Neurostimulation Versus Therapy for Problems With Emotions
Study Details
Study Description
Brief Summary
The primary goal of this clinical trial is to evaluate the unique neural and behavioral effects of a one-session training combining cognitive restructuring (CR), an emotion regulation skill, 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 participate in brain imaging while undergoing an emotional regulation task. Participants will be randomly assigned to CR training or to psychoeducation about emotions. Participants will be reminded of recent stressors and will undergo real or sham high frequency rTMS, targeted using fMRI (functional MRI) results. Participants who learned CR will practice this skill during rTMS 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
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 cognitive restructuring (CR), an emotion regulation skill, with excitatory 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. To achieve these aims, 240 rTMS naïve, community adults who meet criteria for affective or stress DSM-5 disorders (excluding if co-occurring anorexia, alcohol and substance use, bipolar I, or psychotic disorders) and who self-report high emotional dysregulation and low use of CR will participate in brain imaging while undergoing an emotional regulation task. Both structural (anatomical and DTI) and functional MRI (fMRI) images will be collected. Participants will be randomly assigned to CR training (groups 1 & 2) or to psychoeducation about emotions (group 3; aimed to control for nonspecific factors). Participants will be reminded of recent autobiographical stressors and will undergo real (groups 1 & 3) or sham (group 2) high frequency rTMS, targeted using fMRI results. Participants who learned CR will practice this skill during rTMS in a one-time session, and physiological arousal will be monitored throughout the emotion induction and regulation practice. 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 the Brief-Treatment History Inventory (THI) to check for any changes. As part of the exit interview with the study doctor or another study team member, participants will be told if they were randomized to either active or sham stimulation and opportunities for questions will be allowed. 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 affective and stress disorders.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cognitive Restructuring + Active Repetitive Transcranial Magnetic Stimulation (rTMS) Group 1 (G1)- 80 eligible participants will receive training in Cognitive Restructuring (CR). These participants will use CR while receiving active rTMS over their individual dlPFC target and will partake in short term and long term follow up testing. |
Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS)
excitatory rTMS over the right dlPFC
Other Names:
Behavioral: Cognitive Restructuring
Cognitive restructuring is a cognitive behavioral intervention throughwhich 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.
Other Names:
|
| Sham Comparator: Cognitive Restructuring + Sham rTMS Group 2 (G2) - 80 eligible participants will receive training in CR alone as an active intervention. These participants will use CR while receiving sham rTMS over their individual dlPFC target and will partake in short term and long term follow up testing. |
Device: Sham Repetitive Transcranial Magnetic Stimulation (rTMS)
sham rTMS over the right dlPFC
Other Names:
Behavioral: Cognitive Restructuring
Cognitive restructuring is a cognitive behavioral intervention throughwhich 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.
Other Names:
|
| Active Comparator: Emotional Awareness Training + Active Repetitive Transcranial Magnetic Stimulation (rTMS) Group 3 (G3) - 80 eligible participants will receive emotional awareness training that includes the same amount of time and interaction with the experimenter. These participants will receive active rTMS over their individual dlPFC target and will partake in short term and long term follow up testing. |
Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS)
excitatory rTMS over the right dlPFC
Other Names:
Behavioral: Emotional Awareness training
Emotional awareness training will be conducted that includes the same amount of time and interaction with the experimenter
Other Names:
|
Outcome Measures
Primary Outcome Measures
- High frequency Heart Rate Variability (HF-HRV) during regulation blocks during the neurostimulation day, [Within a month of the initial assessment]
Calculation of physiological data High frequency HRV (HF-HRV) during regulation blocks during the neurostimulation day, controlling for baseline HF-HRV
- Time to return to Heart Rate (HR) baseline measured during regulation period [Within a month of the initial assessment]
During the 3 runs of the negative mood induction task of neurostimulation, calculating the time it takes to return baseline HR will be calculated during each of the 3 regulation periods.
- Percent signal change in vlPFC for the [restructure-flow_negative] contrast [baseline Neuroimaging Scan vs post Neuroimaging scan (1 week follow-up post neurostimulation)]
the percent change in the signal in the ventral lateral Prefrontal Cortex (vlPFC) from pre-post neuroimaging
- Difference in dorsolateral prefrontal cortex (dlPFC)-left_amygdala connectivity during [restructure - flow_negative] [baseline Neuroimaging Scan, post Neuroimaging Scan (1 week follow-up post neurostimulation)]
Using Generalized Psychophysiological Interaction (gPPI) analysis the difference in dlPFC-left amygdala connectivity pre-post neuromaging
Secondary Outcome Measures
- Change in Subjective units of distress (SUDS) [Neurostimulation visit (which will occur within a month of the initial assessment) - pre/post stressor task]
Subjective units of distress measured after baseline, stressor and every two minutes during regulation, including at the end of regulation during the neurostimulation day. This will be calculated with each of the 3 stressors.
- Difficulties in Emotion Regulation Scale (DERS) self-report change [Baseline DERS, 1 week follow-up after neurostimulation, 1 month follow-up]
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)
- Emotion Regulation Questionnaire (ERQ) self-report change [Baseline ERQ, 1 week follow-up after neurostimulation, 1 month follow-up]
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.
- Percent signal change in dlPFC for the [restructure - flow_negative] contrast [baseline Neuroimaging scan, post Neuroimaging Scan (1 week follow-up neurostimulation)]
the percent change in the signal in the dlPFC from pre-post neuroimaging
Other Outcome Measures
- HF-HRV during regulation block at one week follow-up and one month after training [Neurostimulation day (which will occur within a month of the initial assessment), one week follow-up, 1 month follow-up]
Change in HF-HRV mean during regulation block of stressor task at neurostimulation visit at one week follow-up and one month follow-up
- Time to return to HR baseline measured during regulation period at one week after training, and one month after. [Neurostimulation day (which will occur within a month of the initial assessment), one week follow-up, 1 month follow-up]
time it takes to return baseline HR will be calculated during the behavioral stressor computer task at one week follow-up and one month follow-up
- Percent signal change in the left insula for the [restructure -flow_negative contrast [baseline Neuroimaging scan, post Neuroimaging Scan (1 week follow-up neurostimulation)]
the percent change in the signal in the left insula in pre-post neuroimaging
- Insula connectivity with the ventral medial prefrontal cortex (vmPFC) and dlPFC [baseline Neuroimaging scan, post Neuroimaging Scan (1 week follow-up neurostimulation)]
change in insula connectivity with the vmPFC and dlPFC in pre-post neuroimaging
- Percent signal change in Orbitofrontal cortex (OFC) for the [restructure -flow_negative contrast [baseline Neuroimaging scan, post Neuroimaging Scan (1 week follow-up neurostimulation)]
the percent change in the signal in the OFC in pre-post neuroimaging
- Percent signal change in the temporoparietal junction (TPJ) for the [restructure -flow_negative contrast [baseline Neuroimaging scan, post Neuroimaging Scan (1 week follow-up neurostimulation)]
the percent change in the signal in the TPJ in pre-post neuroimaging
Eligibility Criteria
Criteria
Inclusion Criteria:
-
age 18 to 55
-
elevated overall score on Difficulties with Emotion Regulation Scale (DERS total score
=90)
-
has been in the same type of psychotherapy (including none) for the last 4 weeks/1mo (*except for current CBT) and is willing to stay on the same regimen throughout the study.
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low self-reported use of cognitive restructuring (ERQ restructuring subscale average score < 4.7)
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meets criteria for at least one mood (including Bipolar II w/o current hypomania), anxiety, stressor, OCD, Impulse Control, ADHD, or eating DSM-5 disorder (except exclusionary diagnoses such as severe anorexia). Note: Both current or partial remission of the disorder will be ok for inclusion into the study.
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verbal agreement to maintain dose of prescribed psychotropic medication (if any) constant throughout the study, provided they are stable on it for the past 4 weeks (except exclusion medication and except if there is a medical emergency requiring changes in medication).
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Naïve to rTMS
Exclusion Criteria:
-
current hypomania (Note: Bipolar II w/o current hypomanic episode is ok for inclusion)
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meets diagnostic criteria for current or history of psychotic disorder, or psychotic features,
-
meets diagnostic criteria for Bipolar I disorder
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meets diagnostic criteria on SCID5 for current alcohol or substance use disorder (moderate and high severity) or meets past history of severe alcohol use disorder
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unable to read, blind, or deaf, or unwilling to give consent
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non-English speaker,
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verbal IQ < 90 on the North American Adult Reading Test (NART).
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current uncontrolled anorexia or other condition requiring hospitalization
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high risk for suicide defined as either having attempted suicide in past 6 months or reporting current suicidal ideation that includes a method, plan, or intent to die
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current serious medical illness, including current severe migraine headaches
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started/changed psychotropic medications in the prior 4 weeks, or plans to change medication during the study
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history of seizure except those therapeutically induced by ECT (childhood febrile seizures are acceptable and these subjects may be included in the study), history of epilepsy in self or first degree relatives, stroke, brain surgery, head injury, cranial metal implants, known structural brain lesion, devices that may be affected by TMS (pacemaker, medication pump, cochlear implant, implanted brain stimulator)
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conditions associated with increased intracranial pressure, space occupying brain lesion, transient ischemic attack, cerebral aneurysm, dementia, Parkinson's or Huntington's disease, multiple sclerosis
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on medications that reduce seizure threshold (e.g., stimulants, Wellbutrin, Clozaril, Provigil)
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use of investigational drug or devices within 4 weeks of screening
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cochlear implants
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Pregnancy
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metal in body that would exclude them from the MRI scan; severe claustrophobia
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is a prisoner or in police custody at time of screening, or has pending court case jeopardizing the participation in the study
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has had TMS in their lifetime
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has had CBT in the past 4 weeks or plans to start therapy during the study
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weighs over 300 pounds (could not fit in MRI scanner)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
Sponsors and Collaborators
- Duke University
- National Institute of Mental Health (NIMH)
Investigators
- Principal Investigator: Andrada D Neacsiu, PhD, Duke University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Pro00111390
- 1R01MH129302-01A1