Neurotherapeutics

DOI 10.1007/s13311-017-0534-y

REVIEW

Virtual Reality-Enhanced Extinction of Phobias

and Post-Traumatic Stress
Jessica L. Maples-Keller 1 & Carly Yasinski 1 & Nicole Manjin 1 &
Barbara Olasov Rothbaum 1

# The American Society for Experimental NeuroTherapeutics, Inc. 2017

Abstract Virtual reality (VR) refers to an advanced techno- interface in which the user is actively participating in a com-
logical communication interface in which the user is actively puter generated 3-dimensional (3D) virtual world that in-
participating in a computer-generated 3-dimensional virtual cludes computer sensory input devices used to simulate
world that includes computer sensory input devices used to real-world interactive experiences [1–3]. Users are outfitted
simulate real-world interactive experiences. VR has been used with a head-mounted display composed of separate displays
within psychiatric treatment for anxiety disorders, particularly screens for each eye along with a head-tracking device. This
specific phobias and post-traumatic stress disorder, given sev- allows the user’s orientation in the virtual world to change
eral advantages that VR provides for use within treatment for naturally based on head and body movements, which pro-
these disorders. Exposure therapy for anxiety disorder is vides users with a sense of presence and immersion within
grounded in fear-conditioning models, in which extinction the virtual environment. Users often wear headphones for
learning involves the process through which conditioned fear auditory stimuli [4], and in some environments users may
responses decrease or are inhibited. The present review will have a sensory pointing device or joystick to interact with
provide an overview of extinction training and anxiety disor- the virtual environment [1, 5].
der treatment, advantages for using VR within extinction VR applications have been developed for use within
training, a review of the literature regarding the effectiveness psychiatric treatment for many different disorders. The
of VR within exposure therapy for specific phobias and post- bulk of the VR applications within psychiatric treatment
traumatic stress disorder, and limitations and future directions have been for anxiety disorders, particularly specific
of the extant empirical literature. phobias and post-traumatic stress disorder (PTSD),
given several advantages that VR provides for use with-
Keywords Extinction training . exposure therapy . in treatment for these disorders. The focus of the current
technology . specific phobias . PTSD . psychiatric treatment article is to provide an overview of extinction training
and anxiety disorder treatment, present the advantages
provided by VR applications within extinction learning
Introduction and anxiety disorder treatment, and review the extant
literature regarding the effectiveness of VR approaches
Virtual reality (VR), a term first coined by Jaron Lamier in to the treatment of specific phobias and PTSD.
1986, refers to an advanced technological communication

Extinction Training and Anxiety Disorder Treatment

* Jessica L. Maples-Keller Anxiety disorders, characterized by pathological fear and anx-

[email protected] iety, account for 14.6% of disability-adjusted life years glob-
ally, indicating that these disorders have a significant disease
1
Department of Psychiatry and Behavioral Sciences, Emory burden [6]. Pavlovian fear-conditioning models have been
University School of Medicine, Atlanta, GA, USA used to understand, behaviorally and neurobiologically, how
 Maples-Keller et al.

fear responses are acquired (i.e., fear acquisition) and maximize the fit between the exposure and the patient’s
inhibited (i.e., fear extinction) [7]. Within this paradigm, feared stimuli. First, VR technology provides the oppor-
a neutral stimulus, or conditioned stimulus (CS), is repeat- tunity to include aspects of feared stimuli that could oth-
edly paired with an innately aversive unconditioned stim- erwise be too expensive or impractical. For instance, mul-
ulus (US), causing the subject to demonstrate conditioned tiple virtual flights can be implemented, which could be
fear responses to the previously neutral CS. Fear-extinction prohibitively costly, and labor- and time-intensive if
training is the process through which conditioned fear attempted in vivo. Additionally, VR provides the ability
responses decrease or are inhibited. In this process, the for the therapist to have total control over all aspects of
patient is presented with the CS without the presence of the exposure. For example, a therapist conducting an ex-
the US and after multiple presentations will demonstrate a posure for flight phobia can assess the patient’s specific
decrease in the conditioned fear response, known as fears in detail prior to the VR exposures (VREs) and tailor
Bextinction learning^ [8]. This process has strong clinical aspects of the exposure, such as the weather on the flight,
relevance as it provides a foundation for how to under- the amount of turbulence, or the time of day, to maximize
stand and treat excessive fear and anxiety. the match. This level of control also allows for repetition
Extinction learning provides the basis for exposure of aspects of the exposure which may not be possible in
therapy, in which patients confront feared stimuli in a real life, such as repeating the take-off several times with-
systematic, gradual, and therapeutic manner. The empiri- in session. VRE provides a safe and controlled environ-
cal literature provides strong support for the effectiveness ment for the patients in which they are able to engage
of exposure therapy for anxiety disorders [9]. Based on with specific feared stimuli under the direction of a pro-
emotional processing theory [10], fear responses are con- vider, in order to most effectively and efficiently generate
ceptualized as pathological when the associations among changes in conditioned fear responses and maladaptive
stimuli, responses, and meaning propositions, referred to patterns of thoughts and feelings. Additionally, patient
as the Bfear network^, are inaccurate such that neutral acceptability may be higher than other types of exposure
stimuli or responses are associated with an exaggerated for some patients.
probability of threat or danger. Consistent with extinction VRE may help patients more effectively attend during ex-
learning, exposure therapy involves activating the fear posures. First, through the 3D visuals and position sensors that
network via exposure to feared stimuli, resulting in the dynamically move with the patient’s natural head movement,
patient learning that their feared outcome will not occur VR can provide a high level of presence and immersion within
and that their conditioned fear response will decrease. In the exposure, which may allow for higher engagement and
traditional exposure therapy, treatment may involve fewer distractions than other methods. VR provides the ability
in vivo exposures, in which the patient confronts the to engage multiple senses during the exposure, through tailor-
feared stimuli in real life, or imaginal exposure, in which ing the visual and auditory stimuli in the virtual environment,
the feared stimuli is confronted in the patient’s imagina- engaging the patient’s sense of touch and vibration (by mod-
tion during the therapy session. VR was proposed as a ifying vibrotactile platforms), and the adding relevant smells.
new medium for presenting the feared stimuli approxi- This dynamic interaction between the patient and the virtual
mately 2 decades ago [11]. environment and the ability to engage multiple senses facili-
tates a sense of truly Bbeing there^. Indeed, a previous study
found that adding additional types of sensory input within VR,
Advantages of Using VR for Extinction Training such as olfactory and auditory cues, increased participant’s
sense of presence and memory of the virtual environment
Foa and Kozak [10] propose multiple variables as crucial [12]. These higher levels of presence may result in increased
for optimal activation of the fear network during exposure attention to feared stimuli and lower levels of cognitive avoid-
therapy, including: 1) the information presented during ance, which would facilitate effective extinction learning. In
therapeutic exposures must demonstrate strong match particular, VRE may remove barriers to exposure treatment
with the patient’s feared stimuli; and 2) the patient must for patients who might struggle with traditional imaginal ex-
attend to and engage with the information. Effective acti- posure due to difficulties with visualization or imagination.
vation of fear is essential to extinction learning, as the fear Additionally, the privacy of the VRE, as opposed to in vivo
response is only expected to decrease when feared stimuli exposures conducted in public, may allow some patients to
is repeatedly presented in the absence of aversive conse- engage more openly without concern of embarrassment or
quences. VR technology provides several potential advan- violation of confidentiality. VR provides the advantage of
tages for the process of extinction learning during expo- allowing exposures to be conducted in multiple different con-
sure therapy. Consistent with Foa and Kozak’s [10] texts with relative ease. As there is evidence that extinction
highlighted variables, VR provides the opportunity to training is context-specific, and therefore fear is more likely to
Virtual Reality-Enhanced Extinction

return in contexts other than the one in which extinction train- needed for those unwilling to try or tolerate this treatment
ing occurred, VR exposure across multiple contexts may in- [16]. One recent study found that more participants chose
crease generalization and decrease the risk of fear renewal. VRE than in vivo exposure for specific phobia when given a
The sense of presence elicited by VR and the ability to choice and that greater numbers refused treatment when of-
tailor the virtual environment to specific feared stimuli makes fered in vivo exposure (27%) than VRE (3%), suggesting that
VR technology ideal for use within exposure therapy for anx- VRE may be more palatable to potential patients [17].
iety disorders. Within fear-based disorders, extinction and Additionally, VR exposure for certain specific phobias (e.g.,
learning and VRE are particularly well suited to PTSD and flying) may be more practical and less expensive to complete
specific phobias. PTSD could be thought of as the quintessen- regularly on an outpatient basis.
tial learned fear disorder, as experiencing a traumatic event
(US) can lead to excessive fear responses to previously neutral
cues (CS) that are associated with the traumatic event, and the
traumatic event can be conceptualized as the conditioning Flying Phobia
episode. For specific phobia, the nature of excessive fear re-
lated to a specific object provides a strong opportunity to At this time, 10 RCTs comparing VRE for flight phobia to
conduct extinction training by implementing repeated expo- other treatment conditions (both active and waitlist controls)
sures to the specific feared stimuli. As such, the present review have been performed [18–26]. Seven additional clinical trials
will focus on empirical literature surrounding VRE for specif- have been performed, including 4 open trials or case series
ic phobias and PTSD. Regarding the scope of the present [27–30] and 3 within-subject randomized trials comparing
review, our main focus was efficacy studies, including open different forms of or augmentations to VRE [31–33].
trials and randomized controlled trials (RCTs), investigating Findings from these RCTs suggest that VRE for flight
VRE for specific phobias or PTSD. However, case studies or phobia leads to significant reductions in the cognitive and
case series studies were also included when relevant in pre- physiological symptoms of fear, as well as reductions in
liminary work with VRE in specific areas. The literature re- behavioral avoidance in the real world (e.g., willingness to
view was conducted using PsychInfo and reviewing all rele- take a flight). VRE has consistently outperformed waitlist
vant published articles that focused on PTSD or any specific control conditions [21–23] and tended to outperform non-
phobia. The authors also reviewed the references of the iden- specific attention control conditions, such as relaxation [20],
tified articles in order to identify any studies that may have bibliotherapy [18], and nondirective group therapy (although
been missed. The authors did not solicit unpublished data or only on cognitive measures of anxiety [19]). Two trials have
include unpublished dissertations within the current review. suggested that VRE may outperform imaginal exposure for
flight phobia, perhaps due to leading to greater fear activa-
tion and habituation [24] and less avoidance [34], although
VR and Specific Phobias both trials had small sample sizes. Furthermore, multiple
RCTs have found most outcomes from VRE to be equiva-
According to the Diagnostic and Statistical Manual of Mental lent to those from in vivo exposure [22, 23, 26], although 1
Disorders, 5th Edition [13], specific phobias are characterized study suggested that more participants receiving VRE used
by Bmarked fear or anxiety about a specific object or situation alcohol or drugs to cope with flying over a 12-month fol-
(e.g., flying, heights, animals, receiving an injection, seeing low-up than those receiving in vivo exposure [35]. Almost
blood)^, that is out of proportion to the actual danger posed by all studies reviewed found robust treatment effects for VRE
the object/situation and is accompanied by active avoidance of that were maintained over follow-up (1 month–3 years), and
it (or endurance with intense fear/anxiety). Recent epidemio- out of those trials that found reductions in effects following
logical research found that specific phobia is the second most treatment, each found symptomatology was still lower than
common mood or anxiety disorder in the USA, with a lifetime at pretreatment [19, 25]. Importantly, the effects of VRE
prevalence and morbidity risk rate of 15.6% and 18.4%, re- appear to hold, regardless of whether motion simulation
spectively [14]. The current gold-standard treatment for spe- was included in treatment, indicating that visual and audito-
cific phobia is in vivo exposure, in which the patient directly ry simulation alone may lead to a sufficient experience of
confronts the feared stimulus, usually in a graduated manner, presence for effective activation and habituation of fear [21,
to promote extinction of fear through habituation and correc- 33]. In summary, most existing trials suggest that VRE for
tive learning. In vivo exposure treatment is highly effective in flight phobia results in significant and long-term reductions
treating specific phobia, resulting in large effect sizes and in cognitive, behavioral, and physiological symptomatology
superior results to nonexposure treatments in 1 to 5 sessions that are greater than those shown by nonspecific control
[15]. However, drop-out and treatment refusal rates for in vivo conditions and similar to those shown after in vivo exposure,
exposure are high, suggesting that alternative approaches are the gold-standard treatment.
 Maples-Keller et al.

Height Phobia VRE for spider phobia to lead to significant improvements

in self-reported anxiety and behavioral avoidance compared
To date, 4 trials comparing VRE to other treatments or waitlist with waitlist controls [45, 46]. Additionally, 2 RCTs compar-
for acrophobia (fear of heights) have been performed [11, ing VRE to in vivo exposure for spider phobia have been
36–38]. Two trials have found VRE to be superior to waitlist performed [47, 48]. Michaliszyn et al. [46] showed VRE
on all measures, including self-reported anxiety, behavioral and in vivo exposure for spider phobia were equally effective
avoidance, and attitudes towards heights [11, 38]. Krijn et al. at improving self-reported fear of spiders and behavioral
[38] also compared VRE using a head-mounted display to a avoidance, although in vivo was more successful at improving
computer automatic virtual environment, a more immersive self-reported beliefs about spiders than VRE. St-Jacques et al.
method that led to higher self-reported levels of presence [47] found that VRE and in vivo exposure led to similar be-
among participants. While computer automatic virtual envi- havioral outcomes in a small sample of children undergoing
ronment was associated with slightly fewer dropouts owing to treatment for spider phobia.
insufficient activation of anxiety than head-mounted display, An elegant series of studies by Shiban et al. [48–50] demon-
this difference was not statistically significant and outcomes strated how VR technology can provide an ideal medium for
were equivalent across both treatments, suggesting that the testing mechanisms of extinction learning and exposure therapy
less expensive method of VRE may be sufficient for adequate in a controlled environment. In the 2013 study by Shiban et al.
treatment. An additional trial comparing VRE to in vivo ex- [48], participants with spider phobia were randomized to either
posure using matched stimuli (i.e., the same environments receive exposure in one context (a virtual room) or multiple
virtually and in vivo) found the 2 treatments lead to equivalent contexts (a virtual room with different-colored lighting during
gains that were maintained over 6 months [37]. each exposure trial). The results indicated that self-reported fear,
Five additional trials have been completed, including 2 skin conductance, and behavioral avoidance all showed greater
within-group comparison trials [18, 39] and 2 RCTs compar- reductions in the multiple context condition immediately follow-
ing VRE augmented with D-cycloserine (DCS), a N-methyl- ing the 1-session treatment than in the single-context condition.
D-aspartate partial agonist shown to facilitate extinction in In their next study, Shiban et al. performed a 2 × 2 RCT that
animal models, or placebo [40, 41]. Emmelkamp et al. [39] randomized spider-phobic participants receiving VRE according
provided 2 sessions of VRE followed by 2 sessions of in vivo to context (1 virtual room vs multiple) and stimuli (1 virtual
exposure to 10 participants with acrophobia and found that spider vs multiple) [50]. This study also found that multiple
VRE led to such improvements that a ceiling effect occurred, contexts during exposure (regardless of stimuli) led to better
leaving little room for additional improvement through outcomes in the short term; however, multiple stimuli combined
in vivo. While the 2 RCTs found mixed results regarding the with a single context led to the best outcomes in the long-term.
effectiveness of augmentation with DCS both found that VRE Additionally, Shiban et al. [49] were able to test whether reacti-
led to significant improvements, even at low doses (e.g., 2 vation of fear prior to VRE led to greater therapeutic gains, a
sessions) [40–42]. Krijn et al. [18] found VRE to be effective phenomenon demonstrated in previous animal studies. While no
regardless of whether the patient was instructed to use coping differences between groups were found in this study, neither
self-statements or not. In summary, while sample sizes have group experienced a spontaneous recovery of fear in the 24-h
been small, extant studies suggest that VRE for acrophobia period following the 1-session treatment, providing further evi-
outperforms waitlist and leads to significant reductions in cog- dence of VRE’s efficacy in this population. Overall, the use of
nitive and behavioral symptoms with as few as 2 sessions and VR technology for exposure allowed for precise delineation of
regardless of level of treatment adjuncts such as coping state- therapeutic factors in these studies and allowed for the ability to
ments or higher-immersion VR systems. control variables that could be easily confounded in real life.
In summary, VRE treatments for spider phobia have been
shown to lead to robust reductions in cognitive, behavioral,
Spider Phobia and physiological indicators of fear that are maintained over
follow-up in as little as 1 session. The effects of these treat-
Multiple open trials and RCTs have demonstrated significant ments are similar to that of in vivo exposure with minor ex-
effects of VRE for spider phobia. An early open trial found ceptions (e.g., less improvement in self-reported beliefs in 1
that 5 VRE sessions for spider phobia led to large and signif- study [46]).
icant improvements in behavioral avoidance, information pro-
cessing biases, and psychophysiological measures [43].
Similarly, a case series examining VRE treatment for spider Other Specific Phobias
phobia using a modified 3D computer game showed signifi-
cant reductions in behavioral avoidance and maladaptive be- While no RCTs examining VRE for other specific phobias
liefs about spiders [44]. Subsequently, 2 trials have shown have been completed at this time, some case studies and
Virtual Reality-Enhanced Extinction

therapeutic analog studies have suggested it may be effective treatment acceptance, lower expense, and greater
for additional conditions. A case study by Botella et al. [51] customizability than in vivo exposure. Research with larger
described how EMMA’s world, a VR environment built to be sample sizes, particularly when comparing active treatments,
adaptable to many different situations depending on the pa- is needed, as are longer follow-up periods. Furthermore, while
tient’s needs, was used successfully to treat a 70-year-old VRE may be effective in treating storm phobia, claustropho-
woman with a phobia of storms. A case series examining bia, and driving phobia, controlled studies are needed.
VRE for driving phobia showed efficacy for approximately
half of participants, suggesting it may be a promising first-line
treatment for some [52]. Another case series demonstrated PTSD
efficacy of VRE for specific phobias in young people with
autism spectrum disorder [53]. While not a clinical trial, a Within the Diagnostic and Statistical Manual of Mental
study on participants with claustrophobia demonstrated that Disorders, 5th Edition, a diagnosis of PTSD requires exposure
perceptual information presented in a virtual environment to a traumatic event and symptoms from each of the 4 PTSD
(e.g., seeing a door close on you in a virtual room) effectively symptom clusters, including intrusive symptoms, avoidance
led to an increase in the activation of self-reported and phys- symptoms, negative alterations in cognitions and mood, and
iological fear, suggested that VRE might be effective in this alterations in arousal and reactivity [13]. Epidemiological data
population as well [54]. While together these studies are from the USA indicates that PTSD has a lifetime morbid risk
promising, more controlled studies with larger sample sizes and 12-month prevalence rate of 10.1% and 3.7%, respective-
are needed to test VRE’s effectiveness in a wider range of ly [14], suggesting that this disorder represents a significant
specific phobias. disease burden. As noted previously, PTSD is an apt example
of a learned fear disorder, as conditioned fear to previously
neutral stimuli associated with the traumatic event fail to ex-
Summary of Specific Phobia Literature tinguish over time leading to pathological and excessive con-
ditioned fear responses to trauma cues. As such, PTSD can be
Extant research examining VRE for specific phobias has dem- conceptualized as a disorder of extinction, in which the failure
onstrated promising results. VR treatment for flight phobia, of natural recovery of fear responses are related to a
height phobia, and spider phobia has consistently peritraumatic overburden of fear followed by a failure of fear
outperformed waitlist conditions and nonexposure control extinction following the trauma. As such, it is a prime candi-
treatments, requiring relatively few sessions. Frequently, date for application of extinction learning principles, and con-
VRE has demonstrated equivalent outcomes to in vivo expo- sistent with this notion, extant research provides the strongest
sure, the gold-standard treatment [22, 26, 35, 37, 39, 47] with support for exposure-based interventions for PTSD treatment
a few exceptions [23, 46]. Additionally, the gains experienced [56]. The use of VR technology within PTSD treatment pro-
in VRE for specific phobia generalize to real-life behavioral vides the opportunity to conduct exposures that may not be
change, as a review of clinical trials with post-treatment be- possible otherwise, such as virtual Iraq and Afghanistan, and
havioral assessments suggests that patients receiving VRE offers another treatment option that may be appealing to a
demonstrate better performance on behavioral assessments video generation.
than waitlist patients and no significant difference from pa- The extant empirical literature provides support for the ef-
tients receiving in vivo exposure [55]. ficacy of VRE for PTSD. Overall, VRE is related to a signif-
However, it is important to acknowledge that most of the icant reduction in PTSD symptoms, performs significantly
existing studies have small sample sizes, with treatments better than waitlist controls, and performs comparably to stan-
groups usually composed of < 20 participants and sometimes dard exposure therapy [57, 58]. Results suggest that patients
< 10 participants. Such small sample sizes limit generalizabil- report high acceptability and satisfaction regarding the use of
ity, particularly of between-group comparisons, such as those VR technology within PTSD treatment [59, 60]. Early empir-
contrasting different variants of VRE or comparing VRE to ical investigation of this treatment was conducted using case
other active treatments. Furthermore, most studies do not in- study and series methodology. For instance, the first use in-
clude long-term follow-up (1 year or more) of participants, volved a treatment-resistant Vietnam combat veteran who was
although those that did tended to show that most treatment exposed to 2 different environments, including a virtual heli-
effects were maintained or improved, (with 1 exception copter flying over Vietnam and a clearing surrounded by jun-
[25]). In particular, studies examining treatment of phobias gle, and experienced a 34% decrease in clinician-rated symp-
other than flight phobia and spider phobia are very few and toms and a 45% decrease in self-reported symptoms, provid-
most have small and uncontrolled samples, from which little ing preliminary evidence for the feasibility and efficacy of this
can be generalized. However, some existing studies do high- approach [61]. Promising reductions in PTSD symptoms
light the unique beneficial features of VRE, including higher within VRE have been reported for a case study of a World
 Maples-Keller et al.

Trade Center attack survivor [62], a survivor of a deadly ter- usual consisted of several different approaches; as such, there
rorist bulldozer attack [63], an Operation Iraqi Freedom vet- was likely variability in what patients received. Recently, a
eran [64], and a military service member who experienced RCT compared VRE, PE, and a waitlist control in active duty
combat trauma [65]. soldiers with PTSD who had been deployed to Iraq and
Several uncontrolled case series studies have provided Afghanistan (n = 162) [74]. Both VRE and PE demonstrated
promising preliminary support for using VR technology for significantly more improvement on PTSD and depressive
extinction training within PTSD. In an uncontrolled case se- symptoms relative to waitlist control. No significant differ-
ries of motor vehicle crash survivors (n = 6), 10 sessions of ences were identified at post-treatment, but contrary to au-
VRE was associated with significant reductions in PTSD thors’ hypotheses, PE demonstrated greater improvement in
symptoms [66]. An uncontrolled case series in a sample of 6 PTSD symptoms at the 3- and 60 month follow-up compared
active duty members of the Navy with combat PTSD found with VRE. The study did not assess variables related to the
signification improvements, including reductions in PTSD, patient’s subjective experience of the virtual environment or
depression, and anxiety symptoms [67]. Another uncontrolled their degree of presence or emotional activation related to the
case series (n = 10) of combat veterans in theater found that environment. The authors note that there may have been var-
both VRE and traditional exposure therapy results in signifi- iation in how activating patients found the virtual environ-
cant improvement in PTSD symptoms [68], providing prelim- ment, and that increased options in the VR software may lead
inary support of the feasibility and effectiveness of using VRE to better VRE outcomes in the future.
in combat theater. Notably, secondary analyses of these 2 mil- Two studies have investigated VRE for PTSD augmented
itary PTSD case series [67, 68] found that VRE for PTSD also by pharmacological agents thought to either facilitate or im-
resulted in significant improvements with regard to anxiety pede the fear extinction process. A double-blind randomized
severity and performance on an the emotional Stroop test, a trial investigated the effectiveness of VRE for PTSD augment-
neuropsychological task using emotionally charged and trau- ed with D-cycloserine, which has been found to facilitate ex-
ma relevant words, while measuring reaction time and cogni- tinction in other fear-based disorders [40], or alprazolam, an
tive processing [69], providing evidence for effectiveness be- anxiolytic, versus placebo in a sample of Iraq and Afghanistan
yond PTSD specific symptoms. Across 2 trials on VRE for combat veterans (n = 156). Across all groups, VRE treatment
Vietnam veterans with PTSD (n = 21), significant reductions resulted in significant PTSD symptom improvement at post-
in PTSD were found, and notably these changes persisted at a treatment, and at 3-, 6-, and 12-month follow-up assessments,
6-month follow-up assessment [70]. In a comparison of VRE despite being purposely underdosed at only 6 sessions.
(n = 13) with waitlist control (n = 8) in World Trade Center Notably VRE resulted in improvement in psychobiological
Attack survivors, the VRE group demonstrated a significantly measures of startle and cortisol reactivity to a trauma-
greater decline in clinician-rated PTSD scores [71]. VRE re- relevant scene, providing further support for the effectiveness
sulted in a large effect size with regard to PTSD symptom of extinction training within VR approaches. Another ran-
improvement, which is particularly notable as 5 of the VRE domized trial compared VRE for PTSD with placebo and with
participants had previously completed other PTSD treatment D-cycloserine in World Trade Center survivors [75]. Both
that did not result in meaningful improvement. This study groups demonstrated significant decreases in PTSD symp-
provides preliminary support for VRE as a beneficial interven- toms at post-treatment compared with baseline, although the
tion for treatment nonresponders. The participants also had DCS group demonstrated greater improvements in both PTSD
varying traumatic experiences, including firefighters, disaster and secondary measures, providing further support for the
workers, and civilians, exposed to the World Trade Center efficacy of VRE for PTSD.
attack in varying manners, providing support to the idea that VRE has also facilitated clinical research findings in addi-
the VRE can effectively emotionally engage a variety of indi- tion to treatment effectiveness. Additional research findings
vidual and specific traumatic experiences. with regard to VRE and extinction training have been identi-
The first randomized trial to compare VRE for PTSD with fied above and beyond investigating treatment effectiveness.
an active treatment involved a comparison with present- For instance, within the trial of VRE for Iraq and/or
centered therapy for Vietnam veterans (n = 11). No significant Afghanistan veterans [76], results from cross-lagged panel
differences were found across the groups, but VRE demon- design analyses suggest that re-experiencing symptoms at
strated a moderate advantage at a 6-month follow-up assess- mid-treatment demonstrated a significant effect on the 3 other
ment. As noted by the authors, the lack of a significant differ- PTSD symptom clusters (avoidance, numbing, and hyper-
ence post-treatment was likely related to the small sample size arousal), while controlling for symptom levels at the previous
and insufficient power. In a randomized trial comparing VRE time point [77]. Re-experiencing symptoms demonstrated the
for PTSD with treatment as usual in active duty military per- largest standardized reduction across VRE treatment. This is
sonnel, the VRE group demonstrated significantly greater re- consistent with the process of extinction learning, as fear con-
ductions in PTSD symptoms [72, 73]. Notably, treatment-as- ditioning leads to stimulus-danger associations that are
Virtual Reality-Enhanced Extinction

elicited by a wide range of stimuli (e.g., re-experiencing the additional training required for providers to be able to use
symptoms). This finding also suggests that VRE effectively proficiently and skillfully the VR programs during treatment.
targets re-experiencing symptoms within PTSD treatment. Notably, the cost for VR equipment has decreased significant-
Consistent with animal fear-conditioning models, physiologi- ly in recent history, making it significantly less cost-
cal reactivity to trauma cues has been proposed as an objective prohibitive for use within clinical research and practice. For
marker of post-traumatic stress symptoms [78]. In this same instance, there is now a VR system that can be used with a
veteran sample, baseline startle responses to VR trauma- smartphone or personal computer that costs approximately
relevant cues predicted greater improvement in PTSD symp- $700; more cost-effective options such as this provide more
tom severity over time for the D-cycloserine group [78]. This opportunity for dissemination of VRE and access to VR
suggests that increased engagement with the feared VR stim- equipment. The software has also improved significantly in
uli, coupled with cognitive-enhancing properties of D-cyclo- recent years, improving both the usability and potential patient
serine, may enhance the extinction training process within experience. As noted in the previous sections, the empirical
VRE. Physiological reactivity to trauma cues was assessed literature surrounding VRE for specific phobia and PTSD
in another study in 58 veterans while they were exposed to does demonstrate limitations with regard to methodological
standardized VR combat-related stimuli [79]. Groups includ- rigor. VRE is not standardized across specific phobia or
ed veterans with PTSD, veterans who were trauma-exposed PTSD studies generally—the number of sessions can vary
but did not have PTSD, and veterans without trauma exposure significantly (from 5 to 20 [57]), which is notable given that
or PTSD, and results indicated significant differences in phys- a meta-analytic review found that an increase in VRE sessions
iological arousal across the groups. This provides support for resulted in greater effect sizes with regard to treatment out-
the relevance of extinction learning with VRE, suggesting that come [82]. Additionally, VRE often is one facet of treatment
virtual stimuli are able to represent meaningfully feared stim- that may involve several other components, such as
uli and engage conditioned fear responses. Additionally, clas- psychoeducation, anxiety management/coping skills, and cog-
sification accuracy was well above chance, suggesting that nitive restructuring. As such, dismantling studies could be
physiological activation while viewing standardized VR stim- beneficial to delineate more clearly the specific impact of
uli provides meaningful data regarding PTSD symptoms and VR within extinction training/exposure therapy. More re-
could be used as an objective assessment or outcome within search is also needed comparing VRE to standard exposure
clinical and experimental research. therapy, and to other active treatment approaches. Finally,
many of the purported advantages of VRE and its consistency
with extinction learning principles have not been directly em-
Summary of PTSD Literature pirically tested. Future research should focus on evaluating
specific aspects of the therapeutic process as opposed to a
Overall, the extant literature suggests that VRE for PTSD continued emphasis on treatment outcome [83], and could
results in significant reductions in PTSD symptoms and supe- empirically test proposed mechanisms of action within VRE.
rior outcomes compared with waitlist control conditions. Past It is notable that VRE provides several unique opportuni-
studies also suggest that VRE typically results in comparable ties for conducting clinical research. Fear-based disorders are
outcomes with standard exposure-based interventions for prime targets for translational methodology and approaches in
PTSD (e.g., prolonged exposure). However, significant vari- psychiatry, as animal models and methods can directly inform
ability with regard to methodological rigor across VR PTSD psychiatric treatment. VRE provides an opportunity to con-
studies has been noted [80]. Additionally, PTSD is frequently duct methodologically rigorous and controlled research.
comorbid with other psychiatric disorders [81], but many Specifically, VRE provides the ability to standardize exposure
studies do not provide information related to pre- and post- dose across participants, which is more difficult with tradition-
treatment comorbid conditions or symptoms. Future research al exposure therapy approaches. For instance, a recent RCT
on VRE for PTSD should include assessment of treatment investigated if receiving a reminder of feared stimulus prior to
impact on other commonly occurring comorbid symptoms, VRE/extinction training would lead to greater reductions in
as this might reveal additional effects of treatment, or, con- fear of flying compared with receiving a neutral cue based on
versely, cautions. preclinical studies suggested that reconsolidation paradigms
in animal models resulted in extinguished fear responses dur-
ing extinction training [84]. This study utilized a translational
Limitations, Future Directions, and Conclusion extinction training paradigm and was able to implement con-
trolled delivery of the reactivation/neutral cues within VR
Several limitations to the use of VRE and the extant literature while also controlling the dose of VRE. VRE also provides
exist. First, disadvantages of VRE for specific phobia include an opportunity to include more objective assessment of treat-
the initial cost, the possibility of technological glitches, and ment or experimental outcomes, such as physiological
 Maples-Keller et al.

reactivity [79]. Consistent with this notion, standardized VR 4. Anderson P, Rothbaum BO, Hodges L. Virtual reality: using the
virtual world to improve quality of life in the real world. Bull
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Menninger Clin 2001;65:78-91.
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and is being utilized in several PTSD treatment centers and the treatment of anxiety disorders. Behav Modif 1999;23:507-525.
laboratories across the country allowing for standardization of 6. Whiteford HA, Degenhardt L, Rehm J, et al. Global burden of
disease attributable to mental and substance use disorders: findings
treatment response.
from the Global Burden of Disease Study 2010. Lancet 2013;382:
In summary, VRE is consistent with models of extinction 1575-1586.
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exposure-based interventions. VR allows clinicians to engage ical activity of the cerebral cortex 1927. London: Oxford Univ.
Press.
patients in multisensory virtual environments specifically tai-
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American Psychiatric Association; 2014.
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psychiatric treatment will only increase in the future, provid- HU. Twelve-month and lifetime prevalence and lifetime morbid
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and experimental research. Psychological approaches in the treatment of specific phobias: a
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Acknowledgments Dr. Rothbaum owns equity in Virtually Better, Inc.,
Clin Psychol Rev 2007;27:266-286.
which creates virtual reality products. The terms of this arrangement have
17. Garcia-Palacios A, Botella C, Hoffman H, Fabregat S. Comparing
been reviewed and approved by Emory University in accordance with its
acceptance and refusal rates of virtual reality exposure vs. in vivo
conflict of interest policies. Dr. Rothbaum has funding from Wounded
exposure by patients with specific phobias. Cyberpsychol Behav
Warrior Project, Department of Defense Clinical Trial Grant
2007;10:722-724.
No.W81XWH-10-1-1045, BEnhancing Exposure Therapy for PTSD:
18. Krijn M, Emmelkamp PM, Ólafsson RP, et al. Fear of flying treat-
Virtual Reality and Imaginal Exposure with a Cognitive Enhancer^,
ment methods: virtual reality exposure vs. cognitive behavioral
National Institute of Mental Health Grant No. 1R01MH094757-01,
therapy. Aviat Space Environ Med 2007;78:121-128.
BProspective Determination of Psychobiological Risk Factors for
19. Maltby N, Kirsch I, Mayers M, Allen GJ. Virtual reality exposure
Posttraumatic Stress^, and McCormick Foundation BBrave Heart:
therapy for the treatment of fear of flying: a controlled investigation.
MLB’s Welcome Back Veterans SouthEast Initiative^. Dr. Rothbaum
J Consult Clin Psychol 2002;70:1112-1118.
receives royalties from Oxford University Press, Guilford, APPI, and
20. Mühlberger A, Herrmann MJ, Wiedemann G, Ellgring H, Pauli P.
Emory University and received one advisory board payment from
Repeated exposure of flight phobics to flights in virtual reality.
Genentech. All other authors have no disclosures or grant funding to
Behav Res Ther 2001;39:1033-1050.
report.
21. Mühlberger A, Wiedemann G, Pauli P. Efficacy of a one-session
virtual reality exposure treatment for fear of flying. Psychother Res
Required Author Forms Disclosure forms provided by the authors are
2003;13:323-336.
available with the online version of this article.
22. Rothbaum BO, Anderson P, Zimand E, Hodges L, Lang D, Wilson
J. Virtual reality exposure therapy and standard (in vivo) exposure
therapy in the treatment of fear of flying. Behav Ther 2006;37:80-
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