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.

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.

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.

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 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.

Enhanced exposure therapy for combat-related Posttraumatic Stress Disorder (PTSD): Study protocol for a randomized controlled trial.

BACKGROUND: PTSD, which has been identified in up to 23% of post-9-11 veterans, often results in a chronic, pernicious course. Thus, effective treatments are imperative. The Institute of Medicine (IOM) concluded that the only intervention for PTSD with sufficient evidence to conclude efficacy is exposure therapy. This Phase III trial compares the efficacy of exposure therapy for combat-related PTSD delivered in two different formats- via virtual reality exposure therapy (VRE) or prolonged exposure therapy (PE)- combined with D-Cycloserine (DCS), a cognitive enhancer shown to facilitate the extinction of fear. METHODS/DESIGN: Military personnel of any duty status and civilians deployed to Iraq and Afghanistan were eligible. Participants were randomly assigned to 9 sessions of exposure therapy (VRE or PE) and medication (50 mg DCS or placebo). Participants were treated at three geographically diverse sites. Participants were re-assessed at 3-months post-treatment. The co-primary hypotheses are that (1) DCS will augment response to exposure therapy (both VRE and PE) on PTSD symptoms; (2) VRE will be associated with greater improvement than PE. Genetic and psychophysiological markers will be evaluated as potential moderators and mediators of treatment outcomes as well as secondary outcomes. DISCUSSION: This study is the first to compare the relative efficacy of DCS-augmented VRE versus PE on PTSD symptoms. The design has several advantages: participants received an active, effective treatment and predictors of response to treatment included genetic and psychobiological measures. The results may directly influence the future delivery of services, and contribute to the development of a standardized treatment protocol. TRIAL REGISTRATION: NCT01352637.

You can do that?!: Feasibility of virtual reality exposure therapy in the treatment of PTSD due to military sexual trauma.

This initial feasibility study examined the use of virtual reality exposure therapy (VRE) in the treatment of MST-related PTSD, with newly developed content tailored to MST. Participants included 15 veterans (26% male) with MST-related PTSD. Assessment of PTSD, depression, and psychophysiological indicators of distress occurred at pre-treatment, post-treatment, and 3-month follow-up. Treatment included 6-12 VRE sessions. There were significant reductions in pre- to post-treatment PTSD (CAPS severity: t(10) = 3.69, p = .004; PCL-5: t(10) = 3.79, p = .004) and depressive symptoms, (PHQ-9: t(8) = 2.83, p = .022), which were maintained at follow-up. There also was a significant pre- to post-treatment reduction in heart rate response to a trauma cue. Cohen's d effect sizes were large (CAPS: d = 1.11; PCL-5: d = 1.14, PHQ-9: d = .94), and the percentage of participants meeting PTSD criteria continued to decline from post-treatment (53%) to follow-up (33%). Findings indicate VRE can be safely delivered and is a promising treatment for MST-related PTSD.

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.

Randomized controlled trial of prolonged exposure using imaginal exposure vs. virtual reality exposure in active duty soldiers with deployment-related posttraumatic stress disorder (PTSD).

OBJECTIVE: Prolonged exposure (PE) is an evidence-based psychotherapy for posttraumatic stress disorder (PTSD) but there is limited research with active-duty military populations. Virtual reality exposure (VRE) has shown promise but randomized trials are needed to evaluate efficacy relative to existing standards of care. This study evaluated the efficacy of VRE and PE for active duty soldiers with PTSD from deployments to Iraq and Afghanistan. METHOD: Active-duty soldiers (N = 162) were randomized to 10-sessions of PE, VRE, or a minimal attention waitlist (WL). Blinded assessors evaluated symptoms at baseline, halfway through treatment, at posttreatment, and at 3- and 6-month follow-ups using the Clinician Administered PTSD Scale (CAPS). RESULTS: Intent-to-treat analyses found that both PE and VRE resulted in significant reductions in PTSD symptoms relative to those in the WL. The majority of patients demonstrated reliable change in PTSD symptoms. There was no difference between PE and VRE regarding treatment drop out before completing 10 sessions (44 and 41% for VRE and PE, respectively). Contrary to hypotheses, analyses at posttreatment did not show that VRE was superior to PE. Post hoc analyses found that PE resulted in significantly greater symptom reductions than VRE at 3- and 6-month follow-up. Both treatments significantly reduced self-reported stigma. CONCLUSIONS: PE is an efficacious treatment for active-duty Army soldiers with PTSD from deployments to Iraq or Afghanistan. Results extend previous evidence supporting the efficacy of PE to active-duty military personnel and raise important questions for future research on VRE. (PsycINFO Database Record

Allostatic Load as a Complex Clinical Construct: A Case-Based Computational Modeling Approach.

Allostatic load (AL) is a complex clinical construct, providing a unique window into the cumulative impact of stress. However, due to its inherent complexity, AL presents two major measurement challenges to conventional statistical modeling (the field's dominant methodology): it is comprised of a complex causal network of bioallostatic systems, represented by an even larger set of dynamic biomarkers; and, it is situated within a web of antecedent socioecological systems, linking AL to differences in health outcomes and disparities. To address these challenges, we employed case-based computational modeling (CBM), which allowed us to make four advances: (1) we developed a multisystem, 7-factor (20 biomarker) model of AL's network of allostatic systems; (2) used it to create a catalog of nine different clinical AL profiles (causal pathways); (3) linked each clinical profile to a typology of 23 health outcomes; and (4) explored our results (post hoc) as a function of gender, a key socioecological factor. In terms of highlights, (a) the Healthy clinical profile had few health risks; (b) the pro-inflammatory profile linked to high blood pressure and diabetes; (c) Low Stress Hormones linked to heart disease, TIA/Stroke, diabetes, and circulation problems; and (d) high stress hormones linked to heart disease and high blood pressure. Post hoc analyses also found that males were overrepresented on the High Blood Pressure (61.2%), Metabolic Syndrome (63.2%), High Stress Hormones (66.4%), and High Blood Sugar (57.1%); while females were overrepresented on the Healthy (81.9%), Low Stress Hormones (66.3%), and Low Stress Antagonists (stress buffers) (95.4%) profiles.

Catecholamine responses to virtual combat: implications for post-traumatic stress and dimensions of functioning.

Posttraumatic stress disorder (PTSD) symptoms can result in functional impairment among service members (SMs), even in those without a clinical diagnosis. The variability in outcomes may be related to underlying catecholamine mechanisms. Individuals with PTSD tend to have elevated basal catecholamine levels, though less is known regarding catecholamine responses to trauma-related stimuli. We assessed whether catecholamine responses to a virtual combat environment impact the relationship between PTSD symptom clusters and elements of functioning. Eighty-seven clinically healthy SMs, within 2 months after deployment to Iraq or Afghanistan, completed self-report measures, viewed virtual-reality (VR) combat sequences, and had sequential blood draws. Norepinephrine responses to VR combat exposure moderated the relationship between avoidance symptoms and scales of functioning including physical functioning, physical-role functioning, and vitality. Among those with high levels of avoidance, norepinephrine change was inversely associated with functional status, whereas a positive correlation was observed for those with low levels of avoidance. Our findings represent a novel use of a virtual environment to display combat-related stimuli to returning SMs to elucidate mind-body connections inherent in their responses. The insight gained improves our understanding of post-deployment symptoms and quality of life in SMs and may facilitate enhancements in treatment. Further research is needed to validate these findings in other populations and to define the implications for treatment effectiveness.

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.

Compelling Evidence that Exposure Therapy for PTSD Normalizes Brain Function.

Functional magnetic resonance imaging (fMRI) is helping us better understand the neurologic pathways involved in posttraumatic stress disorder (PTSD). We previously reported that military service members with PTSD after deployment to Iraq or Afghanistan demonstrated significant improvement, or normalization, in the fMRI-measured activation of the amygdala, prefrontal cortex and anterior cingulate gyrus following exposure therapy for PTSD. However, our original study design did not include repeat scans of control participants, rendering it difficult to discern how much of the observed normalization in brain activity is attributable to treatment, rather than merely a practice effect. Using the same Affective Stroop task paradigm, we now report on a larger sample of PTSD-positive combat veterans that we treated with exposure therapy, as well as a combat-exposed control group of service members who completed repeat scans at 3-4 month intervals. Findings from the treatment group are similar to our prior report. Combat controls showed no significant change on repeat scanning, indicating that the observed differences in the intervention group were in fact due to treatment. We continue to scan additional study participants, in order to determine whether virtual reality exposure therapy has a different impact on regional brain activation than other therapies for PTSD.

Heart rate response to fear conditioning and virtual reality in subthreshold PTSD.

Posttraumatic stress disorder (PTSD) is a significant health concern for U.S. military service members (SMs) returning from Afghanistan and Iraq. Early intervention to prevent chronic disability requires greater understanding of subthreshold PTSD symptoms, which are associated with impaired physical health, mental health, and risk for delayed onset PTSD. We report a comparison of physiologic responses for recently deployed SMs with high and low subthreshold PTSD symptoms, respectively, to a fear conditioning task and novel virtual reality paradigm (Virtual Iraq). The high symptom group demonstrated elevated heart rate (HR) response during fear conditioning. Virtual reality sequences evoked significant HR responses which predicted variance of the PTSD Checklist-Military Version self-report. Our results support the value of physiologic assessment during fear conditioning and combat-related virtual reality exposure as complementary tools in detecting subthreshold PTSD symptoms in Veterans.

Validity of the Virtual Reality Stroop Task (VRST) in active duty military.

Virtual environments provide the ability to systematically deliver test stimuli in simulated contexts relevant to real world behavior. The current study evaluated the validity of the Virtual Reality Stroop Task (VRST), which presents test stimuli during a virtual reality military convoy with simulated combat threats. Active duty Army personnel (N = 49) took the VRST, a customized version of the Automated Neuropsychological Assessment Metrics (ANAM)-Fourth Edition TBI Battery (2007) that included the addition of the ANAM Stroop and Tower tests, and traditional neuropsychological measures, including the Delis-Kaplan Executive Function System version of the Color-Word Interference Test. Preliminary convergent and discriminant validity was established, and performance on the VRST was significantly associated with computerized and traditional tests of attention and executive functioning. Valid virtual reality cognitive assessments open new lines of inquiry into the impact of environmental stimuli on performance and offer promise for the future of neuropsychological assessments used with military personnel.