Neuromodulation Enhanced Cognitive Restructuring: A Proof of Concept Study

NCT02573246 | Completed Results

• 1 other identifier: Pro00066383
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Anxiety; Depression; Personality Disorders; Trauma and Stress-related Disorders; Somatic Disorders; Obsessive Compulsive Disorders; Eating Disorders; Difficulties With Cognitive Emotion Regulation

Keywords

neurostimulation; cognitive restructuring; TMS; emotion regulation; MRI; Emotional Memory Task; Reappraisal; Distraction

Outcome Measures

Primary Outcomes (4)

• Time to Return to Heart Rate Baseline During the Regulation Period During Training

  The estimated marginal mean of the difference in length of time that it takes participants to reduce emotional arousal after three emotional inductions when they use Cognitive Restructuring (CR) with or without the enhancing effects of transcranial magnetic stimulation (TMS). Psychophysiological measurements were collected continuously using the BIOPAC MP-150. For each baseline, heart rate (HR) was averaged from the last 240s. Time to return to one's HR baseline was defined as the amount of time (e.g., number of seconds) it took from the beginning of regulation for the continuously monitored HR to reach a value that was lower than the average pre-stimulus baseline HR. Lower numbers indicate quicker regulation (desirable outcome). A baseline value for regulation duration was computed as the time it took during habituation for the person to return to HR baseline. Number of seconds was transformed with a logarithmic function for analyses to achieve normality.

  1 week after intake

• Time to Return to Heart Rate Baseline During the Regulation Period at Follow up

  The investigators will examine difference in length of time that it takes participants to reduce emotional arousal (as measured with physiological indicators) after an emotional induction when they use CR. This measure, was collected at the 1 month follow up assessment. Only one stressor-regulation period was presented at follow up. The number of seconds it took for participants to return to the pre-stimulus baseline during the regulation period was transformed with a log function for normality. Lower numbers indicate quicker regulation, a desirable outcome.

  1 month

• Physiological Emotion Regulation

  The investigators will record heart rate continuously throughout the intervention and then extract high frequency heart rate variability (an index of emotion regulation) from the regulation periods. Continuously recorded HR was divided into 120 s bins, and HF-HRV was extracted from cleaned raw ECG from each bin. Baseline HF-HRV was measured at the beginning of the experiment and right before each autobiographical stressor presentation. The treatment condition (active left, active right, or sham), baselines, the experimental condition (regulation 1, 2, and 3), and the time within each experimental condition (0 to 4 for each 120 s segment within that period) were used to predict HF-HRV. Higher HF-HRV indicates enhanced regulation, a desirable outcome. To make interpretation easier, the raw HF-HRV score was multiplied with 1000000. To achieve normality, this multiplied score was transformed with a logarithmic function.

  1 week after study start

• Changes in Activation in the Neural Emotion Regulation Network

  For groups 4 \&5, the investigators collected functional imaging data while participants engaged in an emotion regulation task. We examined the BOLD response change in the contrast between down-regulating negative emotions and feeling negative emotions a week after intervention controlling for the maximum change in this contrast at intake. Specifically we examined changes in activation in the dorsolateral prefrontal cortex (dlPFC), ventrolateral PFC (vlPFC), ventromedial PFC (vmPFC), the amygdala and insula. Data were first preprocessed with fMRIprep and MRIQC. At the first level, functional data were analyzed as individual runs, using a general linear model (GLM) in which trial events were convolved with a double-gamma hemodynamic response function. The \[Restructure- Feel\_negative\] contrast was then used to generate Level 2 analysis, in which BOLD activity for each of the four runs were combined using a fixed-effect model. Higher numbers indicate more activation (desired outcome).

  1 week

Secondary Outcomes (5)

• Acceptability, as Measured by Qualitative Exit Interview

  1 month

• Feasibility, as Measured by Qualitative Exit Interview

  1 month

• Change in General Psychological Distress, as Measured by the Outcome Questionaire -45

  1 week and 1 month

• Change in Daily General Emotional Distress

  1 week

• Change in Emotion Dysregulation and Functional Impairment

  1 week and 1 month after the intervention

Study Arms (3)

Cognitive Restructuring+rTMS (left)

EXPERIMENTAL

Participants in this arm will be administered the neuromodulation enhanced cognitive restructuring intervention over the left side of the brain and will partake in short term and long term follow up testing.

Behavioral: Cognitive Restructuring; Device: rTMS

Cognitive Restructuring + sham rTMS

SHAM COMPARATOR

Participants in this arm will receive cognitive restructuring alone as an active intervention and will partake in short term and long term follow up testing.

Behavioral: Cognitive Restructuring; Device: Sham rTMS

Cognitive Restructuring+rTMS (right)

EXPERIMENTAL

Participants in this arm will be administered the neuromodulation enhanced cognitive restructuring intervention over the right side of the brain and will partake in short term and long term follow up testing.

Behavioral: Cognitive Restructuring; Device: rTMS

Interventions

Cognitive Restructuring BEHAVIORAL

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.

Cognitive Restructuring + sham rTMS; Cognitive Restructuring+rTMS (left); Cognitive Restructuring+rTMS (right)

rTMS DEVICE

rTMS is a neurostimulation intervention where the participant receives 15 minutes of high frequency (10 HZ) transcranial magnetic stimulation pulses

Cognitive Restructuring+rTMS (left); Cognitive Restructuring+rTMS (right)

Sham rTMS DEVICE

Sham rTMS is a placebo intervention aimed to mimic the effects of repetitive transcranial magnetic stimulation with no known direct benefit for the participant.

Cognitive Restructuring + sham rTMS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has difficulty thinking differently in emotional situations
• Meets diagnostic criteria for a current DSM-5 depressive, anxiety, obsessive-compulsive, somatic, personality, eating, or trauma and stress-related disorders (including in partial remission): major depressive disorder, persistent depressive disorder, panic disorder, agoraphobia, social anxiety disorder, specific phobia, generalized anxiety disorder, obsessive-compulsive disorder, trichotillomania, excoriation disorder, hoarding disorder, body dysmorphic disorder, other specified, or unspecified obsessive-compulsive disorder, posttraumatic stress disorder, acute stress disorder, adjustment disorders, somatic symptom disorder, conversion disorder, anorexia nervosa, bulimia nervosa, binge-eating disorder, borderline personality disorder, narcissistic personality disorder, histrionic personality disorder, antisocial personality disorder, paranoid personality disorder, schizoid personality disorder, schizotypal personality disorder, avoidant personality disorder, dependent personality disorder, obsessive-compulsive personality disorder, personality disorder unspecified, depressive disorder unspecified, anxiety disorder unspecified.
• Willing and able to participate in the intervention and all required study visits, stay on the same dose of psychiatric medication (if any) throughout the study, not participate in cognitive-behavioral therapy throughout their participation in the study.
• Has cellphone that can be used during the ambulatory assessment portion of the study.

You may not qualify if:

• Current or recent (within the past 6 months) substance dependence disorder(excluding nicotine and caffeine)
• Current serious medical illness, including migraine headaches. '
• Currently on psychotropic medications with dosage unchanged for less than four weeks prior to study entry OR plan to make changes in medication within 2 months after starting the study
• History of seizure except those therapeutically induced by electroconvulsive therapy (ECT), 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).
• Diagnosed with the following conditions: psychotic disorder, any DSM disorder secondary to a general medical condition, or substance-induced, Bipolar I disorder (current or lifetime), life-threatening anorexia or any other disorder requiring immediate hospitalization, high-risk for suicidal behavior, including current suicidal ideation with a method and plan or hospitalization for suicidal behavior within 1yr before the study.
• Currently engaged or planning to engage in other treatment during the course of the study (including behavior therapy, or other types of individual, family, or group psychotherapy/counseling).
• Is diagnosed with a clinically defined neurological disorder including, but not limited to: any condition likely to be associated with increased intracranial pressure; space occupying brain lesion; history of stroke, transient ischemic attack within two years; cerebral aneurysm; dementia; Parkinson's disease; Huntington's disease; Multiple sclerosis.
• Has increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure (such as after large infarctions or trauma), or currently taking medication that lowers the seizure threshold (e.g Wellbutrin, Adderall, Clozaril).
• Has any of the following treatment histories: TMS treatment at any point in their lifetime; use of any investigational drug or device within 4 weeks of the screening.
• Subjects with cochlear implants
• Women who are pregnant or breast feeding
• Chronic absence of shelter or impending jail that would make consistent participation in the study difficult
• Cannot easily come to Duke several times for the study procedures
• Does not have a mobile phone or is unwilling to use mobile phone for ambulatory assessment
• Does not speak/understand English enough to benefit from the psychotherapeutic intervention

Sponsors & Collaborators

• Duke University: lead
• Brain & Behavior Research Foundation: collaborator

Study Sites (1)

Duke University Medical Center-Civitan Bldg

Durham, North Carolina, 27710, United States

Location

Related Publications (6)

• Gross, J. J. Handbook of Emotion Regulation, Second Edition. (The Guilford Press, 2013).

  BACKGROUND

• Neacsiu AD, Eberle JW, Kramer R, Wiesmann T, Linehan MM. Dialectical behavior therapy skills for transdiagnostic emotion dysregulation: a pilot randomized controlled trial. Behav Res Ther. 2014 Aug;59:40-51. doi: 10.1016/j.brat.2014.05.005. Epub 2014 May 27.

  PMID: 24974307 BACKGROUND

• Kazdin AE, Blase SL. Rebooting Psychotherapy Research and Practice to Reduce the Burden of Mental Illness. Perspect Psychol Sci. 2011 Jan;6(1):21-37. doi: 10.1177/1745691610393527. Epub 2011 Feb 3.

  PMID: 26162113 BACKGROUND

• Luber B, Steffener J, Tucker A, Habeck C, Peterchev AV, Deng ZD, Basner RC, Stern Y, Lisanby SH. Extended remediation of sleep deprived-induced working memory deficits using fMRI-guided transcranial magnetic stimulation. Sleep. 2013 Jun 1;36(6):857-71. doi: 10.5665/sleep.2712.

  PMID: 23729929 BACKGROUND

• Feeser M, Prehn K, Kazzer P, Mungee A, Bajbouj M. Transcranial direct current stimulation enhances cognitive control during emotion regulation. Brain Stimul. 2014 Jan-Feb;7(1):105-12. doi: 10.1016/j.brs.2013.08.006. Epub 2013 Sep 21.

  PMID: 24095257 BACKGROUND

• Pitman RK, Orr SP, Forgue DF, de Jong JB, Claiborn JM. Psychophysiologic assessment of posttraumatic stress disorder imagery in Vietnam combat veterans. Arch Gen Psychiatry. 1987 Nov;44(11):970-5. doi: 10.1001/archpsyc.1987.01800230050009.

  PMID: 3675137 BACKGROUND

MeSH Terms

Conditions

Anxiety Disorders; Depression; Personality Disorders; Trauma and Stressor Related Disorders; Compulsive Personality Disorder; Feeding and Eating Disorders; Emotional Regulation

Interventions

Cognitive Restructuring

Condition Hierarchy (Ancestors)

Mental Disorders; Behavioral Symptoms; Behavior; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Self-Control; Social Behavior

Intervention Hierarchy (Ancestors)

Cognitive Behavioral Therapy; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Results Point of Contact

• Title: Dr. Andrada D. Neacsiu
• Organization: Duke University Health System

andrada.neacsiu@duke.edu

919-684-6714

Study Officials

• Andrada D Neacsiu, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 8, 2015
• First Posted: October 9, 2015
• Study Start: March 1, 2016
• Primary Completion: February 17, 2020
• Study Completion: February 17, 2020
• Last Updated: July 16, 2021
• Results First Posted: May 10, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)