Quantitative imaging workshop XIX: Utilizing quantitative thoracic imaging to optimize population health final summary.

Lung cancer screening involves the use of thoracic CT for both detection and measurements of suspicious lung nodules to guide the screening management. Since lung cancer screening eligibility typically requires age over 50 years along with >20 pack-year tobacco exposure, thoracic CT scans also frequently reveal evidence for pulmonary emphysema as well as coronary artery calcification. These three thoracic diseases are collectively three of the leading causes of premature death across the world. Screening for the major thoracic diseases in this heavily tobacco-exposed cohort is broadening the focus of lung cancer screening to a more comprehensive health evaluation including discussing the relevance of screen-detected findings of the heart and lung parenchyma. The status and implications of these emerging issues were reviewed in a multidisciplinary workshop focused on the process of quantitative imaging in the lung cancer screening setting to guide the evolution of this important new area of public health.

Psychophysiology during exposure to trauma memories: Comparative effects of virtual reality and imaginal exposure for posttraumatic stress disorder.

BACKGROUND: This investigation involved an in-depth examination of psychophysiological responses during exposure to the trauma memory across 10 sessions among active duty soldiers with combat-related posttraumatic stress disorder (PTSD) treated by Prolonged Exposure (PE) or Virtual Reality Exposure (VRE). We compared psychophysiological changes, session-by-session, between VRE and traditional imaginal exposure. METHODS: Heart rate (HR), galvanic skin response (GSR), and peripheral skin temperature were collected every 5 min during exposure sessions with 61 combat veterans of Iraq/Afghanistan and compared to the PTSD Checklist (PCL-C) and Clinician-Administered PTSD Scale (CAPS) outcomes using multilevel modeling. RESULTS: Over the course of treatment, participants in the PE group had higher HR arousal compared to participants in the VRE group. With reference to GSR, in earlier sessions, participants demonstrated a within-session increase, whereas, in later sessions, participants showed a within-session habituation response. A significant interaction was found for GSR and treatment assignment for within-session change, within-person effect, predicting CAPS (d = 0.70) and PCL-C (d = 0.66) outcomes. CONCLUSION: Overall, these findings suggest that exposure to traumatic memories activates arousal across sessions, with GSR being most associated with reductions in PTSD symptoms for participants in the PE group.

Predictors of involuntary and voluntary emotional episodic memories of virtual reality scenarios in Veterans with and without PTSD.

This study investigated predictors of involuntary and voluntary memories of stressful virtual reality scenarios. Thirty-two veterans of the two Persian Gulf Wars completed verbal memory tests and diagnostic assessments. They were randomly assigned to a Recounting (16) or a Suppression (16) condition. After immersion in the VR scenarios, the Recounting group described the scenarios and the Suppression group suppressed thoughts of the scenarios. One week later, participants completed surprise voluntary memory tests and another thought suppression task. The best predictors of voluntary memory were verbal memory ability, dissociation, and to a lesser extent, physiological arousal before and after scenarios. Dissociation and physiological stress responses selectively affected memory for neutral elements. Higher distress during scenarios impaired voluntary memory but increased the frequency of involuntary memories. Physiological stress responses promoted more frequent involuntary memories immediately after the scenarios. More frequent initial involuntary memories, tonic physiological arousal, and stronger emotional responses to dangerous events predicted difficulty inhibiting involuntary memories at follow-up. The effects of thought suppression were transient and weaker than those of other variables. The findings suggest that posttraumatic amnesia and involuntary memories of adverse events are more related to memory ability and emotional and physiological stress responses than to post-exposure suppression.

Virtual reality exposure versus prolonged exposure for PTSD: Which treatment for whom?

BACKGROUND: The majority of studies comparing active psychological treatments for posttraumatic stress disorder (PTSD) do not find significant differences at posttreatment. This was the case in a recent trial examining prolonged exposure (PE) and virtual reality exposure (VRE) among active-duty soldiers with combat-related PTSD. Matching individual patients to specific treatments provides a potential avenue to improve significantly the public health impact of effective treatments for PTSD. A composite moderator approach was used to identify profiles of patients who would see superior PTSD symptom reduction in VRE or PE to inform future treatment matching. METHODS: Active duty U.S. army soldiers (N = 108) were enrolled in a randomized clinical trial comparing VRE and PE in the treatment of PTSD stemming from deployments to Iraq or Afghanistan. Eighteen baseline variables were examined to identify treatment response heterogeneity in two patient groups: those with a superior response to PE and those with a superior response to VRE. The final composite moderator comprised four of 18 baseline variables. RESULTS: Results revealed that patients who were predicted to see greater PTSD symptom reduction in VRE were likely to be younger, not taking antidepressant medication, had greater PTSD hyperarousal symptoms, and were more likely to have greater than minimal suicide risk. CONCLUSIONS: Results suggest that treatment matching based on patient profiles could meaningfully improve treatment efficacy for combat-related PTSD. Future research can build on these results to improve our understanding of how to improve treatment matching for PTSD.

Camera-tracking gaming control device for evaluation of active wrist flexion and extension.

STUDY DESIGN: Cross sectional. INTRODUCTION: Measuring wrist range of motion (ROM) is an essential procedure in hand therapy clinics. PURPOSE OF THE STUDY: To test the reliability and validity of a dynamic ROM assessment, the Camera Wrist Tracker (CWT). METHODS: Wrist flexion and extension ROM of 15 patients with distal radius fractures and 15 matched controls were assessed with the CWT and with a universal goniometer. RESULTS: One-way model intraclass correlation coefficient analysis indicated high test-retest reliability for extension (ICC = 0.92) and moderate reliability for flexion (ICC = 0.49). Standard error for extension was 2.45° and for flexion was 4.07°. Repeated-measures analysis revealed a significant main effect for group; ROM was greater in the control group (F[1, 28] = 47.35; P < .001). The concurrent validity of the CWT was partially supported. CONCLUSION: The results indicate that the CWT may provide highly reliable scores for dynamic wrist extension ROM, and moderately reliable scores for flexion, in people recovering from a distal radius fracture. LEVEL OF EVIDENCE: N/A.

Psychophysiological response to virtual reality and subthreshold posttraumatic stress disorder symptoms in recently deployed military.

OBJECTIVE: Subthreshold posttraumatic stress disorder (PTSD) has garnered recent attention because of the significant distress and functional impairment associated with the symptoms as well as the increased risk of progression to full PTSD. However, the clinical presentation of subthreshold PTSD can vary widely and therefore is not clearly defined, nor is there an evidence-based treatment approach. Thus, we aim to further the understanding of subthreshold PTSD symptoms by reporting the use of a virtual combat environment in eliciting distinctive psychophysiological responses associated with PTSD symptoms in a sample of subthreshold recently deployed US service members. METHODS: Heart rate, skin conductance, electromyography (startle), respiratory rate, and blood pressure were monitored during three unique combat-related virtual reality scenarios as a novel procedure to assess subthreshold symptoms in a sample of 78 service members. The Clinician-Administered PTSD Scale was administered, and linear regression analyses were used to investigate the relationship between symptom clusters and physiological variables. RESULTS: Among the range of psychophysiological measures that were studied, regression analysis revealed heart rate as most strongly associated with Clinician-Administered PTSD Scale-based measures hyperarousal (R = 0.11, p = .035,) reexperiencing (R = 0.24, p = .001), and global PTSD symptoms (R = 0.17, p = .003). CONCLUSIONS: Our findings support the use of a virtual reality environment in eliciting physiological responses associated with subthreshold PTSD symptoms.

Virtual reality paced serial assessment test for neuropsychological assessment of a military cohort.

The assessment and treatment of traumatic brain injury (TBI) has become a difficult challenge for the DoD medical health system. Clinical neuropsychologists are being asked to make statements regarding a soldier's functional skills, ability to return to active duty, and competence in tasks of community living. Given the increasing prevalence of blast injuries to the head, and the fact that many brain injuries may have no external marker of injury, there is need for researching innovative assessment methods in detecting blast-related brain injury. To address these issues, two virtual reality-based Paced Auditory/Visual Serial Addition Tests (PA/VSAT) were developed that involve the participant being immersed in a Virtual Middle Eastern City as serial addition stimuli are presented. This study is an initial validation of the VRPASAT and VRPVSAT as assessments of neurocognitive functioning. When compared to the paper-and-pencil version of the test, as well as the Automated Neuropsychological Assessment Metrics, the VRPASAT and VRPVSAT appear to have enhanced capacity for providing an indication of a participant's performance while immersed in a military relevant simulation.

Enhancing exposure therapy for posttraumatic stress disorder (PTSD): a randomized clinical trial of virtual reality and imaginal exposure with a cognitive enhancer.

Posttraumatic stress disorder (PTSD) is a significant public health issue. Yet, there are limited treatment options and no data to suggest which treatment will work for whom. We tested the efficacy of virtual reality exposure (VRE) or prolonged imaginal exposure (PE), augmented with D-cycloserine (DCS) for combat-related PTSD. As an exploratory aim, we examined whether brain-derived neurotrophic factor (BDNF) and fatty acid amide hydrolase (FAAH) moderated treatment response. Military personnel with PTSD (n = 192) were recruited into a multisite double-blind randomized controlled trial to receive nine weeks of VRE or PE, with DCS or placebo. Primary outcome was the improvement in symptom severity. Randomization was stratified by comorbid depression (MDD) and site. Participants in both VRE and PE showed similar meaningful clinical improvement with no difference between the treatment groups. A significant interaction (p = 0.45) suggested VRE was more effective for depressed participants (CAPS difference M = 3.51 [95% CI 1.17-5.86], p = 0.004, ES = 0.14) while PE was more effective for nondepressed participants (M = -8.87 [95% CI -11.33 to -6.40], p < 0.001, ES = -0.44). The main effect of DCS vs. placebo was not significant. Augmentation by MDD interaction (p = 0.073) suggested that depressed participants improved more on placebo (M = -8.43 [95% CI -10.98 to -5.88], p < 0.001, ES = -0.42); DCS and placebo were equally effective for nondepressed participants. There was an apparent moderating effect of BDNF Val66Met polymorphism on DCS augmentation (ES = 0.67). Met66 allele carriers improved more on DCS (ES = -0.25). FAAH 385 A carriers improved more than non-carriers (ES = 0.33), particularly those with MDD (ES = 0.62). This study provides a step toward precision therapeutics for PTSD by demonstrating that comorbid MDD and genetic markers may help guide treatment selection.ClinicalTrials.gov Identifier: NCT01352637.

Technology and Mental Health: State of the Art for Assessment and Treatment.

Technology is ubiquitous in society and is now being extensively used in mental health applications. Both assessment and treatment strategies are being developed and deployed at a rapid pace. The authors review the current domains of technology utilization, describe standards for quality evaluation, and forecast future developments. This review examines technology-based assessments of cognition, emotion, functional capacity and everyday functioning, virtual reality approaches to assessment and treatment, ecological momentary assessment, passive measurement strategies including geolocation, movement, and physiological parameters, and technology-based cognitive and functional skills training. There are many technology-based approaches that are evidence based and are supported through the results of systematic reviews and meta-analyses. Other strategies are less well supported by high-quality evidence at present, but there are evaluation standards that are well articulated at this time. There are some clear challenges in selection of applications for specific conditions, but in several areas, including cognitive training, randomized clinical trials are available to support these interventions. Some of these technology-based interventions have been approved by the U.S. Food and Drug administration, which has clear standards for which types of applications, and which claims about them, need to be reviewed by the agency and which are exempt.

Effectiveness of virtual reality exposure therapy for active duty soldiers in a military mental health clinic.

Exposure therapy is an evidence-based treatment for posttraumatic stress disorder (PTSD), but research evaluating its effectiveness with active duty service members is limited. This report examines the effectiveness of virtual reality exposure therapy (VRE) for active duty soldiers (N = 24) seeking treatment following a deployment to Iraq or Afghanistan. Relative to their pretreatment self-reported symptoms on the PTSD Checklist, Military Version (M = 60.92; SD = 11.03), patients reported a significant reduction at posttreatment (M = 47.08; SD = 12.70; p < .001). Sixty-two percent of patients (n = 15) reported a reliable change of 11 points or more. This study supports the effectiveness of exposure therapy for active duty soldiers and extends previous research on VRE to this population.

An intelligent virtual human system for providing healthcare information and support.

Over the last 15 years, a virtual revolution has taken place in the use of Virtual Reality simulation technology for clinical purposes. Shifts in the social and scientific landscape have now set the stage for the next major movement in Clinical Virtual Reality with the "birth" of intelligent virtual humans. Seminal research and development has appeared in the creation of highly interactive, artificially intelligent and natural language capable virtual human agents that can engage real human users in a credible fashion. No longer at the level of a prop to add context or minimal faux interaction in a virtual world, virtual humans can be designed to perceive and act in a 3D virtual world, engage in spoken dialogues with real users and can be capable of exhibiting human-like emotional reactions. This paper will present an overview of the SimCoach project that aims to develop virtual human support agents to serve as online guides for promoting access to psychological healthcare information and for assisting military personnel and family members in breaking down barriers to initiating care. The SimCoach experience is being designed to attract and engage military Service Members, Veterans and their significant others who might not otherwise seek help with a live healthcare provider. It is expected that this experience will motivate users to take the first step--to empower themselves to seek advice and information regarding their healthcare and general personal welfare and encourage them to take the next step towards seeking more formal resources if needed.

Methylphenidate effect in children with ADHD can be measured by an ecologically valid continuous performance test embedded in virtual reality.

BACKGROUND: Continuous performance tasks (CPTs) embedded in a virtual reality (VR) classroom environment have been shown to be a sensitive and user-friendly assessment tool to detect cognitive deficits related to attention-deficit/hyperactivity disorder (ADHD). The aim of the current study was to compare the performance of children with ADHD on a VR-CPT while on and off treatment with methylphenidate (MPH) and to compare the VR-CPT to a currently used CPT, Test of Variables of Attention (TOVA). METHODS: Twenty-seven children with ADHD underwent the VR-CPT, the same CPT without VR (no VR-CPT), and the TOVA, 1 hour after the ingestion of either placebo or 0.3 mg/kg MPH, in a double-blind, placebo-controlled, crossover design. Immediately following CPT, subjects described their subjective experiences on the Short Feedback Questionnaire. RESULTS: MPH reduced omission errors to a greater extent on the VR-CPT compared to the no VR-CPT and the TOVA, and decreased other CPT measures on all types of CPT to a similar degree. Children rated the VR-CPT as more enjoyable compared to the other types of CPT. CONCLUSIONS: It is concluded that the VR-CPT is a sensitive and user-friendly assessment tool in measuring the response to MPH in children with ADHD.

User-centered virtual environment design for virtual rehabilitation.

BACKGROUND: As physical and cognitive rehabilitation protocols utilizing virtual environments transition from single applications to comprehensive rehabilitation programs there is a need for a new design cycle methodology. Current human-computer interaction designs focus on usability without benchmarking technology within a user-in-the-loop design cycle. The field of virtual rehabilitation is unique in that determining the efficacy of this genre of computer-aided therapies requires prior knowledge of technology issues that may confound patient outcome measures. Benchmarking the technology (e.g., displays or data gloves) using healthy controls may provide a means of characterizing the "normal" performance range of the virtual rehabilitation system. This standard not only allows therapists to select appropriate technology for use with their patient populations, it also allows them to account for technology limitations when assessing treatment efficacy. METHODS: An overview of the proposed user-centered design cycle is given. Comparisons of two optical see-through head-worn displays provide an example of benchmarking techniques. Benchmarks were obtained using a novel vision test capable of measuring a user's stereoacuity while wearing different types of head-worn displays. Results from healthy participants who performed both virtual and real-world versions of the stereoacuity test are discussed with respect to virtual rehabilitation design. RESULTS: The user-centered design cycle argues for benchmarking to precede virtual environment construction, especially for therapeutic applications. Results from real-world testing illustrate the general limitations in stereoacuity attained when viewing content using a head-worn display. Further, the stereoacuity vision benchmark test highlights differences in user performance when utilizing a similar style of head-worn display. These results support the need for including benchmarks as a means of better understanding user outcomes, especially for patient populations. CONCLUSIONS: The stereoacuity testing confirms that without benchmarking in the design cycle poor user performance could be misconstrued as resulting from the participant's injury state. Thus, a user-centered design cycle that includes benchmarking for the different sensory modalities is recommended for accurate interpretation of the efficacy of the virtual environment based rehabilitation programs.

[The utility of a continuous performance test embedded in virtual reality in measuring the effectiveness of MPH treatment in boys with ADHD].

BACKGROUND: Continuous performance tasks (CPT) are popular in the diagnostic process of attention deficit hyperactivity disorder (ADHD), providing an objective measure of attention for a disorder with otherwise subjective criteria. AIMS: The study aimed to: 1) examine whether the VR-CPT is sensitive to methylphenidate (MPH); 2) assess how the virtual reality (VR) environment is experienced. METHODS: Twenty boys, 9-17 years, with ADHD underwent 3 CPTs: VR-CPT, the same CPT without VR (no VR-CPT) and the Test of Variables of Attention (T.O.V.A.). Subsequently, those with ADHD repeated the tests 1 hour following MPH ingestion. Immediately following the CPT, the subjects described their subjective experiences on the Short Feedback Questionnaire. Results were analyzed using ANOVA with repeated measures. RESULTS: MPH reduced the omission and commission errors on all tests to a similar degree. Subjective feelings of enjoyment were most positive for VR-CPT. CONCLUSION: The VR-CPT is a sensitive and user-friendly assessment tool for evaluating the effectiveness of MPH treatment in boys with ADHD.

Virtual Remediation Versus Methylphenidate to Improve Distractibility in Children With ADHD: A Controlled Randomized Clinical Trial Study.

Objective: Virtual environments have been used to assess children with ADHD but have never been tested as therapeutic tools. We tested a new virtual classroom cognitive remediation program to improve symptoms in children with ADHD. Method: In this randomized clinical trial, 51 children with ADHD (7-11 years) were assigned to a virtual cognitive remediation group, a methylphenidate group, or a psychotherapy group. All children were evaluated before and after therapy with an ADHD Rating Scale, a Continuous Performance Test (CPT), and a virtual classroom task. Results: After therapy by virtual remediation, children exhibited significantly higher numbers of correct hits on the virtual classroom and CPT. These improvements were equivalent to those observed with methylphenidate treatment. Conclusion: Our study demonstrates for the first time that a cognitive remediation program delivered in a virtual classroom reduces distractibility in children with ADHD and could replace methylphenidate treatment in specific cases.

Heart Rate Variability as an Index of Resilience.

INTRODUCTION: Resilience is the ability to maintain or quickly return to a stable physical and psychological equilibrium despite experiencing stressful events. Flexibility of the autonomic nervous system is particularly important for adaptive stress responses and may contribute to individual differences in resilience. Power spectrum analysis of heart rate variability (HRV) allows measurement of sympathovagal balance, which helps to evaluate autonomic flexibility. The present study investigated HRV as a broad index of resilience. MATERIALS AND METHODS: Twenty-four male participants from the Army National Guard Special Forces completed psychological measures known to relate to resilience and had HRV measured while undergoing stressful virtual environment scenarios. Pearson product-moment correlations were used to explore the relationships between HRV and resilience factors. All research was conducted with the oversight of the Human Subjects Review Committee of Fuller Theological Seminary. RESULTS: Trends toward significance were reported in order to provide results that would reasonably be expected in a study of higher power. Trends between resilience factors and HRV were found only during specific stress-inducing simulations (see Tables III). CONCLUSION: Greater resilience to stress was associated with HRV during nonstress periods. Higher levels of resilience to traumatic events were associated with HRV during circumstances that were more stressful and emotionally distressing. Post hoc analysis revealed that specific factors including flexibility, emotional control, and spirituality were driving the relationship between general resilience and HRV following emotionally laden stressors. Less stress vulnerability was associated with HRV following intermittent brief stressors. In sum, HRV appears to represent some aspects of an individual's overall resilience profile. Although resilience remains a complex, multidimensional construct, HRV shows promise as a global psychophysiological index of resilience. This study also offers important perspectives concerning ways to optimize both physical and psychological health.

Soldier evaluation of the virtual reality Iraq.

Repeated combat deployments to Iraq and Afghanistan are resulting in increased rates of posttraumatic stress disorder (PTSD) among military personnel. Although exposure therapy is an effective treatment for this disorder, some personnel do not significantly respond to treatment, possibly due to poor activation of the trauma memory or a lack of emotional engagement during therapy. In addition, some service members do not seek mental healthcare due to treatment stigma. Researchers recently developed a virtual reality (VR) Iraq to attempt to improve activation of the traumatic memory during exposure therapy and to provide a treatment approach that may be more appealing to some service members, relative to traditional face-to-face talk therapy. Initial validation of the application requires an assessment of how well it represents the experiences of previously deployed service members. This study evaluated the realism of the VR Iraq application according to the subjective evaluation of 93 U.S. Army soldiers who returned from Iraq in the last year. Those screening negative for PTSD used and evaluated a VR tactical convoy and a VR dismounted patrol in a simulated Middle Eastern city. Results indicated that 86% of soldiers rated the overall realism of the VR convoy as ranging from adequate to excellent. Eighty-two percent of soldiers reported adequate-to-excellent overall realism of the city environment. Results provide evidence that the VR Iraq presents a realistic context in which VR exposure therapy can be conducted. However, clinical trials are needed to assess the efficacy of VR exposure therapy for Iraq veterans with PTSD.

Neurocognitive and psychophysiological analysis of human performance within virtual reality environments.

Monitoring the neurocognitive and psychophysiological activity of persons operating within a complex environment poses exacting measurement challenges. Three experiments are reported in this paper. In these experiments we made use of VRCPAT to assess persons' neurocognitive and psychophysiological responses to high-fidelity, immersive virtual environments. The first experiment provided continued support for the validity of the VRCPAT as a measure of learning and memory through the use of an increased sample size. In the second experiment we aimed at assessing whether an increase in stimulus complexity would result in a significant decrease in performance on attentional tasks. We also wanted to see whether an increase in stimulus intensity would result in a significant decrease in performance on attentional tasks. The third experiment looked at participants' psychophysiological responses in both low and high immersion virtual environments.

A virtual human agent for assessing bias in novice therapists.

Monitoring the psychological and physiological activity of persons interacting with virtual humans poses exacting measurement challenges. Three experiments are reported in this paper. In these experiments we made use of Virtual Human Agent technology to assess persons' psychological and physiological responses to Virtual Standardized Patients. The first experiment provided support for the usability of the Virtual Standardized Patients through the use of a virtual character emulating an adolescent male with conduct disorder. In the second experiment we further developed the technology and aimed at assessing whether novice mental health clinicians could conduct an interview with a virtual character that emulates an adolescent female who has recently been physically traumatized. The third experiment looked at the usability of Virtual Standardized Patients for eliciting psychophysiological responses following exposure to virtual humans representing different ethnicities.

VR PTSD exposure therapy results with active duty OIF/OEF combatants.

Post Traumatic Stress Disorder (PTSD) is reported to be caused by traumatic events that are outside the range of usual human experience including military combat, violent personal assault, being kidnapped or taken hostage and terrorist attacks. Reports indicate that at least 1 out of 6 Iraq War veterans are exhibiting symptoms of depression, anxiety and PTSD. Virtual Reality exposure therapy has been previously used for PTSD with reports of positive outcomes. This paper will present a brief description of the USC/ICT Virtual Iraq/Afghanistan PTSD therapy application and present clinical outcome data from active duty patients treated at the Naval Medical Center-San Diego (NMCSD) as of October 2009. Initial outcomes from the first twenty patients to complete treatment indicate that 16 no longer meet diagnostic criteria for PTSD at post treatment. Research and clinical tests using the Virtual Iraq/Afghanistan software are also currently underway at Weill Cornell Medical College, Emory University, Fort Lewis and WRAMC along with 20 other test sites.