Psychological Trauma:

Theory, Research, Practice, and Policy

In the public domain 2020, Vol. 12, No. 7, 756 –764
ISSN: 1942-9681 http://dx.doi.org/10.1037/tra0000567

Changes in Physiological Reactivity in Response to the Trauma Memory

During Prolonged Exposure and Virtual Reality Exposure Therapy for
Posttraumatic Stress Disorder

Andrea C. Katz Aaron M. Norr and Benjamin Buck

VA Puget Sound Healthcare System, Seattle Division, Seattle, VA Puget Sound Healthcare System, Seattle Division, Seattle,
Washington Washington, and University of Washington School of Medicine

Emily Fantelli, Amanda Edwards-Stewart, Barbara O. Rothbaum

Patricia Koenen-Woods, Kimberlee Zetocha, Emory University School of Medicine
Derek J. Smolenski, and Kevin Holloway
National Center for Telehealth and Technology,
Tacoma, Washington

JoAnn Difede Albert Rizzo

Cornell University University of Southern California

Nancy Skopp, Matt Mishkind, and Gregory Gahm Greg M. Reger

National Center for Telehealth and Technology, VA Puget Sound Healthcare System, Seattle Division, Seattle,
Tacoma, Washington Washington, and University of Washington School of Medicine

Frank Andrasik
The University of Memphis

Objective: A key symptom of posttraumatic stress disorder (PTSD) is hyperreactivity to trauma-relevant

stimuli. Though physiological arousal is reliably elevated in PTSD, the question remains whether this
arousal responds to treatment. Virtual reality (VR) has been posited to increase emotional engagement
during prolonged exposure therapy (PE) for PTSD by augmenting imaginal exposures with trauma-
relevant sensory information. However, the comparative effects of VR exposure therapy (VRE) have
received limited empirical inquiry. Method: Ninety active-duty soldiers with combat-related PTSD

This article was published Online First April 27, 2020.
X Andrea C. Katz, V A Puget Sound Healthcare System, Seattle Divi-
sion, Seattle, Washington; Aaron M. Norr and Benjamin Buck, VA Puget
Sound Healthcare System, Seattle Division, and Department of Psychiatry
and Behavioral Sciences, University of Washington School of Medicine;
Emily Fantelli, Amanda Edwards-Stewart, Patricia Koenen-Woods, Kim-
berlee Zetocha, Derek J. Smolenski, and Kevin Holloway, National Center
for Telehealth and Technology, Tacoma, Washington; X Barbara O.
Rothbaum, Department of Psychiatry, Emory University School of Medi-
cine; JoAnn Difede, Weill Medical College, Cornell University; Albert
Rizzo, Institute for Creative Technologies, University of Southern Califor-
nia; Nancy Skopp, Matt Mishkind, and Gregory Gahm, National Center for
Telehealth and Technology; Greg M. Reger, VA Puget Sound Healthcare
System, Seattle Division, and Department of Psychiatry and Behavioral
Sciences, University of Washington School of Medicine; Frank Andrasik,
Department of Psychology, The University of Memphis.
Aaron M. Norr is now at the VISN 20 Northwest Network Mental Illness
Research, Education and Clinical Center (MIRECC), Seattle, Washington.
Amanda Edwards-Stewart, Derek J. Smolenski, and Nancy Skopp are now
at the Psychological Health Center of Excellence, Tacoma, Washington.
Patricia Koenen-Woods is now at the Rockland Psychiatric Center, Or-
angeburg, New York, and Advanced Psychological Specialists, Ridge-
wood, New Jersey. Kimberlee Zetocha is now at the St. Cloud VA Health
System, St. Cloud, Minnesota. Matt Mishkind is now at the Departments of
Psychiatry and Family Medicine, Helen and Arthur Johnson Depression
Center, School of Medicine, University of Colorado Anschutz Medical
Campus.
The authors would like to disclose the following: JoAnn Difede serves
as a consultant for Pear Therapeutics, Inc. and BehaVR, LLC; Barbara O.
Rothbaum is a co-owner of Virtually Better, Inc.; and Matt Mishkind is a
paid advisory board member of Meta Pro. This research was supported by
Grant W81XWH-08-2– 0015 from the U.S. Army Medical Research and
Materiel Command Military Operational Medicine Research Program. This
material is the result of work supported with resources and the use of
facilities at VA Puget Sound Health Care System. The authors would like
to acknowledge all who contributed to the study including two Army
Departments of Psychology. The opinions or assertions contained herein
are the private views of the authors and are not to be construed as official
or reflecting the views of the Department of Army, the Department of
Defense, or the Department of Veterans Affairs.
Correspondence concerning this article should be addressed to Greg M.
Reger, VA Puget Sound Healthcare System, Seattle Division, 9600 Vet-
erans Drive, A-116, Tacoma, WA 98493. E-mail: greg.reger@va.gov

756
 CHANGES IN GSR DURING VRE VERSUS PE FOR PTSD 757

participating in a randomized-controlled trial to receive PE, VRE, or a waitlist-control (WL) condition

had their physiological reactivity, indexed by galvanic skin response (GSR), to their trauma memories
assessed at pre-, mid-, and posttreatment. Results: Although both VRE and PE conditions showed
reduced GSR reactivity to trauma memories from pre- to posttreatment, only the VRE group differed
significantly from WL. Across the sample, reductions in GSR were significantly correlated with
reductions in self-reported PTSD and anxiety symptoms. Conclusions: This was the first study com-
paring effects of VRE and PE on psychophysiological variables. Given previous research finding limited
differences between VRE and PE in PTSD symptom reduction, these findings lend support to the
rationale for including VR in exposure therapy protocols while raising important questions about the
potential benefits of VRE.

Clinical Impact Statement

This study is among the first to examine how physiological processes change throughout PTSD
treatment and the first to compare standard exposure therapy to therapy augmented with virtual
reality (VR) in active-duty soldiers with PTSD. Results showed that soldiers in VR therapy had
smaller physical reactions to trauma memories compared to those who did not receive treatment,
whereas those who got standard treatment did not. These findings provide insight into possible
mechanisms of PTSD treatment, point to potential objective indicators of early treatment response in
active-duty soldiers, and suggest that VR treatment might lead to earlier symptom reduction.

Keywords: posttraumatic stress disorder, virtual reality, prolonged exposure, psychophysiology, military
personnel

Supplemental materials: http://dx.doi.org/10.1037/tra0000567.supp

A core feature of posttraumatic stress disorder (PTSD) is ele-
vated arousal in response to trauma-related stimuli (American
Psychiatric Association, 2013). In addition to subjective experi-
ences of hyperarousal, evidence from psychophysiological studies
has repeatedly shown that people with PTSD demonstrate height-
ened physiological reactivity to threatening and trauma-related
cues (Grillon, 2002; Orr, Metzger, & Pitman, 2002; Pitman et al.,
2012). In particular, elevated heart rate (HR) and galvanic skin
response (GSR; i.e., changes in sweat gland activity corresponding
to emotional arousal) have evidenced robust associations with
PTSD (Pole, 2007) and are specific to fear-based disorders (i.e.,
PTSD and phobias), rather than generalized anxiety and depression
(O’Kearney & Parry, 2014). Specifically, PTSD was associated
with slower GSR habituation to startling sounds, heightened rest-
ing HR, and larger HR responses to both standardized (e.g.,
generic sounds of explosions) and idiosyncratic (i.e., individual-
specific) trauma cues. A meta-analysis found that idiosyncratic
trauma cue studies had the largest effect sizes (compared to gen-
erally threatening stimuli) across the widest number of psycho-
physiological measures (Pole, 2007).
In hopes of identifying physiological markers of PTSD that
may be more objective and/or treatment-sensitive than patient
self-report, researchers are increasingly focusing on whether
(and how) physiological correlates of PTSD change with treat-
ment (Pitman et al., 2012). For example, Robison-Andrew et al.
(2014) found that reductions in the fear-potentiated startle eye-
blink response distinguished responders to prolonged exposure
(PE; Foa, Hembree, & Rothbaum, 2007) from nonresponders.
Others found that combat veterans with PTSD who completed
PE displayed reduced HR and GSR reactivity to a script-driven
imagery task from pre- to posttreatment (Wangelin & Tuerk,
2015).
PE is grounded in emotional processing theory (EPT), which
postulates that trauma memories are represented in a neural net-
work comprising feared stimuli, behavioral and psychological
avoidance of feared stimuli, and the meaning of this formed
association (Foa & Kozak, 1986). Although avoidance of feared
stimuli can be evolutionarily adaptive, in the context of PTSD, the
fear network generalizes to nonthreatening stimuli. This resultant
avoidance makes these generalized fear responses difficult to
change without treatment (Foa & Kozak, 1986). According to
EPT, effective treatment must repeatedly activate this maladaptive
fear network to modify it. To do this, patients must engage emo-
tionally with traumatic memories during “imaginal exposures.”
Findings supporting EPT have shown that early, strong emotional
engagement (EE) during imaginal exposure predicts better out-
comes when EE is defined as subjective distress (Jaycox, Foa, &
Morral, 1998) or physiological response (Wangelin & Tuerk,
2015).
A variant of PE, virtual reality exposure therapy (VRE), has
repeatedly demonstrated efficacy for treating PTSD (Carl et al.,
2019; Difede et al., 2014; Reger et al., 2011, 2016; Rizzo et al.,
2011; Rothbaum, Hodges, Ready, Graap, & Alarcon, 2001; Roth-
baum et al., 2014). VRE is hypothesized to increase EE by en-
hancing imaginal exposure with trauma-relevant sensory stimuli
(Robison-Andrew et al., 2014). This increased EE should, theo-
retically, further increase activation of the fear structure and yield
larger reductions in fear responses to nondangerous trauma stimuli
over time. However, few studies have examined this question
empirically, and none have directly compared changes in psycho-
physiology between VRE and PE. Case studies on US Navy
corpsmen found reduced GSR to distressing deployment memories
from pre- to posttreatment and improved recovery during rest
periods following recall (Wood et al., 2007, 2008). The only
758 KATZ ET AL.
controlled trial addressing this topic compared various psycho-
physiological responses (GSR, startle, and HR) of 50 combat
veterans randomly assigned to VRE with D-cycloserine enhance-
ment, VRE with alprazolam, or VRE with placebo. Veterans
across groups showed significant reductions in startle and GSR
(but not HR) responses to standardized VR combat scenarios from
pre- to posttreatment (Norrholm et al., 2016). As all participants
received VRE, it was not possible to compare these results to an
existing psychotherapy standard of care.
In the current study, we investigated how physiological reactiv-
ity—as indexed by GSR—to trauma memories changed over the
course of a randomized controlled trial (RCT) comparing PE,
VRE, and a waitlist control. Though multiple markers of physio-
logical arousal have been examined in the context of PTSD, we
focused on GSR given its robust associations with PTSD symp-
toms, the research highlighting its response to treatment, and its
minimally invasive nature. The specific aims were: to examine
how GSR changes over the course of exposure-based treatment for
PTSD; to test whether VRE reduces physiological reactivity to
trauma cues over and above the effects of PE; and to explore how
changes in psychophysiological correlates of PTSD relate to
changes in PTSD symptoms. Because habituation to a feared
stimulus is the rationale for exposure-based treatment, we expected
that GSR reactivity to idiosyncratic trauma memories would de-
crease for both active treatment groups (i.e., VRE and PE) over
time; that is, that the magnitude of the GSR to trauma memories
would diminish over the course of treatment. Though we expected
changes in GSR reactivity in both exposure therapy groups com-
pared to the control group, we expected greater GSR reductions in
the VRE group than the PE group, as VRE is posited to increase
EE and promote further reductions in fear responses during treat-
ment. We did not generate specific hypotheses about the relation-
ship between psychophysiology and self-reported symptoms, as
this aim was exploratory.
Method
Participants
Sample data were drawn from an RCT evaluating the compar-
ative efficacy of PE and VRE among active-duty U.S. soldiers
with combat-related PTSD in a minimal-attention waitlist-
controlled design (Reger et al., 2016). Participants (N ⫽ 162)
Table 1
Sample Demographics and Baseline Characteristics by Treatment Group
Characteristic PE
Number of males (%) 29 (95)
Mean Age (SD) 31.258 (6.633)
Mean CAPS weekly (SD) 77.516 (17.605)
Mean BAI (SD) 20.936 (8.752)
Mean BDI (SD) 26.226 (11.026)
Mean GSR rise (SD) 1.2113 (1.084)
Mean GSR recovery (SD) 0.117 (1.140)
Note. PE ⫽ prolonged exposure; VRE ⫽ virtual reality exposure; WL ⫽ waitlist control; CAPS ⫽ Clinician
Administered PTSD Scale; BAI ⫽ Beck Anxiety Inventory; BDI ⫽ Beck Depression Inventory-II; GSR ⫽
galvanic skin response. p values indicate statistically significant differences based on one-way analysis of
variance or ␹2 test.
provided written informed consent prior to participation and the
local Institutional Review Board reviewed and approved the study.
This article reports on GSR collected during assessments con-
ducted as part of the study. Although the physiological assess-
ments were in place at study launch, it became evident that the
quality of the physiological data initially being collected was
inadequate, and a higher quality, research-grade physiological
assessment package was subsequently acquired (Biopac MP150;
Biopac Systems Inc., 2002). This study consequently reports on
the subsample of soldiers (N ⫽ 90) with valid physiological data
collected with the improved equipment. Of the total sample, 82
completed the midtreatment assessment, and 73 completed the
posttreatment assessment. Analyses for this study retained all
randomized participants who had baseline psychophysiological
data.
Soldiers were predominantly male (94.444%). Consistent with
the sample for the parent study (Reger et al., 2016), no statistically
significant differences were found between groups in the distribu-
tion of demographic variables or baseline outcome measures (see
Table 1) for this study’s subsample.
Materials
Clinician Administered PTSD Scale (CAPS). The CAPS
(Blake et al., 1995) is a structured clinical interview that assesses
the frequency and intensity of PTSD symptoms according to
criteria in the Diagnostic and Statistical Manual of Mental
Disorders-Fourth Edition (DSM–IV; American Psychiatric Asso-
ciation, 2000). Frequency and intensity are separately coded 0 to 4.
This study used the ‘last week’ reference at all assessments. CAPS
assessors were clinical psychologists trained to diagnostic compe-
tency (␬ ⬎ .800 agreement with trauma expert; Reger et al., 2016)
who were blind to treatment group assignment. Participants were
instructed not to disclose their treatment condition to assessors.
The CAPS has demonstrated excellent convergent and discrimi-
nant validity, diagnostic sensitivity, sensitivity to symptom
change, and reliability (Weathers, Keane, & Davidson, 2001).
Consistent with previous findings, the intensity and frequency
scales demonstrated adequate internal consistency (␣ ⫽ .869 and
.870, respectively).
Beck Anxiety Inventory (BAI). The BAI (Beck & Steer,
1990) is a 21-item self-report measure of symptoms of anxiety
symptoms in the prior week. Items range from 0 (not at all) to 3
VRE WL p
27 (94) 29 (94) .292
29.931 (6.923) 30.833 (6.968) .807
84.551 (16.302) 82.600 (17.350) .261
24.310 (10.351) 24.467 (11.557) .321
28.345 (9.469) 29.233 (10.699) .514
1.296 (1.384) 1.069 (1.969) .747
0.173 (0.705) 0.471 (1.077) .338
 CHANGES IN GSR DURING VRE VERSUS PE FOR PTSD
(severely) and reflect subjective somatic or panic-related symptoms.
The BAI has been well-validated in clinical samples (Bardhoshi,
Duncan, & Erford, 2016). Consistent with previous findings, the scale
demonstrated excellent internal consistency (␣ ⫽ .888) within the
study sample.
Beck Depression Inventory-II (BDI). The BDI-II (Beck,
Steer, & Brown, 1996) is a 21-item self-report measure of depres-
sion severity over the past two weeks. Items are rated 0 (least
severe) to 3 (most severe) and reflect the core symptoms of
depression (e.g., anhedonia, depressed mood, sleep disturbance),
as well as overlapping constructs (e.g., hopelessness, helpless-
ness). The BDI-II has been well-validated in clinical samples
(Erford, Johnson, & Bardoshi, 2016). Consistent with previous
findings, the scale demonstrated excellent internal consistency
(␣ ⫽ .898) within the study sample.
Biopac MP-150 and AcqKnowledge. Psychophysiological
data were collected with the Biopac MP150 modular data acqui-
sition system and analyzed with the corresponding AcqKnowledge
4.1 software (Biopac Systems Inc., U.S.A.). Two disposable
Biopac EL507 Ag/AgCl electrodes, pregelled with isotonic gel
(0.5% chloride salt) to stabilize measurements and reduce motion
artifact, were adhered to participants’ most distal phalange (i.e.,
the fleshy part of the fingertip) on the inside surfaces of the third
and fourth fingers on their nondominant hand. Our data collection
and analysis procedures were consistent with established guide-
lines (Boucsein et al., 2012; Dawson, Schell, & Filion, 2016).
Procedure
Enrollment. Participants were active-duty soldiers with
PTSD stemming from military deployment to Iraq or Afghanistan.
Participants were either referred by clinicians at an Army medical
center or self-referred after encountering recruitment materials.
Inclusion criteria were: 1) a nonsexual assault index event that met
the diagnostic criterion for trauma according to the CAPS; 2) the
index trauma occurred at least 3 months prior to study enrollment;
and 3) the trauma occurred in an environment similar to those
available in the Virtual Iraq/Afghanistan software. Soldiers were
excluded if they had: 1) initiated a new psychotropic medication or
dosage change in the previous 30 days; 2) a history of organic
mental disorder, schizophrenia, other psychotic disorder, or bipolar
disorder; 3) been hospitalized for suicidal risk or self-harm in past
6 months; 4) an ongoing threatening situation (e.g., domestic
violence); 5) current drug or alcohol dependence; 6) a history of
seizures; 7) prior PE treatment; 8) ongoing psychotherapy for
PTSD; 9) a physical condition interfering with the ability to use a
VR head-mounted display or gaming joystick; or 10) a history of
a loss of consciousness for longer than 15 min since entering
active-duty military service.
Treatment conditions. Participants were randomly assigned
to PE, VRE, or a minimal-attention waitlist control (WL). The two
active treatments (PE and VRE) involved 10 weekly or twice-
weekly (to accommodate soldiers’ military schedules; Reger et al.,
2016) 90- to 120-min psychotherapy sessions. Both PE and VRE
were delivered in accordance with the PE manual (Foa et al.,
2007), with the exception of VRE participants’ use of the virtual
reality system during exposure to the trauma memory.
Prolonged exposure. PE is a trauma-focused, evidence-based
psychotherapy that involves psychoeducation on PTSD and com-
759
mon reactions to traumatic events, breathing retraining, repeated
imaginal exposure to the index trauma memory, cognitive and
emotional processing of material and emotions that emerge during
imaginal exposure, and in vivo exposure to safe but anxiogenic
circumstances that are avoided (Foa et al., 2007).
Virtual reality exposure. VRE was identical to PE, except
imaginal exposure was augmented with VR. VRE participants
wore a head-mounted display and were placed in a trauma-relevant
virtual Iraq/Afghanistan environment (Rizzo et al., 2010). As
participants revisited the memory, therapists customized the envi-
ronment with relevant stimuli (e.g., sights, sounds, events) to
match the memory. Participants navigated the environment using a
joystick, and manufactured smells (e.g., gun powder, body odor)
could be triggered when relevant. During treatment, participants
sat or stood on a platform with bass shaker speakers such that low
frequency sounds (e.g., engines, explosions) were also experienced
as vibrations (see Rizzo et al., 2010, 2011 for details).
Waitlist control. Participants randomized to the WL condition
completed all assessments over the course of five weeks without
receiving treatment. After completing all study procedures, they
were offered participation in PE or VRE.
Assessments. Assessments were conducted at pretreatment,
midpoint (i.e., after 5 PE or VRE sessions or 2.5 weeks of WL),
and posttreatment (i.e., after 10 PE or VRE sessions or 5 weeks of
WL). Assessments included a CAPS, self-report measures, and a
physiological activation paradigm.
Activation paradigm. After completing the CAPS and self-
report measures, participants underwent a 15-min activation par-
adigm to examine their physiological stress response (i.e., GSR) to
trauma cues. The paradigm comprised three 5-min phases. During
phase one (baseline), participants sat still, without talking, to
habituate to the psychophysiology equipment. During phase two
(trauma recall), participants thought about their index trauma.
They were asked to recall the memory in vivid sensory and
emotional detail and cue the assessor once the memory was clear
so that they would begin recording GSR for this phase. During
phase three (rest), participants relaxed using pleasant imagery.
Physiological data collection and processing. GSR was as-
sessed with research-grade physiological assessment equipment
and analyzed with a corresponding software package. GSR data
were collected with a gain setting of 5 ␮Ʊ/V and a low-pass filter
of 1.0 Hz and DC high-pass filter. Data were collected at a
sampling frequency of 1000 Hz. Skin impedances were under 10
k⍀. After data acquisition, raw GSR data were then averaged
across 1-min intervals for each 5-min phase of the stress test,
yielding 15 average GSR measurements.
Data Analysis
Physiological reactivity was operationalized in two ways: the
change in GSR (in microsimiens) from baseline to the trauma
recall (GSR-rise) and the change in GSR from trauma recall to rest
(GSR-recovery). GSR-rise was calculated by subtracting the av-
erage GSR during baseline from the average GSR during trauma
recall (larger numbers indicating greater GSR activity during
trauma recall relative to baseline). GSR-recovery was calculated
by subtracting the average GSR during recall from the average
GSR during rest (negative values indicating a drop in GSR from
recall to rest).
760 KATZ ET AL.
Mixed-effects regression models were used to examine the
changes in GSR-rise and recovery over the course of treatment. In
response to attrition throughout the study, maximum likelihood
estimates were used to account for missing data. Omnibus tests
examining the overall effects of assessment (i.e., time), treatment
group, and assessment-by-treatment interaction were conducted,
and specific hypotheses were tested with linear contrasts. The first
contrast used WL as a reference group to test whether the slopes of
GSR reactivity of the two exposure treatments (i.e., PE and VRE)
each differed from that of WL. A second contrast compared the
slopes of GSR reactivity over time in VRE and PE. Two models
were run to examine the effects of treatment on GSR-rise and
GSR-recovery. Each model included linear effects of assessment,
treatment group, and treatment group-by-assessment interaction as
fixed effects; intercept was included as a random effect. Given the
association between GSR and ambient temperature (Boucsein et
al., 2012; Dawson et al., 2016), room temperature was included as
a covariate. Pearson correlation coefficients were used to examine
the relationship between changes in psychophysiology and
changes in PTSD symptoms.
Results
Results from the ombinus mixed-effects regression model
(MRM; see Table 2) for GSR-rise indicated an overall downward
trend of assessment, meaning that across groups, the magnitude of
GSR reactivity decreased over time F(1, 151.9) ⫽ 24.501, p ⬍
.001. Results from the omnibus test also showed a significant
treatment-assessment interaction F(2, 152.3) ⫽ 3.898, p ⫽ .022.
Examination of the fixed and random effects (see Table 3) re-
vealed that the significant treatment-assessment interaction was
driven by the VRE group. Specifically, the negative slope of the
GSR-rise over time for the VRE group was significantly steeper
than that of the WL (b ⫽ ⫺.713, 95% CI [⫺1.220, ⫺.206]).
Although the negative slope of the GSR-rise over time for the PE
group was also steeper than that of the WL, this difference was not
statistically significant (b ⫽ ⫺.401, 95% CI [⫺.891, .090]). Ad-
ditionally, the difference in slopes between VRE and PE was not
statistically significant (b ⫽ .312, 95% CI [⫺.193, .817]; See
Figure 1). Results from MRMs examining GSR-recovery over
time between treatment groups did not yield any statistically
significant effects (all ps ⬎ .350).
Pearson correlations examining the relationship between change in
PTSD symptoms (e.g., CAPS-weeklyTime 3 ⫺ CAPS-weeklyTime 1)
and changes in physiological reactivity (i.e., GSR-riseTime 3 ⫺
GSR-riseTime 1) over the course of treatment showed positive
Table 2
Results of Omnibus Mixed-Effects Regression Models for GSR Rise and Recovery Over Time
Model Variable Numerator df
Rise Assessment
Treatment
Treatment ⴛ Assessment
Recovery Assessment
Treatment
Treatment ⫻ Assessment
Note. df ⫽ degrees of freedom; GSR ⫽ galvanic skin response. Parameters in boldface indicate significant
fixed effects.
relationships. Specifically, positive correlations were found be-
tween change in CAPS-weekly score and change in GSR-rise from
Time 1 to Time 3, r ⫽ .243, p ⫽ .049 as well as change in general
anxiety symptoms (BAITime 3 ⫺ BAITime 1) and change in GSR-
rise from Time 1 to Time 3 (r ⫽ .272, p ⫽ .028; see Figures 2 and
3 in online supplemental materials). No significant relationship
was observed between change in GSR-rise and change in depres-
sive symptoms.
Discussion
Our findings show that physiological reactivity to trauma-
related cues, as measured by GSR-rise, reduced over time among
individuals in trauma-focused treatments as well as those assigned
to a waitlist control condition. These changes were most evident in
the VRE group, as individuals in VRE experienced a significantly
greater decrease over time compared to those in WL. The visual
presentation of the slopes for each group over time were in the
expected direction, and favor VRE, though the difference in slopes
between VRE and PE was not statistically significant. Interest-
ingly, PE participants’ trajectories did not differ significantly from
the WL group, either. Further, across the entire sample, changes in
physiological reactivity evidenced small-to-moderate correlations
with changes in general anxiety and PTSD symptoms. Our find-
ings did not show any effects of time or treatment condition on the
second index of physiological reactivity, GSR-recovery.
The lack of significant difference between VRE and PE in
changes in physiological reactivity is consistent with the primary
RCT results demonstrating no statistically significant difference in
clinician-assessed PTSD symptoms between the two treatments at
posttreatment (Reger et al., 2016). However, the visual differences
in the slopes between VRE and PE could offer preliminary support
for the underlying rationale of VRE: that it presents more emo-
tionally engaging representations of the trauma memory, thus
yielding greater activation of the fear structure, in turn causing
greater reductions in physiological and emotional reactions to
trauma (Robison-Andrew et al., 2014). It is possible the current
study was simply underpowered to detect these differences. It
may be that differences between PE and VRE in psychophysi-
ology only emerge at follow-up. It could also be that VRE
might yield earlier treatment response, even if its overall effi-
cacy is equal to PE.
In conjunction with prior work (Reger et al., 2016), our results
present a more nuanced picture regarding outcomes when com-
paring PE to VRE. Although VRE appears to enhance reductions
in physiological responses to trauma relative to WL (while PE did
Denominator df F p
1 152.254 24.762 <.001
2 196.472 1.157 .317
2 152.174 3.931 .022
1 162.294 .105 .746
2 208.586 .375 .687
2 162.240 .544 .581
 CHANGES IN GSR DURING VRE VERSUS PE FOR PTSD 761

Table 3
Estimates of Fixed and Random Effects for GSR Rise and Recovery Over Time by
Treatment Group

Model Variable B LCI UCI

Rise Intercept ⴚ fixed .870 .357 1.382

Assessment ⫺.142 ⫺.490 .205
Treatment (VRE v. WL) .533 ⫺.196 1.262
Treatment (PE v. WL) .410 ⫺.298 1.118
Treatment (PE v. VRE) ⫺.125 ⫺.837 .588
Treatment (VRE v. WL) ⴛ Assessment ⴚ.714 ⴚ1.220 ⴚ.208
Treatment (PE v. WL) Assessment ⫺.401 ⫺.892 .088
Treatment (PE v. VRE) Assessment .313 ⫺.192 .817
Intercept ⴚ random .502 .251 .998
Recovery Intercept ⴚ fixed .453 .013 .893
Assessment .027 ⫺.302 .355
Treatment (VRE v. WL) ⫺.210 ⫺.837 .417
Treatment (PE v. WL) ⫺.252 ⫺.857 .354
Treatment (PE v. VRE) ⫺.042 ⫺.652 .567
Treatment (VRE v. WL) Assessment ⫺.118 ⫺.595 .359
Treatment (PE v. WL) Assessment .133 ⫺.330 .597
Treatment (PE v. VRE) Assessment .251 ⫺.226 .728
Intercept ⫺ random .083 .006 1.158
Note. PE ⫽ prolonged exposure; VRE ⫽ virtual reality exposure; WL ⫽ waitlist control; GSR ⫽ galvanic skin
response. Parameters in boldface indicate significant fixed or random effects.

not), and changes in these processes are associated with symptom
changes across all participants, these differences did not result in
a clear advantage for VRE over PE in symptom reduction. These
findings are consistent with previous work showing that treatment
group differences in VRE trials are more pronounced for psycho-
physiological, rather than clinical, measures (Maples-Keller et al.,
2017; Rothbaum et al., 2014). Data from this trial also showed no
difference between VRE and PE in relation to average or peak
subjective distress during exposures (Reger et al., 2019), which
was originally proposed as the method by which VRE could result
in superior treatment response (Parsons & Rizzo, 2008). If future
studies with larger samples find VRE superior to PE vis a vis
psychophysiology, this would lend support to the idea that VRE
works by increasing EE; however, at this time, the mechanism of
VRE (as compared to PE) is not clear. It is possible that EE is a
critical mechanism, but that subjective units of distress do not fully
capture this construct. Alternatively, it is possible that an unrelated
and/or unmeasured mechanism is at play. It is, of course, also
possible that these differences could be attributable to random
error, or that despite differences in point estimates for GSR, no

Figure 1. Changes in physiological reactivity throughout treatment interval by treatment condition. Results
showed that the slopes of VRE and WL groups over the course of treatment differed significantly. PE ⫽
prolonged exposure; VRE ⫽ virtual reality exposure; WL ⫽ waitlist control; GSR ⫽ galvanic skin response.
762 KATZ ET AL.
measurable benefits accrue to VRE in terms of symptom reduction
and improvement.
Identifying mechanisms of change for PE remains an important
goal of continued research, with one leading mechanism being
between-session habituation of fear responses to trauma-related
cues (Cooper, Clifton, & Feeny, 2017). However, some studies
have shown that symptom change is not dependent on within- or
between-session habituation to trauma-related cues (Bluett, Zoell-
ner, & Feeny, 2014). Our results suggest that while decreases in
physiological reactivity correlated somewhat with PTSD symptom
decreases, factors not fully captured by our physiological measure
may contribute to treatment benefit. One obvious and previously
demonstrated factor is subjective discomfort during session (Reger
et al., 2019). It is possible that a disconnect exists between phys-
iologically measured and subjectively experienced reactions to
trauma, or that physiological reactivity is merely an indicator of
treatment change rather than a central mechanism. Additional
factors may further account for treatment changes, such as cogni-
tive changes (Foa et al., 2004), out-of-session homework comple-
tion (Keller, Zoellner, & Feeny, 2010), therapeutic alliance
(McLaughlin, Keller, Feeny, Youngstrom, & Zoellner, 2014), or
even therapist effects (Laska, Smith, Wislocki, Minami, &
Wampold, 2013).
It was somewhat surprising that no effects were observed for the
GSR recovery variable, given findings from case studies of faster
GSR recovery from trauma cues post-VRE (Wood et al., 2007,
2008). It is possible that the rest phase was too brief to allow for
adequate recovery from the trauma recall. Another possibility is
that the instructions to use pleasant imagery to recover actually
stimulated the sympathetic nervous system—rather than the para-
sympathetic nervous system—which perhaps confounded the ac-
tual recovery.
This study is not without limitations. First, we encountered a
relatively high dropout rate, with only approximately 60% of
individuals in the VRE and PE groups completing all 10 sessions
of psychotherapy (Reger et al., 2016). Although the dropout rates
did not differ by treatment group (Reger et al., 2016) and missing
data were handled in a manner consistent with best practices (i.e.,
maximum likelihood estimation; Graham, 2009), attrition may
have adversely affected the results. Second, the smaller subsample
attenuated statistical power. Third, participants were all active-
duty soldiers, and most were White males, which limits general-
izability of our results. It has been shown that healthy military
personnel and civilians differ in their physiological responses to
stressful scenarios (Parsons et al., 2009), though physiological
stress reactions have not been compared in military and civilian
populations with PTSD. Given the differential scores for clinically
significant PTSD symptoms (McDonald & Calhoun, 2010), it is
possible that even disproportionate GSRs seen in PTSD might
differ between soldiers and the general population. Additionally,
the waitlist period was five weeks, and completion of treatment
usually took longer. We elected to accept this limitation rather than
ask soldiers with combat-related PTSD to wait longer for treat-
ment. Finally, the trauma recall phase relied solely on soldiers’
imaginations (without verbal recounting or audio elements).
Though this was an intentional methodological distinction between
the assessment sessions and exposure treatment sessions, it may
have allowed for experiential avoidance.
Because VRE did not generate increased subjective distress
during exposure or symptom change relative to PE (Reger et al.,
2016, 2019), these results invite continued research pertaining to
broader questions about mechanisms underlying PE and VRE.
Physiological responding is often considered an objective marker
of emotional arousal, and it appears there are divergent effects of
VRE on subjective and objective treatment responses. The nature
of psychophysiological changes in response to treatment clearly
warrant further investigation. For example, it is possible that
psychophysiological changes represent early indicators of treat-
ment response, as studies have demonstrated that reductions in
physiological response to trauma cues differentiate treatment re-
sponders from nonresponders (Griffin, Resick, & Galovski, 2012;
Robison-Andrew et al., 2014). One might also assess whether
change in physiological responding is a necessary or sufficient
condition of treatment benefits from PE. Given the heterogeneity
of PTSD presentations (Galatzer-Levy & Bryant, 2013), factor
analytic studies might examine whether posttreatment physiologic
changes are associated with particular PTSD symptoms. If repli-
cated, these results could also have important clinical implications
for providers choosing a treatment approach. Future research could
examine whether different PE paradigms might better suit sub-
groups of individuals with PTSD, such as those with primarily
hypervigilance, avoidance, or cognitive symptoms.
Overall, these results provide some support for hypothesized
mechanisms of VRE: participants in VRE had greater reductions in
GSR over time relative to waitlist, and these changes were mod-
estly correlated with changes in anxiety and PTSD symptoms.
With replication, this could provide support for proposed mecha-
nisms of benefits of VRE, though important questions remain
about whether VRE has clinical benefits above and beyond stan-
dard PE.
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Received September 13, 2019
Revision received January 31, 2020
Accepted February 13, 2020 䡲