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.
