Enhancement of PTSD Treatment With Computerized Executive Function Training

This study focuses on helping Iraq and Afghanistan Veterans with posttraumatic stress disorder (PTSD) benefit fully from therapy by first enhancing their thinking abilities. PTSD has been associated with thinking problems, including difficulty planning/organizing, thinking flexibly, and inhibiting distracting emotional information. There is some evidence that computerized training programs are helpful for improving thinking. Therefore, this study tests whether computerized cognitive training will in fact improve individuals' thinking abilities and if this will in turn improve PTSD treatment outcomes and lead to more individuals completing treatment and showing greater improvements in emotional symptoms and quality of life than standard therapy (when paired with a word training condition).

PTSD affects approximately 14% of OEF/OIF Veterans and leads to considerable personal and societal costs (e.g., increased morbidity, reduced work productivity, poorer relationships). Although cognitive behavioral therapy (CBT) is one of the most effective treatments for PTSD, a substantial portion (approximately 50%) of individuals drop out prematurely, do not respond to treatment, or relapse. Treatment engagement is worse for OEF/OIF Veterans, who attend fewer sessions and have higher dropout rates than civilians and Veterans from other eras. One likely barrier to treatment engagement and effectiveness is the executive functioning problems present in individuals with PTSD. Executive functions (EFs) are the set of higher-level cognitive skills that organize and integrate lower-level cognitive processes in order to perform complex, goal-directed tasks. PTSD has been associated with EF deficits, including impairments in inhibitory control, working memory, and cognitive flexibly, as well as dysfunction in a network of brain regions that support EFs (e.g., prefrontal cortex [PFC], cingulate). EFs are essential for CBT in order to engage the cognitive skills involved in treatment (e.g., self-monitoring, inhibiting distorted thoughts, and flexibly generating/evaluating alternative thoughts). This is particularly true for Cognitive Processing Therapy (CPT), a frontline CBT treatment for PTSD, which involves identifying and challenging maladaptive trauma-related thoughts to alter their impact on emotions and behavior. Thus, EF deficits may lead to reduced CPT engagement and responsivity. In fact, worse EF at baseline has been associated with poorer response to CBT in several disorders (e.g., generalized anxiety disorder, obsessive compulsive disorder, and schizophrenia). Further, a study of brain functioning during an EF task demonstrated that dysfunction in EF-related brain regions including PFC and cingulate cortex at baseline predicted nonresponse to CBT for PTSD. Directly targeting EF prior to CPT via cognitive training would strengthen executive networks and likely boost treatment effectiveness, allowing Veterans to fully engage in and benefit more from components of CPT (e.g., cognitive restructuring). Evidence suggests that computerized cognitive training improves EF and functioning in EF-related brain regions, increases mental health treatment completion rates, and goal of the proposed study is to examine whether administering computerized EF training (CEFT) immediately prior to CPT will improve executive functioning and enhance treatment adherence, completion rates, and psychological and functional outcomes in OEF/OIF Veterans with PTSD. Objective (neuropsychological) and subjective (self- report) measures of EF will be collected to determine if CEFT enhances EF and if this in turn mediates the relationship between treatment condition and PTSD symptom improvement. Functional neuroimaging during EF tasks will also be collected at baseline to determine whether functioning within an EF network predicts treatment response, above and beyond traditional paper-and-pencil measures of EF. Veterans will be randomized to either 12 weeks of CEFT-CPT or a placebo word training condition plus CPT. Assessments will be administered at baseline, immediately after CEFT or word training (prior to CPT), and after CPT completion. The proposed research aims to reduce barriers to treatment engagement and has potential to significantly enhance current treatments for PTSD by combining cognitive and psychotherapeutic approaches. Targeting EF directly and independently represents a logical, innovative, and empirically-informed method for augmenting existing treatments for PTSD in order to optimize outcomes. Findings from the proposed study will not only directly inform clinical practice, but also have the potential to significantly improve the quality of Veterans' lives, reduce societal costs and burden, improve access to care, and reveal ways to better match individuals with treatments they are most likely to benefit from.

PTSD, treatment, posttraumatic stress disorder, therapy, cognition, thinking, executive function, computer, training

Participants randomized to the CEFT-CPT arm will receive 6 weeks of computerized executive function training and then 6 weeks of standard Cognitive Processing Therapy for PTSD (total of 12 sessions)

Participants randomized to the WT-CPT arm will receive 6 weeks of computerized word game training and then 6 weeks of standard Cognitive Processing Therapy for PTSD (total of 12 sessions)

WCST is a neuropsychological measure of executive functioning, will be examined separately as well as in a composite with the other neuropsychological measures of executive functioning

PASAT is a neuropsychological measure of executive functioning, will be examined separately as well as in a composite with the other neuropsychological measures of executive functioning

D-KEFS is a neuropsychological measure of executive functioning, will be examined separately as well as in a composite with the other neuropsychological measures of executive functioning

change in subjective executive functioning from baseline to completion of computerized cognitive training (6 weeks)

WAIS-IV Digit Span Sequencing subtest is a neuropsychological measure of executive functioning, will be examined separately as well as in a composite with the other neuropsychological measures of executive functioning

CAPS-5 is a clinical interview assessing PTSD symptoms that will be administered at 3 time points: baseline, after completion of cognitive training, and after completion of Cognitive Processing Therapy

change in PTSD symptoms from baseline to completion of Cognitive Processing Therapy (12 sessions completed after cognitive training), approximately 12 weeks after baseline assessment

PCL-5 is a self-report questionnaire that will be administered at 15 time points: at baseline, after completion of cognitive training, at each of the 12 therapy sessions, and after completion of Cognitive Processing Therapy

change in PTSD symptoms from baseline to completion of Cognitive Processing Therapy (12 sessions completed after cognitive training), approximately 12 weeks after baseline assessment

WHOQOL-BREF is a self-report questionnaire assessing quality of life that will be administered at 3 time points: baseline, after completion of cognitive training, and after completion of Cognitive Processing Therapy. Four subscales are computed (range 4-20): physical health, psychological, social relationships, and environment, higher scores indicate higher quality of life in each domain.

change in quality of life from baseline to completion of Cognitive Processing Therapy (12 sessions completed after cognitive training), approximately 12 weeks after baseline assessment

At each of the CPT sessions, participants will report how much time they spent completing homework since the previous session

time (in minutes) spent completing homework from CPT session 1 to CPT session 12 (across approximately 6 weeks, weeks 7-12 after baseline)

CPT sessions completed (out of a possible 12) after completing the cognitive training (across approximately 6 weeks, weeks 7-12 after baseline)

Inclusion Criteria: Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans enrolled at Veterans Affairs San Diego Healthcare System (VASDHS) aged 18-55 current posttraumatic stress disorder (PTSD) diagnosis endorsement of cognitive complaints no pending medication changes English-speaking. Exclusion Criteria: active substance use disorder in the last month suicidal intent or attempt within the last month schizophrenia, psychotic disorder and/or bipolar disorder dementia premorbid IQ < 70 participation in other concurrent PTSD intervention studies previous completion of more than 4 Cognitive Processing Therapy (CPT) sessions history of a documented neurological disorder (e.g., Parkinson's disease, multiple sclerosis, epilepsy) moderate to severe traumatic brain injury (TBI) (i.e., loss of consciousness greater than 30 minutes or post-traumatic amnesia greater than 24 hours).

A de-identified, anonymized dataset will be created and shared. Requests for access must be made in writing signed by a requestor from the United States and include an email address for delivery and an assurance that the recipient will not attempt to identify or re-identify any individual. The request should reference the publication underlying the request. Requests may be made to the Principal Investigator/lead point-of-contact for the publication. If the investigator leaves the VA San Diego Healthcare System, the requests may be sent to the Associate Chief of Staff for Research.