The primary goal of this clinical trial is to evaluate the unique neural and behavioral effects of a one-session training combining emotion regulation skills training, with excitatory repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (dlPFC). The secondary aim is to identify key changes in the emotion regulation neural network following the combined intervention versus each of the components alone. The third aim is to explore personalized biomarkers for response to emotion regulation training. Participants will undergo brain imaging while engaging in an emotional regulation task. Participants will be randomly assigned to learn one of two emotion regulation skills. Participants will be reminded of recent stressors and will undergo different types of neurostimulation, targeted using fMRI (functional MRI) results. Participants who may practice their emotion regulation skills during neurostimulation in a one-time session. Following this training, participants will undergo another fMRI and an exit interview to assess for immediate neural and behavioral changes. Measures of emotion regulation will be assessed at a one week and a one month follow up visit.
Emotional dysregulation constitutes a serious public health problem and novel approaches are needed to effectively address it transdiagnostically. Despite rapid advancements in affective and cognitive neuroscience, there have been few attempts to translate basic findings into novel interventions. In addition, the relevance of different nodes in the emotion regulation network to psychopathology and to successful reduction of emotional arousal is not yet fully understood. Noninvasive neurostimulation, such as repetitive transcranial magnetic stimulation (rTMS), is a powerful tool with which dysfunction can be alleviated temporarily, by modulating neural activation. Therefore, the objective of the current study is to examine immediate neural and behavioral changes following neuromodulation enhanced emotion regulation training for transdiagnostic adults who report difficulties calming down when upset. The central hypothesis is that neurostimulation enhances the acquisition of emotion regulation skills and leads to remediated neural function in the emotion regulation network. The investigators' long-term goal is to develop novel interventions that harness neuroscientific findings to advance behavioral treatments. The primary aim of this project is to evaluate the unique neural and behavioral effects of a one-session training combining emotion regulation skills with excitatory neurostimulation over the dorsolateral prefrontal cortex (dlPFC). The secondary aim is to identify key changes in the emotion regulation neural network following the combined intervention versus each of the components alone. The third aim is to explore personalized biomarkers for response to emotion regulation training. To achieve these aims, 240 rTMS naïve, community adults who meet criteria for a DSM-5 disorders (excluding if co-occurring anorexia, moderate to severe alcohol and substance use, bipolar I, or psychotic disorders) and who self-report high emotional dysregulation will participate in brain imaging while undergoing an emotional regulation task. Both structural and functional MRI (fMRI) images will be collected. Participants will be randomly assigned to one of three experimental groups that blend neurostimulation and behavioral skills training in different ways. Participants will be reminded of recent autobiographical stressors and will undergo different types of neurostimulation, targeted using fMRI results. Physiological arousal will be monitored throughout the experimental visit. Following this training, 1 week later, participants will undergo another functional scan to assess for immediate neural and behavioral changes. Bio-behavioral measures of emotion regulation will be assessed at this one week visit. The 1-month follow up will occur 1 month after the one week follow-up visit. At this final follow-up visit, participants will also complete an exit interview that assesses acceptability and expectancies as well as a battery of self reports. One final set of bio-behavioral measures of emotion regulation will be completed as well. If successful, the investigators' line of research will provide key mechanistic information to develop a novel transdiagnostic treatment for DSM-5 disorders.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
240
high frequency rTMS over the right dlPFC
electrical scalp stimulation over the right dlPFC
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.
Emotional awareness training is a behavioral intervention through which participants learn how to identify and evaluate their emotions and the components that make up each emotion.
Duke University Medical Center
Durham, North Carolina, United States
RECRUITINGHigh Frequency Heart Rate Variability (HF-HRV) during regulation blocks during the neurostimulation day
Calculation of physiological data High frequency HRV (HF-HRV) during regulation blocks during the neurostimulation day accounting for baseline controlling for baseline HF-HRV
Time frame: Within a month of the initial assessment
Time to return to Heart Rate (HR) baseline measured during regulation period
Following each negative mood induction during the neurostimulation experiment, the time it takes to return baseline HR will be calculated for each of the three regulation periods.
Time frame: Within a month of the initial assessment
Change in the ventrolateral prefrontal cortex (vlPFC) for the [restructure-flow_negative] contrast
Change in the maximum activation in the vlPFC from pre-post neuroimaging in the contrast of interest
Time frame: baseline Neuroimaging Scan vs post Neuroimaging scan (1 week follow-up post neurostimulation)
Change in the dorsomedial prefrontal cortex (dmPFC) for the [restructure-flow_negative] contrast
Change in the maximum activation in the dmPFC from pre-post neuroimaging in the contrast of interest
Time frame: baseline Neuroimaging Scan, post Neuroimaging Scan (1 week follow-up post neurostimulation)
Change in the ventromedial prefrontal cortex (vmPFC) for the [restructure-flow_negative] contrast
Change in the maximum activation in the vmPFC from pre-post neuroimaging in the contrast of interest
Time frame: baseline Neuroimaging Scan, post Neuroimaging Scan (1 week follow-up post neurostimulation)
Change in the insular cortex for the [restructure-flow_negative] contrast
Change in the maximum activation in the insula from pre-post neuroimaging in the contrast of interest
Time frame: baseline Neuroimaging Scan, post Neuroimaging Scan (1 week follow-up post neurostimulation)
Change in dorsolateral prefrontal cortex (dlPFC)-insula connectivity during [restructure - flow_negative]
Using Generalized Psychophysiological Interaction (gPPI) analysis the difference in dlPFC-insula connectivity pre-post neuromaging
Time frame: baseline Neuroimaging Scan, post Neuroimaging Scan (1 week follow-up post neurostimulation)
Change in dorsolateral prefrontal cortex (dlPFC)-amygdala connectivity during [restructure - flow_negative]
Using Generalized Psychophysiological Interaction (gPPI) analysis the difference in dlPFC-amygdala connectivity pre-post neuromaging
Time frame: baseline Neuroimaging Scan, post Neuroimaging Scan (1 week follow-up post neurostimulation)
Difficulties in Emotion Regulation Scale (DERS) self-report change
Change in self-reported DERS will be investigated immediately after the followup neuroimaging session and one month after training. DERS inclusion for study is a score of 90 or higher. Min-Max score ranges from 36-180 (with higher scores signifying more difficulties with emotion regulation)
Time frame: Baseline, 1 week follow-up after neurostimulation, 1 month follow-up
Emotion Regulation Questionnaire (ERQ) self-report change
Change in Self-reported use of Cognitive Restructuring (CR) as measured with the Emotion Regulation Questionnaire (ERQ) one week and one month after training. We will also examine pre-post changes in ERQ-Reappraisal scale using a similar growth model approach, accounting for severity of psychopathology and baseline. The ERQ is a 10-item scale designed to measure respondents' tendency to regulate their emotions in two ways: (1) Cognitive Reappraisal (6 scale items) and (2) Expressive Suppression (4 scale items). Scores for the 2 scales are reported the average score of the total items in that scale. The lower the average score on the reappraisal scale the more problems with regulating emotions.
Time frame: Baseline, 1 week follow-up after neurostimulation, 1 month follow-up
Change in the dlPFC for the [restructure - flow_negative] contrast
Change in the maximum activation in the dlPFC from pre-post neuroimaging in the contrast of interest
Time frame: baseline Neuroimaging scan, post Neuroimaging Scan (1 week follow-up neurostimulation)
Change in the amygdala for the [restructure - flow_negative] contrast
Change in the maximum activation in the amygdala from pre-post neuroimaging in the contrast of interest
Time frame: baseline Neuroimaging scan, post Neuroimaging Scan (1 week follow-up neurostimulation)
Outcome Questionnaire (OQ-45) self-report change
Change in self-reported psychopathology as measured by the OQ-45 one week and one month after training. The Outcome Questionnaire-45 (OQ-45) is a 45-item self-report measure used to track severity of psychopathology throughout treatment. It consists of subscales that identify three types of problems that lead to general stress: psychological symptoms, interpersonal conflicts, and problems with social roles. Items are rated on a Likert scale ranging from 0 (never) to 4 (almost always). Scores range from 0 to 180. Higher scores indicate higher psychopathological distress than lower scores.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Baseline, 1 week follow-up after neurostimulation, 1 month follow-up
Cognitive Skills Questionnaire (CSQ) self-report change
Change in self-reported use of cognitive skills as measured by the CSQ one week and one month after training. The CSQ is the Unified Protocol Cognitive Skills Questionnaire (UPCSQ; unpublished) that contains 8 items that ranges from "1" Never to "5" Always or When Needed with higher scores indicating more use of tools or skills than lower scores. Scores range from 8 to 40 (highest skill use).
Time frame: Baseline, 1 week follow-up after neurostimulation, 1 month follow-up
Self Efficacy with Emotion Regulation (PROMIS-SEME)
Change in effective regulation as measured by PROMIS-SEME from baseline to follow up. PROMIS Self-Efficacy for Managing Emotions measures one's confidence to manage emotions such as anxiety, helplessness, and discouragement on a scale of 1 "not at all confident" to 5 "I am very confident." There are total of 25 items with a score ranging from 25 to 125. Higher scores indicate higher confidence in the ability to use emotion regulation skills. Scores are then reported using the PROMIS manual for T-scores.
Time frame: Baseline, 1 week follow-up after neurostimulation, 1 month follow-up
Change in subjective units of distress (SUDS)
SUDS measured after baseline, stressor and every three minutes during regulation, including at the end of regulation during the neurostimulation experiment
Time frame: Neurostimulation visit (which will occur within a month of the initial assessment)
HF-HRV during regulation block at follow up
Change in HF-HRV mean during regulation block of stressor task at neurostimulation visit at follow-up
Time frame: one week follow-up, 1 month follow-up
Time to return to HR baseline measured during regulation period at follow up
time it takes to return baseline HR will be calculated during the behavioral stressor computer task at follow up
Time frame: one week follow-up, 1 month follow-up