometric questionnaires were
analyzed with correlations; due to multiple testing, Bonferroni
corrections were applied. Third, hierarchical regression analyses
were performed to further evaluate inuences on open arms
avoidance by those psychometric measures found to correlate
with open arms avoidance before. Finally, differences between
anxiety ratings on arms were analyzed with a 2 ×2 repeated
measures ANOVAs with the within-subjects factors arm type
(open vs. closed) and oor texture (solid vs. grid) and
correlations were calculated to analyze associations between
anxiety ratings on open and closed arms with psychometric
Exploration Behavior
Analyses of the motion tracking data (see Figure 4B) with an
ANOVA with the within-subjects factors arm type (open vs.
closed) and oor texture (solid vs. grid) revealed no signicant
main or interaction effects (all pvalues >0.05), hence indicating
no general preference of arm type or oor texture (see Figure 4).
Walking distance was averaged at 62.37 (SD 28.54) meters for
closed grid arm, 53.68 (SD 22.56) meters for closed solid, 44.47
(SD 24.12) meters for open grid, and 47.19 (SD 18.50) meters
for open solid arm, respectively. In addition, the mean of total
walking distance was M194.43 (SD 49.89). Statistical
comparison of walking distances with an ANOVA for within-
subject factor arm type and oor texture revealed a signicant
main effect for arm type, F
4.384, p0.041, η
0.068, and a
signicant interaction effect,F
5.621, p0.021, η
No signicant effect for oor type was found, F
p0.387, η
0.012.Bonferroni-corrected post hoc t-tests
for paired samples (p0.008) revealed a signicant difference
between walking distance on closed and open arm with solid
oor, t
−3.33, p0.002.
In sum, no general arm preference was observed, and walking
distances differed between open and closed arms with solid oor
but not between open and closed arms with grid oor or oor
textures in general.
Correlational analyses (see Table 4) revealed that increase in
AQ Anxiety and AQ Avoidance was associated with less time on the
open arm with grid oor (Anxiety: r
−0.36, p0.004;
FIGURE 3 | Screenshot of the virtual EPM used in the second study.
Walls on closed arms were lowered to handrail level and oor texture was
modied to consist of see-through mesh and solid metal oor.
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Madeira et al. Exploration in a Virtual EPM
Avoidance: r
-0.40, r0.001). Somewhat unexpected are the
observations that trait anxiety was associated with more time on the
open arm with grid oor (r
0.30, p0.021) and less time on the
closed arm with grid oor (r
−0.25, p0.05). No effect for
claustrophobic fear was detected. However, after Bonferroni
correction (p0.0025), only the negative correlation between
AQ Avoidance and time spent on the open grid oor arm
remained signicant (p0.0013). These ndings corroborate
study 1 and emphasize the importance of height perception for
human EPM behavior, whereas trait anxiety and claustrophobia
either play a subordinate or no role.
Moreover, a negative correlation (Bonferroni-corrected to p
0.003) was found between walking distance on open arm with
grid oor texture and AQ Avoidance, r
A subsequent four-step hierarchical multiple regression
analysis was conducted to determine predictors for time spent
on open arms irrespective of oor texture, similar to study 1. Only
low levels of multicollinearity were present, and there was no
violation of relevant assumptions for regression analyses. The
predictors selected based on the correlational analyses and study
1ndings were consecutively included in the model, i.e., trait anxiety,
fear of height (AQ Anxiety), and sensation seeking (SSS-V Total). To
estimate the inuence of claustrophobia, we added the CLQ total
score in the fourth step.
The best-tting model according to adjusted R
score for
predicting time spent on open arms included a linear
combination of STAI-Trait and AQ-Anxiety, R
5.35, p0.007 (Step 2). Within this model, AQ
Anxiety was the most important variable predicting the
avoidance of open arms (see Table 5). These results
replicate the ndings of study 1 and also point to some
inuence of trait anxiety.
Anxiety Ratings
A2×2 ANOVA on anxiety ratings with the within-subject factor
arm type (open vs. closed), and oor texture (grid vs. solid)
returned signicant main effects of arm type, F
27.61, p<
0.001, η
0.33, and oor texture, F
12.33, p0.001, η
0.18, but no interaction effect, F
These ndings implicate that participants rated open vs. closed
arms and grid oor vs. solid oor arms as more anxiety inducing.
Further correlation analyses revealed that the anxiety reported on
all EPM armsexcept the safestwith closed arm and solid
oorwere positively correlated (Bonferroni-corrected p0.0025)
FIGURE 4 | (A) Top view screenshot of the virtual EPM depicting the different oor textures; vertical arms are open, horizontal arms are closed. (B) Heatmap of
motion tracking data during the exploration phase (N61). Areas with lighter colors depict areas with greater activity.
TABLE 4 | Results of correlation analyses of time spent on various maze arms and psychometric questionnaires.
Closed grid Closed solid Open grid Open solid
rprp r prp
Trait 0.25 0.050 0.10 0.463 0.29 0.021 0.08 0.548
Anxiety 0.02 0.863 0.15 0.253 0.36 0.004 0.12 0.377
Avoidance 0.04 0.768 0.02 0.859 0.40* 0.001 0.02 0.877
Total 0.19 0.150 0.09 0.492 0.13 0.328 0.06 0.656
Total 0.04 0.773 0.05 0.717 0.08 0.539 0.06 0.633
Note: *Bonferroni-corrected to p <0.0025; AQ, Acrophobia Questionnaire; STAI, State-Trait-Anxiety Inventory; SSS-V, Sensation Seeking Scale; CLQ, Claustrophobia Questionnaire.
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Madeira et al. Exploration in a Virtual EPM
with both AQ subscales (see Table 6). Furthermore, a signicant
negative relationship was found between SSS-V Total score and all
arms except the open arm with a grid oor. Finally, signicant positive
correlations were found between the CLQ total score and anxiety
ratings on all arms, whereas correlations between STAI-Trait and
anxiety ratings did not reach signicance.
Correlations of Trait Anxiety Measures
Replicating study 1, we found again that AQ scores of both subscales
were uncorrelated with STAI-Trait (Anxiety: r
Avoidance: r
0.12, p0.347). Furthermore, we observed that
both AQ Anxiety and AQ Avoidance were positively associated
with the CLQ total score (Anxiety: r
0.39, p0.002;
Avoidance: r
0.43,p0.001). In addition, CLQ total score
and SSS-V-Total score correlated negatively, r
−0.28, p0.028
(see Supplementary Table S4 in supplementary materials). This
suggests that in this sample acrophobia is associated with
claustrophobia whereas sensation seeking is not or even
reversely linked to phobic anxiety.
With respect to the rst hypothesis for this study, we again found no
general open arm avoidance in humans and no area preference in
general. Finally, the ndings on fear ratings assessed on the various EPM
arms replicated study 1. Acrophobia but not trait anxiety positively
related to fear on all maze arms, except the least acrophobicone,
i.e., the closed arm with a solid oor. Also, sensation seeking was in
general negatively associated with fear ratings on EPM arms although
only the associations with ratings on the closed arm with grid oor and
open arm with solid oor survived signicance. Unexpectedly, we
observed that claustrophobia was positively associated with fear ratings
on all areas of the maze, which may be due to the claustrophobic
situation of being in the CAVE system.
In sum, these results conrm the importance of acrophobia as
the driving factor for human EPM behavior, while trait anxiety
seems to play a rather subordinate role in open arm activity if any.
established animal model of anxietymeasurement,toahumancontext
usingvirtualrealitytechnology.Equallytoanimalstudies(Pellow et al.,
1985), the participantsbehaviors during 5 min of free exploration of a
virtual copy of an animal EPM adjusted to human proportions (study
1) or a human-adapted EPM (study 2) were registered. The construct
validity of human EPM behavior as a measure of anxiety was evaluated
by testing associations with psychometric measures of anxiety or
sensation seeking and fear ratings.
Exploration Behavior
Both of our studies observed no general open arm avoidance of
humans, which we expected based on animal studies and the
human EPM study of Biedermann et al. (2017). As a result, this
nding implies that exploration behavior on the animal and
human EPM is driven by mechanisms different from those in
the animal EPM. Unlike the human open eld test, which
reproduced human thigmotaxis, we could not produce similar
evolutionary conserved behaviors (Walz et al., 2016). Therefore,
we conclude that we have no convincing evidence for cross-
species open arm avoidance suggested by Biedermann et al.
TABLE 5 | Summary of hierarchical regression analyses for psychometric
questionnaire scores predicting time spent on open arms of the virtual maze in
study 2.
Step 1 0.04 616.50 0.122
Intercept 96.62 18.99 <0.001**
STAI Trait 0.77 0.49 0.20 0.122
Step 2 0.16 610.67 0.007**
Intercept 111.83 18.76 <0.001**
STAI Trait 0.83 0.46 0.22 0.079
AQ Anxiety 1.03 0.36 0.34 0.007**
Step 3 0.11 612.56
Intercept 118.74 28.87 <0.001**
STAI Trait 0.80 0.47 0.21 0.095
AQ Anxiety 1.05 0.37 0.35 0.007*
SSS-V Total 0.27 0.84 0.04 0.753
Step 4 0.10 614.52
Intercept 116.93 30.90 <0.001**
STAI Trait 0.80 0.48 0.21 0.098
AQ Anxiety 1.07 0.40 0.36 0.010*
SSS-V Total 0.23 0.87 0.04 0.791
CLQ Total score 0.08 0.43 0.02 0.862
Note: *p <0.05, **p <0.01; R
adjusted R
; AQ, Acrophobia Questionnaire; STAI,
State-Trait-Anxiety Inventory; SSS-V, Sensation Seeking Scale.
TABLE 6 | Results of correlation analyses of anxiety ratings on various EPM arms with psychometric questionnaires in study 2.
Closed grid Closed solid Open grid Open solid
Trait 0.05 0.712 0.18 0.171 0.01 0.921 0.13 0.309
Anxiety 0.57* <0.001 0.36 0.004 0.49* <0.001 0.49* <0.001
Avoidance 0.46* <0.001 0.34 0.008 0.51* <0.001 0.50* <0.001
Total 0.43* <0.001 0.38* 0.002 0.38 0.003 0.45* <0.001
Total 0.45* <0.001 0.42* <0.001 0.43* <0.001 0.45* <0.001
Note: *p <0.0025. STAI, State-Trait-Anxiety Inventory; AQ, Acrophobia Questionnaire; SSS-V, Sensation Seeking Scale; CLQ, Claustrophobia Questionnaire.
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Madeira et al. Exploration in a Virtual EPM
Several differences between ours and the study of Biedermann
et al. (2017) might explain the discrepancy. At rst, the denition
of the EPM zones differed from each other. The exploration
activity in the center area center activity remains a highly
discussed topic in animal research. It was found that it merely
associates with general locomotor activity but not anxiety (Braun
et al., 2011). Thus we decided not to incorporate center
movement into our nal analyses. In addition, we followed the
advice of other authors to not merge maze areas for data analysis
(Hogg, 1996;Carobrez and Bertoglio, 2005;Braun et al., 2011).
Nonetheless, Biedermann et al. (2017) dened their mazes closed
and center area as a safe area. Consequently, comparing a rather
large (safe) area to a much smaller area (open arms) likely leads to
an overestimation of time spent on these safe areas. In addition,
increased closed arm activity might also be the result of perceived
dangerousness in the context of the height situation. Considering
that human EPM behavior is mainly modulated by acrophobic
fear, it seems conceivable that the mixed virtual reality design
using a wooden cross with an arm width of 30 cm and a height of
20 cm amplies fear in reaction to height cues, which prompted a
stronger avoidance of open arms than we observed in our studies.
Exploration Behavior and Anxiety
Both of our human EPM studies identied acrophobia to be the
dominant factor modulating open arm avoidance. Our results
corroborate Biedermann et al.s(2017), who also reported
modulatory effects of acrophobia on open arm avoidance and
also added further insight. First, the modulatory effects of
acrophobia on human EPM behavior are observable for elevated
mazes of quite various designs, but visual height perception seems
to be a crucial factor in humans. Thus, the strongest associations
between acrophobia and open arm avoidance were observed in
EPMs with strong height simulation, i.e., in our study 2 with an
open arm with a see-through mesh ground and in Biedermann
et al. (2017) comparing elevated arms of 55 m height with safe
arms. A priori screening excluded participants with acrophobic
fear with the goal to unravel trait anxiety effects on EPM behavior.
Nonetheless, acrophobic fear was still the strongest modulator of
human EPM behavior as revealed by correlational and hierarchical
regression analyses. Second, our studies including Biedermann
et al. (2017) demonstrated that sensation seeking also has a
modulatory role for human EPM behavior. We observed that
an increase in sensation seeking is associated with less time on
closed arms. In contrast, Biedermann et al. (2017) reported that
subjects with higher sensation seeking levels tend to spend more
time on open arms. However, it remains questionable whether
these effects can be seen independent of acrophobia as both
questionnaires correlate negatively. Supporting this view, we
noticed that several items of the SSS-V (Zuckerman, Eysenck,
and Eysenck, 1978) refer to typical acrophobic situations (e.g., I
like to dive off the high board.vs Idont like the feeling I get
standing on the high board (or I dontgonearitatall).). Further
studies have to evaluate whether acrophobia and sensation seeking
modulate human EPM behavior independently. Third, closed arms
with walls may be a safe area for rodents, but not for humans,
according to our studies. We speculate that humans feel conned
in such hallways and therefore are motivated to leave them. The
replacement of high solid walls by natural handrails allowing the
overview of the virtual environment may have reduced the
participantsmotivation (e.g., due to claustrophobia or curiosity)
to leave the closed arms. Finally, we found some evidence for a
modulatory effect of trait anxiety on human EPM behavior.
However, these effects were weak and not consistent across the
two studies. This is in line with that of Biedermann et al. (2017)
who also found no modulatory role of trait anxiety. Newer studies
suggest that transdiagnostic concepts like fear of the unknown
(FOTU) and intolerance of uncertainty (IU) are underlying
mechanisms of trait anxiety, which are easier to target in an
experimental setting (Carleton et al., 2012;Carleton, 2016;
Shihata et al., 2016). Therefore, we suggest that future studies
introduce instruments to examine FOTU or IU (Carleton et al.,
2007) to gain further insights into nonphobic anxiety mechanisms
in a human EPM.To sum it up, we haveto conclude that, based on
the existing evidence, the human virtual EPM is instead a
behavioral test for acrophobia than for anxiety in general.
Anxiety Ratings
The anxiety ratings assessed on different EPM arms partly mirrored
the association of acrophobia and behavioral movement measures.
For example, participants reported enhanced anxiety on open vs.
closed arms and arms with see-through mesh oor vs. solid oor,
emphasizing the importance of visual height perception again. In
line, these ratings were associated with acrophobia but not trait
anxiety, and we found some negative associations between
sensation seeking and anxiety rating. In sum, these results
suggest that acrophobia and, to some extent sensation, seeking,
modulate human EPM behavior via the anxiety experienced on
different EPM arms. Interestingly, claustrophobic tendencies were
associated with anxiety ratings on all arms. Therefore, we speculate
that the ve-sided CAVE system is a claustrophobic context
intrinsically, as we did not observe a consistent distinction
between arm types or oor texture in the second study.
Consequently, future studies have to consider and evaluate how
the technology used to present virtual environments moderates the
experienced anxiety and perhaps human EPM behavior.
Our studies assessed behavioral and verbal measures of anxiety but
lack psychophysiological measures. Future studies should consider
psychophysiological measures as they may indicate anxiety responses
independent of self-report or behavioral measures (Lang, 1985). In
addition, more detailed analyses of movement patterns should be
considered. Besides exploration time as assessed here, rodent EPM
studies also assess other fear-like responses, such as freezing. In
humans, freezing is dened as reduced mobility and bradycardia
and has already been observed in specic human experimental settings
(Roelofs et al., 2010;Hagenaars et al., 2014;Rösler and Gamer, 2019).
Assessing freezing as human EPM behavior would be especially
valuable as participants may enter open arm alleys but abruptly
freeze, increasing the time spent on that specicmazearealeading
to erroneous interpretation of results.
Besides, the generalization of these ndings might be limited
by the small age range within the sample consisting
predominantly of students.
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Madeira et al. Exploration in a Virtual EPM
Finally, several participants reported that the virtual
environments appeared somewhat articial. Thus, future
studies should think about naturalistic EPM environments to
increase the tests validity.
Our studies show that human movement in a virtual human EPM is
primarily inuenced by acrophobia but not by trait anxiety, as we
initially hypothesized. The results are even more interesting, as, in
the second study, participants were selected for low levels of
acrophobia to avoid distortion of results. To address the
inuence of trait anxiety on exploration behavior, it is essential to
reshape the virtual EPM in future studies to avoid the inuence of
fear of heights. To target trait anxiety-related processes, we suggest
the subliminal induction of a threat to trigger a generalized fear state
typically associated with high trait anxiety (e.g., Van Den Hout et al.,
1995;Li et al., 2007;Reuman et al., 2015). This can either be achieved
by a threat of shock paradigm (Clark et al., 2012;Morriss et al., 2019)
or by emotional priming (Yang et al., 2016).
The present studies examined the inuence of anxiety and
personality traits on human exploration behavior in detail. In
conclusion, we consider the virtual EPM an essential apparatus in
the investigation of anxiety-related issues as the virtual scenario
can easily be modied.
The original contributions presented in the studies can be found
on Further inquiries can be directed to the
corresponding author.
The studies involving human participants were reviewed and
approved by the Ethical Board of the Department of Human-
Computer-Interaction of the University of Würzburg. All
participants provided their written informed consent to
participate in this study.
OM, DG, MEL, and PP contributed to the study concept and
design. Data collection was done by OM. OM and DG performed
data analysis and interpretation. OM and PP drafted the
manuscript, and all other co-authors provided critical revisions
and feedback. All authors contributed to the article and approved
the submitted version.
The studies were supported by the Volkswagen Foundation
(AZ 94 102). This work was carried out with the support of
the structural doctoral program Graduate School of Life
Sciences (GSLS)by the University of Würzburg, and the two
studies are part of the doctoral project The human-
experimental virtual Elevated Plus-Maze as an anxiety
Open Access Publication Fund of the University of
We would like to thank Jan Philipp Gast for assisting in data
collection and preparation.
The Supplementary Material for this article can be found online at:
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Frontiers in Virtual Reality | April 2021 | Volume 2 | Article 63504812
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Conict of Interest: PP is a shareholder of a commercial company that develops
virtual environment research systems (VTplus GmbH) for empirical studies in the
eld of psychology, psychiatry, and psychotherapy.
The remaining authors declare that the research was conducted in the absence of
any commercial or nancial relationships that could be construed as a potential
conict of interest.
Copyright © 2021 Madeira, Gromer, Latoschik and Pauli. This is an open-access
article distributed under the terms of the Creative Commons Attribution License (CC
BY). The use, distribution or reproduction in other forums is permitted, provided the
original author(s) and the copyright owner(s) are credited and that the original
publication in this journal is cited, in accordance with accepted academic practice. No
use, distribution or reproduction is permitted which does not comply with these terms.
Frontiers in Virtual Reality | April 2021 | Volume 2 | Article 63504813
Madeira et al. Exploration in a Virtual EPM
... This allows for the comprehensive characterization of emotional states on a cognitive-verbal, physiological-humoral, and motor-behavioral level (Fox 2008). Furthermore, the use of virtual environments facilitates translational work (Fig. 2b), such that certain experimental protocols, which are traditionally used in animals, can now be easily recreated in VR to allow for a more direct comparison between animal and human research (e.g., Biedermann et al. 2017;Madeira et al. 2021). ...
... (a) Participants can be located within a CAVE and by means of a gamepad they can freely move within a virtual environment including, for example, a tower inducing fear of height (Gromer et al. 2018). (b) Protocols of animal studies can be easily translated to VR settings as demonstrated with the elevated plus maze (EPM; Biedermann et al. 2017;Madeira et al. 2021). (c) The realism of the virtual environments can be manipulated in order to induce a stronger sense of presence (Gromer et al. 2019) VR tricks our minds to believe in a world that does not exist. ...
Emotions are frequently considered as the driving force of behavior, and psychopathology is often characterized by aberrant emotional responding. Emotional states are reflected on a cognitive-verbal, physiological-humoral, and motor-behavioral level but to date, human research lacks an experimental protocol for a comprehensive and ecologically valid characterization of such emotional states. Virtual reality (VR) might help to overcome this situation by allowing researchers to study mental processes and behavior in highly controlled but reality-like laboratory settings. In this chapter, we first elucidate the role of presence and immersion as requirements for eliciting emotional states in a virtual environment and discuss different VR methods for emotion induction. We then consider the organization of emotional states on a valence continuum (i.e., from negative to positive) and on this basis discuss the use of VR to study threat processing and avoidance as well as reward processing and approach behavior. Although the potential of VR has not been fully realized in laboratory and clinical settings yet, this technological tool can open up new avenues to better understand the neurobiological mechanisms of emotional responding in healthy and pathological conditions.KeywordsApproachAvoidanceEmotionsPresenceVirtual reality
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Anxiety research is one of the major psychological research domains and looks back on decades of research activity. Traditionally, novel theories and approaches are tested utilizing animal models. One way to study inherent anxiety in rodents is the elevated plus-maze (EPM). The EPM is a plus-shaped platform with two closed, i.e., walled, arms and two open unwalled arms. If given the opportunity to freely explore the apparatus, rodents instinctively avoid the open arms to protect themselves from predators. Hence, they spent less time on open and more time on closed arms, which is behaviorally associated with general anxiety. In the course of the pharmacological validation, it was found that this exploratory pattern can be reversed by anxiolytic substances, e.g., benzodiazepines, or potentiated by anxiogenics. One of the significant advantages of the EPM is that no prior training session is required in contrast to conditioning studies, thus allowing to observe natural behavior. Therefore, together with the economic and uncomplicated setup, the EPM has become a standard preclinical rodent anxiety test over the decades. In order to validate these rodent anxiety tests, there have recently been attempts to retranslate them to humans. A paramount of cross-species validation is not only the simple transferability of these animal tests but also the observation of anxiety behaviors that are evolutionarily conserved across species. Accordingly, it could be possible to conclude various factors associated with the etiology and maintenance of anxiety disorders in humans. So far, convincing translations of the EPM to humans are still lacking. For that reason, the primary aim of this dissertation is to retranslate the EPM throughout three studies and to evaluate cross-species validity critically. Secondly, the undertaken studies are set out to observe ambulatory activity equivalent to rodent EPM behavior, i.e., open arm avoidance. Thirdly, the undertaken studies aimed to assess the extent to which trait anxiety influences human exploratory activity on the platform to associate it with the assumption that rodent EPM-behavior is a reflection of general anxiety. Finally, virtual reality (VR) was the method of choice to maintain the economic advantage and adjust the EPM size to humans. Study 1 (N = 30) was set up to directly transfer the rodent EPM regarding test design and experimental procedure using a Computer Automatic Virtual Environment (CAVE). The results revealed that humans unlike rodents display a general open arms approach during free exploration. However, open arm avoidance was associated with high trait anxiety and acrophobia (fear of height), which was initially assessed as a control variable due to the virtual platform height. Regression analyses and subjective anxiety ratings hinted at a more significant influence of acrophobia on open arm avoidance. In addition, it was assumed that the open arms approach might have resulted from claustrophobic tendencies experienced in the closed arms due to the high walls. Study 2 (N = 61) sought to differentiate the influence of trait anxiety and acrophobia and adapt the virtual EPM to humans. Therefore, parts of the platform held a semi-transparent grid-floor texture, and the wall height on the closed arms was reduced to standard handrail level. Moreover, participants were priorly screened to exclude clinically significant levels of acrophobia, claustrophobia, and agoraphobia. The data on general exploratory activity showed no arm preference. Regression analyses confirmed that acrophobia is related to open arm avoidance, corroborating the finding of Study 1. Surprisingly, for trait anxiety, the result of Study 1 could not be replicated. Instead, for trait anxiety, no significant effect was found indicating that predominantly fear of heights shapes human EPM behavior even on a subclinical stage. In Study 3 (N = 57), the EPM was embedded into a city setting to 1) create a more natural human environment and 2) eliminate height. Furthermore, a head-mounted display was utilized for VR presentation, and arousal ratings were introduced. Participants were screened for high and low levels of trait anxiety and agoraphobia, and claustrophobia. Replicating the findings of Study 2, no difference in open and closed arm activity was observed, and no effect was found in relationship with trait anxiety. The data on anxiety ratings and claustrophobia suggest a positive correlation indicating that in this city EPM, claustrophobic tendencies might play a role in closed arm avoidance. In summary, this thesis added valuable insights into the retranslation of a well-established standard anxiety test used in rodents. However, it also majorly challenges current findings on the cross-species validity of the EPM. Various explanatory models for the results are critically discussed and associated with clinical implications concerning future research.
This work is concerned with the modelling and control of the state of presence of a user in a virtual reality system (VRS). The manner how the state of a user interacting with the VRS is measured by some of its physiological signals is discussed. Based on the user-VRS interaction, a novel feedback control schema to manipulate the user state is proposed. In this, the error between the required and the actual user behavior is used by a controller to select the appropriate stimulus that must be executed by the VRS core scenario to reduce the error. The schema includes the modelling of the presence state by a discrete event strategy based on Petri Nets. Based on the obtained model, the control strategy to select the appropriate stimuli is devised. Finally, some real experiments with a VRS prototype are carried out to show the effectiveness of the proposal.
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When confronted with threatening stimuli, animals typically respond with freezing behavior characterized by reduced movement and heart rate deceleration. Freezing-like responses during threat anticipation have also been observed in humans and are associated with anxiety. Recent evidence yet suggests that freezing does not necessarily reflect helpless immobility but can also aid the preparation of a threat escape. To investigate which further behavioral responses human freezing encompasses, we presented 50 young adults (10 male) with aversive stimuli that could sometimes be avoided while measuring gaze, cardiovascular and electrodermal activity. In trials in which the threat could be escaped, participants displayed reduced heart rate, increased electrodermal activity and reduced visual exploration. Furthermore, heart rate deceleration and restricted visual exploration predicted the speed of flight responses. These results provide evidence for freezing behavior in measures of visual exploration and suggest that such responding is adaptive in preparing the subsequent escape of approaching threats.
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Translational neuroscience bridges insights from specific mechanisms in rodents to complex functions in humans and is key to advance our general understanding of central nervous function. A prime example of translational research is the study of cross-species mechanisms that underlie responding to learned threats, by employing Pavlovian fear conditioning protocols in rodents and humans. Hitherto, evidence for (and critique of) these cross-species comparisons in fear conditioning research was based on theoretical viewpoints. Here, we provide a perspective to substantiate these theoretical concepts with empirical considerations of cross-species methodology. This meta-research perspective is expected to foster cross-species comparability and reproducibility to ultimately facilitate successful transfer of results from basic science into clinical applications.
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Star­tle re­flex po­ten­ti­a­tion ver­sus star­tle at­ten­u­a­tion to un­pleas­ant ver­sus pleas­ant stim­uli likely re­flect prim­ing of the de­fen­sive ver­sus ap­pet­i­tive mo­ti­va­tional sys­tems, re­spec­tively. This re­view sum­ma­rizes and sys­tem­izes the lit­er­a­ture on af­fec­tive star­tle mod­u­la­tion re­lated to psy­chopatholo­gies with the aim to re­veal un­der­ly­ing mech­a­nisms across psy­chopatholo­gies. We found ev­i­dence for psy­chopatholo­gies char­ac­ter­ized by in­creased star­tle po­ten­ti­a­tion to un­pleas­ant stim­uli (anx­i­ety dis­or­ders), de­creased star­tle po­ten­ti­a­tion to un­pleas­ant stim­uli (psy­chopa­thy), de­creased star­tle at­ten­u­a­tion to pleas­ant stim­uli (ADHD), as well as a gen­eral hy­pore­ac­tiv­ity to af­fec­tive stim­uli (de­pres­sion). In­creased ver­sus de­creased star­tle re­sponses to dis­or­der-spe­cific stim­uli char­ac­ter­ize spe­cific pho­bia and drug de­pen­dence. No psy­chopathol­ogy is char­ac­ter­ized by in­creased star­tle at­ten­u­a­tion to stan­dard pleas­ant stim­uli or a gen­eral hy­per­re­ac­tiv­ity to af­fec­tive stim­uli. This re­view in­di­cates that the de­fen­sive and the ap­pet­i­tive sys­tems op­er­ate in­de­pen­dently mostly in ac­cor­dance with the mo­ti­va­tional prim­ing hy­poth­e­sis and that af­fec­tive star­tle mod­u­la­tion is a highly valu­able par­a­digm to un­rav­el­ing dys­func­tions of the de­fen­sive and ap­pet­i­tive sys­tems in psy­chopatholo­gies as re­quested by the Re­search Do­main Cri­te­ria ini­tia­tive.
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Intolerance of uncertainty (IU) is associated with difficulty in updating contingencies from threatening to safe during extinction learning. However, it is unknown whether high IU individuals have difficulty (1) generally with updating threat to safe associations when contingencies change or (2) specifically with updating threat to safe associations during extinction learning, where direct threat is omitted. To address this question, we recorded IU, expectancy ratings, and skin conductance in 44 healthy participants during an associative learning paradigm, where threat and safety contingencies were reversed. During acquisition and reversal, we observed larger skin conductance response (SCR) magnitude and expectancy ratings for threat versus safety cues. However, during reversal, higher IU was associated with larger SCR magnitude to new threat versus new safety cues, compared with lower IU. These results were specific to IU-related variance, over shared variance with trait anxiety (State-Trait Anxiety Inventory, Trait Version). Overall, these findings suggest that individuals high in IU are able to reverse threat and safety associations in the presence of direct threat. Such findings help us understand the recently revealed link between IU and threat extinction, where direct threat is absent. Moreover, these findings highlight the potential relevance of IU in clinical intervention and treatment for anxiety disorders.
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Virtual reality plays an increasingly important role in research and therapy of pathological fear. However, the mechanisms how virtual environments elicit and modify fear responses are not yet fully understood. Presence, a psychological construct referring to the ‘sense of being there’ in a virtual environment, is widely assumed to crucially influence the strength of the elicited fear responses, however, causality is still under debate. The present study is the first that experimentally manipulated both variables to unravel the causal link between presence and fear responses. Height-fearful participants (N = 49) were immersed into a virtual height situation and a neutral control situation (fear manipulation) with either high versus low sensory realism (presence manipulation). Ratings of presence and verbal and physiological (skin conductance, heart rate) fear responses were recorded. Results revealed an effect of the fear manipulation on presence, i.e., higher presence ratings in the height situation compared to the neutral control situation, but no effect of the presence manipulation on fear responses. However, the presence ratings during the first exposure to the high quality neutral environment were predictive of later fear responses in the height situation. Our findings support the hypothesis that experiencing emotional responses in a virtual environment leads to a stronger feeling of being there, i.e., increase presence. In contrast, the effects of presence on fear seem to be more complex: on the one hand, increased presence due to the quality of the virtual environment did not influence fear; on the other hand, presence variability that likely stemmed from differences in user characteristics did predict later fear responses. These findings underscore the importance of user characteristics in the emergence of presence.
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Background: A dearth of laboratory tests to study actual human approach-avoidance behavior has complicated translational research on anxiety. The elevated plus-maze (EPM) is the gold standard to assess approach-avoidance behavior in rodents. Methods: Here, we translated the EPM to humans using mixed reality through a combination of virtual and real-world elements. In two validation studies, we observed participants' anxiety on a behavioral, physiological, and subjective level. Results: Participants reported higher anxiety on open arms, avoided open arms, and showed an activation of endogenous stress systems. Participants' with high anxiety exhibited higher avoidance. Moreover, open arm avoidance was moderately predicted by participants' acrophobia and sensation seeking, with opposing influences. In a randomized, double blind, placebo controlled experiment, GABAergic stimulation decreased avoidance of open arms while alpha-2-adrenergic antagonism increased avoidance. Conclusion: These findings demonstrate cross-species validity of open arm avoidance as a translational measure of anxiety. We thus introduce the first ecologically valid assay to track actual human approach-avoidance behavior under laboratory conditions.
The laws of animal behavior have been revised and revealed through research performed by zoologists, physiologists and experimental psychologists. Each has contributed much. Their main meeting ground has been the study of mammals, especially rats. This classic book is unique in bringing together the principal conclusions of these researchers in a compact, well illustrated, and lucid form. The author himself made important original contributions to wild rat behavior; his account of “white rat psychology�? and of relevant work on other species is equally authoritative. Experience as a teacher enabled him to write an unusually logical and comprehensive text, suitable for students of zoology, psychology and medicine. This book belongs to no particular school of biology or psychology. Rather it admits the work of all schools and strict adherence to none. The principal topics covered include: movement in the living space; feeding behavior; social and reproductive behavior; the analysis of “instinct�?; the analysis of learned behavior; “motivation�? and “drive�?; the brain and behavior. The book includes a full, carefully selected bibliography, current up to the time of original publication of the original edition.
Animal models of anxiety disorders are important for elucidating neurobiological defense mechanisms. However, animal models are limited when it comes to understanding the more complex processes of anxiety that are unique to humans (e.g., worry) and to screen new treatments. In this review, we outline how the Experimental Psychopathology approach, based on experimental models of anxiety in healthy subjects, can mitigate these limitations and complement research in animals. Experimental psychopathology can bridge basic research in animals and clinical studies, as well as guide and constrain hypotheses about the nature of psychopathology, treatment mechanisms, and treatment targets. This review begins with a brief review of the strengths and limitations of animal models before discussing the need for human models of anxiety, which are especially necessary to probe higher-order cognitive processes. This can be accomplished by combining anxiety-induction procedures with tasks that probe clinically relevant processes to identify neurocircuits that are potentially altered by anxiety. The review then discusses the validity of experimental psychopathology and introduces a methodological approach consisting of five steps: (1) select anxiety-relevant cognitive or behavioral operations and associated tasks, (2) identify the underlying neurocircuits supporting these operations in healthy controls, 3) examine the impact of experimental anxiety on the targeted operations in healthy controls, (4) utilize findings from step 3 to generate hypotheses about neurocircuit dysfunction in anxious patients, and 5) evaluate treatment mechanisms and screen novel treatments. This is followed by two concrete illustrations of this approach and suggestions for future studies.
Avoidance behavior in clinical anxiety disorders is often a decision made in response to approach-avoidance conflict, resulting in a sacrifice of potential rewards to avoid potential negative affective consequences. Animal research has a long history of relying on paradigms related to approach-avoidance conflict to model anxiety-relevant behavior. This approach includes punishment-based conflict, exploratory, and social interaction tasks. There has been a recent surge of interest in the translation of paradigms from animal to human, in efforts to increase generalization of findings and support the development of more effective mental health treatments. This article briefly reviews animal tests related to approach-avoidance conflict and results from lesion and pharmacologic studies utilizing these tests. We then provide a description of translational human paradigms that have been developed to tap into related constructs, summarizing behavioral and neuroimaging findings. Similarities and differences in findings from analogous animal and human paradigms are discussed. Lastly, we highlight opportunities for future research and paradigm development that will support the clinical utility of this translational work.