Virtual reality exposure therapy is an innovative treatment for PTSD that uses VR simulations to gradually expose patients to trauma-related stimuli in a safe environment. A study found VR therapy significantly reduced PTSD symptoms in WTC responders compared to a waitlist group. Adding D-cycloserine to VR therapy further improved outcomes. VR therapy principles have also been applied to treat combat-related PTSD and specific phobias. While promising, wider adoption of VR therapy faces challenges related to cost and technology limitations. Continued research aims to enhance VR systems and applications for additional mental health conditions.

1. JoAnn Difede, Ph.D.
Professor, Department of Psychiatry, Director of Program for
Anxiety and Traumatic Stress Studies
Weill Cornell Medical College of Cornell University
On the precipice of a paradigm shift: transforming the way we
treat trauma(and phobias) using virtual reality simulations

2. Innovations in the Treatment of PTSD:
On the Precipice of a Paradigm Shift?
1. Delivering empirically-validated treatments
2. Virtual Reality treatment for PTSD
3. Novel pharmacotherapeutic interventions for PTSD
4. Genetics: Toward precision medicine
5. From the laboratory to your home: is virtual reality technology almost “turnkey”?

3. “Practice two things in your dealings with
disease: either help or do not harm the
patient”
Epidemics, Book 1, Hippocratic School of Medicine

4. September 10th, 2001: The State of PTSD Treatment
• One evidence-based treatment with persuasive evidence:
Prolonged exposure (PE) therapy (Foa, 1999)
• Recommended by Expert Consensus Guidelines
• No controlled clinical trials for PTSD in first responders
• One FDA approved medication for PTSD: Zoloft

5. CORNELLU N I V E R S I T Y
16% of 71,000 people in WTC registry had
probable PTSD six years after the event
(Thorpe, et al., JAMA, 2009)
Rates of combat-related PTSD in U.S. soldiers
returning from Iraq and Afghanistan are
estimated at up to 20.7% in active duty and
30.5% in National Guard (Thomas, 2010)

6. At first, there was the Word
• Established psychotherapies rely on verbal communication of
experience
• Virtual Reality Therapy incorporates many of the non-verbal or
sensory elements of experience
• May allow for the emotional processing of non-verbal elements of
experience (sight, sound, olfaction, kinesthesis)
• Bypasses personal sense of “agency” or effortful recall (esp. useful
for those who are avoidant)

7. Rationale for Using VR
• VR enhances emotional involvement
• VR provides multisensory cues that help the patient to engage
with the story.VR affords opportunities to enhance patients’
normal narrative capacities with visual, auditory, and haptic
computer-generated experiences. These multi-sensory cues can
facilitate emotional engagement for exposure treatment
• VR makes it possible to have graded exposure

8. Rationale for VR Treatment
• VR as a tool to enhance emotional learning
• In vivo exposure often impractical or impossible
• Manipulate environment without the constraints of the “real” world
• Cost
• Patient preference: studies suggest patients prefer VR to imaginal or in
vivo

9. What is Virtual
Reality Exposure
Therapy?
• In the context of anxiety and trauma disorders, VR
technology and VR simulations of trauma and phobic experiences, may best be viewed as tools
to facilitate learning, e.g., extinction learning
• An immersive virtual reality system for trauma treatment hastypically consisted of
special 3-D software, head tracking sensors, and a helmet mounted visual display
• For ex., a ‘high presence’ simulation software used to create the WTC simulation allowed
for the creation in 3-D of explosions, realistic fire, billowing smoke and converging audio
sound (Is high presence necessary to facilitate a therapeutic effect?)

10. A marriage of the modern and the classical
Virtual Reality Therapy integrates cutting edge technology with
established and well validated principles of behavioral
psychotherapies

11. Fear Conditioning in Humans: Escape down a
stairwell at the WTC 9/11/01

12. Virtual Reality Exposure Therapy for the Treatment of PTSD
Following the World Trade Center Attack (Difede, Cukor,
Jayasinghe, Hoffman J Clinical Psychiatry, 2007, Cyberpsychology, 2002)
Battalion Chief
Naval reserve pilot
No prior psychiatric history
Second patient in VR study when it was very
much still an experiment

14. VR Exposure Hierarchy
1. WTC and surrounding buildings, clear, blue skies
2. Plane flies overhead, no crash
3. Plane crashes, no explosion
4. Plane crashes, explosion, no sound
5. Plane crashes, explosion, with sound
6. Building burns, no screams
7. Building burns, screams heard
8. Building burns, screams heard, people jumping
9. Second plane hits, full visual effects with sound
10. Second tower falls
11. First tower falls
12. Full sequence

15. Results: Significant decrease in PTSD Severity in
the VR group but not in the waitlist group(Difede, Hofman,
et al, J Clin Psychiatry, 2007, Cyberpsychology, 2002)
•Main effect of time: ns
•Time by Group interaction: p < .01
•Between groups effect size: 1.54
•Interaction effect size=.40

16. Translational Study Design: From Bench to
Bedside
• 100 mg D-Cycloserine (DCS) or placebo taken orally 90 minutes before
exposure sessions
• D-Cycloserine (DCS)
• Anti-tuberculosis drug for 50 years
• Recognized as an NMDA partial agonist, and potential cognitive
enhancer in late ’80s
• Facilitates extinction of fear response
• Genotyping for the BDNF SNP (Val66Met) by standard PCR methods from
saliva samples
• To assess for polymorphism associated with higher trait anxiety/resistance
to extinction

17. RCT VR +/-DCS for WTC Related PTSD: Mean
Caps Scores over Time (Difede, et al., 2013, Neuropsychopharmacology)

18. PTSD Remission Rates
 Defined as CAPS total score of ≤ 20 and minimal or no
impairment in social, occupational and other important
areas of functioning (CAPS Items F21 and F22 ≤ 1)
(Difede, et al., 2013, Neuropsychopharmacology)
p<.05
VRE-DCS VRE-Placebo
Posttreatment 6/13 (46%) 1/12 (8%)
6 month Follow-up 9/13 (69%) 2/12 (17%)

20. Enhancing Exposure Therapy for
PTSD: Virtual Reality and
Imaginal Exposure with a
Cognitive Enhancer
DoD Award #: W81XWH-10-1-1045 (Lead PI: Difede)

21. The Foundation of the Virtual Reality Treatment
Protocol for Combat-Related PTSD
Virtual Vietnam 1998
• Rothbaum, B. O., Hodges, L., Alarcon, R.,
Ready, D., Shahar, F. Graap, K. Pair, J.,
Hebert, P., Gotz, D., Wills, B. & Baltzell,
D. (1999). Virtual reality exposure
therapy for PTSD Vietnam veterans: A case
study. Journal of Traumatic Stress,12,
263-271.
• Rothbaum, B. O., Hodges, L. F., Ready, D.,
Graap, K., & Alarcon, R. (2001). Virtual
reality exposure therapy for Vietnam
veterans with posttraumatic stress disorder.
Journal of Clinical Psychiatry, 62, 617-
622.
Virtual WTC 2001
• Difede, J., & Hoffman, H. (2002). Virtual
reality exposure therapy for PTSD following
the WTC: A case report. Cyberpsychol
Behav, 5(6): 529-535.
• Difede, J., Cukor, J., Patt, I., Giosan, C., &
Hoffman, H. (2006). The application of
virtual reality to the treatment of PTSD
following the WTC attack. Ann NY Acad Sci,
1071: 500-501.
• Difede, J., Cukor, J., Jayasinghe, N., Patt, I.,
Jedel, S., Giosan, C., & Hoffman, H. (2007).
Virtual reality exposure therapy for the
treatment of posttraumatic stress disorder
following September 11, 2001. Journal of
Clinical Psychiatry, 68: 1639-1647.

22. Design and Methodology
• Multi-site, randomized, controlled clinical trial
• 2 x 2 design
• VRE or IE protocol
• 50 mg D-Cycloserine (DCS) or placebo given 30 minutes prior to
session only
• 9 weekly sessions, including 7 exposure therapy sessions
• Genotyping for the BDNF SNP (Val66Met) by standard PCR
methods from saliva samples
• Psychophysiological assessment including laboratory startle
assessment and fear conditioning

23. VR Iraq

24. Combat-related PTSD video

25. VR Iraq: Desert Scene

26. Market_Ambient_Prayer_Call

27. • Other VR “worlds” for the treatment of
PTSD

28. Burn World: “The Grandmother Burn” (Design by Difede, Biosan, et al.)

29. Hurricane Katrina (Design by Ken Graap, Mirtha Ferrer, JoAnn Difede,

30. Hurricane Katrina:Attic entrance(Design by Ken Graap, Mirtha
Ferrer, JoAnn Difede, and the Virtually Better Team)

31. Virtual Vietnam
(Hodges, Rothbaum, Pair, et al.)
This occurred over 20 years
following the end of the
Vietnam War
35%-45% decrease in PTSD

32. VR PTSD Examples
• Terrorist Bus Bombing - U. of Haifa/U of Wash.
HIT Lab

33. Future Directions: Developing a third-person
perspective (3PP) in Virtual Reality
– Existing VR applications in PTSD and phobias are
implemented exclusively in first-person perspective
(1PP)
• Traditionally rooted in exposure, which requires this
• 3PP and 1PP are cognitively, emotionally, and
neurobiologically distinct

34. • Though 1PP is generally more immersive (which is why it is used in exposure), 3PP may
enhance certain learning tasks
- In depressive rumination, self-distancing by adopting 3PP narrative enhances learning
• Using a 3PP in VR is specifically hypothesized to be useful in:
- Cognitive processing of traumatic events (developing new insights)
- For cases of PTSD with comorbid depression (addressing rumination)
- When VR 1PP is emotionally overwhelming for patients

35. Challenges in wide-spread adoption of VR
technology for trauma and anxiety disorder
treatment
• Cost (25K HMD in 2001)
• Technology not yet “turn-key”
• Need platform that is web-based and flexible to be
used across multiple brain-based disorders
(neurologic, psychiatric)
• Healthcare inherently conservative professions

36. March 2014:
Facebook purchases Oculus VR
(creator of Oculus Rift) for $2 Billion

37. Treatment of phobias

38. Current Virtual Worlds for Phobias:
• Airplane
• Bridges
• Elevators
• Heights
• Job Interview
• Public Speaking
• Thunderstorms

39. Journal of Journal of
Behavior Therapy
VR Anxiety Disorders
Meta-Analysis
2008

41. Other psychological/psychiatric
disorders
• Eating Disorders
• ADHD
• Autism
• Pain
• Personality Disorders?