Neuromodulation Enhanced Cognitive Restructuring: A Proof of Concept Study
Condition: Anxiety; Depression; Personality Disorders; Trauma and Stress-related Disorders; Somatic Disorders; Obsessive Compulsive Disorders; Eating Disorders; Difficulties With Cognitive Emotion Regulation
MeSH terms: Feeding and Eating Disorders; Obsessive-Compulsive Disorder; Personality Disorders; Trauma and Stressor Related Disorders
Study type: Interventional

Summary: 
      Psychological treatments are effective, but take a long time and can be burdensome.
      Therefore, avenues to optimize behavioral treatments are needed. Despite important
      advancements, neuroscience has had a limited effect on psychotherapy development. Therefore,
      one paradigm shift would be to develop neuroscience informed behavioral treatments.

      The investigators identified from the literature a problem that affects several mental
      disorders (emotion dysregulation) and a neural circuit that underlies this important concern.
      They found that this circuit is dysfunctional in those with psychopathology but can be
      changed with treatment. The goal is in one session to train this brain network to operate
      more efficiently and to test the short and long term effects of this intervention. The
      investigators plan to engage this brain network using a traditional psychotherapy strategy
      (cognitive restructuring) and to enhance learning using repetitive transcranial magnetic
      stimulation (rTMS), a neuromodulation technique through which magnetic stimulation enhances
      the electrical activity in brain areas close to the scalp.

      The study team proposed two studies to examine this novel approach, In one of the studies 83
      participants were enrolled and 47 eligible participants were divided into 3 groups. All
      participants were trained in emotion regulation by first being asked to remember an event
      where they experienced a negative emotion and then being instructed either to think
      differently about the event, or to wait. Participants simultaneously underwent either active
      (left or right side of brain) or sham rTMS. In a second study 65 participants were enrolled,
      and 31 were assigned to either active left or sham rTMS guided using neuroimaging results.
      Across both studies, the investigators measured regulation in the lab and during a-week long
      naturalistic assessment. Participants in the second study returned for a follow up
      neuroimaging visit at the end of this week. Participants returned for a one moth follow up
      assessment and to rate feasibility, acceptability, and provide feedback. This proof of
      concept set of studies demonstrated feasibility and preliminary efficacy for this approach,
      which opens new frontiers for neuroscience informed treatment development.
    

Detailed description: 
      Despite significant advancements in psychiatric research, the majority of adults with mental
      health disorders do not benefit from current evidence-based treatments, especially if they
      have difficulties managing negative emotions. One solution to this unmet clinical need is to
      take a neuroscience-informed approach to treatment development in order to radically change
      patient care. Despite an explosion of research on the neurobiological underpinnings of
      emotion, emotion regulation, and psychopathology, there have been few attempts to use such
      findings to advance behavioral treatments. Neuroscience-informed treatment development could
      optimize psychotherapy gains and reduce burden on therapists and clients. Therefore, we
      propose to build a fundamentally novel approach to treating difficulties managing negative
      emotions (or emotion dysregulation) that builds on the strength of current therapies, but
      that also accelerates and enhances gains.

      Adults with several different psychiatric disorders have difficulty managing negative
      emotions, a problem that has been traced back to impairments in the fronto-limbic brain
      circuitry. In healthy samples this neural network is activated in response to tasks requiring
      regulation of emotional arousal and disrupting this circuit leads to psychiatric symptoms. In
      psychiatric samples, this circuit is underperforming as evidenced by (1) hyperactivity in the
      amygdala (the brain structure that signals emotional arousal), (2) slow return to baseline
      after amygdala activation, (3) hypoactivity in frontal regions (responsible for regulation),
      and (3) insufficient cross-talk between these regions when patients experience negative
      emotional arousal. Evidence-based cognitive-behavioral psychotherapy and neurostimulation are
      two different interventions that can remediate function in impaired brain circuits. Both
      interventions have evidence of success in changing the fronto-limbic network but also need
      improvement. Therefore, the investigators plan to combine magnetic brain stimulation and
      cognitive restructuring (an evidence-based behavioral treatment for difficulties managing
      emotions) in a one-session intervention.

      The investigators recruited participants for two studies. In one study, 83 transdiagnostic
      adults (i.e., who meet criteria for any DSM 5 disorder) who engage in cognitive restructuring
      with low frequency as measured by an established questionnaire were enrolled and 47 were
      randomly assigned to either active (left or right) or sham repetitive transcranial magnetic
      stimulation (rTMS). In a second study, 65 transdiagnostic adult participants with high
      emotional dysregulation were enrolled, and 31 were randomly assigned to active left or sham
      rTMS guided using neuroimaging analyses. All included participants practiced reducing
      negative emotions (induced with standardized autobiographical stressors) using cognitive
      restructuring while undergoing high frequency or sham rTMS to the right or left dorsolateral
      prefrontal cortex. Standardized, established procedures were used to teach cognitive
      restructuring, to generate personalized stressors, to induce negative emotional arousal, and
      to implement the one session of rTMS. Immediate effects were evaluated using measures of
      emotional arousal and regulation during the intervention and for one week afterwards using 8
      daily automated mobile phone calls. Long-term effects in emotion regulation, functional and
      psychiatric impairment were examined at 1-week and 1-month follow-up interviews.

      Participants in the imaging portion of the study underwent an MRI before the intervention
      day. This imaging session included training in the emotion regulation task to be performed in
      the scanner, including practice in reappraisal and distraction; a memory cue assessment to
      rehearse cuing of memories; a mock scan if necessary, MRI safety screening confirmation,
      structural (Diffusion tensor imaging and anatomical) and functional MRI (fMRI) images will be
      collected. During the fMRI scan, participants completed the emotional regulation task where
      they were asked to recall an emotional memory from the Emotional Memory selection tasks and
      then be cued to reappraise, distract or allow negative emotions. At the end of the trials,
      participants rated their current emotional state. At the one week follow up, in addition to
      the tasks described above, they returned to complete a second MRI after 1 week where they
      were reoriented to the emotion regulation task, had structural and functional MRI images
      collected with the emotion regulation task occurring during the fMRI portion.

      The investigators hypothesized that rTMS would enhance cognitive restructuring by yielding a
      quicker reduction in emotional arousal when compared to sham TMS, and would lead to more
      frequent use of the cognitive restructuring in the natural environment. This set of studies
      is intended to launch a series of investigations using innovative paradigms to optimize
      treatments for psychiatric disorders and it could lead to the next generation of
      neuroscience-informed behavioral interventions.
    

Intervention name(s): Cognitive Restructuring; rTMS; Sham rTMS
Intervention type(s): Behavioral; Device; Device
Intervention description(s): Cognitive restructuring is a cognitive behavioral intervention through which participants learn how to think differently about stressful events in order to feel less emotional arousal. Specifically, participants learn how to distance themselves from the situation, think of the memory as just a memory, or focus on alternative explanations or facets of the situation that are less emotionally upsetting.; rTMS is a neurostimulation intervention where the participant receives 15 minutes of high frequency (10 HZ) transcranial magnetic stimulation pulses; Sham rTMS is a placebo intervention aimed to mimic the effects of repetitive transcranial magnetic stimulation with no known direct benefit for the participant.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants were assigned to one of 2 studies (main and supplement) that ran concurrently. 83 participants were enrolled in the main study, and 65 in the supplement.
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: neurostimulation; cognitive restructuring; TMS; emotion regulation; MRI; Emotional Memory Task; Reappraisal; Distraction