Neural Markers and Rehabilitation of Executive Functioning in Veterans With Traumatic Brain Injury and Posttraumatic Stress Disorder

Background: It is estimated that up to half of all military service members with combat-related traumatic brain injury (TBI) also meet criteria for Posttraumatic Stress Disorder (PTSD). TBI and PTSD are both characterized by deficits in multiple cognitive domains, including attention, executive function, and affective and cognitive control. However, cognitive and affective sequelae associated with TBI are compounded by the presence of PTSD symptoms in returning veterans. Specifically, it has been shown that significant frontal lobe dysfunction, particularly disinhibition, occurs more often among veterans with both TBI and PTSD than among veterans diagnosed with only one of these conditions. The combination of TBI and PTSD in veterans has also been linked to problems with anger and violence, which are common complaints of veterans seeking mental health services post-deployment and have been shown to predict poor treatment outcomes in Iraq and Afghanistan veterans. Executive dysfunction, especially difficulty with attentional processing, is strongly related to hostility and aggressiveness in Iraq and Afghanistan veterans; increasingly so in the presence of TBI and PTSD.

Objective/Hypothesis: Although the relationship between combined TBI/PTSD diagnoses and post-deployment adjustment problems has been clearly demonstrated, there has been little empirical research into clinical interventions designed to reduce the severity of cognitive and affective symptoms in veterans with both TBI and PTSD. Therefore, the investigators propose to conduct a randomized trial of theoretically based cognitive rehabilitation to improve executive function and affective control among Iraq and Afghanistan veterans with both TBI and PTSD, and to measure clinical outcomes using a comprehensive array of functional and structural methods. The investigators hypothesize that improved executive function among those in the experimental group as well as reduced irritability/impulsivity and improved social/occupational functioning. The investigators further hypothesize that, as a group, veterans participating in the cognitive rehabilitation program will show significant changes in neural activity associated with executive functions when comparing pre- and post-treatment EEG and fMRI responses.

Specific Aims: Better understanding of the neural circuitry and neurocognitive function underlying executive function and associated affective control deficits in veterans with both TBI and PTSD, and how they relate to treatment outcome, will allow us to better identify therapeutic targets for cognitive rehabilitation. The current proposal aims to explore the relationship between brain function and connectivity in selective pathways/circuits, neuropsychological functioning, and cognitive rehabilitation response in veterans with both TBI and PTSD.

Study Design: Toward this end, the investigators propose a randomized clinical trial involving a cognitive rehabilitation intervention that targets improved executive functioning, with the participation of N=100 veterans diagnosed with both TBI and PTSD (n=50 in experimental group and n=50 receiving usual care). As part of the study, all participants will receive an iPod touch. Participants will be placed into one of the two study groups randomly. Based on which group participants are placed in, they will receive one of two different sets of iPod touch apps and programs that address and aim to improve different facets of cognitive functioning. Regardless of which group, Veterans will be instructed to daily practice iPod touch applications on cognitive functioning. Also, family members will be trained as "mentors" to reinforce use of the applications in everyday living environments. Trained facilitators will also travel to participants' homes to meet with veterans and family to review their respective applications and mentoring processes. The investigators will examine both cognitive and behavioral changes, as well as neural changes associated with cognitive rehabilitation using EEG and fMRI at baseline and six months.

Military Benefit: This study of the neurobiology and neuropsychology associated with intervention efficacy will allow us to identify veterans with both TBI and PTSD who are predisposed to positive treatment outcomes. To our knowledge, this will be the first attempt to integrate neurobiological and neurocognitive techniques with information about the efficacy of a theoretically and empirically driven cognitive rehabilitation intervention in veterans with combined TBI/PTSD diagnoses. This research may suggest additional avenues for assessment of clinical intervention efficacy and the identification of therapeutic targets (e.g. alteration of function in fronto-limbic circuits) relevant to the military population. Given links between TBI/PTSD, executive dysfunction, and anger, impulsivity, and aggression, efforts to rehabilitate cognitive function will be particularly important to ensure that current and future veterans adjust successfully when they return home to their families, workplaces, and communities.