Cognitive Training for PTSD
Condition: Posttraumatic Stress Disorder
MeSH terms: Stress Disorders, Post-Traumatic
Study type: Interventional

Summary: 
      Posttraumatic stress disorder (PTSD) is a chronic, disabling condition that occurs in a
      subgroup of individuals after experiencing traumatic stress, and is common in Veterans
      seeking mental health treatment at the VA. Although evidence-based psychosocial treatments
      exist for PTSD, a substantial portion of individuals do not fully respond to treatment. Thus,
      there is a clear need to continue researching novel interventions for PTSD in Veterans.
      Recently, new interventions for mental health disorders have utilized computerized cognitive
      training techniques in order to improve the functioning of cognitive systems and reduce
      symptoms. This type of intervention, often referred to as neurotherapeutics, may hold promise
      for PTSD as a method for ameliorating symptoms and improving cognition. Individuals with PTSD
      demonstrate difficulties with cognitive control functions, which appear to be causally
      implicated in symptoms of the disorder (e.g., intrusive trauma-related memories). To date the
      efficacy of neurotherapeutics for PTSD has been understudied in Veterans.

      The current proposal aims to bridge research on basic neurocognitive mechanisms of PTSD with
      intervention research by conducting a randomized controlled trial (RCT) of a cognitive
      control training program in 80 Veterans with PTSD. Veterans will complete computer-based
      training exercises designed to specifically target and improve aspects of cognitive control.
      Veterans will complete the program twice per week for eight weeks. Symptoms will be assessed
      before and after treatment, as well as at a two month follow up time point. The primary goal
      of the study is to examine the effect of the intervention on PTSD symptoms and cognitive
      deficits. Evaluating symptom change as a result of the intervention will provide critical
      data regarding the utility of this program as a PTSD treatment. If effective, this training
      program could serve as alternative treatment option for Veterans with PTSD, and could be
      translated into an easily transportable intervention for dissemination (e.g., through
      web-based platforms). A secondary goal is to use functional magnetic resonance imaging (fMRI)
      to better understand the mechanisms by which cognitive training culminates in symptom
      reduction. If training cognitive control with neurotherapeutics directly enhances functioning
      of specific neural substrates as hypothesized, improvements in affective processes relying on
      shared neural regions would also be predicted. Modifying functioning in these substrates with
      training may thus reduce symptoms by improving neural functioning while processing and
      managing trauma-related affect and information. Neural systems used for cognitive control
      targeted in the training described (e.g., dorsolateral prefrontal cortex [dlPFC]) are also
      recruited when individuals mentally manipulate emotional information, such as when
      individuals use reappraisal to change the way that they think about negative emotional
      situations or content. In this study, Veterans will complete a neutral cognitive control task
      and a reappraisal task while undergoing fMRI before and after completing the training
      treatment. This will be the first study to evaluate neurobiological mechanisms of this type
      of training in PTSD, which is a fundamental next step for understanding how to improve the
      training program and who may be best served by completing it.
    

Detailed description: 
      Posttraumatic Stress Disorder (PTSD) is one of the most prevalent service-related mental
      health conditions in treatment-seeking Veterans, yet even gold standard interventions are not
      universally effective. Veterans would be greatly served by development of novel intervention
      approaches for PTSD, particularly those could be easily transportable. The emerging field of
      neurotherapeutics, which uses computerized training techniques to modulate cognitive
      processing, is one such approach that has shown promise for improving cognitive and emotional
      symptoms in mental health disorders. The current proposal represents the first effectiveness
      study of a cognitive control training intervention for reducing PTSD symptoms in Veterans,
      with a goal of exploring neurobiological mechanisms of affective and cognitive generalization
      of training effects.

      PTSD is characterized by deficits in "top-down" cognitive control abilities, as evidenced by
      neuropsychological findings of poor executive functioning and neurobiological evidence of
      diminished prefrontal cortical activity coupled with exaggerated limbic activity. Cognitive
      control deficits are causally implicated in re-experiencing symptoms, suggesting that
      cognitive control may be a novel and effective treatment target. The investigator developed a
      cognitive control training intervention that has demonstrated initial evidence of efficacy in
      civilian women with PTSD secondary to sexual assault. However, the effects of this program in
      Veteran participants and the precise neurocognitive mechanisms of symptom reduction in the
      intervention remain poorly understood. If training cognitive control directly enhances
      functioning of specific cognitive systems that are causally implicated in the etiology of
      emotional and cognitive symptoms, treatment-related improvements in affective symptoms and
      neuropsychological performance within the trained domain would be predicted. From a
      neurobiological perspective, training cognition is thought to operate via modification of
      specific neural substrates, suggesting that training effects should generalize to affective
      processes relying on shared neural regions. One such affective process is reappraisal (i.e.,
      generating different ways of thinking about emotional content in order to regulate emotion),
      which requires cognitive control over affective emotional information, and depends on brain
      circuits identified as key cognitive control regions (e.g., dorsolateral prefrontal cortex,
      dlPFC). PTSD is characterized by aberrant affective and neurobiological patterns during
      reappraisal that likely contribute to persistent re-experiencing and hyperarousal symptoms.
      Training may reduce symptoms by improving neural functioning of cognitive control regions
      during affective control processes (e.g., reappraisal) that are critical to managing
      trauma-related affect.

      In this proposal, the applicant's prior clinical trials research experience will be
      integrated with new mentoring in functional neuroimaging (fMRI) to facilitate identification
      of treatment-related symptom and neural change following cognitive control training. Bridging
      research on basic neurocognitive mechanisms of PTSD with intervention research in this way
      will ultimately facilitate precise neurotherapeutic treatment development and personalization
      techniques. In this randomized controlled trial (RCT), 80 Veterans with PTSD will be assigned
      to the cognitive control training program developed by the applicant (intervention condition:
      COGnitive ENhancement Training [COGENT]), or a minimal cognitive control program (sham
      training condition [ST]) completed twice week for 8 weeks. The COGENT training program
      requires participants to repeatedly utilize specific cognitive control functions (i.e.,
      interference control) in the context of a modified working memory capacity task, with the
      goal of improving performance through implicit, practice-based learning. The primary outcome
      will be PTSD symptom reduction, and cognitive generalization will be assessed with a brief
      neuropsychological assessment. To evaluate changes in the neural bases proposed to underlie
      COGENT, participants will undergo fMRI while completing two cognitive control tasks
      (affectively neutral and emotionally balanced) before and after treatment. Assessments will
      occur at baseline, post-treatment, and at follow-up.

      Aim 1: To examine the effects of the training program on PTSD and neurocognitive symptoms in
      Veterans. PTSD symptoms will be measured using the Clinician Administered PTSD Scale (CAPS)
      interview and neurocognitive functioning will be assessed with Delis Kaplan Executive
      Functioning System subtests. Individuals completing COGENT are hypothesized to show a)
      greater reduction in PTSD re-experiencing symptoms and b) improved neurocognitive performance
      relative to those in ST over time. Exploratory aims will also examine changes in PTSD
      diagnostic status across groups.

      Aim 2: To examine neurobiological changes in COGENT versus ST during neutral and affective
      cognitive control tasks. Neurobiological response to treatment will be assessed using fMRI
      during cognitive control tasks (one affectively neutral working memory capacity task and one
      affectively balanced reappraisal task with negative emotional information). Individuals
      completing the COGENT program are predicted to demonstrate increased neural activation of
      dlPFC and anterior cingulate regions from pre- to post-training during the tasks. Exploratory
      aims will evaluate corresponding physiological change during the affective fMRI task and the
      utility of fMRI neural functioning at baseline for predicting treatment response.
    

Intervention name(s): COGENT COGNITIVE TRAINING; Non training computer condition
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Computer-administered cognitive training program. COGENT is a modified working memory capacity task designed to train cognitive functioning. COGENT was designed to contain high interference across trials. By requiring repeated practice with utilization of interference control across trials, COGENT is thought to enhance plasticity of cognitive systems and improve performance. That is, training is based on the premise that learning-based neural changes will occur via repeated exposure to a task demanding cognitive control resources; The non-training condition requires participants to complete a similar computer task for the same length of time. The non-training is a modified working memory capacity task designed to be inert. The non-training condition was designed to contain relatively less interference demands across trials. Participants are required to remember the same total number of items as in COGENT (i.e., storage requirements were equivalent), but the task contains relatively less interference inherent in the task.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Two arm randomized controlled trial
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: trauma; PTSD; cognition