Network Dysregulation Among Individuals With Comorbid Tinnitus and PTSD
Phase: NA
Conditions: Stress Disorders, Post-Traumatic, Tinnitus
Sponsor: The University of Texas Health Science Center at San Antonio

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COVER PAGE FOR PROTOCOL AND STATISTICAL ANALYSIS 
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PLAN 
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Official Study Title: Network Dysregulation Among Individuals with 
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Co-Morbid Tinnitus and PTSD 
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NCT number: NCT03702166 
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IRB Approval Date: 02/28/2020 
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1.  PROTOCOL TITLE:  Network Dysregulation Among Individuals with Co-Morbid Tinnitus and PTSD 
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2.  ABSTRACT   
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Tinnitus and posttraumatic stress disorder (PTSD) are two of the most common combat-related disorders. Although the 
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defining symptoms of tinnitus (an illusory auditory percept) and PTSD (a trauma-related disorder) are clearly different, they 
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are highly comorbid. Neurobiologically, each disorder has been characterized as functional network dysregulations, applying 
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functional co-variance (FCov) metrics to resting-state functional magnetic resonance imaging (rs-fMRI). In PTSD, network 
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abnormalities have been reported in the attention, limbic and default-mode networks. In tinnitus, the same networks have 
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been reported as abnormal, with the addition of the auditory network. Given the hypothesized shared neurobiological resting 
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state networks between tinnitus and PTSD, it is anticipated that treatment of PTSD will also help alleviate tinnitus distress.  
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The purpose of this study is to characterize tinnitus and PTSD symptomatically, neurobiologically, and causally, applying 
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causal modeling to psychometric and neurofunctional data. We will enroll 30 individuals with both tinnitus and PTSD. 
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Participants will be asked to complete baseline assessments of subjective tinnitus distress, PTSD, depression, and resting-
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state fMRI at baseline. Individuals with comorbid tinnitus and PTSD who are eligible for the study will receive Cognitive 
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Processing Therapy (CPT) over a 6- to 15-week period and a mid-treatment resting-state fMRI (after Session 6 of CPT and 
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before Session 7 of CPT). CPT is a trauma-focused treatment for PTSD that guides individuals on how to recognize and 
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challenge thoughts that are erroneous and dysfunctional. One-month follow-up assessments of tinnitus-related distress, 
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PTSD, depression, and anxiety will be conducted, along with resting-state fMRI. 
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3.  OBJECTIVES/SPECIFIC AIMS/RESEARCH QUESTIONS  
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Objective: 
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The primary objective of this study is to evaluate the overlap between tinnitus-related distress and symptoms of PTSD, 
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identify functional covariance among resting-state networks among individuals with tinnitus and PTSD, and determine 
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psychometric and neurobiological changes among participants who receive Cognitive Processing Therapy (CPT for 
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PTSD). 
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Aim 1: To identify the cognitive, behavioral, and emotional symptoms that are both shared and unique to PTSD and 
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tinnitus-related distress. 
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Hypothesis 1: There will be significant overlap between tinnitus distress and PTSD symptoms, as measured by the 
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Clinician Administered PTSD Scale for DSM-5 (CAPS-5), the PTSD Checklist for DSM-5 (PCL-5), the Tinnitus Functional 
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HUMAN SUBJECTS RESEARCH PROTOCOL  

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Index (TFI), and Tinnitus Acceptance Questionnaire (TAQ). Findings will help clinicians’ understanding of the distinct ways 
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in which each disorder contributes to functional impairment. Results will substantially improve clinicians’ ability to 
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conceptualize patients with comorbid tinnitus and PTSD. 
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Aim 2: To identify the functional covariance among resting-state networks, including the limbic, attentional, auditory, and 
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default-mode networks associated with tinnitus and PTSD. Resting state fMRI techniques will be conducted among 
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individuals with comorbid PTSD and tinnitus.  
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Hypothesis 2: There will be similar neurological activity associated with PTSD and tinnitus as measured by resting state 
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fMRI. Down-regulation and up-regulation of neurobiological connectivity of the networks will be examined within the 
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auditory, limbic, default-mode, and attentional networks. Results will provide insight concerning the neurological 
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maintenance factors for both disorders. Study findings will be utilized to generate new and innovative therapeutic 
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approaches that target specific brain regions to alleviate tinnitus and PTSD. 
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Aim 3: To determine relationships psychometrically, neurobiologically (as rs-fMRI network differences), and conjointly 
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(between psychometrics and rs-fMRI). Longitudinal measures will determine both psychometric and neurobiological 
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changes among participants who complete Cognitive Processing Therapy for PTSD (CPT for PTSD). 
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Hypothesis 3:  
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Individuals with tinnitus and PTSD who received Cognitive Processing Therapy will demonstrate significant 
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reductions in both PTSD symptoms and tinnitus-related distress at a one-month follow-up assessment. This study 
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will be the first to demonstrate the importance of addressing PTSD in order to target tinnitus-related distress.  
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After one month of completing CPT for individuals with both PTSD and tinnitus, a decrease in neurobiological 
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connectivity will be demonstrated between the attention network and limbic network, demonstrating the role of 
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cognitive control in reducing psychological distress. 
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4. BACKGROUND AND SIGNIFICANCE.   
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Tinnitus and PTSD 
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The genesis of tinnitus and PTSD can both be potentially associated to the same psychological and acoustic traumatic 
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event while deployed, with clinical implications concerning the recovery of both auditory and psychological disorders. 
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Tinnitus can be conceptualized as one such conditioned stimulus, continuing to serve as a reminder of the traumatic event 
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(Criterion B of PTSD). In a study of Cambodian refugees, significantly more participants with PTSD had tinnitus compared 
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to participants without tinnitus (Hinton, Chhean, Pich, Hofmann, & Barlow, 2006). Tinnitus patients were significantly more 
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likely to have PTSD compared to participants without tinnitus. In the same study, most participants with tinnitus indicated 
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experiencing flashbacks and an overwhelming 91.7% of those flashbacks accompanied tinnitus. Second, symptoms of 
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avoidance (Criterion C of PTSD) are also demonstrated among individuals with tinnitus. Fagelson (2007) found similarities 
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in avoidant symptoms between veterans with both tinnitus and PTSD; and those with only tinnitus.  Individuals in both 
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groups reported similar aversions to loud warning signals and a reduction in tolerance to loud noises. Andersson and 
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Westin (2008) explain that individuals may choose to avoid noise and seek quieter places. Third, negative alterations in 
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mood and cognition (Criterion D of PTSD) are observed among individuals with tinnitus. Tinnitus-associated trauma recall 
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and catastrophic cognitions significantly predicted PTSD severity, while controlling for tinnitus severity, among Cambodian 
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refugees suffering from both tinnitus and PTSD (Hinton et al., 2006). Fourth, individuals with tinnitus demonstrate 
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emotional reactions that overlap with hypervigilance or hyperarousal (Criterion E of PTSD). Fagelson and Smith (2016) 
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found that individuals with tinnitus and PTSD had significantly more negative emotional responses compared to 
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individuals with tinnitus only and those with tinnitus and other psychological problems. These emotional reactions are 
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similar to hyperarousal symptoms (e.g., anger, irritability, nervousness). Fagelson (2007) indicated that sleep disturbance 
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is also a symptom of hypervigilance observed in tinnitus patients (McKenna, 2000). These studies suggest the synergistic 
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effects between the audiologic disorder and PTSD, suggesting common etiologies and symptom presentation. 
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Few studies have examined the neurobiological contributions of the auditory network among PTSD patients. Researchers 
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have noticed that PTSD patients are more sensitive to auditory sounds associated with trauma than linguistic associations 
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(van der Kolk, 1997). Paige et al. (1990) suggested that PTSD patients inhibit stimulation that could overload their 
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capacity for accurate discrimination, and other studies have shown cortical abnormalities of auditory processing among 
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patients with PTSD (Lewine, 1997). Overall, it is proposed that individuals with tinnitus and PTSD 1) fail to adequately 
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distinguish between threat and non-threat sounds, resulting in hyperarousal, hypervigilance, avoidance of activities, and 
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abnormalities can be observed  within the auditory cortex; 2) fail to accurately interpret their traumatic event and current-
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day events, resulting in changes in cognition and mood, feeling distant or cut off from others, lack of ability to find pleasure 
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in activities, and reexperiencing symptoms, and decreased activation within the executive control network can be 
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observed; 3) failure to discriminate threat versus non-threat and accurate interpretation of the traumatic event and current 
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day events will result in an increased activation within the limbic system, resulting in an inability to regulate emotional 
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experiences, hyperreactivity to non-threat related cues, and lack of experiencing positive emotions. 
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Neuroimaging studies have demonstrated that individuals with tinnitus show increased activation in brain regions also 
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common in psychiatric conditions (Bartels et al., 2007; Landgrebe et al., 2009; Møller, 2011). Imaging studies have 
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implicated the auditory network, limbic network, default mode network, visual network, and dorsal attention and executive 
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control of attention networks among patients with tinnitus (Figure 4). Similar networks are observed among individuals 
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with PTSD, including the default mode network and central executive network. 
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Treatment of PTSD 
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Cognitive Processing Therapy (CPT). CPT is a cognitive behavioral treatment for PTSD consisting of 12 one-hour 
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sessions (Resick, Monson, & Chard, 2017; Resick & Schnicke, 1993). CPT is delivered in three phases: education, 
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processing, and challenging. The manualized treatment focuses on challenging beliefs and assumptions related to the 
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trauma, oneself, and the world. Randomized clinical trials conducted by Dr. Resick of our STRONG STAR Consortium 
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and others support CPT as an effective treatment for PTSD and other comorbid conditions in a variety of civilian trauma 
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populations. Initial randomized clinical trials using wait-list comparisons found that CPT was effective for treating PTSD in 
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sexual abuse survivors (Resick & Schnicke, 1992; Chard, 2005) and incarcerated males (Ahrens & Rexford, 2002). A 
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large randomized controlled trial (N=171) compared CPT, Prolonged Exposure (PE) therapy, and a minimal-attention 
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control group (Resick, Nishith, Weaver, Astin, & Feuer, 2002). At post-treatment, 80% of the participants treated with 
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either CPT or PE achieved remission and no longer met criteria for PTSD. These treatment gains were maintained over 
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the 9-month posttreatment follow-up period. Furthermore, these same participants were again assessed approximately 6 
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years later, and about 80% of the participants in each group continued to do well and no longer met criteria for PTSD 
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(Resick et al., 2012). Also, 89% of the patients treated with CPT improved by at least 20 points, a clinically significant 
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improvement, on the Clinician Administered PTSD Scale (CAPS; Blake et al. 1995). 
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Resick and colleagues also conducted a dismantling study (N=150) comparing the full CPT protocol to a cognitive therapy 
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only condition (CPT-C) and a condition comprised only of the written accounts of the trauma (Resick, Galovski, et al., 
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2008). Each condition consisted of 2 hours of therapy per week for 6 weeks, and blind assessments were conducted 
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before treatment, 2 weeks following the last session, and 6 months following treatment. Intent-to-treat analyses indicated 
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that patients in all three treatment conditions improved substantially on PTSD and depression. Patients also improved on 
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other indices of adjustment such as anxiety, anger, shame, guilt, and dysfunctional cognitions. However, there were 
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significant group differences in symptom reduction during the course of treatment whereby the CPT-C condition reported 
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greater improvement in PTSD than the written account condition and demonstrated more rapid clinical improvement than 
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the full CPT condition. The cognitive-only version (CPT-C) was equally effective to the full version of CPT and was 
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perhaps more efficient. This study will use the CPT-C version of the protocol, now re-branded as CPT (Resick, Monson, & 
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Chard, 2017). 
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Treatment of PTSD and Implications for Tinnitus 
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This study will be the first to characterize tinnitus and PTSD independently and comorbidly, before and after treatment in 
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terms of overt cognitive, emotional, and behavioral symptom profiles and connectivity between resting-state networks. A 
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greater understanding of the shared and unique cognitive, emotional, and behavioral symptoms between tinnitus and 
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PTSD is the first step toward the long-term goal of recognizing the bidirectional relationship between tinnitus and PTSD. 
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The second long-term goal is to use identify the functional covariance among resting-state networks, including the limbic, 
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attentional, auditory, and default mode networks associated with tinnitus and PTSD by using resting-state fMRI 
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techniques among individuals with comorbid tinnitus and PTSD. This study will be the first to identify common functional 
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covariance among relevant resting-state networks implicated in both tinnitus and PTSD. The third long-term goal is to 
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determine relationships psychometrically, neurobiologically (pre-post treatment), and conjointly between psychometrics 
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and rs-fMRI). For co-morbid PTSD/tinnitus, we will use longitudinal measures to examine changes in resting-state 
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networks. Individuals with both tinnitus and PTSD, who participate in fMRI imaging, will receive Cognitive Processing 
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Therapy (CPT) for PTSD and post-treatment fMRI imaging will be conducted. It is hypothesized that the attention, default-
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mode, and limbic resting-state networks will be altered from participants’ baseline fMRI, decreasing the awareness of 
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tinnitus sensation, and improving functional outcomes. 
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5.  RESEARCH DESIGN  
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The study will use a one-way experimental design, with one level of intervention: Cognitive Processing Therapy (CPT). 
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Participants will complete initial baseline assessments to determine eligibility, as well as resting-state fMRI scans. After 
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completing baseline assessments and fMRI scans, participants will be scheduled 1 therapy session to discuss 
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psychosocial history, trauma, and current functioning, which will last approximately 1 hour. Afterwards, participants will be 
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scheduled for 12 50–minute sessions of CPT, either once or twice per week, for 6 to 15 weeks. After completing Session 
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6 of CPT and before Session 7 of CPT, participants will be scheduled for a mid-treatment fMRI scan. After completing 
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CPT, participants will be scheduled for a one-month follow-up assessment, as well as a one-month follow-up fMRI scan. 
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Figure 1. Study Design Overview. 
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6.  RESEARCH PLAN 
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6.1 Selection of Subjects 
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Screening
Week -1
Consent/Baseline Assessment
Week 0
fMRI scan
Week 0
Trauma Interview/Psychosocial History
Cognitive Processing Therapy
Sessions 1-6
fMRI scan after Session 6
Cognitive processing Therapy 
Sessions 7-12
Follow-up Assessment
1 month after completing therapy
Follow-up fMRI scan
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6.1.1. Subject Population.  This study will consent and screen 30 male and female veterans seeking treatment for PTSD to 
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include 10 for analysis.  Subjects will be recruited from the San Antonio community.  
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6.1.2. Source of Research Material.  All measures are being administered for research purposes. For a complete list of 
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measures, see Section 6.2. 
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6.1.3. Inclusion and Exclusion Criteria.  
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Inclusion Criteria 
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Adult male and female military Veterans (age 18-60) who deployed in support of combat operations post-9/11 
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seeking behavioral health treatment for PTSD and/or tinnitus 
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Diagnosis of PTSD determined by the Clinician-Administered PTSD Scale - Interview – Version 5 (CAPS-5) 
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Ability to speak and read English 
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Meets criteria for tinnitus and considers their tinnitus bothersome, as defined by a score on the Tinnitus Functional 
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Index of 32 or greater 
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Exclusion Criteria 
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Currently receiving evidence based treatment for PTSD 
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Current suicidal ideation severe enough to warrant immediate attention (as determined by the Depressive Symptoms 
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Index- Suicidality Subscale and corroborated by a clinical risk assessment by a credentialed provider  
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Psychiatric hospitalization in the last 12 months 
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Current and severe alcohol use warranting immediate intervention based on clinical judgment 
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Current manic episode or psychotic symptoms requiring immediate stabilization or hospitalization (as determined by 
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the manic and psychosis modules of the MINI) 
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Evidence of a moderate or severe traumatic brain injury (as determined by the inability to comprehend the baseline 
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screening questionnaires) 
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Neurobiological disorders 
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Meniere’s disease, temporomandibular joint disorders 
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History of seizures 
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History of penetrating head trauma or neurosurgery 
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Metal objects implanted in the head, ferrous metal filings in the eye 
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Inflammation of the brain 
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Cardiac pacemaker 
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Implanted medical pump or cardiac lines 
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Heart disease 
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Currently taking certain types of medication for depression or seizures (tricyclic antidepressants or neuroleptics which 
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lower seizure threshold) 
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6.1.4. Description of the Recruitment and Prescreening Process.   
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The study will be conducted in collaboration with the STRONG STAR Multidisciplinary PTSD Research Consortium.  
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Primarily potential participants will self-refer to the study.  General announcements and flyers will be posted on public 
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media and at various community sites that will allow self-referral of Veterans. Potential participants may also self-refer in 
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response to recruitment information on the STRONG STAR website.  Potential participants may contact STRONG STAR 
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if they feel that they are eligible. In addition to self-referral recruitment study staff will work closely with staff at hospital 
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clinics (Mental Health Clinics, Substance Abuse Treatment Clinics, Primary Care Clinics, Audiology Clinics) and Veteran 
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advocacy groups, which have been found to be reliable and productive sources of participants.  Referring providers and 
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staff can give their patients contact information for the study staff so that interested individuals may contact STRONG 
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STAR directly. Providers can also obtain consent to contact from interested individuals so that study staff can contact 
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them directly about study participation.  In addition, there may be events where information about STRONG STAR studies 
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is provided and those interested may fill out a “consent to contact” form indicating that they would like a member of the 
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research team to contact them at a later date to learn more about the study and schedule or complete pre-screening.  
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Under an IRB approved HIPAA Waiver of Authorization, we will also review the STRONG STAR 
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records of previous STRONG STAR and CAP study participants who met criteria for PTSD and 
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indicated they suffered from tinnitus.  Protected health information (PHI) from baseline assessments, 
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such as scores on the CAPS-5 and Tinnitus Functional Index, will be used to determine 
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appropriateness for the study.  A member of the research team will contact by telephone individuals 
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who appear to be appropriate for the study. Potential participants who are interested in the study will 
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complete a pre-screening questionnaire over the phone. 
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Under an IRB approved HIPAA Waiver of Authorization, Alteration of Informed Consent, and Waiver of Documentation of 
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Informed Consent, study personnel will conduct a brief telephone  pre-screening where the basic study inclusion and 
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exclusion criteria will be reviewed to help the individual determine if he or she meets the study criteria or has obvious 
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exclusions from the study protocol so as to prevent individuals from making unnecessary travel for consent and more in-depth 
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screening (see Appendix C).  This information will be entered into a secure database as a phone call to a potential participant 
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or a phone call from a potential participant: name, phone number, name of study the caller is interested in, referral date, 
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referral source, potential eligibility status, reason if not eligible, and verbal permission to contact the caller in the future for 
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other studies. We will also record the date and time of the call, outcome of the call, and any notes.  Subjects who present at 
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the Northwest Center will also be shown a video that explains the step-by-step MRI procedures to ensure that they are 
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comfortable with scanning (Appendix D is the video to be shown, minutes 2:22 to 3:39). Appendix E is the script of this 
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segment of the video. Subjects who agree to study participation will sign a consent document before any further screening will 
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take place.  Any individually identifiable information and Protected Health Information (PHI) collected on individuals who do 
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not consent to participation will not become part of the research data.  If participants agree to participate in the research, the 
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identifiable data collected will become part of the participants’ research records and will be stored according to the research 
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confidentiality plan.   
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Veterans who phone screen out from other IRB-approved STRONG STAR protocols will be offered the opportunity to be 
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phone screened for participation in this study.  If interested, a member of the research team will review eligibility with these 
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potential participants (e.g., pre-screen) over the phone.  If the person believes they may qualify for the study, the participant 
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will be scheduled for an appointment in which consent will be obtained, and if authorized, the baseline assessment will be 
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completed. If not interested or Veterans who phone screen out from this study, Veterans will be offered the opportunity to be 
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phone screened for participation in other IRB-approved STRONG STAR protocols.   
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6.1.5. Consent Process.  
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Potential participants will have the study explained to them in a safe and private location in person.  The potential 
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participant will be given a copy of the informed consent document (ICD) to read.  The research team member obtaining 
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informed consent will then engage the potential participant in an interactive explanation of the study guided by the ICD.  
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After the subject has read the ICD, he or she will be given the opportunity to consider participation and discuss the 
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research with family and friends.  The Research Team will be available to answer any questions about the research.  
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Once the potential participant has reached a decision, the advising staff member will review the risks and benefits of study 
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participation and ensure the subject has an understanding of the material discussed, and the risks and benefits of their 
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potential involvement in the study.  The advising staff member will have the participant sign the consent form.  A copy of 
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the signed ICD will be given to the subject. 
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6.1.6. Subject Screening Procedures. 
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Following consent, screening and baseline assessment will take place to determine participant eligibility.  The entire 
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screening process will take approximately 3 hours.  This will include the completion of the questionnaires and interviews 
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outlined in the table in Section 6.2 below. For individuals not meeting study inclusion criteria, the Study Staff will assist 
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coordinating appropriate care outside of the study.  
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6.1.7. Compensation for participation.   
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Participants will be compensated $75 for each neuroimaging scan: once prior to enrolling in Cognitive Processing 
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Therapy, once at mid-treatment (after Session 6 and before Session 7), and once at the one-month follow-up after 
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receiving Cognitive Processing Therapy.  Payment will be provided via a rechargeable MasterCard® ClinCard. The 
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MasterCard® ClinCard is a debit card issued to the study participant.  Funds are loaded onto card through the ClinCard 
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website at www.clincard.com.  Only authorized users will be able to access the ClinCard website to add funds with a 
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username and password.  The ClinCard funds will be available to recipients within 1 business day and can be used as the 
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participant chooses.  The participant will be notified that their name, address and date of birth will be shared with a third-
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party (ClinCard) solely for the purposes of payment processing.  This information will only be used for the administration 
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of the payment and will be kept strictly confidential.   
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6.1.8. Treatment Procedures.   
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This study will examine the effectiveness of Cognitive Processing Therapy (CPT) for the alleviation of PTSD and tinnitus-
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related distress among individuals with co-morbid PTSD and tinnitus.  
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Cognitive Processing Therapy (CPT).  Prior to engaging in therapy, one session will be devoted to gathering 
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information regarding psychosocial history, trauma, and current functioning. During the first session, a brief explanation of 
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the connection between tinnitus and PTSD will be provided for the participants, to increase motivation and understanding 
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of the treatment (Appendix F). The following sessions will follow the standard outpatient CPT protocol. The standard 
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outpatient CPT (Resick, Monson, & Chard, 2017) consists of 12 one-hour sessions conducted over a 6- to 12-week period 
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(Resick, Monson, & Chard, 2008). An additional 3 weeks will be provided in case of participant and therapist vacation 
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and/or sick days. Participants will be considered treatment completers if they attended at least 75% of the full 12-session 
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protocol (9 sessions). The three phases of CPT include psychoeducation, processing, and challenging beliefs and 
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assumptions related to the trauma, oneself, and the world. CPT begins with an impact statement in which the patient 
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describes why he or she thinks the index (worst trauma) happened, the impact of the trauma on his or her perspective of 
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self, others, and the world. The impact statement helps to identify maladaptive cognitions about the trauma, such as “it’s 
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all my fault” and “I can’t trust anyone.” These cognitions can emerge when a traumatic experience does not make sense 
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in the context of previous beliefs. Throughout therapy, problematic cognitions are identified and challenged through 
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Socratic questioning until more accurate beliefs about self, others, and the world replace any distorted cognitions. The last 
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five sessions of CPT focus on cognitions related to specific topics that are often particularly problematic in PTSD, 
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including safety, trust, power, esteem, and intimacy. CPT is based on cognitive theory in which traumatic events are 
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inconsistent with prior positive beliefs or seemingly confirm negative beliefs. Because people tend to hold just world 
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beliefs, they have difficulty reconciling events that appear to be unfair or random. People also tend to blame themselves 
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for events or try to mentally “undo” the event and feel guilt, shame or anger, rather than the natural emotions that may 
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have emanated directly from the event (sadness/grief, fear, horror) (Resick, Galovski, et al., 2008).  All study participants 
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will receive treatment with CPT, as it is typically conducted in the VA or another clinic, face-to-face. The patient will be 
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seen either once or twice a week in the clinic office and the therapist will follow the protocol as specified in the manual.  
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The patient will be given assignments that will be placed into a patient binder for them to keep.  However, the therapist will 
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also keep a folder with a copy of the stuck point log and extra copies of worksheets in case the patient forgets to bring the 
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binder to the session. 
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Training, Certification, and Supervision of CPT Therapists 
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A detailed CPT training, certification, and supervision process has been developed to ensure that CPT is delivered 
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according to protocol and with the highest levels of quality and fidelity. The Principal Investigator (John Moring, PhD) is a 
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licensed clinical psychologist with extensive training and consultation provided by one of the developers of CPT, Dr. 
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Patricia Resick. Dr. Resick, Consultant on this research study, will provide consultation on an as-needed basis.  
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Treatment Adherence and Competence. The fidelity to the treatment will be closely monitored to ensure that the 
380 
therapy is being delivered true to the protocol.  Treatment adherence and competence will be determined by independent 
381 
raters who are not otherwise involved in the project. The raters will be affiliated STRONG STAR investigators who have 
382 
served on prior CPT studies as adherence and competence raters. In order to ensure that the CPT treatment is 
383 
administered in accordance with the manual, all sessions in the study will be audio recorded for fidelity rating. Audio 
384 
recordings will be uploaded onto the secure STRONG STAR server so they can be reviewed remotely. The raters will 
385 
determine adherence to the CPT therapies and competence in delivering the therapies. Five percent of all audiotapes for 
386 
listening and determination of inter-rater reliabilities (kappas). 
387 
 
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6.2. Study Procedures.   
389 
 
390 
Study Procedures 
BL 
Week 0 
fMRI 
Scan 
Week 0 
Prior to 
Tx 
CPT 
Sessions 
1, 3, 5, 7, 
9, 11 
CPT 
Sessions 
2, 4, 6, 8, 
10, 12 
fMRI Scan 
Mid-
Treatment 
FU Assessment 
 (1-Month Post 
Tx) 
FU fMRI Scan 
 (1-Month Post 
Tx) 
Informed 
Consent 
X 
 
 
 
 
 
 
 
1. 
Demographics and 
Military Service 
Characteristics Form 
X 
 
 
 
 
 
 
 
2. 
Deployment Risk and 
Resilience Inventory 
(DRRI-2) Subscales: 
-Combat Experience 
–Postbattle Experiences  
X 
 
 
 
 
 
 
 
3. 
MRI Participant 
Information and 
Screening 
Questionnaire 
X 
 
 
 
 
 
X 
 
4. 
Life Events Checklist-5 
(LEC-5) 
X 
 
 
 
 
 
X 
 
5. 
Trauma Related Guilt 
Inventory (TRGI)  
X 
 
 
 
X 
 
X 
 
6. 
Depressive Symptom 
Index Suicide Subscale 
(DSI-SS) 
X 
 
 
 
 
 
X 
 
7. 
Generalized Anxiety 
Disorder-7 (GAD-7) 
X 
 
 
 
 
 
X 
 
8. 
Selection of Index Event 
for CAPS-5 
X 
 
 
 
 
 
 
 
9. 
Clinician-Administered 
PTSD Scale – 5 (CAPS-
5) 
X 
 
 
 
 
 
X 
 
10. PTSD Check List – 
DSM-5 (PCL-5)  
X 
 
 
 
X 
 
X 
 
11. Self-Injurious Thoughts 
and Behaviors 
Interview- Short Form 
(SITBI-Short Form) 
X 
 
 
 
 
 
X 
 
12. Health Questionnaire  
X 
 
 
 
 
 
X 
 
13. History of Head Injuries  
X 
 
 
 
 
 
X 
 
14. Veterans Rand 12-Item 
Health Survey (VR-12) 
X 
 
 
 
 
 
X 
 
15. Insomnia Severity Index 
(ISI) 
X 
 
 
 
 
 
X 
 
16. PROMIS Sleep-Related 
Impairment and Sleep 
Disturbance 
X 
 
 
 
 
 
X 
 
17. Snoring, Tired, 
Observed, Blood 
Pressure (STOP) Sleep 
Apnea Screen  
X 
 
 
 
 
 
X 
 
18. Patient Health 
Questionnaire – 9 
(PHQ-9) 
X 
 
 
X 
 
 
X 
 
19. Fagerstrom Test for 
Nicotine Dependence 
(FTND) 
X 
 
 
 
 
 
X 
 
20. Fagerstrom Test for 
Nicotine Dependence- 
Smokeless Tobacco 
(FTND-ST) 
X 
 
 
 
 
 
X 
 

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21. Alcohol Use Disorders 
Identification Test 
(AUDIT) 
X 
 
 
 
 
 
X 
 
22. Quick Drinking Screen 
(QDS) 
X 
 
 
 
 
 
X 
 
23. Mini-International 
Neuropsychiatric 
Interview (MINI)- Manic 
and Psychosis modules 
X 
 
 
 
 
 
 
 
24. Tinnitus Functional 
Index (TFI) 
X 
 
 
X 
 
 
X 
 
25. Tinnitus Acceptance 
Questionnaire (TAQ)  
X 
 
 
 
 
 
X 
 
26. Brief Inventory of 
Psychosocial 
Functioning (BIPF) 
X 
 
 
 
 
 
X 
 
27. Homework Compliance 
 
 
 
X 
X 
 
 
 
28. fMRI scan 
 
X 
 
 
 
X 
 
X 
29. Trauma Interview 
 
 
X 
 
 
 
 
 
 
391 
 
392 
6.3.2 Data Collection.   
393 
 
394 
6.3.2.1 Instrumentation:  
395 
See the table at Section 6.2 above for a summary of the assessments and timing of administration.  A description of each of 
396 
the assessments can be found at the end of this protocol.  Assessments will be administered in person whenever possible.  
397 
However, in order to accommodate participant schedules and/or instances in which a participant does not reside in the local 
398 
area at the time of a follow up assessment, we may collect full or partial assessments in person or via phone.  Reasonable 
399 
efforts will be made to collect all data as described in this protocol, but we expect some participants may not be able to 
400 
complete part or all of any given follow up assessment. 
401 
 
402 
6.3.2.2. Resting state fMRI.  
403 
Participants who are eligible to continue in the study after consent and screening will undergo a function magnetic resonance 
404 
imaging (MRI) session at the Research Imaging Institute (RII) at the University of Texas Health Science Center at San 
405 
Antonio.  Participants who cannot tolerate the MRI procedure will be withdrawn from the study.  Participants will receive a mid-
406 
treatment scan (after Session 6 of CPT and before Session 7 of CPT), and a follow-up fMRI scan one month after completing 
407 
therapy.  Each MRI scan may take up to 2 hours. 
408 
 
409 
6.3.2.3 Data Storage and Access:  
410 
Data will be coded using an assigned number. Paper research data will be kept in locked file cabinets in locked offices at 
411 
the University of Texas Health Science Center San Antonio (UTHSCSA) STRONG STAR offices.  Data collected will be 
412 
entered into a spreadsheet located on a secure STRONG STAR server.  Audio-recordings will be uploaded to a secure 
413 
STRONG STAR server over an encrypted network connection.  Neuroimaging data will be kept on secure networks at the 
414 
Research Imaging Institute. Every member of the Research Team will be trained and monitored about how to handle and 
415 
protect both medical and research records.  Furthermore, the Research Team strictly controls access to study data using 
416 
policies and procedures developed specifically for the STRONG STAR Research Consortium. 
417 
 
418 
Every member of the Research Team will be trained and monitored about how to handle and protect research records.  
419 
Furthermore, the Research Team strictly controls access to study data.   
420 
 
421 
 
422 
6.4 Statistical Consideration  
423 
 
424 
6.4.1 Sample Size Estimation.   
425 
The recruited sample size will be 30 participants. Based on work by Salinas and Szabo (2017), 10 participants will provide 
426 
adequate power to detect differences in resting-state networks, from pre-, mid- and to posttreatment fMRI scans. In their 
427 

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paper, they examined 14 baboons, pre- and posttreatment injection of valproic acid, at three different time points, with 
428 
adequate power. 
429 
 
430 
Estimate Required Sample Size 
10 
Estimate Participant Screen Out 
18 (~60%) 
Estimate Participant Withdrawal 
2 (~7%) 
Total Enrollment Requirement 
30 
 
431 
 
432 
 
433 
6.4.2 Primary (i.e., primary outcome variables) and secondary endpoints.  
434 
 
435 
Primary outcomes include changes in scores on measures of PTSD (CAPS-5 and PCL-5) and tinnitus-related distress (TFI 
436 
and TAQ). The additional primary outcome is changes in functional activity within resting-state networks, provided by fMRI 
437 
scans. 
438 
 
439 
Secondary outcome variables include changes in scores on measures of depression and suicide (DSSI-SS; PHQ-9), anxiety 
440 
(GAD-7), sleep impairment (PROMIS; ISS; STOP), general health and functioning (VR-12; BIPF), and alcohol and substance 
441 
use (FTND; FTND-ST; AUDIT).  
442 
 
443 
 
444 
 
445 
 
446 
6.4.3 Hypotheses and Specific Data Analysis Plans.  
447 
 
448 
Hypothesis 1: There will be significant overlap between tinnitus distress and PTSD symptoms, as measured by the 
449 
Clinician Administered PTSD Scale for DSM-5 (CAPS-5), the PTSD Checklist for DSM-5 (PCL-5), the Tinnitus Functional 
450 
Index (TFI), and Tinnitus Acceptance Questionnaire (TAQ). Findings will help clinicians’ understanding of the distinct ways 
451 
in which each disorder contributes to functional impairment. Results will substantially improve clinicians’ ability to 
452 
conceptualize patients with comorbid tinnitus and PTSD. 
453 
Analysis plan: Non-inferential statistics will be calculated to include central tendencies, standard deviations, and 
454 
alpha coefficients. Unusual distributions, missing data, or outliers will be identified. PTSD symptom cluster 
455 
severity (intrusions, avoidance, negative alterations in mood and cognition, and hyperarousal) will be calculated 
456 
using the data gathered from the CAPS-5. Tinnitus domains of distress will be calculated using the data gathered 
457 
from the Tinnitus Functional Index. Pearson product-moment correlation coefficient analyses will be used to 
458 
examine the overlap between tinnitus and PTSD. 
459 
 
460 
Hypothesis 2: There will be similar neurological activity associated with PTSD and tinnitus as measured by resting state 
461 
fMRI. Down-regulation and up-regulation of neurobiological connectivity of the networks will be examined within the 
462 
auditory, limbic, default-mode, and attentional networks. Results will provide insight concerning the neurological 
463 
maintenance factors for both disorders. Study findings will be utilized to generate new and innovative therapeutic 
464 
approaches that target specific brain regions to alleviate tinnitus and PTSD. 
465 
Analysis plan: An inter-regional connectivity mapping using an extended time-series (typically 200-400 whole-
466 
brain volumes acquired over 8-15 minutes) of BOLD fMRI images acquired in an unstimulated state (Biswal et al., 
467 
1995; Xiong et al., 1999) will be utilized for Aim 2. Inter-connected regions show temporally correlated variations, 
468 
allowing connectivity to be detected and quantified. Resting-state networks (RSNs) have been used to map 
469 
scores of functional systems. They are now viewed as reflecting the intrinsic architecture of the brain (Smith et al. 
470 
2009). Resting-state connectivity analysis of the auditory system in normal subjects demonstrated highly coherent 
471 
within-system connectivity, as well as strong projections to the frontal limbic circuitry (Hunter et al., 2006). 
472 
Resting-state connectivity analyses will be used to characterize tinnitus-related network abnormalities. 
473 
 
474 
Hypothesis 3:  
475 

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 
Individuals with tinnitus and PTSD who received Cognitive Processing Therapy will demonstrate significant 
476 
reductions in both PTSD symptoms and tinnitus-related distress at a one-month follow-up assessment, AND 
477 
 
After one month of completing CPT for individuals with both PTSD and tinnitus, a decrease in neurobiological 
478 
connectivity will be demonstrated between the attention network and limbic network, demonstrating the role of 
479 
cognitive control in reducing psychological distress. 
480 
Analysis plan: Post-treatment outcome data will be compared to participants’ baseline measures of tinnitus-related 
481 
distress and PTSD. Data will be analyzed using a general linear mixed (GLM) model with baseline scores of tinnitus-
482 
related distress used as a covariate. The analyses will demonstrate whether individuals who received CPT 
483 
experienced a reduction in tinnitus-related distress and PTSD symptoms. 
484 
 
485 
An inter-regional connectivity mapping using an extended time-series (typically 200-400 whole-brain volumes 
486 
acquired over 8-15 minutes) of BOLD fMRI images acquired in an unstimulated state will be utilized for Aim 3. 
487 
Resting-state connectivity analyses will be used to better characterize tinnitus-related network abnormalities using 
488 
Independent Components Analysis, using analysis of variance (ANOVA) comparing Baseline versus Posttreatment 
489 
factors, while regressing out demographic variables. The mid-treatment scan will be used to infer causal effects of 
490 
Cognitive Processing Therapy by demonstrating the temporal changes in resting-state networks.  
491 
 
492 
Missing data. If missing data can be assumed to be missing at random, likelihood-based mixed model analysis will 
493 
provide valid inferences using data from all cases with any outcome data. The impact of attrition on analyses will be 
494 
addressed by comparing those who are available for analysis at each assessment with those who are not using 
495 
appropriate data from prior assessments.  
496 
 
497 
6.7 Confidentiality.  All in-person therapy sessions and interview assessments will be delivered in private offices at the 
498 
STRONG STAR Clinic at the UTHSCSA.  Data will be stored by an assigned participant code number.  Digital audio 
499 
recordings of assessments and CPT sessions will be labeled with the participant’s study id number and uploaded onto the 
500 
secure STRONG STAR server. Encrypted email will be used to securely send recordings to research experts who are part 
501 
of the research team for review of fidelity.  Every member of the Research Team will be trained and monitored about how 
502 
to handle and protect both medical and research records.  Furthermore, the Research Team strictly controls access to 
503 
study data.   
504 
 
505 
6.7.1 Certificate of Confidentiality.   
506 
We are not seeking a Certificate of Confidentiality. 
507 
 
508 
6.7.2. Data Protection.  Data will be coded using an assigned number. Assessments and data collected during the 
509 
treatment sessions will be stored in a locked cabinet at the STRONG STAR Clinic at the UTHSCSA.  Digital audio 
510 
recordings of assessments and CPT sessions will be labeled with the participant’s study id number and uploaded onto the 
511 
secure STRONG STAR server.  All UTHSCSA STRONG STAR network connectivity is segmented with Access Control 
512 
Lists and is not accessible to any other UTHSCSA network segments. STRONG STAR data server is physically located at 
513 
the Advanced Data Center (ADC)  has 24x7 onsite security, card key, biometric access controls and video surveillance. 
514 
University of Texas Health Science Center at San Antonio (UTHSCSA) ADC facility also maintains Gen 2 firewall devices 
515 
to protect and prohibit any unauthorized access to UTHSCSA data. All UTHSCSA network devices are monitored by state 
516 
of the art monitoring applications that include configuration audit, management, and availability 24x7.   
517 
 
518 
7.0  RISKS/BENEFITS ASSESSMENT 
519 
 
520 
7.1  Risks.   
521 
 
522 
Risks and Side Effects related to Cognitive Processing Therapy 
523 
Likely, but not Serious, expected to occur in more than 20 out of 100 participants: 
524 
• 
Emotional distress or experiencing an initial increase of PTSD symptoms due to the discussion of traumatic 
525 
events. However, in past research conducted by STRONG STAR investigators using CPT-C, there have been no 
526 
serious adverse events or related difficulties with emotionally upset participants due to the treatments. 
527 
 
528 
Risks and Side Effects related to the Assessment of Tinnitus 
529 

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Rare, but not Serious, expected to occur in less than 5 out of 100 participants: 
530 
• 
Emotional distress due to tinnitus or more attention toward tinnitus sensation may occur; however, since tinnitus is 
531 
a chronic and stable condition, it is unlikely that a change will occur because of the assessment procedures 
532 
 
533 
Risks and Side Effects related to the Resting-State fMRI 
534 
Rare, but not Serious, expected to occur in less than 5 out of 100 participants: 
535 
• 
Confinement claustrophobia (fear of tight spaces). During the MRI scan, participants will be asked to remain 
536 
perfectly still. The MRI can cause individuals to feel claustrophobic (fear of tight spaces). However, the incidence 
537 
of claustrophobia with the MRI is low (approximately 1 per 150 persons). 
538 
 
539 
Rare and Serious, expected to occur in less than 5 out of 100 participants: 
540 
• 
Foreign bodies which may interact with the magnetic field of the MRI can have risk for persons with foreign bodies 
541 
implanted in their body. Cardiac pacemakers and cochlear implants may cease to function and can be 
542 
permanently damaged by the MRI. Surgical clips on aneurysms and intestines may be moved by the magnetic 
543 
field. Ferrous metal filings in the eye (e.g., in machinists) can be moved by the magnetic field. Foreign body risk is 
544 
minimized by including only volunteers with no known foreign bodies and no exposure to circumstances, which 
545 
might predispose to foreign bodies (e.g., metal machine workers). Before any MRI you receive, we will ask you 
546 
about any metal objects that may be in your body in order to ensure your safety. 
547 
 
548 
Risks of PTSD Diagnosis regardless of Treatment 
549 
One of the risks of PTSD both in and out of treatment is attempted suicide, which can result in death. 
550 
 
551 
Safeguards for Protecting Participants:  During the early sessions of treatment, participants will be provided immediate 
552 
coping tools and techniques used to manage distressing emotions by the study therapist.  Distress experienced by 
553 
participants is expected to be temporary.  Any indication that the participant is considering suicide will be handled using 
554 
processes developed by military and civilian Consultants for the STRONG STAR Consortium studies.  Trained clinicians 
555 
and evaluators will assess history of suicide and current suicidal ideation using the following standardized measures: Self-
556 
Injurious Thoughts and Behaviors Interview- Short Form (SITBI- Short Form) and the Patient Health Questionnaire-9 
557 
(PHQ-9).  For participants identified as having low to moderate risk for suicide based on the assessment results, the 
558 
patient will be maintained on protocol and additional risk management procedures will be implemented within the context 
559 
of the study treatment.  For participants identified as being at high risk for suicide based on the assessment results, 
560 
disenrollment will be considered if it is unlikely that standard treatment plus additional risk management procedures will 
561 
maintain safety.  High risk participants who are disenrolled from the study will be referred for more intensive treatment 
562 
(outpatient or inpatient). 
563 
 
564 
A STRONG STAR Data Safety and Monitoring Plan (DSMP) has been developed in accordance with the National 
565 
Institutes of Health (NIH) Office of Human Research Protection (OHRP) to assure the appropriate clinical safety and 
566 
adverse event monitoring of study subjects participating in STRONG STAR studies. 
567 
 
568 
7.2 Potential Benefits.   
569 
Potential benefits of participation in this study may include a reduction in PTSD symptoms and tinnitus-related distress over 
570 
the course of therapy.  Our primary goal is to treat participants to the point of symptom reduction below the level of diagnostic 
571 
criteria for PTSD.  In addition, the knowledge gained from this study will serve to inform the most effective early interventions 
572 
for the treatment of co-morbid tinnitus and PTSD in Veterans. 
573 
 
574 
7.3 Alternatives: Other treatments for PTSD that are available include the following:  
575 
• 
Various forms of psychotherapy (talk therapy) including CPT for PTSD.  
576 
• 
Various forms of psychotherapy (talk therapy) including Acceptance and Commitment Therapy for tinnitus 
577 
• 
Drug treatments for PTSD 
578 
• 
There may be other research studies involving experimental treatments that could be helpful in treating PTSD 
579 
and/or tinnitus 
580 
 
581 
Not participating in this study is an option. 
582 
 
583 

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8.0  ADVERSE EVENTS, UNANTICIPATED PROBLEMS, AND DEVIATIONS 
584 
 
585 
8.1   Adverse Events will be assessed and monitored according to the established STRONG STAR SOP and the IRB of 
586 
record’s policies and procedures. 
587 
 
588 
8.2  Reporting Adverse Events, Unanticipated Problems Involving Risks to Subjects or Others (UPIRSOs), and 
589 
Deviations to the Office of the IRB.   
590 
 
591 
All adverse events, unanticipated problems involving risk to subjects or others, and deviations will be reported 
592 
to the Institutional Review Board (IRB) in accordance with current IRB policy.  UPIRSOs and recurrent non-
593 
compliance with study procedures will be reported promptly to the IRB.  All adverse events that do not meet 
594 
the UPIRSO criteria and deviations that are not non-compliance will be summarized at Continuing Review per 
595 
the IRB of record’s policy.   
596 
 
597 
9.0 WITHDRAWAL FROM STUDY PARTICIPATION.   
598 
Participation in the study may be discontinued by the principal investigator if continued participation is considered a 
599 
danger to a participant’s welfare. Reasons for discontinuation include: 1) a serious adverse event such that continued 
600 
participation would be a danger to the participant; 2) clinical worsening for any reason that is deemed to necessitate non-
601 
study psychological or psychiatric treatment; 3) exacerbation of PTSD, anxiety, or depressive symptoms that the 
602 
participant cannot tolerate; 4) inability to tolerate the MRI procedure; or 5) discontinuation would be in the participant's 
603 
best interest.  
604 
 
605 
Participants who are discontinued from the study for any reason will be scheduled for a final evaluation within one week 
606 
and given appropriate treatment referrals. If participants are discontinued due to a serious adverse event, they will 
607 
continue to be followed clinically by the therapist and/or member of the research staff until the adverse event is resolved 
608 
or becomes stable. If participants are discontinued for a medical or psychiatric reason, they will be given the opportunity to 
609 
either complete the balance of their CPT sessions or to receive a full course of CPT after the condition has resolved or 
610 
stabilized and the endpoint assessment has been completed.  The reason the participants are discontinued from the study 
611 
and any referrals made will be documented.  Participants will be told they will be contacted for follow-up assessments 
612 
(excluding fMRI scans) whether or not they complete the treatment trial.  
613 
 
614 
 
615 
10.0  REFERENCES.  
616 
 
617 
Ahrens, J., & Rexford, L. (2002). Cognitive processing therapy for incarcerated adolescents with PTSD.Journal Of 
618 
Aggression, Maltreatment & Trauma, 6(1), 201-216. 
619 
Andersson, G., & Westin, V. (2008). Understanding tinnitus distress: Introducing the concepts of moderators and 
620 
mediators. International Journal of Audiology, 47(Suppl 2), S106-S111.   
621 
Bartels, H., Staal, M.J., & Albers, F.W.J. (2007). Tinnitus and neural plasticity of the brain. Otological Neurotology, 28, 
622 
178-184. 
623 
Biswal, B., Yetkin, F.Z., Haughton, V.M., & Hyde, J.S. (1995). Functional connectivity in the motor cortex of resting human 
624 
brain using echo-planar MRI. Magnetic Resonance Medicine, 34, 537-541. 
625 
Chard, K. M. (2005). An evaluation of cognitive processing therapy for the treatment of posttraumatic stress disorder 
626 
related to childhood sexual abuse. Journal of Consulting and Clinical Psychology, 73, 965–971. 
627 
Fagelson, M.A. (2007). The association between tinnitus and posttraumatic stress disorder. American Journal of 
628 
Audiology, 16, 107-117. 
629 
Fagelson, M.A., & Smith, S.L. (2016). Tinnitus self-efficacy and other tinnitus self-report variables in patients with and 
630 
without post-traumatic stress disorder. Ear and Hearing. Advance online publication. 
631 
Hinton, D.E., Chhean, D., Pich, V., et al. (2006). Tinnitus among Cambodian refugees: Relationship to PTSD severity. 
632 
Journal of Traumatic Stress, 19, 541-546. 
633 
Hunter, M.D., Eickhoff, S.B., Miller, T.W.R., et al. (2006). Neural activity in speech-sensitive auditory cortex during silence. 
634 
PNAS, 103, 189-194. 
635 
Landgrebe, M., Langguth, B., Rosengarth, K., et al. (2009). Structural brain changes in tinnitus: Grey matter decrease in 
636 
auditory and non-auditory brain areas. Neuroimage, 46, 213-218. 
637 

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Lewine, J.D., Canive, J.M., Orrison, W.W., et al. (1997). Electrophysiological abnormalities in PTSD. Annals of the New 
638 
York Academy of Sciences, 821, 508-511. 
639 
McKenna L (2000). Tinnitus and insomnia. In R. Tyler (Ed.), Tinnitus handbook (pp. 59-84). San Diego, CA: Singular. 
640 
Møller, A.R. (2011). The role of neural plasticity in tinnitus. In A.R. Møller, B. Langguth, D. De Ridder, & T. Kleinjung 
641 
(Eds.), Textbook of tinnitus (pp. 99-102). New York, NY: Springer Science. 
642 
Paige, S., Reid, G., Allen, M. et al. (1990). Psychophysiological correlates of posttraumatic stress disorder in Vietnam 
643 
veterans. Biological Psychiatry, 27, 419-430. 
644 
Resick, P.A., Galovski, T.A., Uhlmansiek, M. O., Scher, C.D., Clum, G. A., & Young-Xu, Y. (2008). A randomized clinical 
645 
trial to dismantle components of cognitive processing therapy for posttraumatic stress disorder in female victims of 
646 
interpersonal violence. Journal of Consulting and Clinical Psychology, 76, 243–258. 
647 
Resick, P.A., Monson, C.M., & Chard, K.M. (2017). Cognitive Processing Therapy: A comprehensive manual. New York, 
648 
NY: The Guilford Press. 
649 
Resick, P. A., Nishith, P., Weaver, T. L., Astin, M. C., & Feuer, C. A. (2002). A comparison of cognitive processing 
650 
therapy, prolonged exposure and a waiting condition for the treatment of posttraumatic stress disorder in female rape 
651 
victims. Journal of Consulting and Clinical Psychology, 70, 867–879. 
652 
Resick, P. A., & Schnicke, M. K. (1992). Cognitive processing therapy for sexual assault victims. Journal of Consulting 
653 
and Clinical Psychology, 60(5), 748–756. 
654 
Resick, P. A., Williams, L. F., Suvak, M. K., Monson, C. M., & Gradus, J. L. (2012). Long-term outcomes of cognitive–
655 
behavioral treatments for posttraumatic stress disorder among female rape survivors. Journal of Consulting and 
656 
Clinical Psychology, 80, 201–210. 
657 
Smith, S.M., Fox, P.T., Miller, K.L. et al. (2009). Correspondence of the brain’s functional architecture during activation 
658 
and rest. Proceedings of the National Academy of Sciences, 106, 13040-13045. 
659 
Van der Kolk, B.A., Pelcovitz, D., Roth, S. et al. (1996). Dissociation, somatization, and affect dysregulation: The 
660 
complexity of adaptation of trauma. American Journal of Psychiatry, 153, 83-93. 
661 
Xiong, J., Gao, J.H., Lancaster, J.L., Fox, P.T. (1999). Interregional connectivity to primary motor cortex revealed using 
662 
MRI resting state images. Human Brain Mapping, 8, 151-156. 
663 
 
664 
10.1 Measurement Bibliography: 
665 
Adhikari, B., Jahanshad, N., Shukla, D., Glahn, D.C., Blangero, J., Fox, P.T., Reynolds, R.C., Cox, R.W., Fierearms, El, 
666 
Veraart, J., Novikov, D.S., Nichols, T.E., Hong, L.E., Thompson, P.M., & Kochunov, P. (2018). Comparison of 
667 
heritability estimates on resting state fMRI connectivity phenotypes using the ENIGMA analysis pipeline. Human Brain 
668 
Mapping, 1-10. DOI: 10.1002/hbm.24331 
669 
Babor, T. F., Higgins-Biddle, J. C., Saunders, J. B. & Monteiro, M. G. (2001). The Alcohol Use Disorders Identification 
670 
Test: Guidelines for Use in Primary Care, 2nd Edition. Geneva, Switzerland: World Health Organization. 
671 
Bastien, C. H., Vallieres, A., Morin, C. M., (2001). Validation of the Insomnia Severity Index as an outcome measure for 
672 
insomnia research. Sleep Medicine, 2(4), 297-307. 
673 
Batterham, P. J., Ftanou, M., Pirkis, J., Mackinnon, A. J., Beautrais, A., Fairweather-Schmidt, A. K., & Christensen, H. 
674 
(2014, December 15). A systematic review and evaluation of measures for suicidal ideation and behaviors in 
675 
population-based research. Psychological Assessment. Advance online publication. 
676 
http://dx.doi.org/10.1037/pas0000053 
677 
Buysse, D. J., Yu, L., Moul, D. E., Germain, A., Stover, A., Dodds, N. E., Johnston, K. L., Shablesky-Cade, M. A., & 
678 
Pilkonis, P. A. (2010). Development and validation of patient-reported outcome measures for sleep disturbance and 
679 
sleep-related impairments. Sleep, 33, 781-792. 
680 
Cameron, I. M., Crawford, J. R., Lawton, K., & Reid, I. C. (2008). Psychometric comparison of PHQ-9 and HADS for 
681 
measuring depression severity in primary care. British Journal of General Practice, 58, 32-36. 
682 
Chung, F., Yegneswaran, B., Liao, P., Chung, S. A., Vairavanathan, S., Islam, S., Khajehdehi, A., & Shapiro, C. M. 
683 
(2008). STOP questionnaire: A tool to screen patients for obstructive sleep apnea. Anesthesiology, 108, 812-921. 
684 
De Menses-Gaya, I. C., Zuardi, A. W., Loureiro, S. R., de Souza Crippa, J. A. (2009). Psychometric properties of the 
685 
Fagerstrom Test for Nicotine Dependence. Jornal Brasileiro de Pneumologia, 35, 73-82. 
686 
Ebbert, J. O., Patten, C. A., & Schroeder, D. R. (2006). The Fagerstrom Test for Nicotine Dependence – Smokess 
687 
Tobacco (FTND-ST). Addictive Behaviors,31, 1716-1721. 
688 
Ferketich, A. K., Wee, A. G., Schultz, J., & Wewers, M. E. (2007). A measure of nicotine dependence for smokeless 
689 
tobacco users. Addictive Behaviors, 9, 1970-1975. 
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Gray, M. J., Litz, B. T., Hsu, J. L., Lombardo, T. W. (2004). Psychometric properties of the Life Events Checklist. 
691 
Assessment, 11, 330-341. 
692 
Heatherton, T. F., Kozlowski, L. T., Frecker, R. C., & Fagerstrom, K. O. (1991). The Fagerstrom Test for Nicotine 
693 
Dependence: A revision of the Fagerstrom Tolerance Questionnaire. British Journal of Addiction, 86, 1119-1127. 
694 
Henry, J.A., Stewart, B.J., Abrams, H.B., Newman, C.W., Griest, S., Martin, W.H., Myers, P.J., & Searchfield, G. (2014) 
695 
Tinnitus Functional Index—Development and Clinical Application. Audiology Today, 26, 40-48. 
696 
Kazis, L. E., Selim, A., Rogers, W., Ren, X. S., Lee, A., & Miller, D. R. Veterans RAND 12-Item Health Survey (VR-12): A 
697 
White Paper Summary. Unpublished manuscript. 
698 
http://www.hosonline.org/surveys/hos/download/veterans_rand_12_item_health_survey_white_paper_summary.pdf 
699 
Kroenke, K., Spitzer, R. L., & Williams, J. B. W. (2001). The PHQ-9: Validity of a brief depression severity measure. 
700 
Journal of General Internal Medicine, 16, 606-613. 
701 
Kroenke, K., Spitzer, R. L., Williams, J. B., & Lowe, B. (2010). The Patient Health Questionnaire Somatic, Anxiety, and 
702 
Depressive Symptom Scales: A systematic review. General Hospital Psychiatry, 32, 345-359. 
703 
Kubany, E. S., Haynes, S. N., Abueg, F. R., Manke, F. P., Brennan, J.M., Stahura, C. (1996). Development and validation 
704 
of the Trauma-Related Guilt Inventory (TRGI). Psychological Assessments, 8, 423-444. 
705 
Lowe, B., Decker, O., Muller, S., Brahler, E., Schellberg, D., Herzog, W., & Herzberg, P. Y. (2008). Validation and 
706 
standardization of the Generalized Anxiety Disorder Screener (GAD-7) in the general population. Medical Care, 46, 
707 
266-274. 
708 
Marx, B. P. (2013). Development and validation of a PTSD-related impairment scale. Retrieved from www.dtic.mil/cgi-
709 
bin/GetTRDoc?AD=ADA585414 
710 
Metalsky, G. I., & Joiner, T. E. (1997). The Hopelessness Depression Symptom Questionnaire. Cognitive Therapy and 
711 
Research, 21, 359-384. 
712 
Morin, C.M. (1993). Insomnia: Psychological Assessment and Management. New York, NY: The Guilford Press. 
713 
Nock, M. K., Holmberg, E. B., Photos, V. I., & Michel, B. D. (2007). Self-Injurious Thoughts and Behaviors Interview: 
714 
Development, reliability, and validity in an adolescent sample. Psychological Assessment, 19, 309-317. 
715 
Roy, M., Dum, M., Sobell, L. C., Sobell, M. B., Simco, E. R., Manor, H., & Palmerio, R. (2008). Comparison of the Quick 
716 
Drinking Screen and the alcohol Timeline Followback with outpatient alcohol abusers. Substance Use and Misuse, 43, 
717 
2116-2123. 
718 
Saunders, J. B., Aasland, O. G., Babor, T. F., De La Fuente, J. R. & Grant, M. (1993). Development of the Alcohol Use 
719 
Disorders Identification Test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol 
720 
consumption-II. Addiction, 88, 791-804. 
721 
Schwab, K. A., Baker, G., Ivins, B., Sluss-Tiller, M., Lux, W., & Warden, D. (2006). The Brief Traumatic Brain Injury 
722 
Screen (BTBIS): Investigating the validity of a self-report instrument for detecting traumatic brain injury (TBI) in troops 
723 
returning from deployment in Afghanistan and Iraq. [Abstract]. Neurology, 66(5)(Supp. 2), A235. 
724 
Schwab, K. A., Ivins, B., Cramer, G., Johnson, W., Sluss-Tiller, M., Kiley, K., Lux, W. & Warden, D. (2006). Screening for 
725 
traumatic brain injury in troops returning from deployment in Afghanistan and Iraq: Initial investigation of the 
726 
usefulness of a short screening tool for traumatic brain injury. Journal of Head Trauma Rehabilitation, 22(6), 377-389. 
727 
Sobell, L. C., Agrawal, S., Sobell, M. B., Leo, G. I., Young, L. J., Cunningham, J. A., Simco, E. R. (2003). Comparison of a 
728 
Quick Drinking Screen with the Timeline Followback for individuals with alcohol problems. Journal of Studies on 
729 
Alcohol, 64, 858-861. 
730 
Spitzer, R. L., Kroenke, K., & Williams, J.  B. W. (1999). Validation and utility of a self-report version of the PRIME-MD: 
731 
The PHQ primary care study. Journal of the American Medical Association, 282, 1737-1744. 
732 
Spitzer, R. L., Kroenke, K., Williams, J. B., & Lowe, B. (2006). A brief measure for assessing generalized anxiety disorder: 
733 
The GAD-7. Archives of Internal Medicine, 166, 1092-1097. 
734 
Vogt, D. S., Smith, B. N., King, L. A., King, D. W., Knight, J. A., & Vasterling, J. J. (2013). Deployment Risk and Resilience 
735 
Inventory-2 (DRRI-2): An updated tool for assessing psychosocial risk and resilience factors among service members 
736 
and veterans. Journal of Traumatic Stress, 26, 710-717.  
737 
Weathers, F.W., Blake, D.D., Schnurr, P.P., Kaloupek, D.G., Marx, B.P., & Keane, T.M. (2013). The Clinician-
738 
Administered PTSD Scale for DSM-5 (CAPS-5). Interview available from the National Center for PTSD at 
739 
www.ptsd.va.gov. 
740 
Weathers, F. W., Blake, D. D., Schnurr, P. P., Kaloupek, D. G., Marx, B. P., & Keane, T. M. (2013). The Life Events 
741 
Checklist for DSM-5 (LEC-5). Instrument available from the National Center for PTSD at www.ptsd.va.gov. 
742 
Weathers, F. W., Keane, T. M., & Davidson, J. R. (2001). Clinician-administered PTSD scale: A review of the first ten 
743 
years of research. Depression and Anxiety, 13, 132–156. 
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Weathers, F. W., Litz, B. T., Herman, D. S., Huska, J. A., & Keane, T. M. (1993). The PTSD Checklist (PCL): Reliability, 
745 
validity, and diagnostic utility. Paper presented at the 9th Annual Conference of the ISTSS, San Antonio, TX. 
746 
Weathers, F. W., Litz, B. T., Keane, T. M., Palmieri, P. A., Marx, B. P., & Schnurr, P. P. (2013). The PTSD Checklist for 
747 
DSM-5 (PCL-5). Instrument available from the National Center for PTSD at www.ptsd.va.gov. 
748 
Weise, C., Kleinstauber, M., Hesser, H., Westin, V.Z., & Andersson, G. (2013). Acceptance of tinnitus: Validation of the 
749 
Tinnitus Acceptance Questionnaire. Cognitive Behaviour Therapy, 42, 100-115. 
750 
Westin, V., Hayes, S.C., & Andersson, G. (2008). Is it the sound or your relationship to it? The role of acceptance in 
751 
predicting tinnitus impact. Behavior Research and Therapy, 46, 1259-1265. 
752 
Yu, L., Buysse, D. J., & Germain, A. (2012). Development of short forms from the PROMIS Sleep Disturbance and Sleep-
753 
Related Impairment item banks. Behavioral Sleep Medicine, 10, 6-24. 
754 
 
755 
11.0  TIME REQUIRED TO COMPLETE THE RESEARCH (including data analysis).  24 months 
756 
   
757 
12.0  STUDY CLOSURE PROCEDURES  At the conclusion of the study (following completion of manuscripts) or termination 
758 
by either the Investigators or the IRB, all data not included in the STRONG STAR Repository ( UTHSCSA IRB protocol  
759 
HSC20100475H) will be stripped of identifiers. De-identified (anonymized) data will be maintained indefinitely. Informed 
760 
consent documents will be stored securely for a minimum of three years following completion of the research; HIPAA 
761 
authorizations will be stored for a minimum of six years IAW Federal regulations. A protocol completion form will be filed with 
762 
the IRB. 
763 
 
764 
  13.0 Funding:  
765 
This study is being funded by the National Center for Advancing Translational Sciences, National Institutes of 
766 
Health, through Grant KL2 TR002646. 
767 
 
768 
14.0 Description of Assessments: 
769 
 
770 
Assessments will take place at baseline and one month following treatment.  
771 
 
772 
Personality & History 
773 
1. Demographics and Military Service Characteristics Form. The Demographics Form measures standard 
774 
demographics (race, gender, age) and military service information (e.g., rank).  
775 
 
776 
2. MRI Participant Information and Screening Questionnaire. The MRI Participant Information and Screening 
777 
Questionnaire measures demographics (race, gender, age), as well as information necessary to evaluate whether 
778 
an individual is able to receive an fMRI scan based on medical history (for example, neurostimulators, hearing 
779 
aids, any type of coil, filter, or stent, any type of metal object). 
780 
 
781 
Deployment Stress, Adversity & Trauma 
782 
3. Deployment Risk and Resilience Inventory (DRRI-2) Combat Experience.  
783 
 
784 
4. Deployment Risk and Resilience Inventory (DRRI-2) Postbattle Experiences. High- and low-intensity deployment 
785 
stress exposure will be assessed using scales from the DRRI-2 (Vogt, Smith, King, & King, 2012). The DRRI-2 is 
786 
an update of the original DRRI (King, King, Vogt, Knight, & Samper, 2006), which was developed and tested in 
787 
three separate national samples of veterans of the first Gulf War. It has been revised and tested with 
788 
OEF/OIF/OND returnees (Vogt et al., 2008). The DRRI-2 provides an update of the DRRI’s assessment of 
789 
deployment-related factors to ensure the instrument’s applicability across a variety of deployment circumstances 
790 
(e.g., different eras of service) and military subgroups (e.g., men and women), as well as to validate updated 
791 
measures in a contemporary Veteran cohort (Vogt, et al., 2012). High intensity stressor exposures will be 
792 
assessed using the DRRI Combat Experiences and Postbattle Experiences subscales. Responses to these 
793 
scales are on a 6-point Likert scale. The total score is the sum of the item scores, where higher scores signify 
794 
greater exposure to combat or exposure to the consequences of combat, respectively. Both subscales have very 
795 
good internal consistency (α = .90 to .92) and construct validity (Vogt et al., 2012). 
796 
 
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5. Life Events Checklist-5 (LEC-5).  The LEC-5 includes a list of 24 potentially traumatic life events commonly 
798 
associated with PTSD symptoms. The instrument was designed to facilitate the diagnosis of PTSD (Weathers, 
799 
Blake, Schnurr, Kaloupek, Marx, & Keane, 2013a).). In this study, the LEC-5 will also be used to identify the index 
800 
event and focus of the PTSD treatment. For each potentially traumatic life event, respondents rate their 
801 
experience of that event on a 5-point nominal scale (1 = happened to me, 2 = witnessed it, 3 = learned about it, 4 
802 
=part of my job, 5= not sure, and 6 = does not apply). Each nominal point will be scored separately, as either 0 
803 
(=not endorsed by participant) or 1 (=endorsed by participant). 
804 
 
805 
6. Trauma Related Guilt Inventory (TRGI). The TRGI was developed to assess guilt feelings and attitudes about a 
806 
specific traumatic event (Kubany, Haynes, Abueg, Manke, Brennan, Stahura, 1996).  Often survivors of trauma 
807 
experience guilt related to the trauma about things they did or did not do or feelings they had or did not have.  A 
808 
combat veteran may experience guilt about having provided first aid to some of his or her wounded colleagues 
809 
but not others even though it was not possible to care for everyone.  Or, an individual may experience survivor’s 
810 
guilt not understanding why he lived while others died.  These feelings of guilt can be important in evaluating the 
811 
various treatments for PTSD.  The TRGI is scored into three scales (i. e., 4-item Global Guilt Scale, 6-item 
812 
Distress Scale, and a 22-item Guilt Cognitions Scale) and 3 subscales (i. e., the Hindsight-Bias / Responsibility 
813 
Subscale, the Wrongdoing Subscale, and the Lack of Justification Subscale).  Psychometric testing has been 
814 
conducted using almost 600 individuals including 357 university students, 163 women receiving counseling 
815 
services in a battered women’s program, and 74 Vietnam veterans.  Internal consistency was high across all the 
816 
testing samples.  In the sample of Vietnam veterans the alpha coefficient ranged from 0.66 to 0.94.  In the 
817 
Vietnam veterans, the scores on the various scales and subscales were significantly correlated with the 
818 
Posttraumatic CheckList – Military (PCL-M), the Mississippi Scale for Combat-Related Posttraumatic Stress 
819 
Disorder, the Zung Self-Rating Depression Scale, the Guilt Inventory, and the Social Avoidance and Distress 
820 
Scale with reliability coefficients ranging from 0.36 to 0.77 (p<.05).  In a sample of 32 university students, the test-
821 
retest correlations after two days ranged from 0.74 to 0.83.  An abbreviated 16-item version of the TRGI will be 
822 
used in the STRONG STAR studies allowing only for the calculation of the three subscale scores.  The Hindsight-
823 
Bias / Responsibility Subscale score = (sum of scores on Items 1, 5, 9, 14, 19, 23, and 26) divided by 7. The 
824 
Wrongdoing Subscale score = (sum of scores on Items 3, 7, 11, 16, and 21) divided by 5. And, the Lack of 
825 
Justification Subscale score = [sum of scores on Items 4 (R), 8 (R), 12 (R), and 17 (R)] divided by 4. 
826 
 
827 
Psychiatric Status & History 
828 
7. Depressive Symptom Index Suicide Subscale (DSI-SS). The DSI-SS (Metalsky & Joiner, 1997) will be used to 
829 
assess current suicidal ideation. The DSI-SS is a 4-item self-report measure of suicidal ideation that focuses on 
830 
ideation, plans, perceived control over ideation, and impulses for suicide. It is being used as a core measure in 
831 
the Military Suicide Research Consortium. Scores on each item range from 0 to 3, with higher scores reflecting 
832 
greater severity of suicidal ideation. Instructions will instruct the participants to respond based on the past two 
833 
weeks (for baseline and follow up visits) or the past week (for interim assessment visits). A systematic review of 
834 
measures of suicidal ideation and behaviors found that the DSI-SS had evidence of excellent internal consistency 
835 
and concurrent validity (Batterham et al., 2014).  
836 
  
837 
8. Generalized Anxiety Disorder-7 (GAD-7). The GAD-7 (Spitzer, Kroenke, Williams, & Lowe, 2006) will be used to 
838 
assess generalized anxiety symptomology. This is a 7-item measure that asks participants to rate the frequency 
839 
with which they have been bothered by anxiety symptoms within the past two weeks on a scale ranging from 0 
840 
(“not at all”) to 3 (“nearly every day”). Scores on all items are summed to obtain a total severity score.  Scores 
841 
reflect no significant anxiety symptoms (0-4), mild anxiety symptoms (5-9), moderate anxiety symptoms (10-14), 
842 
and severe anxiety symptoms (>15).  Respondents also indicate the degree to which their anxious symptoms 
843 
have made it difficult for them to do their work, take care of things at home, or get along with other people, from 
844 
“not difficult at all” to “extremely difficult.” The GAD-7 has been shown to have high internal consistency (e.g., α = 
845 
.89; Lowe et al., 2008) and has been shown to reliably discriminate between anxious and non-anxious diagnostic 
846 
groups (Kroenke, Spitzer, Williams, & Lowe, 2010). 
847 
 
848 
9. Selection of Index Event for CAPS-5.  This form will be used as a supplement to the CAPS-5 interview to help 
849 
determine which event to select as the Index Event. This form is standardly used in conjunction with the CAPS-5 
850 
and does not represent a separate assessment. 
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852 
10. Clinician-Administered PTSD Scale – 5 (CAPS-5).  The CAPS-5 is structured interview that assesses the DSM-5 
853 
criteria for PTSD (Weathers et al., 2013). Each item is rated on a severity scale ranging from 0 (Absent) to 4 
854 
(Extreme/incapacitating) and combines information about frequency and intensity for each of the 20 symptoms. 
855 
Additional items that are not included in the total score evaluate overall symptom duration, distress, impairment, 
856 
dissociative symptoms, and global ratings by the interviewer. Validation studies are nearly complete to establish 
857 
the psychometric properties of the CAPS-5 and findings will be reported in peer-reviewed publications. This 
858 
interview is very similar to its predecessor, the CAPS for DSM-IV, which has been considered the gold standard 
859 
for evaluating PTSD and demonstrated good reliability and validity (Weathers, Keane, & Davidson, 2001). In 
860 
addition to reflecting diagnostic changes for PTSD in DSM-5, the CAPS-5 differs from the CAPS in that frequency 
861 
and intensity ratings for each symptom are no longer scored separately, so the severity rating for each item 
862 
determines whether a symptom is present or not. Subscale scores are calculated by summing severity scores for 
863 
items in the following PTSD symptom clusters: re-experiencing, avoidance, negative alterations in cognitions and 
864 
mood, and hyperarousal. Scores ≥ 25 indicate a probable diagnosis of PTSD. 
865 
 
866 
11. 
PTSD Check List – DSM-5 (PCL-5). The PCL-5 (Weathers, et al., 2010) is a 20-item self-report measure 
867 
update of the PCL designed to assess PSTSD symptoms as defined by the DSM-5. The PCL-5 is currently available 
868 
and has been shown to have good psychometric properties. The PCL-5 evaluates how much participants have been 
869 
bothered by PTSD symptoms in the past month (for baseline and follow up assessments) or the past week (all interim 
870 
assessments) as a result of a specific life event.  Each item of the PCL-5 is scored on a five point scale ranging from 0 
871 
(“not at all”) to 4 (“extremely).  
872 
 
873 
12. Self-Injurious Thoughts and Behaviors Interview- Short Form (SITBI- Short Form). The SITBI-Short Form (Nock, 
874 
Holmberg, Photos, & Michel, 2007) is a structured interview assessing the presence, frequency, and 
875 
characteristics of self-injurious and suicidal thoughts and behaviors. The SITBI-Short Form will be administered 
876 
by an Independent Evaluator, who will instruct the participants to answer the questions based on their entire 
877 
lifetime of experience. The SITBI-Short Form has shown high interrater reliability, test-retest reliability, and 
878 
concurrent validity (Nock et al., 2007).  
879 
 
880 
Functional Impairment 
881 
13. Health Questionnaire. The original Health Care Utilization (HCU) is a 16-item questionnaire developed in 2000 for 
882 
Dr. Patricia A. Resick’s NIH grant, “Cognitive Processes in PTSD: Treatment II.” The questionnaire was based on 
883 
the 1999 Behavioral Risk Factor Surveillance System. The version that will be administered as part of the 
884 
STRONG STAR Consortium has been modified to be of increased relevance to active-duty service personnel. 
885 
The measure includes items regarding use of mental health services, current psychiatric medication, past 
886 
psychiatric medication, hospitalization, and outpatient medical services, as well as items intended to assess 
887 
changes in participants’ military status.  
888 
 
889 
14. History of Head Injuries. The History of Head Injuries form was developed from the Defense and Veterans Brain 
890 
Injury Center (DVBIC) 3-Item Screening Tool (Schwab, Baker, Ivins, Sluss-Tiller, Lux & Warden, 2006; Schwab, 
891 
Ivins, Cramer, Johnson, Sluss-Tiller, Kiley, Lux & Warden, 2006).  The DVBIC Screening Tool, initially called the 
892 
Brief Traumatic Brain Injury Screen (BTBIS), was used as the gold standard for the diagnosis of TBI in a sample 
893 
of soldiers returning from duty in Iraq and/or Afghanistan (Schwab, Ivins, et al., 2006). As recommended by the 
894 
DVBIC, the 3-Question Screen will be considered positive when the participant endorses an injury (question 1) 
895 
and altered consciousness (question 2, items A-E) for the worst head injury sustained while deployed. The form 
896 
was modified for STRONG STAR and now CAP to capture the number of injuries, and to answer question 2 
897 
based on the worst injury; the original form does not recognize the possibility of multiple head injuries during 
898 
deployment. As the 3-Question Screen does not query head injuries prior to deployment, an additional four 
899 
questions have been added to solicit information about each head injury sustained outside of deployment. 
900 
 
901 
15. Veterans Rand 12-Item Health Survey (VR-12). Because a certain level of PTSD symptoms is an occupational 
902 
hazard among service members redeployed for combat, it is critical to pay close attention to functional capacities 
903 
as an important index of intervention efficacy.  The Veterans SF-36 (VR-36) was adapted from the RAND SF-36 
904 
Version 1.0 questionnaire, and spans the range of health domains from physical to psychological health status. It 
905 

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includes two modifications.  The first modification is an increase in the number of response choices for the role 
906 
physical (RP) and role emotional (RE) items from a  two point yes/no choice to a five-point likert scale (no, none 
907 
of the time, yes, a little of the time, yes, some of the time, yes, most of the time, yes, all of the time).  The second 
908 
modification is the use of two items to assess health change, one focusing on physical health and one on 
909 
emotional problems, in contrast to the one general change item in the RAND SF-36 (Kazis, Lee et al., 2004; 
910 
Kazis, Miller, Clark et al 2004). The VR-36 has been widely used, distributed and documented in the Veterans 
911 
Health Administration (VHA) with close to 2 million questionnaires administered nationally in six national surveys 
912 
since 1996. The changes to the survey have increased the overall precision of the instrument and the discriminant 
913 
validity of the physical and mental component summary scales (Kazis, Nethercot, et al 2006). The VR-36 is 
914 
comprised of 37 items and eight scales:  physical functioning, role limitations due to physical problems, bodily 
915 
pain, general health perceptions, energy/ vitality, social functioning, role limitations due to emotional problems, 
916 
and mental health. Also, there are two summary scales:  a physical component summary (PCS) and mental 
917 
component summary (MCS). Higher scores indicate better health. Each summary is expressed as a T score, 
918 
which facilitates comparisons between the VA patients and the general U.S. population. The PCS and MCS 
919 
scores provide at least 90% of the reliable variance in the eight SF-36 concepts (Kazis & Wilson, 1998; Kazis, 
920 
Wilson, et al., 1999). The Veterans SF-12 was developed from the Veterans SF-36 and adapted from the MOS 
921 
SF-36. It includes fewer items for seven of the eight scales and provides 90% of the reliable variance in the two 
922 
component summary measures using the Veterans SF-36. Using independent results from the Veterans Health 
923 
Study and the 1996 National Survey of Ambulatory Care Patients, the results for the Veterans SF-12 
924 
corresponded very closely with the results for the Veterans SF-36 (average differences of 0.06 points between 
925 
them for PCS and 0.31 points for MCS; Kazis et al., 1996; Kazis & Wilson, 1998). 
926 
 
927 
16. Insomnia Severity Index (ISI). The ISI (Morin, 1993) is a 7-item self-report measure that assesses perceived 
928 
severity of insomnia. Each item uses a 4-point Likert type scale from 0 (not at all satisfied) to 4 (very much 
929 
satisfied). The items sum to produce a total score (range 0 – 28). The ISI has an internal consistency alpha 
930 
coefficient of 0.74, and has shown convergent validity with other measures such as the Pittsburgh Sleep Quality 
931 
Index (r = 0.67), the Dysfunctional Beliefs and Attitudes about Sleep (r = 0.55), and sleep diaries (r ranges from 
932 
0.32-0.91) (Bastien, Vallieres & Morin, 2001). 
933 
  
934 
17. PROMIS Sleep-Related Impairment and Sleep Disturbance. The PROMIS Sleep Disturbance and Sleep-Related 
935 
Impairment short forms (Yu, Buysse, & Germain, 2012) are self-report measures of past-week sleep disturbance 
936 
and past-week sleep-related impairment, respectively, derived from the larger PROMIS item banks (Buysse et al., 
937 
2010). Each short-form measure includes 8 items, with most items (symptoms) scored in intensity from 1 (“not at 
938 
all”) to 5 “(very much”). Each measure has shown strong reliability and construct validity (Yu et al., 2012). 
939 
 
940 
18. Snoring, Tired, Observed, Blood Pressure (STOP) Sleep Apnea Screen. To better understand sleep disturbance 
941 
associated with PTSD and PTSD treatment, the STOP screen (Chung et al., 2008) will be administered to screen 
942 
for sleep apnea.  The STOP is a four-item questionnaire developed and validated in 211 pre-operative surgical 
943 
patients.  Based on the endorsement of 2 or more questions, the sensitivity of the STOP ranged from 66% to 80% 
944 
as compared with the apnea-hypopnea index (AHI) of polysomnography depending upon the AHI cut-off used.  
945 
Individuals answering “yes” to 2 or more of the questions will be advised that they may be at risk for having sleep 
946 
apnea and advised that they may want to speak with their primary care provider to consider referral for an 
947 
overnight sleep evaluation  
948 
 
949 
19. Patient Health Questionnaire – 9 (PHQ-9). The PHQ-9 is a widely used and well-validated instrument for 
950 
measuring the severity of depressive symptoms (Kroenke, Spitzer, & Williams, 2001). It consists of 9 items that 
951 
assess both affective and somatic symptoms related to depression and depressive disorders; these 9 items 
952 
correspond to the diagnostic criteria for DSM MDD. Respondents rate the frequency with which they have been 
953 
bothered by depressive symptoms within the past two weeks (for baseline and follow up visits) or the past week 
954 
(for interim assessment visits)on a scale ranging from 0 (“not at all”) to 3 (“nearly every day”). Scores on all items 
955 
are summed to obtain a total severity score. Scores reflect no significant depressive symptoms (0-4), mild 
956 
depressive symptoms (5-9), moderate depressive symptoms (10-14), moderately severe depressive symptoms 
957 
(15-19), and severe depressive symptoms (>19). Respondents also indicate the degree to which their depressive 
958 
symptoms have made it difficult for them to do their work, take care of things at home, or get along with other 
959 

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people, from “not difficult at all” to “extremely difficult.” The PHQ-9 has high internal consistency (e.g., alpha 
960 
ranging from .83 to .92; Cameron, Crawford, Lawton, & Reid, 2008), and correlates strongly with other measures 
961 
of depression (Kroenke et al., 2001).   
962 
 
963 
20. Fagerstrom Test for Nicotine Dependence (FTND). The FTND (Heatherton et al., 1991) is a 6-item self-report 
964 
measure that assesses severity of nicotine dependence. Questions probe both quantity of nicotine use (e.g., 
965 
number of cigarettes per day) and pattern of use (e.g., time to first cigarette in morning). Respondents choose 
966 
among response options, each of which is assigned a numerical value, with higher numbers corresponding to 
967 
greater nicotine dependence. Scores on all items are summed to create a severity index (0-2 = very low 
968 
dependence; 3-4 = low dependence; 5 = medium dependence; 6-7 = high dependence; 8-10 = very high 
969 
dependence). The Fagerstrom scale has been shown to have high convergent validity with biochemical indices of 
970 
nicotine use, and the measure has shown acceptable internal consistency (Heatherton et al., 1991). A review of 
971 
26 studies of the psychometric characteristics of the Fagerstrom found that it is a reliable instrument for 
972 
measuring nicotine dependence in diverse settings and populations (Meneses-Gaya et al., 2009). 
973 
 
974 
21. Fagerstrom Test for Nicotine Dependence- Smokeless Tobacco (FTND-ST). This is a modified version of the 
975 
Fagerstrom Test that focuses on smokeless tobacco use, whereas the original Fagerstrom focuses exclusively on 
976 
smoking. Like the FTND, the FTND-ST is a 6-item self-report measure of severity of nicotine dependence that has 
977 
demonstrated convergent validity with biochemical indices of nicotine use (Ebbert et al., 2006; Ferketich et al., 
978 
2007). As on the original FTND, respondents choose among response options, each of which is assigned a 
979 
numerical value, with higher numbers corresponding to greater nicotine dependence. Scores on all items are 
980 
summed to create a severity index (range = 0–10). 
981 
 
982 
22. Alcohol Use Disorders Identification Test (AUDIT). The AUDIT (Babor et al, 2001) will be used to identify people 
983 
with hazardous or harmful patterns of alcohol consumption. The AUDIT is a 10-item screening measure, 
984 
developed by the World Health Organization (WHO), with three subscales (alcohol consumption, drinking 
985 
behavior, and alcohol-related problems) that are scored on a 4-point scale for a highest possible total score of 40. 
986 
Among those identified as using alcohol in a harmful manner, 92% had scores of 8 or more, though determining a 
987 
cutoff score should be left up to the clinician, depending upon the population being studied. The AUDIT has good 
988 
internal consistency (α = .80-.93) as well as sensitivity and specificity (Saunders, Aasland, Babor, De La Fuente & 
989 
Grant, 1993). 
990 
 
991 
23. Quick Drinking Screen (QDS). The QDS (Sobell et al., 2003) will be used to measure alcohol consumption. It 
992 
consists of 4 items probing frequency and quantity of alcohol consumption. It will be administered in a self-report 
993 
form. The QDS has been validated against the Timeline Followback daily estimation measure of alcohol use, and 
994 
it shows good psychometric properties (Roy et al., 2008; Sobell et al., 2003). The QDS’s time-frame will be 
995 
modified to match the “last two weeks” probed by the mandated depression and anxiety instruments for CAP 
996 
studies (PHQ-9 and GAD-7). Like these other measures, the QDS can be administered frequently throughout 
997 
CAP trials to track changes in alcohol use. 
998 
 
999 
24. Mini-International Neuropsychiatric Interview (MINI)- Manic and Psychosis modules. The MINI 7.0 is a short, 
000 
structured clinical diagnostic interview designed to cover the major psychiatric disorders in  DSM-5 and ICD-10. It 
001 
is widely used in epidemiological studies and multi-site clinical trials. Responses to the interviewer’s questions are 
002 
rated as either “yes” or “no.” As is the case on the SCID, there are skip-outs, which saves time.  However, this 
003 
means that the MINI cannot be used to index the severity of a given psychiatric problem, only caseness. When 
004 
there are many skip-outs, the MINI takes ~15 minutes to administer. The MINI can be used to assess the full 
005 
spectrum of psychiatric problems, or specific modules can be employed (e.g., the schizophrenia module to rule 
006 
out thought disorder). 
007 
 
008 
25. Tinnitus Functional Index (TFI).  The Tinnitus Functional Index (TFI) was reported by Henry et al (2014). They 
009 
report five stages of TFI development through which prototypes were developed, tested, and revised over a four-
010 
year period. The TFI has eight subscales that address the intrusiveness of tinnitus, the sense of control the 
011 
patient has, cognitive interference, sleep disturbance, auditory issues, relaxation issues, quality of life, and 
012 
emotional distress. 
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014 
26. Tinnitus Acceptance Questionnaire (TAQ). The Tinnitus Acceptance Questionnaire (TAQ) was reported by Westin 
015 
et al. (2008). This measure captures the extent to which individuals accept their tinnitus, and attempts to avoid or 
016 
control tinnitus, as well as a patient’s ability to pursue valued life activities and meaningful goals regardless of 
017 
tinnitus. The TAQ was further validated in an English speaking population (Weise et al., 2012). 
018 
 
019 
Psychosocial Functioning 
020 
27. Brief Inventory of Psychosocial Functioning (BIPF). The Brief Inventory of Psychosocial Functioning (Marx et al. 
021 
2013) is a 7-item self-report instrument measuring respondents’ level of functioning in seven life domains: 
022 
romantic relationship, relationship with children, family relationships, friendships and socializing, work, training 
023 
and education, and activities of daily living. Respondents indicate the degree to which they had trouble in the last 
024 
30 days in each area on a 7-point scale ranging from “0 = Not at all” to “6 = Very much.” 
025 
 
026 
Other Key Mediators & Moderators 
027 
28. Homework Compliance. The Homework Compliance form asks questions about how often participants used the 
028 
worksheets, how many minutes were dedicated toward the practice assignments, and how helpful the practice 
029 
assignments were considered.  
030 
29. Resting-state fMRI. Resting state fMRI techniques (Adhikari et al., 2018) will be conducted among individuals with 
031 
comorbid PTSD and tinnitus. Resting-state connectivity will be assessed by mapping inter-regional connectivity 
032 
using an extended time series BOLD fMRI images acquired in an unstimulated state. Connectivity can be 
033 
detected and quantified using inter-connected regions, which show temporally correlated variations and are 
034 
analyzed with a data-driven analytic strategy called Independent Components Analysis. Resting-state networks 
035 
that will be examined include the default-mode network, auditory network, limbic network, and attentional network.  
036 
 
037 
 
038 
Appendices: 
039 
 
040 
A – CPT Treatment Manual 
041 
B – Recruitment Flyer 
042 
C - Telephone Script and Pre-Screen Questionnaire 
043 
D – MRI Prescreening Video 
044 
E – MRI Prescreening Video Script 
045 
F – Explanation for Tinnitus and PTSD (to be discussed during session 1) 
046 
 
047