ViRTICo : Vi rtual R eality T herapy and I maging in Co mbat Veterans

1. ViRTICo: Virtual Reality Therapy and Imaging in Combat Veterans COL Michael J. Roy, M.D., M.P.H. Director, Division of Military Medicine Professor of Medicine Uniformed Services University Bethesda, MD

2. WRAMC/USU Greg Lande Patricia Taylor Jennifer Francis Josh Friedlander Lisa Banks-Williams Vanita Tarpley Wendy Law NIMH Meena Vythilingam James Blair Husseini Manji Jennifer McLellan Allan Mallinger Stephen Sinclair Collaborators

3. Other Key Consultants • Barbara Rothbaum, Emory University • Skip Rizzo, Inst for Creative Technologies, USC • JoAnn Difede, Weill Medical School, Cornell • Ivy Patt (therapist supervision and fidelity assessments)

4. Funding • Office of Naval Research, $900,000 • Russ Shilling, Project Manager

5. Aims of ViRTICo I • Establish utility of functional MRI to distinguish OIF/OEF veterans with PTSD and mild TBI (“blast exposure”) from combat-exposed controls • Identify efficacy of Virtual Reality Exposure Therapy (VRET) for combat-related PTSD, compared to current first-line therapy, Foa’s Prolonged Imaginal Exposure (PE)

6. Mild TBI • No penetrating trauma or shrapnel • < 1-2 mins’ loss of consciousness • Lower end of range ill-defined: • Symptoms attributed to blast include headaches, dizziness, tinnitus, irritability, sleep problems, memory or balance problems • Medical literature: 2/3 don’t meet criteria for concussion, but 15-29% have persistent cognitive impairment (attention span, memory, executive function)

7. Hypotheses • fMRI can reproducibly distinguish between veterans with PTSD, mild TBI, both, and neither • Digital photos may be more effective at this than current validated tests such as the Stroop • VRET is non-inferior to PE in treatment of PTSD • VRET might accelerate response rate

8. Study Questionnaires • CAPS to confirm diagnosis (score of 40), and at end of treatment and follow up • PCL-M and PC-PTSD more frequently • BDI and BAI for depression, anxiety • CAGE, AUDIT for alcohol • SCID-I,II for other psych disorders • DVBIC questionnaire for TBI • SF-36 and WHO-DAS II: functional status

9. Functional MRI • Blood oxygen level dependent (BOLD) • Stimulation causes feedback loop to increase oxygenation within specific brain areas, increases intensity on T2 images • Prior studies show greater amygdala and decreased prefrontal activation for PTSD than trauma-exposed controls

10. fMRI phase of study • Compare 4 groups of 22 each • PTSD and TBI • PTSD only • TBI only • Deployed, no PTSD or TBI • Two stimuli used in scanner • Affective Stroop: previously validated • Digital photos from Iraq & Afghanistan • Repeat fMRI after treatment for PTSD

11. Digital photos taken by soldiers • Emotionally charged scenes • Emotionally neutral scenes • Judged by veterans, providers

12. Treatment phase subjects • 44 subjects randomized to VRET or PE • 22 subjects each with PTSD alone and PTSD plus TBI from fMRI phase • Individuals with shrapnel preventing fMRI may enter treatment phase directly, so additional subjects will be recruited to fill fMRI phase slots

13. VR Exposure Therapy • 12 90-minute sessions, average 2 per week • Manualized treatment adapted from Difede, in turn based on Virtual Vietnam • Begin with CBT approach • Homework, relaxation techniques • VR introduced @ 4th session, ½ of session • 1st person, present tense • Therapist choreographed, following SUDS, physiologic monitoring to guide progression • Includes characteristic audio, video, and olfactory features of Middle East

14. Prolonged Exposure • Manualized treatment, based on work by Edna Foa, UPenn • Same length (90 mins) and number of sessions (12) and overall approach as for VRET arm

16. Visual, Auditory, and Controls

17. Vibration platform • Explosions • Vehicle movement

18. Olfactory stimulation • Theoretic basis: olfactory bulb proximity to hippocampus, and long phylogenetic history • Iraqi spices • Chordite • Body Odor • Burning Rubber • Burning Trash

19. Physiologic Monitoring • Heart rate • Blood pressure • Respiratory rate • Skin conductance • HRV

20. 3 computer set-up

21. Outcome measures • CAPS at end of treatment and q 4 weeks for 12 weeks of follow up • PCL-M and PC-PTSD • BDI, BAI for depression, anxiety • CAGE, AUDIT for alcohol abuse/dep • SF-36 and WHODAS-II for functional status

22. Initial participants (n=17) • 2 withdrew during baseline eval, 2 ineligible due to subthreshold PTSD • 8 completed baseline including fMRI, 2 had shrapnel, 1 aborted fMRI, 2 pending • Four completed treatment; one withdrew during treatment; 3 in active treatment • Demographics: 1 female; 1 Hispanic, 3 African-Americans; age range: 24-49

23. PCL Scores: VR arm

24. CAPS: VR arm

25. PCL Scores: PE arm

26. Challenges encountered • Recruitment: high rate of alcohol abuse • Amended protocol to relax entry criteria • Distinguishing mild TBI problematic • Relies on self-report • Mild TBI rarely unaccompanied by PTSD symptoms • Secondary gain issues sometimes interfere with reported response

27. Summary • Numbers small, but only 1 of 3 in VR arm had a 30% decrease in CAPS; 0/2 in PE arm • But, significant behavioral changes noted • Hard for subjects to acknowledge improvement for fear of losing benefits • fMRI and physiologic measures not yet analyzed

28. Questions?