Neural Markers and Rehabilitation of Executive Functioning in Veterans With Traumatic Brain Injury and Posttraumatic Stress Disorder
Condition: Traumatic Brain Injury; Posttraumatic Stress Disorder
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Study type: Interventional

Summary: 
      Up to half of all military service members with combat-related traumatic brain injury (TBI)
      also suffer from Posttraumatic Stress Disorder (PTSD). TBI and PTSD are each associated with
      cognitive problems in what are called 'executive functions' such as planning actions,
      inhibiting behavior, monitoring one's own thoughts and feelings, and solving problems
      day-to-day. These types of impairments occur more often among veterans with both TBI and PTSD
      than among those 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.

      Although the relationship between combined TBI/PTSD diagnoses and post-deployment adjustment
      problems has been demonstrated, there has been little 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 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 comparison).

      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 observe behaviors in the home
      environment, arrive at strategies for applying new skills in their situations, troubleshoot
      any iPod technical problems, and review family mentoring processes.

      The investigators will measure clinical outcomes using a comprehensive array of functional
      and structural methods at baseline and six months. The investigators hypothesize 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.

      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.

      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.
    

Detailed description: 
      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.
    

Intervention name(s): Cognitive Rehabilitation Intervention; Cognitive Rehabilitation Control Intervention
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Baseline training and follow-up at two months and four months.; Baseline training and follow-up at two months and four months.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: TBI; PTSD; Veterans