Emotion Regulation, Real Versus Sham Transcranial Magnetic Stimulation (TMS)
Conditions
Brief summary
Distancing oneself from a current distressing situation is a mental skill that can help people to manage their emotions. However, little is known about how distancing works in the brain. Recently developed tools in neuroscience that can modify brain activity might be able to make distancing more or less effective. In doing so, the results could lead to a better understanding of the cognitive processes and neural circuits that support distancing as a form of emotion regulation. If successful, this research may lead to the development of new treatments to help those who suffer from stress-related disorders, such as anxiety and depression.
Detailed description
Distancing is an emotion regulation skill that relies in part on self-projection, or the ability to shift perspective from the here and now to a simulated time, place, or person. Based on prior review and meta-analysis of the distancing literature, a new model has been developed of the neurocognitive processes that support distancing. The proposed experiment will test the model causally through a neural intervention that should impair or enhance the ability of healthy adults to successfully apply distancing to down-regulate negative affect. In the model, it is hypothesized that the temporoparietal junction (TPJ) was a key region mediating the self-projection aspect of distancing. Leveraging recent functional magnetic resonance imaging (fMRI) work, the experiment will functionally modulate this region through inhibitory transcranial magnetic stimulation (TMS) to test its causal role in distancing. Importantly, the proposed work shifts emphasis from traditional models of emotion regulation, which implicate frontal executive control mechanisms, to new cognitive processes and brain targets that can ultimately lead to novel approaches to treat affective disorders.
Interventions
DEVICETranscranial magnetic stimulation task
Experimenters will employ a continuous theta-burst stimulation (cTBS) sequence using a figure-8 coil positioned tangentially to the scalp over the target coordinates. Experimenters have defined the target coordinates for stimulation (Montreal Neuroscience Institute coordinates -53, -53, 23) based on peak objective distancing activation in the left temporal parietal junction (TPJ) in previous fMRI studies using the same task.
DEVICESham transcranial magnetic stimulation task
A sham version of the TMS intervention where subjects will receive a small electrical stimulation on the scalp via two small electrodes in conjunction with a TMS coil activation. The TMS coil will be reoriented to stimulate into the air away from the scalp, simulating traditional TMS, without inducing any current to the subject.
Sponsors
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Neither the lead experimenter nor the subject will know which arm they will complete first. The secondary experimenter will use a randomized counter-balanced log to determine the order of sequences will take place. The secondary experimenter will set up the device while the lead experimenter is out of the room to preserve blindness to the intervention.
Eligibility
Sex/Gender
ALL
Age
18 Years to 39 Years
Healthy volunteers
Yes
Inclusion criteria
* Age between 18-39 years inclusive * Willing to provide informed consent * English speaking * Signed HIPAA authorization
Exclusion criteria
* Current or recent (within the past 6 months) substance abuse or dependence, excluding nicotine and caffeine (assessed via urine test). * Current serious medical illness (assessed via self report). * History of seizure except those therapeutically induced by ECT (childhood febrile seizures are acceptable and these subjects may be included in the study), history of epilepsy in self or first degree relatives, stroke, brain surgery, head injury, cranial metal implants, known structural brain lesion, devices that may be affected by TMS or MRI (pacemaker, medication pump, cochlear implant, implanted brain stimulator) \[assessed via TMS Adult Safety Screening form\]. * Subjects are unable or unwilling to give informed consent. * Diagnosed any Axis I Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) disorder (assessed via self report). * Subjects with a clinically defined neurological disorder (assessed via self report) including, but not limited to: 1. Any condition likely to be associated with increased intracranial pressure 2. Space occupying brain lesion. 3. History of stroke. 4. Transient ischemic attack within two years. 5. Cerebral aneurysm. 6. Dementia. 7. Parkinson's disease. 8. Huntington's disease. 9. Multiple sclerosis. * 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 (assess via self report). * Subjects not willing to tolerate the confinement associated with being in the MRI scanner. * Women who are pregnant or breast-feeding (assessed via urine test). * Blindness. * Inability to read or understand English. * Intracranial implants, such as: 1. Cochlear implants; 2. Aneurysms clips; 3. Shunts; 4. Stimulators; 5. Electrodes; 6. Cardiac pacemakers; 7. Vagus Nerve stimulation devices.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Self-reported Valence (Distancing) From Baseline to 30 Minutes Post Stimulation. | baseline, 30 minutes post stimulation | Valence is how positive or negative a subject feels. Subjects will be asked to rate how they feel on a 7 point Likert scale ranging from 1 (very negative) to 7 (very positive) after using an emotion regulation technique (distancing) when shown graphic stimuli. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Self-reported Effort (Distancing) From Baseline to 30 Minutes Post Stimulation. | baseline, 30 minutes post stimulation | Effort is how difficult it was for a subject to use a specific emotion regulation technique. Subjects will be asked to rate how much effort they felt they used on a 7 point Likert scale ranging from 1 (very little effort) to 7 (very high effort) after using an emotion regulation technique (distancing) when shown graphic stimuli. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Self-reported Valence (Distraction) From Baseline to 30 Minutes Post Stimulation. | baseline, 30 minutes post stimulation | Valence is how positive or negative a subject feels. Subjects will be asked to rate how they feel on a 7 point Likert scale ranging from 1 (very negative) to 7 (very positive) after using an emotion regulation technique (distraction) when shown graphic stimuli. |
| Change in Self-reported Effort (Distraction) From Baseline to 30 Minutes Post Stimulation. | baseline, 30 minutes post stimulation | Effort is how difficult is was for a subject to use a specific emotion regulation technique. Subjects will be asked to rate how much effort they felt they used on a 7 point Likert scale ranging from 1 (very little effort) to 7 (very high effort) after using an emotion regulation technique (distraction) when shown graphic stimuli. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from 11/1/18 until 5/17/19. Subjects were recruited and screened from the Duke University Brain Imaging Analysis Center (BIAC) research participant pool as well as from e-flyers on Duke University's electronic community bulletin board (DukeList).
Participants by arm
| Arm | Count |
|---|---|
| Transcranial Magnetic Stimulation (TMS), Then Sham TMS Experimenters will employ a continuous theta-burst stimulation (cTBS) sequence using a figure-8 coil positioned tangentially to the scalp over the target coordinates. Experimenters have defined the target coordinates for stimulation (Montreal Neuroscience Institute coordinates -53, -53, 23) based on peak objective distancing activation in the left temporal parietal junction (TPJ) in previous fMRI studies using the same task. Thirty minutes post stimulation, experimenters will employ a A sham version of the TMS intervention where subjects will receive a small electrical stimulation on the scalp via two small electrodes in conjunction with a TMS coil activation. The TMS coil will be reoriented to stimulate into the air away from the scalp, simulating traditional TMS, without inducing any current to the subject. | 15 |
| Sham TMS, Then Transcranial Magnetic Stimulation A sham version of the TMS intervention where subjects will receive a small electrical stimulation on the scalp via two small electrodes in conjunction with a TMS coil activation. The TMS coil will be reoriented to stimulate into the air away from the scalp, simulating traditional TMS, without inducing any current to the subject.Experimenters have defined the target coordinates for stimulation (Montreal Neuroscience Institute coordinates -53, -53, 23) based on peak objective distancing activation in the left temporal parietal junction (TPJ) in previous fMRI studies using the same task. Thirty minutes post stimulation, experimenters will employ a continuous theta-burst stimulation (cTBS) sequence using a figure-8 coil positioned tangentially to the scalp over the target coordinates. | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Could not establish TMS dosage | 0 | 1 |
| Overall Study | Equipment Error | 1 | 0 |
| Overall Study | Failed drug screen | 1 | 1 |
| Overall Study | Failed health screen | 0 | 1 |
| Overall Study | Ineligible for financial compensation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Transcranial Magnetic Stimulation (TMS), Then Sham TMS | Sham TMS, Then Transcranial Magnetic Stimulation | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 15 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 8 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 6 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 8 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 6 Participants | 13 Participants |
| Sex/Gender, Customized Female | 12 Participants | 8 Participants | 20 Participants |
| Sex/Gender, Customized Male | 3 Participants | 7 Participants | 10 Participants |
| Sex/Gender, Customized Unknown/unlisted | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Change in Self-reported Valence (Distancing) From Baseline to 30 Minutes Post Stimulation.
Valence is how positive or negative a subject feels. Subjects will be asked to rate how they feel on a 7 point Likert scale ranging from 1 (very negative) to 7 (very positive) after using an emotion regulation technique (distancing) when shown graphic stimuli.
Time frame: baseline, 30 minutes post stimulation
Population: All subjects who completed the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Transcranial Magnetic Stimulation (TMS) | Change in Self-reported Valence (Distancing) From Baseline to 30 Minutes Post Stimulation. | .662 score on a scale | Standard Deviation 0.565 |
| Sham TMS | Change in Self-reported Valence (Distancing) From Baseline to 30 Minutes Post Stimulation. | .668 score on a scale | Standard Deviation 0.561 |
Comparison: The null hypothesis was that distancing performance would not differ by arm of the study. Within-subjects factors included task condition (distancing vs. distraction) and study arm. Study arm order was used as a between-subjects factor.p-value: 0.019ANOVA
Comparison: This analysis evaluated the two-way interaction of task condition and study period. The null hypothesis was that distancing performance would not differ by study period. Within-subjects factors included task condition and study period.p-value: 0.021ANOVA
Comparison: A dependent-samples t-test was used to compare distancing performance between study periods 1 and 2. The null hypothesis was that distancing performance would not differ by study period.p-value: 0.108t-test, 2 sided
Comparison: For this analysis, study arm and task condition were used as within-subjects factors, study arm order was used as a between-subjects factor, and TMS stimulator intensity and brain-target-to-scalp distance were used as covariates.p-value: 0.948ANOVA
Secondary
Change in Self-reported Effort (Distancing) From Baseline to 30 Minutes Post Stimulation.
Effort is how difficult it was for a subject to use a specific emotion regulation technique. Subjects will be asked to rate how much effort they felt they used on a 7 point Likert scale ranging from 1 (very little effort) to 7 (very high effort) after using an emotion regulation technique (distancing) when shown graphic stimuli.
Time frame: baseline, 30 minutes post stimulation
Population: All subjects who completed the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Transcranial Magnetic Stimulation (TMS) | Change in Self-reported Effort (Distancing) From Baseline to 30 Minutes Post Stimulation. | 3.610 score on a scale | Standard Deviation 0.841 |
| Sham TMS | Change in Self-reported Effort (Distancing) From Baseline to 30 Minutes Post Stimulation. | 3.546 score on a scale | Standard Deviation 0.959 |
Comparison: The null hypothesis was that distancing self-reported effort would not differ by arm of the study. Within-subjects factors included task condition (distancing vs. distraction) and study arm. Study arm order was used as a between-subjects factor.p-value: 0.862ANOVA
Comparison: A follow-up ANOVA was run with within-subjects factors of task condition and study period.p-value: 0.054ANOVA
Comparison: A follow-up dependent-samples t-test was run to test a potential effect of study period on distancing effort.p-value: 0.012t-test, 2 sided
Comparison: Post-hoc analyses were used to explore treatment effects using covariates related to the treatment parameters. For this analysis, study arm and task condition were used as within-subjects factors, study arm order was used as a between-subjects factor, and TMS stimulator intensity and brain-target-to-scalp distance were used as covariates.p-value: 0.085ANOVA
Comparison: This analysis examined the effect of study arm specifically on distancing effort. The within-subjects factor was study arm, between-subjects factor was study arm order, and TMS stimulator intensity and brain-target-to-scalp distance were used as covariates.p-value: 0.013ANOVA
Other Pre-specified
Change in Self-reported Effort (Distraction) From Baseline to 30 Minutes Post Stimulation.
Effort is how difficult is was for a subject to use a specific emotion regulation technique. Subjects will be asked to rate how much effort they felt they used on a 7 point Likert scale ranging from 1 (very little effort) to 7 (very high effort) after using an emotion regulation technique (distraction) when shown graphic stimuli.
Time frame: baseline, 30 minutes post stimulation
Population: All subjects who completed the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Transcranial Magnetic Stimulation (TMS) | Change in Self-reported Effort (Distraction) From Baseline to 30 Minutes Post Stimulation. | 3.620 score on a scale | Standard Deviation 1.083 |
| Sham TMS | Change in Self-reported Effort (Distraction) From Baseline to 30 Minutes Post Stimulation. | 3.590 score on a scale | Standard Deviation 1.146 |
Comparison: A follow-up dependent-samples t-test was run to test the effect of study period on distraction effort.p-value: 0.415t-test, 2 sided
Comparison: The null hypothesis was that distraction self-reported effort would not differ by arm of the study. Within-subjects factors included task condition (distancing vs. distraction) and study arm. Study arm order was used as a between-subjects factor.p-value: 0.862ANOVA
Comparison: A follow-up ANOVA was run with within-subjects factors of task condition and study period.p-value: 0.054ANOVA
Comparison: Post-hoc analyses were used to explore treatment effects using covariates related to the treatment parameters. For this analysis, study arm and task condition were used as within-subjects factors, study arm order was used as a between-subjects factor, and TMS stimulator intensity and brain-target-to-scalp distance were used as covariates.p-value: 0.085ANOVA
Comparison: This analysis examined the effect of study arm specifically on distraction performance. The within-subjects factor was study arm, between-subjects factor was study arm order, and TMS stimulator intensity and brain-target-to-scalp distance were used as covariates.p-value: 0.535ANOVA
Other Pre-specified
Change in Self-reported Valence (Distraction) From Baseline to 30 Minutes Post Stimulation.
Valence is how positive or negative a subject feels. Subjects will be asked to rate how they feel on a 7 point Likert scale ranging from 1 (very negative) to 7 (very positive) after using an emotion regulation technique (distraction) when shown graphic stimuli.
Time frame: baseline, 30 minutes post stimulation
Population: All subjects who completed the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Transcranial Magnetic Stimulation (TMS) | Change in Self-reported Valence (Distraction) From Baseline to 30 Minutes Post Stimulation. | .617 score on a scale | Standard Deviation 0.608 |
| Sham TMS | Change in Self-reported Valence (Distraction) From Baseline to 30 Minutes Post Stimulation. | .710 score on a scale | Standard Deviation 0.661 |
Comparison: The null hypothesis was that distraction performance would not differ by arm of the study. Within-subjects factors included task condition (distancing vs. distraction) and study arm. Study arm order was used as a between-subjects factor.p-value: 0.019ANOVA
Comparison: This analysis evaluated the two-way interaction of task condition and study period. The null hypothesis was that distraction performance would not differ by study period. Within-subjects factors included task condition and study period.p-value: 0.021ANOVA
Comparison: A dependent-samples t-test was used to compare distraction performance between study periods 1 and 2. The null hypothesis was that distraction performance would not differ by study period.p-value: 0.21t-test, 2 sided
Comparison: Post-hoc analyses were used to explore treatment effects using covariates related to the treatment parameters. For this analysis, study arm and task condition were used as within-subjects factors, study arm order was used as a between-subjects factor, and TMS stimulator intensity and brain-target-to-scalp distance were used as covariates.p-value: 0.948ANOVA