Neurostimulation + Therapy for Emotional Regulation Issues

Overseen By Zoe Brasher

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Must not be taking: Wellbutrin, Stimulants

Disqualifiers: Psychotic disorder, Bipolar I, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 1 day

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine how a one-time session of brain stimulation, specifically Active Repetitive Transcranial Magnetic Stimulation (rTMS), combined with emotion skills training, can help people manage their emotions better. Participants will receive various types of brain stimulation while learning skills to handle stress and emotions. Researchers will track changes in brain activity and behavior. Ideal candidates for this trial are those who struggle with emotion regulation and have a mood, anxiety, or stress-related disorder but have not recently undergone certain therapies or treatments. As an unphased trial, this study offers a unique opportunity to contribute to innovative research and potentially enhance emotional regulation techniques.

Will I have to stop taking my current medications?

You will not have to stop taking your current medications, but you must keep the dose the same throughout the study if you are stable on them for the past 4 weeks. Changes are only allowed in case of a medical emergency.

What prior data suggests that this neurostimulation and therapy protocol is safe for emotional regulation issues?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is generally well-tolerated. It is already used to treat various mental health issues, and studies indicate it helps manage emotions without major safety concerns. Most people experience only mild side effects, such as headaches or scalp discomfort, which typically resolve quickly.

For the Cognitive Restructuring + Electrical Scalp Stimulation approach, specific safety information is less available. However, similar brain stimulation methods have proven safe in controlled settings.

In summary, both treatments in this trial have demonstrated good safety records in similar situations. Participants usually report only minor, temporary side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments because they offer a novel approach to tackling emotional regulation issues. Unlike traditional methods, which often rely on medications or talk therapy alone, these treatments combine cognitive training or emotional awareness exercises with cutting-edge neurostimulation techniques. Repetitive Transcranial Magnetic Stimulation (rTMS) and scalp electrical stimulation directly target the dorsolateral prefrontal cortex (dlPFC), a key brain area involved in emotion regulation. This direct brain stimulation is thought to enhance the effects of cognitive and emotional training, potentially leading to quicker and more robust improvements in emotional regulation.

What evidence suggests that this trial's treatments could be effective for emotional regulation issues?

In this trial, participants will receive different treatment combinations to improve emotional regulation. Research has shown that combining cognitive restructuring with repetitive transcranial magnetic stimulation (rTMS), which participants in one arm of this trial will receive, can greatly enhance emotional management. Studies have found that using rTMS with cognitive skills training effectively engages brain circuits, leading to better emotional control. Another arm of this trial involves participants receiving electrical scalp stimulation with cognitive restructuring, and evidence suggests this combination also aids in managing emotional challenges and reducing distress. Additionally, emotional awareness training with rTMS, another treatment arm in this trial, has been shown to improve emotional management. These treatments stimulate specific brain areas to enhance emotional regulation. ^{1 3 6 7 8}

Who Is on the Research Team?

Andrada D Neacsiu, PhD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-55 who struggle with emotional regulation and have been diagnosed with certain mood, anxiety, stress-related, impulse control, ADHD or eating disorders. They must score high on the Emotion Regulation Scale and agree to keep their psychotherapy and medication doses consistent throughout the study. People are excluded if they have severe psychiatric conditions like bipolar I disorder or psychosis, substance abuse issues, a low verbal IQ, serious medical illnesses that could interfere with neurostimulation or MRI scans.

Inclusion Criteria

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

I have been in the same psychotherapy or none for the last month and am willing to continue it during the study.

I rarely use positive thinking to manage my emotions.

Exclusion Criteria

Verbal IQ < 90 on the North American Adult Reading Test (NART)

I do not have any severe illnesses, including serious migraines.

Non-English speaker

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-session training combining emotion regulation skills with excitatory neurostimulation over the dorsolateral prefrontal cortex (dlPFC).

1 day

1 visit (in-person)

Follow-up

Participants undergo a follow-up neuroimaging scan and bio-behavioral assessments to evaluate neural and behavioral changes.

1 week

1 visit (in-person)

Long-term Follow-up

Participants complete an exit interview and additional bio-behavioral assessments to evaluate long-term effects.

1 month

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Active Repetitive Transcranial Magnetic Stimulation (rTMS)
• Cognitive Restructuring
• Electrical Scalp Stimulation
• Emotional Awareness Training
• Sham Repetitive Transcranial Magnetic Stimulation (rTMS)

Trial Overview The trial tests how well one-session training combining emotion regulation skills with excitatory repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex affects brain function and behavior. It compares this combined intervention against each component alone using fMRI imaging before and after treatment to identify changes in neural networks related to emotion regulation.

How Is the Trial Designed?

Group I: Cognitive Restructuring + Repetitive Transcranial Magnetic Stimulation (rTMS) Experimental Treatment 2 Interventions

Group 1 (G1)- 80 eligible participants will receive training in Cognitive Restructuring (CR). These participants will use CR while receiving rTMS over their individual dlPFC target and will partake in short term and long term follow up testing.

Group II: Cognitive Restructuring + scalp electrical stimulation Active Control 2 Interventions

Group 2 (G2) - 80 eligible participants will receive training in CR. These participants will use CR while receiving scalp electrical stimulation over their individual dlPFC target and will partake in short term and long term follow up testing.

Group III: Emotional Awareness Training + Repetitive Transcranial Magnetic Stimulation (rTMS) Active Control 2 Interventions

Group 3 (G3) - 80 eligible participants will receive emotional awareness training. These participants will receive rTMS over their individual dlPFC target and will partake in short term and long term follow up testing.

Active Repetitive Transcranial Magnetic Stimulation (rTMS) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as rTMS for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder
• Migraines

Approved in European Union as rTMS for:

• Major Depressive Disorder
• Anxiety Disorders

Approved in Canada as rTMS for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

Real-time fMRI can help patients learn to self-regulate brain circuits related to emotion and depression, showing promise as a new approach to treating affective disorders.

Initial results from fMRI-based neurofeedback (fMRI-NF) in depression are encouraging, but further clinical trials are needed to establish its efficacy and to develop practical applications for everyday use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurofeedback and networks of depression. Linden, DE.[2021]

The Emo-regulator, a training system combining virtual reality and EEG-based neurofeedback, effectively improved emotion regulation in subjects over a two-week period, as evidenced by enhanced ability to down-regulate negative emotions.

Participants reported above-average usability of the Emo-regulator, indicating that it not only helps in emotional management but is also user-friendly, promoting the use of cognitive reappraisal techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emo-regulator: An emotion-regulation training system fusing virtual reality and EEG-based neurofeedback. Yu, M., Bai, Y., Li, Y.[2023]

In a study involving 18 subjects with major depression, repetitive transcranial magnetic stimulation (rTMS) for up to 4 weeks was found to be generally safe, with no significant mean deficits in neuropsychologic function or auditory thresholds.

However, two patients experienced mild high-frequency hearing loss, indicating that while rTMS is safe for most, individual responses may vary and warrant further investigation into long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a 2- to 4-week course of repetitive transcranial magnetic stimulation (rTMS) on neuropsychologic functioning, electroencephalogram, and auditory threshold in depressed patients. Loo, C., Sachdev, P., Elsayed, H., et al.[2019]

The study demonstrated that healthy participants could effectively down-regulate activity in the right amygdala using real-time functional MRI (rtfMRI) neurofeedback while exposed to negative emotional stimuli, suggesting a potential method for emotion regulation.

This approach, which involved four training sessions with six participants, indicates that rtfMRI neurofeedback could be a promising tool for treating emotional disorders by targeting the overactive amygdala, which is often dysregulated in such conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-time neurofeedback using functional MRI could improve down-regulation of amygdala activity during emotional stimulation: a proof-of-concept study. Brühl, AB., Scherpiet, S., Sulzer, J., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) is generally safe for older adults with late-life depression, with only 12.4% reporting any adverse events and serious adverse events occurring in just 1.5% of cases, based on a review of 11 studies involving 353 patients.

The most common adverse events were mild, such as headaches (6.9%) and discomfort at the stimulation site (2.7%), although some serious adverse events, including psychiatric hospitalization and increased suicidal ideation, were noted in case reports, highlighting the need for further research to ensure safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. Overvliet, GM., Jansen, RAC., van Balkom, AJLM., et al.[2021]

Rapid transcranial magnetic stimulation (rTMS) effectively improved mood and converted the dexamethasone suppression test (DST) from positive to negative in a 36-year-old woman with recurrent major depressive disorder, indicating a significant therapeutic effect.

The treatment involved 7 to 13 sessions of rTMS, with no reported side effects, suggesting that rTMS is a safe and effective intervention for patients with major depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone suppression test reversal in rapid transcranial magnetic stimulation-treated depression. Reid, PD., Pridmore, S.[2017]

Low frequency (LF) rTMS applied to the right dorsolateral prefrontal cortex (dlPFC) enhances emotional and autonomic responses, as indicated by increased heart rate deceleration when viewing negative and neutral images, suggesting it may improve emotional processing.

High frequency (HF) rTMS, on the other hand, appears to diminish the emotional modulation of cardiac responses, indicating that LF and HF rTMS have opposing effects on emotional perception and autonomic function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of prefrontal rTMS on autonomic reactions to affective pictures. Berger, C., Domes, G., Balschat, J., et al.[2019]

In a study involving 18 healthy individuals, slow repetitive transcranial magnetic stimulation (rTMS) applied to the prefrontal cortex did not result in significant changes in emotions such as happiness, irritability, or anxiety.

The study found that slow rTMS did not affect sleep quality either, suggesting that this specific stimulation method may not be effective for mood modulation in healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect on the emotions of healthy individuals of slow repetitive transcranial magnetic stimulation applied to the prefrontal cortex. Grisaru, N., Bruno, R., Pridmore, S.[2019]

In a study of 63 obese individuals undergoing a 5-week rTMS treatment for weight control, the treatment showed a reassuring safety profile with no unexpected adverse events reported up to one year after treatment.

The most common side effects were moderate headaches (40.4%) and local pain/discomfort (19.2%), particularly more frequent in the high-frequency rTMS group, but overall, rTMS was well tolerated in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of repeated sessions of deep transcranial magnetic stimulation in obesity. Ferrulli, A., Massarini, S., Macrì, C., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) is a powerful tool that can effectively treat clinical depression and potentially other brain disorders, but it carries risks, including the potential to induce seizures, as evidenced by 7 known cases by 1996.

A workshop established safety guidelines for rTMS, emphasizing the importance of monitoring, ethical considerations, and the expertise required for its administration to minimize risks and enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Wassermann, EM.[2022]

In a study involving 13 participants, real-time fMRI was used to train individuals to self-regulate their emotional brain networks, showing that they could effectively upregulate areas like the insula and amygdala after a short training period.

The successful upregulation of these emotion networks was associated with increased activation in other brain regions, such as the precuneus and medial prefrontal cortex, indicating the potential for fMRI-based neurofeedback to be developed as a therapeutic tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurofeedback: A promising tool for the self-regulation of emotion networks. Johnston, SJ., Boehm, SG., Healy, D., et al.[2009]

In a pilot study involving 37 adults with high emotional dysregulation, combining one session of cognitive restructuring (CR) with active repetitive transcranial magnetic stimulation (rTMS) significantly improved emotion regulation, as indicated by higher heart rate variability and increased use of CR techniques in the week following the intervention.

Participants receiving active rTMS experienced greater benefits in emotion regulation compared to those receiving sham treatment, although no long-term differences were observed at the one-month follow-up, suggesting that the combined intervention may be effective for short-term emotional management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing cognitive restructuring with concurrent fMRI-guided neurostimulation for emotional dysregulation-A randomized controlled trial. Neacsiu, AD., Beynel, L., Graner, JL., et al.[2023]

Focal electrical stimulation of the frontalis muscle was found to be an effective sham control for high-frequency repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex, helping to blind participants in studies.

In a study with 19 participants, only 6% correctly identified the sham condition, indicating that this method successfully masked the treatment and can be used in both rTMS and biofeedback research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focal electrical stimulation as an effective sham control for active rTMS and biofeedback treatments. Sheffer, CE., Mennemeier, MS., Landes, RD., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) is generally a well-tolerated treatment for depression, with mild side effects like headaches being the most common, while severe adverse effects are rare.

Special precautions are necessary for certain groups, such as adolescents, pregnant women, and individuals with metal implants, but with proper assessment and monitoring, rTMS can be safely administered to many patients with depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. Taylor, R., Galvez, V., Loo, C.[2019]

Repetitive transcranial magnetic stimulation (rTMS) is a promising non-invasive brain stimulation technique that can enhance brain excitability and potentially improve conditions like stroke, Parkinson's disease, and depression, as discussed in a 2010 symposium with insights from both animal studies and small clinical trials.

While there is significant interest and some signs of therapeutic success with rTMS, the current models explaining its effects may need refinement to fully understand the underlying mechanisms and outcomes observed in various studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain stimulation and brain repair--rTMS: from animal experiment to clinical trials--what do we know? Platz, T., Rothwell, JC.[2013]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05712057

Neurostimulation Versus Therapy for Problems With ... Cognitive restructuring is a cognitive behavioral intervention through which participants learn how to think differently about stressful events in order to feel ...

2. clinicaltrial.be clinicaltrial.be/en/details/190613?per_page=100&only_recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&completed=0&only_eligible=0&only_active=0

Neurostimulation Versus Therapy for Problems With ... The primary aim of this project is to evaluate the unique neural and behavioral effects of a one-session training combining emotion regulation ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9937022/

Enhancing Cognitive Restructuring with Concurrent fMRI ... Enhancing cognitive restructuring with concurrent fMRI-guided neurostimulation for emotional dysregulation: a randomized controlled trial.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0165032724001368?via%3Dihub

An experimental examination of neurostimulation and ... Engaging in cognitive restructuring enhanced with high-frequency neurostimulation led to the lowest misophonic distress, highlighting the best path forward for ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9772290/

Neuromodulatory effects of transcranial electrical ... Emotion Regulation Skills Training Enhances the Efficacy of Inpatient Cognitive Behavioral Therapy for Major Depressive Disorder: A Randomized Controlled Trial.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8891052/

Enhancing Cognitive Restructuring with Concurrent ... We developed and tested a one-time intervention that integrates behavioral skills training with concurrent repetitive transcranial magnetic stimulation (rTMS).

7. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2791248

Efficacy of Augmentation of Cognitive Behavioral Therapy ... This randomized clinical trial examines the use of simultaneous cognitive behavioral therapy and transcranial direct current stimulation in ...

8. researchgate.net researchgate.net/profile/Lawrence-Appelbaum/publication/354771724_Enhancing_Cognitive_Restructuring_with_Concurrent_Repetitive_Transcranial_Magnetic_Stimulation_A_Transdiagnostic_Randomized_Controlled_Trial/links/62f7f0c652130a3cd71b40c4/Enhancing-Cognitive-Restructuring-with-Concurrent-Repetitive-Transcranial-Magnetic-Stimulation-A-Transdiagnostic-Randomized-Controlled-Trial.pdf

Enhancing-Cognitive-Restructuring-with-Concurrent- ... Brain stimulation is one approach to altering pathological brain circuits that has translational potential to mitigate problems with emotion ...