Anxiety, Depression, Personality Disorders, Trauma and Stress-related Disorders, Somatic Disorders, Obsessive Compulsive Disorders, Eating Disorders, Difficulties With Cognitive Emotion Regulation
Conditions
Keywords
neurostimulation, cognitive restructuring, TMS, emotion regulation, MRI, Emotional Memory Task, Reappraisal, Distraction
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.
Detailed description
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.
Interventions
BEHAVIORALCognitive Restructuring
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.
DEVICErTMS
rTMS is a neurostimulation intervention where the participant receives 15 minutes of high frequency (10 HZ) transcranial magnetic stimulation pulses
DEVICESham rTMS
Sham rTMS is a placebo intervention aimed to mimic the effects of repetitive transcranial magnetic stimulation with no known direct benefit for the participant.
Sponsors
Brain & Behavior Research Foundation
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Has difficulty thinking differently in emotional situations 2. 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. 3. 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. 4. Has cellphone that can be used during the ambulatory assessment portion of the study.
Exclusion criteria
1. Current or recent (within the past 6 months) substance dependence disorder(excluding nicotine and caffeine) 2. Current serious medical illness, including migraine headaches. ' 3. 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 4. 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). 5. 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. 6. 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). 7. 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. 8. 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). 9. 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. 10. Subjects with cochlear implants 11. Women who are pregnant or breast feeding 12. Chronic absence of shelter or impending jail that would make consistent participation in the study difficult 13. Cannot easily come to Duke several times for the study procedures 14. Does not have a mobile phone or is unwilling to use mobile phone for ambulatory assessment 15. Does not speak/understand English enough to benefit from the psychotherapeutic intervention 16. Intellectual disability For imaging arm of the study, participants must also be able to tolerate an MRI, thus must be eligible based on the MRI safety screening form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Return to Heart Rate Baseline During the Regulation Period During Training | 1 week after intake | 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. |
| Time to Return to Heart Rate Baseline During the Regulation Period at Follow up | 1 month | 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. |
| Physiological Emotion Regulation | 1 week after study start | 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. |
| Changes in Activation in the Neural Emotion Regulation Network | 1 week | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility, as Measured by Qualitative Exit Interview | 1 month | The investigators will examine how feasible the proposed intervention is. A previously developed in-house interview (A. D. Neacsiu, Luber, et al., 2018) was administered at the 1-month follow up, and it included Likert-type questions about feasibility, acceptability, and overall satisfaction rated on a scale from 0 (not at all) to 9 (extremely; secondary outcomes). |
| Change in Emotion Dysregulation and Functional Impairment | 1 week and 1 month after the intervention | The investigators will examine changes in the reappraisal scale of the Emotion Regulation Questionnaire (ERQ; range 1-7), in the total score from the Difficulties with Emotion Regulation Scale (DERS; range 36-180), and in the total score from the work and social adjustment functional impairment scale (WSAS; range 0-40) from before to after the one time intervention. Higher ERQ-Reappraisal scores indicate more use of cognitive restructuring (a favorable outcome). Lower DERS total score and lower WSAS average score indicate lower overall emotional dysregulation and lower impairment in functioning, which are desirable outcomes. Outcomes were analyzed using HLM models and the data presented below represents the estimate marginal means for each condition for the growth in each outcome controlling for baseline. |
| Acceptability, as Measured by Qualitative Exit Interview | 1 month | The investigators will examine how acceptable participants find the intervention. A previously developed in-house interview (A. D. Neacsiu, Luber, et al., 2018) was administered at the 1-month follow up, and it included Likert-type questions about feasibility, acceptability, and overall satisfaction rated on a scale from 0 (not at all) to 9 (extremely; secondary outcomes). |
| Change in General Psychological Distress, as Measured by the Outcome Questionaire -45 | 1 week and 1 month | The investigators will examine change in general psychological distress after the intervention. 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). We computed the total score (ranging from 0 to 180) from data collected at intake, at 1 week after the intervention, and at 1 month after the intervention. Higher score indicate higher psychopathological distress than lower scores. The estimated marginal means from the growth model comparing differences between conditions are presented in the table below. |
| Change in Daily General Emotional Distress | 1 week | The investigators will examine change in emotional distress after the intervention as measured by daily mobile phone ratings 8 times/day for 7 days of subjective units of distress; SUDS). The 8 ratings/day will then be averaged into a mean/day. This daily SUDS mean (range 0-9) will be entered in analyses. Higher SUDS indicates more distress. |
Countries
United States
Participant flow
Recruitment details
Recruitment from the community occurred between 3/1/2016 and 2/17/2019 . Additional funding was received in 2017 to collect additional data. Two conditions were added where procedures were identical but targeting for neurostimulation was done using functional neuroimaging data. Participants were recruited for both the study and the sub study and assigned to one at intake.
Pre-assignment details
We enrolled 148 participants in both studies of which 78 were randomized in one of the two studies (main study or sub study). Twenty seven participants decided to withdraw after intake.In addition, 42 participants were excluded after enrollment (e.g., TMS was contraindicated, did not meet criteria for any DSM disorder, had current psychosis/mania/addiction, etc). One participant piloted the procedures and was also excluded from analyses.
Participants by arm
| Arm | Count |
|---|---|
| Cognitive Restructuring+rTMS (Left) 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.
Cognitive Restructuring: 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.The specific neurostimulation target will be established using the 10-20 system.
rTMS: rTMS is a neurostimulation intervention where the participant receives 15 minutes of high frequency (10 HZ) transcranial magnetic stimulation pulses | 13 |
| Cognitive Restructuring + Sham rTMS 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. The specific neurostimulation target will be established using the 10-20 system.
Cognitive Restructuring: 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.
Sham rTMS: Sham rTMS is a placebo intervention aimed to mimic the effects of repetitive transcranial magnetic stimulation with no known direct benefit for the participant. | 14 |
| Cognitive Restructuring+rTMS (Right) 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. The specific neurostimulation target will be established using the 10-20 system.
Cognitive Restructuring: 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.
rTMS: rTMS is a neurostimulation intervention where the participant receives 15 minutes of high frequency (10 HZ) transcranial magnetic stimulation pulses | 15 |
| Cognitive Restructuring+rTMS (Left) With Functional Targeting 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. The specific neurostimulation target will be established using neuroimaging functional data.
Cognitive Restructuring: 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.
rTMS: rTMS is a neurostimulation intervention where the participant receives 15 minutes of high frequency (10 HZ) transcranial magnetic stimulation pulses | 14 |
| Cognitive Restructuring + Sham rTMS With Functional Targeting 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.
Cognitive Restructuring: 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.The specific neurostimulation target will be established using neuroimaging functional data.
Sham rTMS: Sham rTMS is a placebo intervention aimed to mimic the effects of repetitive transcranial magnetic stimulation with no known direct benefit for the participant. | 13 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 1 | 1 | 3 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cognitive Restructuring + Sham rTMS | Cognitive Restructuring+rTMS (Right) | Cognitive Restructuring+rTMS (Left) With Functional Targeting | Cognitive Restructuring+rTMS (Left) | Cognitive Restructuring + Sham rTMS With Functional Targeting | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 29.43 years STANDARD_DEVIATION 10.95 | 28.80 years STANDARD_DEVIATION 7.07 | 32.64 years STANDARD_DEVIATION 14.19 | 32.08 years STANDARD_DEVIATION 13.77 | 35.77 years STANDARD_DEVIATION 13.5 | 31.64 years STANDARD_DEVIATION 11.98 |
| DERS Total Score | 118.57 units on a scale STANDARD_DEVIATION 13.72 | 95.67 units on a scale STANDARD_DEVIATION 19.05 | 109.57 units on a scale STANDARD_DEVIATION 17.02 | 93.54 units on a scale STANDARD_DEVIATION 27.55 | 110.39 units on a scale STANDARD_DEVIATION 18.54 | 105.51 units on a scale STANDARD_DEVIATION 21.27 |
| ERQ Reappraisal Score | 3.21 units on a scale STANDARD_DEVIATION 0.76 | 3.51 units on a scale STANDARD_DEVIATION 0.79 | 4.10 units on a scale STANDARD_DEVIATION 1.35 | 3.26 units on a scale STANDARD_DEVIATION 0.87 | 4.44 units on a scale STANDARD_DEVIATION 1.33 | 3.70 units on a scale STANDARD_DEVIATION 1.12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 14 Participants | 13 Participants | 10 Participants | 11 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 3 Participants | 1 Participants | 1 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 9 Participants | 7 Participants | 10 Participants | 9 Participants | 44 Participants |
| Region of Enrollment United States | 14 Participants | 15 Participants | 14 Participants | 13 Participants | 13 Participants | 69 Participants |
| Sex: Female, Male Female | 12 Participants | 13 Participants | 11 Participants | 11 Participants | 11 Participants | 58 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 15 | 0 / 18 | 0 / 16 | 0 / 15 |
| other Total, other adverse events | 9 / 14 | 6 / 15 | 10 / 18 | 9 / 16 | 5 / 15 |
| serious Total, serious adverse events | 0 / 14 | 0 / 15 | 0 / 18 | 0 / 16 | 0 / 15 |
Outcome results
Primary
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).
Time frame: 1 week
Population: This data was not collected from all participants. It was only collected for a subset of participants assigned to the imaging sub study (groups 4 and 5). The numbers presented represent estimated marginal means from the MANCOVA analysis comparing conditions and covarying maximum activation within the contrast at intake.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cognitive Restructuring+rTMS (Left) With Functional Targeting | Changes in Activation in the Neural Emotion Regulation Network | dlPFC | 0.573 Maximum % signal change in ROI | Standard Error 0.065 |
| Cognitive Restructuring+rTMS (Left) With Functional Targeting | Changes in Activation in the Neural Emotion Regulation Network | vmPFC | 2.597 Maximum % signal change in ROI | Standard Error 0.326 |
| Cognitive Restructuring+rTMS (Left) With Functional Targeting | Changes in Activation in the Neural Emotion Regulation Network | vlPFC | 0.965 Maximum % signal change in ROI | Standard Error 0.102 |
| Cognitive Restructuring+rTMS (Left) With Functional Targeting | Changes in Activation in the Neural Emotion Regulation Network | amygdala | 0.664 Maximum % signal change in ROI | Standard Error 0.125 |
| Cognitive Restructuring+rTMS (Left) With Functional Targeting | Changes in Activation in the Neural Emotion Regulation Network | Insula | .543 Maximum % signal change in ROI | Standard Error 0.05 |
| Cognitive Restructuring + Sham rTMS With Functional Targeting | Changes in Activation in the Neural Emotion Regulation Network | amygdala | 0.485 Maximum % signal change in ROI | Standard Error 0.125 |
| Cognitive Restructuring + Sham rTMS With Functional Targeting | Changes in Activation in the Neural Emotion Regulation Network | Insula | .522 Maximum % signal change in ROI | Standard Error 0.05 |
| Cognitive Restructuring + Sham rTMS With Functional Targeting | Changes in Activation in the Neural Emotion Regulation Network | dlPFC | .462 Maximum % signal change in ROI | Standard Error 0.065 |
| Cognitive Restructuring + Sham rTMS With Functional Targeting | Changes in Activation in the Neural Emotion Regulation Network | vlPFC | 0.606 Maximum % signal change in ROI | Standard Error 0.102 |
| Cognitive Restructuring + Sham rTMS With Functional Targeting | Changes in Activation in the Neural Emotion Regulation Network | vmPFC | 2.376 Maximum % signal change in ROI | Standard Error 0.326 |
Comparison: Difference between treatment conditions in dlPFC activation change between feeling negative emotions and downregulation of negative affect a week after intervention, when controlling for baseline activation differencep-value: 0.23695% CI: [-0.078086, 0.300661]ANCOVA
Comparison: Expected significantly higher activation following active intervention in the vlPFC when compared to sham when engaging in downregulation versus passive experience of negative emotions induced with autobiographical stressors. ROI data was extracted using FSL featquery. A univariate general linear model excluding one outlier from the active condition was conducted for this outcome measure.p-value: 0.02034795% CI: [0.061, 0.657049]ANCOVA
Comparison: Expected significantly higher activation following active intervention in the vmPFC when compared to sham when engaging in downregulation versus passive experience of negative emotions induced with autobiographical stressors. ROI data was extracted with FSL featquery.p-value: 0.63595% CI: [-0.732963, 1.17633]ANCOVA
Comparison: Expected significantly lower activation following active intervention in the amygdala when compared to sham when engaging in downregulation versus passive experience of negative emotions induced with autobiographical stressors. ROI data was extracted with featquery (FSL).p-value: 0.32495% CI: [-0.188868, 0.547692]ANCOVA
Comparison: Expected significantly lower activation following active intervention in the insula when compared to sham when engaging in downregulation versus passive experience of negative emotions induced with autobiographical stressors. FSL featquery tool was used to extract ROI (region of interest) data.p-value: 0.7681995% CI: [-0.126027, 0.168489]ANCOVA
Primary
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.
Time frame: 1 week after study start
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Restructuring+rTMS (Left) | Physiological Emotion Regulation | 1.919 lg(1000000*milliseconds) | Standard Error 0.041 |
| Cognitive Restructuring + Sham rTMS | Physiological Emotion Regulation | 1.763 lg(1000000*milliseconds) | Standard Error 0.039 |
| Cognitive Restructuring+rTMS (Right) | Physiological Emotion Regulation | 1.869 lg(1000000*milliseconds) | Standard Error 0.038 |
| Cognitive Restructuring+rTMS (Left) With Functional Targeting | Physiological Emotion Regulation | 1.722 lg(1000000*milliseconds) | Standard Error 0.016 |
| Cognitive Restructuring + Sham rTMS With Functional Targeting | Physiological Emotion Regulation | 1.549 lg(1000000*milliseconds) | Standard Error 0.017 |
Comparison: In the original study (CR+active left rTMS vs CR+ active right rTMS vs CR+sham rTMS), mixed-effects hierarchical linear models (MMANOVA) with analytically determined covariance structures were used to analyze the repeated measures data. We hypothesized that active neurostimulation would increase HF-HRV during regulation.p-value: 0.02295% CI: [0.044, 0.267]Mixed Models Analysis
Comparison: MMANOVAp-value: 0.049995% CI: [0.000037, 0.213074]Mixed Models Analysis
Comparison: In the supplemental study (CR+active left rTMS with functional targeting vs CR+sham rTMS), mixed-effects hierarchical linear models (MMANOVA) with analytically determined covariance structures were used to analyze the repeated measures data. We hypothesized that active neurostimulation would increase HF-HRV during regulation when compared with sham.p-value: <0.00000195% CI: [0.129, 0.215]Mixed Models Analysis
Primary
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.
Time frame: 1 month
Population: only participants who stressed during the follow up stressor task (i.e., their heart rate was above baseline at the beginning of the follow up regulation period) were included in these analyses. Missing participants did not stress at follow up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Restructuring+rTMS (Left) | Time to Return to Heart Rate Baseline During the Regulation Period at Follow up | 1.448 log (seconds) | Standard Error 0.089 |
| Cognitive Restructuring + Sham rTMS | Time to Return to Heart Rate Baseline During the Regulation Period at Follow up | 1.286 log (seconds) | Standard Error 0.062 |
| Cognitive Restructuring+rTMS (Right) | Time to Return to Heart Rate Baseline During the Regulation Period at Follow up | 1.1474 log (seconds) | Standard Error 0.11 |
| Cognitive Restructuring+rTMS (Left) With Functional Targeting | Time to Return to Heart Rate Baseline During the Regulation Period at Follow up | 1.5535 log (seconds) | Standard Error 0.0936 |
| Cognitive Restructuring + Sham rTMS With Functional Targeting | Time to Return to Heart Rate Baseline During the Regulation Period at Follow up | 1.4055 log (seconds) | Standard Error 0.14923 |
Comparison: A univariate general linear model was employed to test of regulation duration, transformed for normality.p-value: 0.5195% CI: [-0.504, 0.256]ANOVA
p-value: 0.9795% CI: [-0.364, 0.378]ANOVA
Comparison: A t test of the variable 'time it took to return to HR baseline', transformed for normality was used to examine between condition differences at the 1 month follow up.p-value: 0.3995% CI: [-0.215936, 0.511921]t-test, 2 sided
Primary
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.
Time frame: 1 week after intake
Population: Each participant went through three stressor-regulation periods during the intervention. Only those who stressed at least during one of the three stressor periods were included in this analysis. Missing participants from the total ITT sample did not stress at all during the intervention stressor tasks. The results presented are estimated marginal means from the MMANOVA analysis that included this information
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Restructuring+rTMS (Left) | Time to Return to Heart Rate Baseline During the Regulation Period During Training | 1.591 log (seconds) | Standard Error 0.093 |
| Cognitive Restructuring + Sham rTMS | Time to Return to Heart Rate Baseline During the Regulation Period During Training | 1.828 log (seconds) | Standard Error 0.095 |
| Cognitive Restructuring+rTMS (Right) | Time to Return to Heart Rate Baseline During the Regulation Period During Training | 1.505 log (seconds) | Standard Error 0.089 |
| Cognitive Restructuring+rTMS (Left) With Functional Targeting | Time to Return to Heart Rate Baseline During the Regulation Period During Training | 1.534475 log (seconds) | Standard Error 0.154 |
| Cognitive Restructuring + Sham rTMS With Functional Targeting | Time to Return to Heart Rate Baseline During the Regulation Period During Training | 1.946232 log (seconds) | Standard Error 0.173 |
Comparison: A mixed models analysis of variance (MMANOVA) examining regulation duration during each regulation period was conducted using treatment condition (active right, active left, sham), experimental condition (regulation1, regulation2, regulation3), and baseline as predictors.p-value: 0.01995% CI: [-0.59, -0.056]Mixed Models Analysis
Comparison: A mixed models analysis of variance (MMANOVA) examining regulation duration during each regulation period was conducted using treatment condition (active right, active left, sham), experimental condition (regulation1, regulation2, regulation3), and baseline as predictors.p-value: 0.0895% CI: [-0.034, 0.508]Mixed Models Analysis
Comparison: Regulation duration was transformed using a logarithmic transformation to achieve normalityp-value: 0.03395% CI: [-0.434, -0.02]Mixed Models Analysis
Secondary
Acceptability, as Measured by Qualitative Exit Interview
The investigators will examine how acceptable participants find the intervention. A previously developed in-house interview (A. D. Neacsiu, Luber, et al., 2018) was administered at the 1-month follow up, and it included Likert-type questions about feasibility, acceptability, and overall satisfaction rated on a scale from 0 (not at all) to 9 (extremely; secondary outcomes).
Time frame: 1 month
Population: Only participants who were not lost to contact by the last session of the study provided data for this outcome measure. One participant did not complete the acceptability portion of the exit interview and as a result their data cannot be included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Restructuring+rTMS (Left) | Acceptability, as Measured by Qualitative Exit Interview | 7.11 units on a scale | Standard Deviation 1.07 |
| Cognitive Restructuring + Sham rTMS | Acceptability, as Measured by Qualitative Exit Interview | 7.48 units on a scale | Standard Deviation 0.92 |
| Cognitive Restructuring+rTMS (Right) | Acceptability, as Measured by Qualitative Exit Interview | 7.20 units on a scale | Standard Deviation 1.34 |
| Cognitive Restructuring+rTMS (Left) With Functional Targeting | Acceptability, as Measured by Qualitative Exit Interview | 6.99 units on a scale | Standard Deviation 1.25 |
| Cognitive Restructuring + Sham rTMS With Functional Targeting | Acceptability, as Measured by Qualitative Exit Interview | 7.65 units on a scale | Standard Deviation 0.91 |
Comparison: Likert-type questions about acceptability were rated on a scale from 0 (not at all) to 9 (extremely) and then averaged to create a mean for acceptability. This average score was normally distributed and therefore was entered into a univariate general linear model where acceptability was entered as a dependent variable and condition as a fixed factor.p-value: 0.6995% CI: [-0.553, 1.293]ANOVA
p-value: 0.5395% CI: [-0.592, 1.139]ANOVA
Comparison: we compared differences in acceptability between conditions using an independent samples t-test (acceptability was normally distributed)p-value: 0.1595% CI: [-1.59, 0.27]t-test, 2 sided
Secondary
Change in Daily General Emotional Distress
The investigators will examine change in emotional distress after the intervention as measured by daily mobile phone ratings 8 times/day for 7 days of subjective units of distress; SUDS). The 8 ratings/day will then be averaged into a mean/day. This daily SUDS mean (range 0-9) will be entered in analyses. Higher SUDS indicates more distress.
Time frame: 1 week
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Restructuring+rTMS (Left) | Change in Daily General Emotional Distress | 1.388 units on a scale per day | Standard Error 0.217 |
| Cognitive Restructuring + Sham rTMS | Change in Daily General Emotional Distress | 1.941 units on a scale per day | Standard Error 0.212 |
| Cognitive Restructuring+rTMS (Right) | Change in Daily General Emotional Distress | 1.791 units on a scale per day | Standard Error 0.205 |
| Cognitive Restructuring+rTMS (Left) With Functional Targeting | Change in Daily General Emotional Distress | 2.026 units on a scale per day | Standard Error 0.269 |
| Cognitive Restructuring + Sham rTMS With Functional Targeting | Change in Daily General Emotional Distress | 1.395 units on a scale per day | Standard Error 0.293 |
Comparison: Hypothesized that active neurostimulation would lead to lower daily distress than sham stimulation. We used a hierarchical linear model (HLM) for this analysis with an identity covariance structure (random intercept and random slope).p-value: 0.03495% CI: [-1.062356, -0.043203]Mixed Models Analysis
Comparison: Hypothesized that active neurostimulation will lead to less daily distress than sham neurostimulation during the ambulatory data collection. An HLM analysis was conducted using an unstructured covariance structure and reported distress right before the intervention as baseline.p-value: 0.13395% CI: [-0.208, 1.47]Mixed Models Analysis
Secondary
Change in Emotion Dysregulation and Functional Impairment
The investigators will examine changes in the reappraisal scale of the Emotion Regulation Questionnaire (ERQ; range 1-7), in the total score from the Difficulties with Emotion Regulation Scale (DERS; range 36-180), and in the total score from the work and social adjustment functional impairment scale (WSAS; range 0-40) from before to after the one time intervention. Higher ERQ-Reappraisal scores indicate more use of cognitive restructuring (a favorable outcome). Lower DERS total score and lower WSAS average score indicate lower overall emotional dysregulation and lower impairment in functioning, which are desirable outcomes. Outcomes were analyzed using HLM models and the data presented below represents the estimate marginal means for each condition for the growth in each outcome controlling for baseline.
Time frame: 1 week and 1 month after the intervention
Population: Only participants who provided data were included. In the first study (first 3 groups) one participant from the active right condition did not complete the 1-week follow-up self-reports. One sham, three active left, and one active right participant could not tolerate the intervention and dropped. In the second study (last 2 groups) two participants could not tolerate the intervention and dropped in each condition. One participant in sham did not complete his self-report measures at follow up.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cognitive Restructuring+rTMS (Left) | Change in Emotion Dysregulation and Functional Impairment | Work and Social Functioning Impairment | 12.176969 score on a scale | Standard Error 1.941534 |
| Cognitive Restructuring+rTMS (Left) | Change in Emotion Dysregulation and Functional Impairment | Difficulties in emotion regulation total score | 88.413631 score on a scale | Standard Error 6.41951 |
| Cognitive Restructuring+rTMS (Left) | Change in Emotion Dysregulation and Functional Impairment | ERQ-Reappraisal | 4.493290 score on a scale | Standard Error 0.2 |
| Cognitive Restructuring + Sham rTMS | Change in Emotion Dysregulation and Functional Impairment | ERQ-Reappraisal | 4.777880 score on a scale | Standard Error 0.19 |
| Cognitive Restructuring + Sham rTMS | Change in Emotion Dysregulation and Functional Impairment | Difficulties in emotion regulation total score | 89.341540 score on a scale | Standard Error 6.4975 |
| Cognitive Restructuring + Sham rTMS | Change in Emotion Dysregulation and Functional Impairment | Work and Social Functioning Impairment | 10.876197 score on a scale | Standard Error 1.834403 |
| Cognitive Restructuring+rTMS (Right) | Change in Emotion Dysregulation and Functional Impairment | ERQ-Reappraisal | 4.795426 score on a scale | Standard Error 0.19 |
| Cognitive Restructuring+rTMS (Right) | Change in Emotion Dysregulation and Functional Impairment | Work and Social Functioning Impairment | 11.853591 score on a scale | Standard Error 1.849822 |
| Cognitive Restructuring+rTMS (Right) | Change in Emotion Dysregulation and Functional Impairment | Difficulties in emotion regulation total score | 79.212163 score on a scale | Standard Error 5.890947 |
| Cognitive Restructuring+rTMS (Left) With Functional Targeting | Change in Emotion Dysregulation and Functional Impairment | Difficulties in emotion regulation total score | 99.447060 score on a scale | Standard Error 86.259744 |
| Cognitive Restructuring+rTMS (Left) With Functional Targeting | Change in Emotion Dysregulation and Functional Impairment | Work and Social Functioning Impairment | 14.255798 score on a scale | Standard Error 2.290357 |
| Cognitive Restructuring+rTMS (Left) With Functional Targeting | Change in Emotion Dysregulation and Functional Impairment | ERQ-Reappraisal | 4.838261 score on a scale | Standard Error 0.267571 |
| Cognitive Restructuring + Sham rTMS With Functional Targeting | Change in Emotion Dysregulation and Functional Impairment | ERQ-Reappraisal | 4.741542 score on a scale | Standard Error 0.281177 |
| Cognitive Restructuring + Sham rTMS With Functional Targeting | Change in Emotion Dysregulation and Functional Impairment | Difficulties in emotion regulation total score | 4.289242 score on a scale | Standard Error 4.489399 |
| Cognitive Restructuring + Sham rTMS With Functional Targeting | Change in Emotion Dysregulation and Functional Impairment | Work and Social Functioning Impairment | 10.963661 score on a scale | Standard Error 2.295986 |
Comparison: Mixed model analyses of variance (MMANOVAs) were conducted to explore the difference between active and sham neurostimulation on self reported indices of regulation and psychopathology. We expected active neurostimulation to lead to less functional impairment than sham neurostimulation.p-value: 0.62906195% CI: [-6.708548, 4.107]Mixed Models Analysis
Comparison: We expected lower functional impairment in the active right versus the sham condition.p-value: 0.7195% CI: [-6.255223, 4.300434]Mixed Models Analysis
Comparison: Mixed model analyses of variance (MMANOVAs) were conducted to explore the difference between active and sham neurostimulation on self reported indices of regulation and psychopathology in the substudy also. We expected active neurostimulation to lead to less impairment than sham neurostimulation.p-value: 0.33195% CI: [-10.157811, 3.573537]Mixed Models Analysis
Comparison: Mixed model analyses of variance (MMANOVAs) were conducted to explore the difference between active and sham neurostimulation on self reported indices of regulation and psychopathology. We expected active neurostimulation to lead to more use of cognitive restructuring than sham neurostimulation.p-value: 0.3195% CI: [-0.27603, 0.845209]Mixed Models Analysis
Comparison: We hypothesized that active right neurostimulation would yield lower emotional dysregulation after the intervention when compared to sham neurostimulation.p-value: 0.27525795% CI: [-8.394724, 28.653479]Mixed Models Analysis
Comparison: Mixed model analyses of variance (MMANOVAs) were conducted to explore the difference between active and sham neurostimulation on self reported indices of regulation and psychopathology. We expected active neurostimulation to lead to less emotional dysregulation than sham neurostimulation.p-value: 0.04495% CI: [-26.002351, -0.372281]Mixed Models Analysis
Comparison: We expected active stimulation to lead to less emotional dysregulation than sham neurostimulation. A MMANOVA model was employed, controlling for baseline.p-value: 0.92495% CI: [-18.508252, 20.364071]Mixed Models Analysis
Comparison: we expected more use of cr following active right neurostimulation then after following sham neurostimulation.p-value: 0.9595% CI: [-0.560994, 0.525901]Mixed Models Analysis
Comparison: Mixed model analyses of variance (MMANOVAs) were conducted to explore the difference between active and sham neurostimulation on self reported indices of regulation and psychopathology. We expected active neurostimulation to lead to more use of cognitive restructuring than sham neurostimulation.p-value: 0.80695% CI: [-0.900919, 0.707481]Mixed Models Analysis
Secondary
Change in General Psychological Distress, as Measured by the Outcome Questionaire -45
The investigators will examine change in general psychological distress after the intervention. 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). We computed the total score (ranging from 0 to 180) from data collected at intake, at 1 week after the intervention, and at 1 month after the intervention. Higher score indicate higher psychopathological distress than lower scores. The estimated marginal means from the growth model comparing differences between conditions are presented in the table below.
Time frame: 1 week and 1 month
Population: Only participants who provided data were included. In the first study (first 3 groups) one participant from the active right condition did not complete the 1-week follow-up self-reports. One sham, three active left, and one active right participant could not tolerate the intervention and dropped. In the second study (last 2 groups) two participants could not tolerate the intervention and dropped in each condition. One participant in sham did not complete his OQ-45 measure at follow up.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Restructuring+rTMS (Left) | Change in General Psychological Distress, as Measured by the Outcome Questionaire -45 | 59.996 score on a scale | Standard Error 5.48 |
| Cognitive Restructuring + Sham rTMS | Change in General Psychological Distress, as Measured by the Outcome Questionaire -45 | 53.955 score on a scale | Standard Error 5.29 |
| Cognitive Restructuring+rTMS (Right) | Change in General Psychological Distress, as Measured by the Outcome Questionaire -45 | 53.049 score on a scale | Standard Error 5.06 |
| Cognitive Restructuring+rTMS (Left) With Functional Targeting | Change in General Psychological Distress, as Measured by the Outcome Questionaire -45 | 74.41 score on a scale | Standard Error 5.45 |
| Cognitive Restructuring + Sham rTMS With Functional Targeting | Change in General Psychological Distress, as Measured by the Outcome Questionaire -45 | 63.95 score on a scale | Standard Error 5.73 |
p-value: 0.295% CI: [-5.971581, 26.892619]Mixed Models Analysis
Comparison: To test the long-term effects of the intervention, a MMANOVA model was conducted examining between-condition differences at the 1-week and 1-month follow-up in the OQ-45. Baseline was co-varied.p-value: 0.6195% CI: [-9.522964, 21.60462]Mixed Models Analysis
p-value: 0.995% CI: [-15.83, 14.02]Mixed Models Analysis
Secondary
Feasibility, as Measured by Qualitative Exit Interview
The investigators will examine how feasible the proposed intervention is. A previously developed in-house interview (A. D. Neacsiu, Luber, et al., 2018) was administered at the 1-month follow up, and it included Likert-type questions about feasibility, acceptability, and overall satisfaction rated on a scale from 0 (not at all) to 9 (extremely; secondary outcomes).
Time frame: 1 month
Population: Only participants who were not lost to contact by the last study session provided data for this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Restructuring+rTMS (Left) | Feasibility, as Measured by Qualitative Exit Interview | 6.4545 units on a scale | Standard Deviation 0.83 |
| Cognitive Restructuring + Sham rTMS | Feasibility, as Measured by Qualitative Exit Interview | 6.7500 units on a scale | Standard Deviation 0.87 |
| Cognitive Restructuring+rTMS (Right) | Feasibility, as Measured by Qualitative Exit Interview | 6.7481 units on a scale | Standard Deviation 0.555 |
| Cognitive Restructuring+rTMS (Left) With Functional Targeting | Feasibility, as Measured by Qualitative Exit Interview | 6.3651 units on a scale | Standard Deviation 0.886 |
| Cognitive Restructuring + Sham rTMS With Functional Targeting | Feasibility, as Measured by Qualitative Exit Interview | 6.4646 units on a scale | Standard Deviation 0.9645 |
Comparison: We compared differences between conditions in the perceived feasibility of the procedures. Feasibility average was normally distributed and therefore a general linear model, univariate was employed to test between condition effects.p-value: 0.55195% CI: [-0.322, 0.912]ANOVA
p-value: 0.99595% CI: [-0.567, 0.571]ANOVA
Comparison: We examined differences in feasibility between the active and sham condition in the sub-study where fMRI targeting was utilized. Average feasibility was normally distributed and therefore an independent samples t-test was used to test this outcome.p-value: 0.79195% CI: [-0.8672, 0.6681]t-test, 2 sided