Using Neuroplasticity-Based Computerized Training to Improve Emotion Regulation in Bipolar Disorder (BRAINS)
Condition: Bipolar Disorder; Bipolar I Disorder; Bipolar Affective Disorder; Bipolar Disorder I; Bipolar Depression
MeSH terms: Bipolar Disorder; Mood Disorders
Study type: Interventional

Summary: 
      The goal of this study is to evaluate the feasibility and potential benefit of a behavioral
      intervention designed to improve emotion regulation in individuals with bipolar disorder. The
      intervention consists of game-like exercises that involve the 'Cognitive Control of Emotion
      (CCE) - i.e. the ability to control the influence of emotional information on behavior.
      Deficits in the cognitive control of emotion are a central feature of Bipolar Disorder that
      contributes to emotion dysregulation, maladaptive mood episodes, and, ultimately, the overall
      chronicity and severity of illness. Neuroimaging studies of bipolar patients demonstrate
      neural abnormalities in brain systems involved in cognitive control and emotion processing.
      Furthermore, these abnormalities predict mood and behavior problems associated with cognitive
      control of emotion, such as emotion lability, disinhibited behavior, and extreme mood states.
      The aim of this study is to determine feasibility and examine whether a computer-based
      program of progressively difficult cognitive control emotion exercises will improve cognitive
      control of emotion skills and, thereby, result in better emotion regulation and daily
      functioning in young adults with bipolar disorder. To test the intervention, a single group
      of young adults (18-30 years old) with Bipolar I Disorder will complete behavioral
      assessments before and after 20 hours (4 weeks) of CCE training. In order to identify
      baseline deficits associated with bipolar disorder, a comparison group of healthy young
      adults will complete behavioral assessments at a single time-point (without CCE training).
    

Detailed description: 
      Difficulty with emotion regulation is a central feature of Bipolar Disorder (BD) that is not
      only apparent during mood episodes but also persists in between episodes and contributes to
      the onset, chronicity, and severity illness. Successful emotion regulation requires the
      cognitive control of emotion (CCE) - i.e. the ability to control emotions and the influence
      of emotions on behavior. CCE is dependent on the coordinated activity of two neural systems:
      1) the cognitive control network includes the lateral prefrontal cortex and superior parietal
      cortex and supports a range of skills (e.g. attention, inhibition, working memory) to control
      and manipulate information from multiple sensory domains; and 2) the emotion processing
      network, which includes the amygdala, insula, and ventral striatum, and supports the
      experience, expression, and perception of emotion. CCE consists of several processes in which
      the cognitive control network modulates neural response in emotion processing regions to
      control the impact of emotion on experience and behavior. Poor recruitment of frontoparietal
      control functions when processing negative emotional stimuli (measured with fMRI)
      prospectively predicts mood and behavioral problems after an interpersonal conflict in daily
      life (Hooker et al 2010). Together the data suggests that compromised CCE capacity makes a
      person more vulnerable to experiencing negative psychological consequences after a stressful
      event (e.g. Hooker et al 2010; Hooker et al 2013; Tully et al 2014).

      Individuals with bipolar disorder have deficits on both behavioral and neural measures of CCE
      (Phillips and Swartz 2014). Typical CCE tasks require identifying a target stimulus (e.g.
      word, facial expression, etc.) while inhibiting irrelevant or conflicting emotional
      information. During such tasks, people with bipolar disorder have difficulty controlling the
      distracting influence of irrelevant emotional information. These behavioral deficits are
      associated with neural abnormalities in both cognitive control and emotion processing neural
      systems. These neural abnormalities are characterized, primarily, by abnormally low activity
      in the cognitive control network, particularly the lateral prefrontal cortex, and abnormally
      high activity in emotion processing regions, particularly the amygdala and ventral striatum.
      Bipolar disorder is also associated with abnormalities in structural elements of these neural
      systems, including abnormal gray matter volume and white matter tracks. Research suggests
      that deficits in CCE and related neural networks are an underlying cause of characteristic
      symptoms of bipolar disorder, including emotional lability, extreme mood states, and
      disinhibited behavior (reviewed in Phillips and Swartz 2014 and Wegbreit et al. 2014). These
      findings point to CCE as a clinically relevant and scientifically tractable treatment target
      for bipolar.

      Study Design & Specific Aims The primary goal of this project is to investigate, in young
      adults with bipolar disorder, whether a computerized training program of CCE exercises
      improves CCE as measured with a range of assessment tasks that require flexible deployment of
      CCE skills. The long-term goal is to evaluate whether CCE training improves emotion
      regulation and maladaptive mood symptoms.The overarching hypothesis is that training-related
      improvement in CCE will facilitate improvements in emotion regulation across multiple
      contexts, and, thus, reduce the symptoms and consequences of emotion dysregulation in
      bipolar.

      The second goal of the project is to collect pilot data, establish feasibility, and gather
      other information necessary to acquire federal funding for a large-scale, double-blind,
      randomized control trial of CCE training for bipolar. To ensure subsequent federal funding,
      the current project design is consistent with an experimental medicine model and NIMH
      guidelines for clinical trial research. NIMH has a progressive funding structure for the
      development of novel biological or behavioral interventions. The current project is designed
      to satisfy requirements of the first phase in this funding structure. Consistent with NIMH
      guidelines for exploratory clinical trials, the current project has a clearly defined
      treatment target (i.e. CCE skills) and a theoretical model regarding how the target mechanism
      is related to psychopathology. The main purpose of an exploratory trial is to verify 'target
      engagement' - i.e. that the intervention influences the intended treatment target. It is not
      necessary to have a comparison group. However, evidence of target engagement in a single,
      active treatment group is a requirement for obtaining more advanced levels of NIMH funding.
      The current project will evaluate target engagement in a single group that completes CCE
      training. The study maximize the potential to detect target engagement by using behavioral
      and neural measures of CCE that are valid, reliable, and sensitive to treatment-related
      improvement.

      Another purpose of the exploratory phase is to gather information about feasibility,
      tolerability, dose, and other potential factors that could influence treatment effectiveness,
      patient compliance, and broad implementation, particularly in non-academic settings. Data
      from the current project will address these issues and provide salient information to guide
      treatment development and implementation in the next phase. This information includes data on
      participants' motivation to continue training, enjoyment of training exercises, compliance to
      the training schedule (e.g. number of days missed, real or perceived obstacles to training,
      strategies that enhance motivation and compliance, etc.).

      In summary, the investigators will conduct an exploratory clinical trial that is consistent
      with NIMH guidelines for clinical trial research and addresses the goals of an initial (first
      phase) NIMH grant for novel interventions. Results from the study will provide the pilot data
      necessary to obtain additional funding for the next phase of treatment development - i.e. An
      "Exploratory/Developmental Grant for Novel Interventions Phase II (R33)" or a "Confirmatory
      Efficacy Clinical Trial of Non-Pharmacological Interventions for Mental Disorders (R01)".
    

Intervention name(s): Cognitive Control of Emotion (CCE) Training
Intervention type(s): Behavioral
Intervention description(s): Training consists of game-like exercises using a software program developed in collaboration with PositScience Corporation (using BrainHQ platform ) - which has exercises targeting cognition and social cognition. The CCE training program incorporates characteristics that optimize learning-induced neuroplasticity - most importantly, exercises are short & rewarding, adapt to individual skill-level, and become increasingly difficult as performance improves. There are 5 CCE exercises that are organized in half-hour sessions and proceed in a predetermined sequence.
Other intervention name(s): Cognitive Control of Emotion Training using a BrainHQ smartphone "App" developed by Posit Science
Intervention model: Single Group Assignment
Intervention model description: This is a single-arm, 'open label' study to examine the feasibility and potential target engagement (i.e. potential benefit) of a behavioral smartphone-based cognitive training program for individuals with bipolar I disorder. Participants with bipolar disorder are assessed before and after the 20 session/4 week intervention. In addition, a comparison group of healthy adults (without bipolar disorder) are assessed at a single time-point as a means of identifying baseline deficits associated with bipolar disorder. Participants in the healthy comparison group do not complete the intervention. (Thus, Number of Intervention Arms = 1.)
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Bipolar; Emotion; Cognitive Control; Affect; Impulsivity; Neuroimaging; Targeted Cognitive Training