Bipolar Disorder
Conditions
Keywords
Bipolar Disorder, Transcranial Magnetic Stimulation, Electroencephalography
Brief summary
Bipolar Disorder (BD) is a common and highly debilitating psychiatric disorder, however, the predisposing brain mechanisms are poorly understood. Here, the investigators will conduct a proof of concept study that will examine the effect of electroencephalography (EEG)-guided theta burst stimulation (TBS) on reducing mania/hypomania-related affect and reward driven behavior in adults with BD. The investigators hypothesize that TBS will reduce mania/hypomania-related affect and reward driven behavior in adults with BD.
Detailed description
This study aims to examine the effect of electroencephalography (EEG)-guided theta burst stimulation (TBS) on reducing mania/hypomania-related affect and reward driven behavior in adults with BD. Eligible participants will undergo 6 study visits: a screening visit, a baseline MRI visit, TBS motor thresholding visit, and 3 cTBS/EEG visits. Participants will receive brain stimulation and have brain activity recorded by EEG at each of the 3 cTBS/EEG study visits. The research associates (except for the research associate administering the TBS) and participants will be blinded to the brain area receiving TBS, which will be randomized and counterbalanced beforehand. Certain information is withheld to protect the scientific integrity of the study design. The goal of the study is to reduce overactivity in the reward neural network (RNet) and increase activity in the central executive control network (CEN) using theta burst stimulation (TBS). The region in the RNet to be targeted by inhibitory (continuous, cTBS) is the left ventrolateral prefrontal cortex (vlPFC); and the region in the CEN to be targeted by excitatory (intermittent, iTBS) is the right dorsolateral prefrontal cortex (dlPFC)
Interventions
cTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely that can decrease the excitability of cortical neurons. It is FDA-approved as a treatment for psychological conditions including depression; however, this device is not approved for the treatment of adults with Bipolar Disorder I or for use in healthy adults. This research study is using the cTBS off label in all participants (those with and without Bipolar Disorder I) to examine research questions
DEVICEIntermittent Theta Burst Stimulation (iTBS)
iTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely to increase the excitability of cortical neurons. It is FDA-approved as a treatment for psychological conditions including depression; however, this device is not approved for the treatment of adults with Bipolar Disorder I or for use in healthy adults. This research study is using the cTBS off label in all participants (those with and without Bipolar Disorder I) to examine research questions.
Sponsors
Milken Institute
Mary Phillips, MD MD (Cantab)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* 18-35 years of age * Diagnosis of BD (DSM-5 criteria) in remission (euthymic for \>2 months) or in a manic/hypomanic episode \[manic/hypomanic or euthymic adults with BD (3-fifths manic/hypomanic); euthymic for \> 2 months from most recent BD episode OR current manic/hypomanic episode\] * Not psychotic * Score \<3 on delusions, hallucinations, unusual thought content, and conceptual disorganization items of the Positive and Negative Syndrome Scale (PANSS) * Unmedicated or on any combination of anxiolytics (benzodiazepines, buspirone, pregabalin, hydroxyzine) as needed, and/or atypical antipsychotics, and/or lithium, and/or other mood stabilizers, and/or non-SNRI antidepressants and/or non benzodiazepine hypnotics, as these are commonly-prescribed medications for BD * Provides the contact information of a medical provider (including but not limited to a PCP) that we may communicate with for any concerns of escalating symptoms of mania
Exclusion criteria
* Not 18-35 years of age * Diagnosis of BD in a depressive episode or Diagnosis of BP in partial remission, euthymia that fails to meet full remission criterion of a period of at least 2 months in which there are no significant symptoms, e.g., only partial remission of symptoms or full remission of symptoms but for \<2 months * Diagnosis of BD in a depressive episode * Personal and family history of epilepsy (TBS exclusion) * Binge alcohol drinking * Taking substances in the last month that can elevate seizure risk including but not limited to SNRI antidepressants, bupropion and stimulants (TBS exclusion) * History of head injury, neurological, pervasive developmental disorder (e.g. autism), systemic medical disease and treatment (medical records, participant report) * Mini-Mental State Examination score (cognitive state) \<24 * Premorbid NAART IQ estimate\<85 * Visual disturbance: \<20/40 Snellen visual acuity * History of alcohol/substance use disorder (SUD; all substances, except nicotine), and/or illicit substance use (except cannabis) over the last 6 months (SCID-5). Note: lifetime/present cannabis use (at non-abuse (\<3 times in the past month) and non SUD levels) will be allowed, given its common usage in BD and young adults. Cannabis SUD over the last 6 months will not be allowed. Urine tests on scan days will exclude current illicit substance use (except cannabis). Salivary alcohol tests on scan days will exclude intoxicated individuals * Binge drinking in the week before, and/or \>3 units/day for the 3 days before, and/or alcohol in the last 12 hrs before, any TBS visit, confirmed at screening and scan days (to avoid TBS during alcohol withdrawal). Alcohol/nicotine/ caffeine/cannabis use (below SCID-5 SUD, binge levels) will be allowed, and used as covariates * MRI exclusion: metallic objects, e.g., surgical implants; claustrophobia; positive pregnancy test for females (at the MRRC) or self-report pregnancy \*Unable to understand English * Scoring greater than or equal to 8 on HRSD at screen visit and depressive episode is confirmed on SCID-5 * Scoring greater than or equal to 18 on HRSD at any study visit * Psychosis * Using psychotropic medications other than those allowed in inclusion criteria * Scoring greater than or equal to 38 on the YMRS at any study visit * Does not provide the contact information of a medical provider (including but not limited to a PCP) that we may communicate with for any concerns of escalating symptoms of mania
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Functional Connectivity Between dlPFC With Other CEN Regions | Change in magnitude of functional connectivity immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins) | The difference in functional connectivity (a measure of interactions between 2 brain regions) among dlPFC and other RNet regions from pre TBS to post TBS. Higher numbers indicate more functional connectivity after TBS, while lower numbers indicate less functional connectivity after TBS. |
| Brain Activity (Beta Power) in Right dlPFC | Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins) | The difference in brain activity (Beta power) in right dLPFC from pre TBS to post TBS. Higher numbers indicate more brain activity (Beta power) after TBS, while lower numbers indicate less brain activity (Beta power) after TBS. |
| Functional Connectivity Between Left and Right vLPFC | Change in magnitude of the functional connectivity immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins) | The difference in functional connectivity (a measure of interactions between 2 brain regions) among left and right vLPFC from preTBS to post TBS. Higher numbers indicate more functional connectivity after TBS, while lower numbers indicate less functional connectivity after TBS. |
| Functional Connectivity Between vLPFC and Other RNet Regions | Change in magnitude of functional connectivity immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins) | The difference in functional connectivity (a measure of interactions between 2 brain regions) among vLPFC and other RNet regions from pre TBS to post TBS. Higher numbers indicate more functional connectivity after TBS, while lower numbers indicate less functional connectivity after TBS. |
| Brain Activity (Beta Power) in Left vLPFC | Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins) | The difference in brain activity (Beta power) in left vLPFC from pre TBS to post TBS. Higher numbers indicate more brain activity after TBS, while lower numbers indicate less brain activity (Beta power) after TBS. |
| Brain Activity (Beta Power) in Right vLPFC | Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins) | The difference in brain activity (Beta power) in right vLPFC from pre TBS to post TBS. Higher numbers indicate more brain activity (Beta power) after TBS, while lower numbers indicate less brain activity (Beta power) after TBS. |
| Brain Activity (Beta Power) in Left dlPFC | Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins) | The difference in brain activity (Beta power) in left dLPFC from pre TBS to post TBS. Higher numbers indicate more brain activity (Beta power) after TBS, while lower numbers indicate less brain activity (Beta power) after TBS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Functional Connectivity Among Other RNet and CEN Regions | Change in magnitude of functional connectivity immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins) | The difference in functional connectivity (a measure of interactions between 2 brain regions) among other RNet and CEN regions from pre TBS to post TBS. Higher numbers indicate more functional connectivity after TBS, while lower numbers indicate less functional connectivity after TBS. |
| Immediate Choices Made on the Delay Discounting Task | 15-30 minutes | The sum (overall total) of the immediate choices (choosing to receive a small immediate reward) made on the delay discounting task |
| Brain Activity (Beta Power) in Other RNet and CEN Regions | Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins) | The difference in brain activity (Beta power) among other RNet and CEN regions from pre TBS to post TBS. Higher numbers indicate more brain activity (Beta power) after TBS, while lower numbers indicate less brain activity (Beta power) after TBS. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Left vLPFC cTBS/Right dlPFC iTBS/Left Som cTBS A random number sequence will be generated for randomization of the 3 EEG/TBS session order to which each participant is assigned:
left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex) right dlPFC iTBS (iTBS applied to the right dorsolateral prefrontal cortex) left Som cTBS (cTBS applied to the left somatosensory cortex) | 3 |
| Left vLPFC cTBS/Left Som cTBS/Right dlPFC iTBS A random number sequence will be generated for randomization of the 3 EEG/TBS session order to which each participant is assigned:
left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex) left Som cTBS (cTBS applied to the left somatosensory cortex) right dlPFC iTBS (iTBS applied to the right dorsolateral prefrontal cortex) | 2 |
| Left Som cTBS/Right dlPFC iTBS/Left vLPFC cTBS A random number sequence will be generated for randomization of the 3 EEG/TBS session order to which each participant is assigned:
left Som cTBS (cTBS applied to the left somatosensory cortex) right dlPFC iTBS (iTBS applied to the right dorsolateral prefrontal cortex) left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex) | 1 |
| Left Som cTBS/Left vLPFC cTBS/Right dlPFC iTBS A random number sequence will be generated for randomization of the 3 EEG/TBS session order to which each participant is assigned:
left Som cTBS (cTBS applied to the left somatosensory cortex) left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex) right dlPFC iTBS (iTBS applied to the right dorsolateral prefrontal cortex) | 2 |
| Right dlPFC iTBS/Left Som cTBS/Left vLPFC cTBS A random number sequence will be generated for randomization of the 3 EEG/TBS session order to which each participant is assigned:
right dlPFC iTBS (iTBS applied to the right dorsolateral prefrontal cortex) left Som cTBS (cTBS applied to the left somatosensory cortex) left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex) | 3 |
| Right dlPFC iTBS/Left vLPFC cTBS/Left Som cTBS A random number sequence will be generated for randomization of the 3 EEG/TBS session order to which each participant is assigned:
right dlPFC iTBS (iTBS applied to the right dorsolateral prefrontal cortex) left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex) left Som cTBS (cTBS applied to the left somatosensory cortex) | 2 |
| Total | 13 |
Baseline characteristics
| Characteristic | Left vLPFC cTBS/Right dlPFC iTBS/Left Som cTBS | Left vLPFC cTBS/Left Som cTBS/Right dlPFC iTBS | Left Som cTBS/Right dlPFC iTBS/Left vLPFC cTBS | Left Som cTBS/Left vLPFC cTBS/Right dlPFC iTBS | Right dlPFC iTBS/Left Som cTBS/Left vLPFC cTBS | Right dlPFC iTBS/Left vLPFC cTBS/Left Som cTBS | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 2 Participants | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 | 0 / 13 |
| other Total, other adverse events | 0 / 13 | 0 / 13 | 0 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 | 0 / 13 |
Outcome results
Primary
Brain Activity (Beta Power) in Left dlPFC
The difference in brain activity (Beta power) in left dLPFC from pre TBS to post TBS. Higher numbers indicate more brain activity (Beta power) after TBS, while lower numbers indicate less brain activity (Beta power) after TBS.
Time frame: Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
Population: Initially, 10 main outcome measures were stated based on the assumption that 25 participants with bipolar disorder (BD) would be recruited and all data (neuroimaging and behavioral) would be collected from at least 20 participants. However, all data was collected from only 12 BD participants. As such, to not jeopardize the power for the 10 main outcome measures, statistical analyses were performed on only 4 of the 10 outcome measures.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Left vLPFC cTBS | Brain Activity (Beta Power) in Left dlPFC | Delayed Choice (larger reward in the future) | 33.83 Percentage of change post versus pre | Standard Deviation 446.73 |
| Left vLPFC cTBS | Brain Activity (Beta Power) in Left dlPFC | Immediate Choice (small immediate reward) | 32.04 Percentage of change post versus pre | Standard Deviation 322.62 |
| Right dlPFC iTBS | Brain Activity (Beta Power) in Left dlPFC | Delayed Choice (larger reward in the future) | -286.13 Percentage of change post versus pre | Standard Deviation 628.89 |
| Right dlPFC iTBS | Brain Activity (Beta Power) in Left dlPFC | Immediate Choice (small immediate reward) | -182.53 Percentage of change post versus pre | Standard Deviation 494.97 |
| Left SS cTBS | Brain Activity (Beta Power) in Left dlPFC | Delayed Choice (larger reward in the future) | -623.68 Percentage of change post versus pre | Standard Deviation 1950.2 |
| Left SS cTBS | Brain Activity (Beta Power) in Left dlPFC | Immediate Choice (small immediate reward) | 99.64 Percentage of change post versus pre | Standard Deviation 512.78 |
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.75298499t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.16043787t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.67902693t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.33832977t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.67902693t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.33832977t-test, 2 sided
Primary
Brain Activity (Beta Power) in Left vLPFC
The difference in brain activity (Beta power) in left vLPFC from pre TBS to post TBS. Higher numbers indicate more brain activity after TBS, while lower numbers indicate less brain activity (Beta power) after TBS.
Time frame: Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
Population: One participant was excluded from the EEG data analysis due to lack of immediate choices on the delayed discounting task
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Left vLPFC cTBS | Brain Activity (Beta Power) in Left vLPFC | Delayed Choice (larger reward in the future) | -88.78 Percentage of change post versus pre | Standard Deviation 224.54 |
| Left vLPFC cTBS | Brain Activity (Beta Power) in Left vLPFC | Immediate Choice (small immediate reward) | -128.00 Percentage of change post versus pre | Standard Deviation 105.32 |
| Right dlPFC iTBS | Brain Activity (Beta Power) in Left vLPFC | Delayed Choice (larger reward in the future) | 1437.64 Percentage of change post versus pre | Standard Deviation 4411.75 |
| Right dlPFC iTBS | Brain Activity (Beta Power) in Left vLPFC | Immediate Choice (small immediate reward) | -612.44 Percentage of change post versus pre | Standard Deviation 1487.43 |
| Left SS cTBS | Brain Activity (Beta Power) in Left vLPFC | Delayed Choice (larger reward in the future) | 13.43 Percentage of change post versus pre | Standard Deviation 346.26 |
| Left SS cTBS | Brain Activity (Beta Power) in Left vLPFC | Immediate Choice (small immediate reward) | 89.70 Percentage of change post versus pre | Standard Deviation 940.52 |
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre).~One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.2938909t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre).~One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.97863544t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre).~One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.60236264t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre).~One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.35845126t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre).~One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.91766025t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delayed discounting task (post versus pre).~One participant was excluded from the EEG data analysis due to lack of immediate choices on the delayed discounting taskp-value: 0.09605169t-test, 2 sided
Primary
Brain Activity (Beta Power) in Right dlPFC
The difference in brain activity (Beta power) in right dLPFC from pre TBS to post TBS. Higher numbers indicate more brain activity (Beta power) after TBS, while lower numbers indicate less brain activity (Beta power) after TBS.
Time frame: Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
Population: One participant was excluded from the EEG data analysis due to lack of immediate choices on the delayed discounting task
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Left vLPFC cTBS | Brain Activity (Beta Power) in Right dlPFC | Delayed Choice (larger reward in the future) | -74.21 Percentage of change post versus pre | Standard Deviation 104.49 |
| Left vLPFC cTBS | Brain Activity (Beta Power) in Right dlPFC | Immediate Choice (small immediate reward) | -128.27 Percentage of change post versus pre | Standard Deviation 363.79 |
| Right dlPFC iTBS | Brain Activity (Beta Power) in Right dlPFC | Delayed Choice (larger reward in the future) | -83.74 Percentage of change post versus pre | Standard Deviation 2072.87 |
| Right dlPFC iTBS | Brain Activity (Beta Power) in Right dlPFC | Immediate Choice (small immediate reward) | -70.27 Percentage of change post versus pre | Standard Deviation 520.4 |
| Left SS cTBS | Brain Activity (Beta Power) in Right dlPFC | Delayed Choice (larger reward in the future) | -398.00 Percentage of change post versus pre | Standard Deviation 1039.5 |
| Left SS cTBS | Brain Activity (Beta Power) in Right dlPFC | Immediate Choice (small immediate reward) | -383.76 Percentage of change post versus pre | Standard Deviation 849.28 |
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre).~One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.73357221t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre).~One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.43954526t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre).~One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.4419898t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre).~One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.39565784t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre).~One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.35602382t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre).~One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.30499144t-test, 2 sided
Primary
Brain Activity (Beta Power) in Right vLPFC
The difference in brain activity (Beta power) in right vLPFC from pre TBS to post TBS. Higher numbers indicate more brain activity (Beta power) after TBS, while lower numbers indicate less brain activity (Beta power) after TBS.
Time frame: Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
Population: Initially, 10 main outcome measures were stated based on the assumption that 25 participants with bipolar disorder (BD) would be recruited and all data (neuroimaging and behavioral) would be collected from at least 20 participants. However, all data was collected from only 12 BD participants. As such, to not jeopardize the power for the 10 main outcome measures, statistical analyses were performed on only 4 of the 10 outcome measures.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Left vLPFC cTBS | Brain Activity (Beta Power) in Right vLPFC | Delayed Choice (larger reward in the future) | -162.37 Percentage of change post versus pre | Standard Deviation 799 |
| Left vLPFC cTBS | Brain Activity (Beta Power) in Right vLPFC | Immediate Choice (small immediate reward) | 131.99 Percentage of change post versus pre | Standard Deviation 409.07 |
| Right dlPFC iTBS | Brain Activity (Beta Power) in Right vLPFC | Delayed Choice (larger reward in the future) | 5.13 Percentage of change post versus pre | Standard Deviation 312.18 |
| Right dlPFC iTBS | Brain Activity (Beta Power) in Right vLPFC | Immediate Choice (small immediate reward) | -136.62 Percentage of change post versus pre | Standard Deviation 702.68 |
| Left SS cTBS | Brain Activity (Beta Power) in Right vLPFC | Delayed Choice (larger reward in the future) | -498.71 Percentage of change post versus pre | Standard Deviation 1022 |
| Left SS cTBS | Brain Activity (Beta Power) in Right vLPFC | Immediate Choice (small immediate reward) | -117.6 Percentage of change post versus pre | Standard Deviation 893.74 |
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.50030946t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.3751738t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.47876971t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.21798816t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.47876971t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.21798816t-test, 2 sided
Primary
Functional Connectivity Between dlPFC With Other CEN Regions
The difference in functional connectivity (a measure of interactions between 2 brain regions) among dlPFC and other RNet regions from pre TBS to post TBS. Higher numbers indicate more functional connectivity after TBS, while lower numbers indicate less functional connectivity after TBS.
Time frame: Change in magnitude of functional connectivity immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
Population: Initially, 10 main outcome measures were stated based on the assumption that 25 participants with bipolar disorder (BD) would be recruited and all data (neuroimaging and behavioral) would be collected from at least 20 participants. However, all data was collected from only 12 BD participants. As such, to not jeopardize the power for the 10 main outcome measures, statistical analyses were performed on only 4 of the 10 outcome measures.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Left vLPFC cTBS | Functional Connectivity Between dlPFC With Other CEN Regions | Delayed Choice (larger reward in the future) | 2.43 Percentage of change post versus pre | Standard Deviation 5.64 |
| Left vLPFC cTBS | Functional Connectivity Between dlPFC With Other CEN Regions | Immediate Choice (small immediate reward) | -0.41 Percentage of change post versus pre | Standard Deviation 4.47 |
| Right dlPFC iTBS | Functional Connectivity Between dlPFC With Other CEN Regions | Delayed Choice (larger reward in the future) | 2.03 Percentage of change post versus pre | Standard Deviation 5.81 |
| Right dlPFC iTBS | Functional Connectivity Between dlPFC With Other CEN Regions | Immediate Choice (small immediate reward) | 3.86 Percentage of change post versus pre | Standard Deviation 6.18 |
| Left SS cTBS | Functional Connectivity Between dlPFC With Other CEN Regions | Delayed Choice (larger reward in the future) | 1.13 Percentage of change post versus pre | Standard Deviation 6.16 |
| Left SS cTBS | Functional Connectivity Between dlPFC With Other CEN Regions | Immediate Choice (small immediate reward) | 1.44 Percentage of change post versus pre | Standard Deviation 6.17 |
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.20047055t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.77922802t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.29196708t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.05605962t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.57368284t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.56397238t-test, 2 sided
Primary
Functional Connectivity Between Left and Right vLPFC
The difference in functional connectivity (a measure of interactions between 2 brain regions) among left and right vLPFC from preTBS to post TBS. Higher numbers indicate more functional connectivity after TBS, while lower numbers indicate less functional connectivity after TBS.
Time frame: Change in magnitude of the functional connectivity immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
Population: Initially, 10 main outcome measures were stated based on the assumption that 25 participants with bipolar disorder (BD) would be recruited and all data (neuroimaging and behavioral) would be collected from at least 20 participants. However, all data was collected from only 12 BD participants. As such, to not jeopardize the power for the 10 main outcome measures, statistical analyses were performed on only 4 of the 10 outcome measures.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Left vLPFC cTBS | Functional Connectivity Between Left and Right vLPFC | Immediate Choice (small immediate reward) | 3.26 Percentage of change post versus pre | Standard Deviation 8.36 |
| Left vLPFC cTBS | Functional Connectivity Between Left and Right vLPFC | Delayed Choice (larger reward in the future) | -0.34 Percentage of change post versus pre | Standard Deviation 5.1 |
| Right dlPFC iTBS | Functional Connectivity Between Left and Right vLPFC | Immediate Choice (small immediate reward) | -1.28 Percentage of change post versus pre | Standard Deviation 6.19 |
| Right dlPFC iTBS | Functional Connectivity Between Left and Right vLPFC | Delayed Choice (larger reward in the future) | -1.84 Percentage of change post versus pre | Standard Deviation 4.92 |
| Left SS cTBS | Functional Connectivity Between Left and Right vLPFC | Immediate Choice (small immediate reward) | 1.07 Percentage of change post versus pre | Standard Deviation 4.16 |
| Left SS cTBS | Functional Connectivity Between Left and Right vLPFC | Delayed Choice (larger reward in the future) | 0.36 Percentage of change post versus pre | Standard Deviation 3.37 |
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.81601415t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.20563452t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.21947623t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.45535329t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.21947623t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.45535329t-test, 2 sided
Primary
Functional Connectivity Between vLPFC and Other RNet Regions
The difference in functional connectivity (a measure of interactions between 2 brain regions) among vLPFC and other RNet regions from pre TBS to post TBS. Higher numbers indicate more functional connectivity after TBS, while lower numbers indicate less functional connectivity after TBS.
Time frame: Change in magnitude of functional connectivity immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
Population: One participant was excluded from the EEG data analysis due to lack of immediate choices on the delayed discounting task
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Left vLPFC cTBS | Functional Connectivity Between vLPFC and Other RNet Regions | Delayed Choice (larger reward in the future) | 0.52 Percentage of change post versus pre | Standard Deviation 6.68 |
| Left vLPFC cTBS | Functional Connectivity Between vLPFC and Other RNet Regions | Immediate Choice (small immediate reward) | 3.50 Percentage of change post versus pre | Standard Deviation 8.29 |
| Right dlPFC iTBS | Functional Connectivity Between vLPFC and Other RNet Regions | Delayed Choice (larger reward in the future) | -1.03 Percentage of change post versus pre | Standard Deviation 7.97 |
| Right dlPFC iTBS | Functional Connectivity Between vLPFC and Other RNet Regions | Immediate Choice (small immediate reward) | 0.69 Percentage of change post versus pre | Standard Deviation 5.91 |
| Left SS cTBS | Functional Connectivity Between vLPFC and Other RNet Regions | Delayed Choice (larger reward in the future) | -0.38 Percentage of change post versus pre | Standard Deviation 4.99 |
| Left SS cTBS | Functional Connectivity Between vLPFC and Other RNet Regions | Immediate Choice (small immediate reward) | 7.03 Percentage of change post versus pre | Standard Deviation 7.58 |
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre).~One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.83462055t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre).~One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.21582586t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre).~One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.59574875t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre).~One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.75948776t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre).~One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.7238414t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre).~One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.00477281t-test, 2 sided
Secondary
Brain Activity (Beta Power) in Other RNet and CEN Regions
The difference in brain activity (Beta power) among other RNet and CEN regions from pre TBS to post TBS. Higher numbers indicate more brain activity (Beta power) after TBS, while lower numbers indicate less brain activity (Beta power) after TBS.
Time frame: Change in magnitude of brain activity (Beta power) immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
Population: Initially, 10 main outcome measures were stated based on the assumption that 25 participants with bipolar disorder (BD) would be recruited and all data (neuroimaging and behavioral) would be collected from at least 20 participants. However, all data was collected from only 12 BD participants. As such, to not jeopardize the power for the 10 main outcome measures, statistical analyses were performed on only 4 of the 10 outcome measures.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Left vLPFC cTBS | Brain Activity (Beta Power) in Other RNet and CEN Regions | Delayed Choice (larger reward in the future)(dorsal anterior cingulate cortex) | 248.65 Percentage of change post versus pre | Standard Deviation 647.87 |
| Left vLPFC cTBS | Brain Activity (Beta Power) in Other RNet and CEN Regions | Immediate Choice (small immediate reward) (dorsal anterior cingulate cortex) | -45.54 Percentage of change post versus pre | Standard Deviation 235.51 |
| Left vLPFC cTBS | Brain Activity (Beta Power) in Other RNet and CEN Regions | Delayed Choice (larger reward in the future) (posterior parietal cortex) | -77.80 Percentage of change post versus pre | Standard Deviation 330.51 |
| Left vLPFC cTBS | Brain Activity (Beta Power) in Other RNet and CEN Regions | Immediate Choice (small immediate reward) (posterior parietal cortex) | -3.29 Percentage of change post versus pre | Standard Deviation 65.09 |
| Right dlPFC iTBS | Brain Activity (Beta Power) in Other RNet and CEN Regions | Immediate Choice (small immediate reward) (posterior parietal cortex) | -89.97 Percentage of change post versus pre | Standard Deviation 266.2 |
| Right dlPFC iTBS | Brain Activity (Beta Power) in Other RNet and CEN Regions | Delayed Choice (larger reward in the future)(dorsal anterior cingulate cortex) | -55.98 Percentage of change post versus pre | Standard Deviation 124.11 |
| Right dlPFC iTBS | Brain Activity (Beta Power) in Other RNet and CEN Regions | Delayed Choice (larger reward in the future) (posterior parietal cortex) | 40.06 Percentage of change post versus pre | Standard Deviation 217.51 |
| Right dlPFC iTBS | Brain Activity (Beta Power) in Other RNet and CEN Regions | Immediate Choice (small immediate reward) (dorsal anterior cingulate cortex) | -352.34 Percentage of change post versus pre | Standard Deviation 1075.2 |
| Left SS cTBS | Brain Activity (Beta Power) in Other RNet and CEN Regions | Immediate Choice (small immediate reward) (posterior parietal cortex) | -156.72 Percentage of change post versus pre | Standard Deviation 289.48 |
| Left SS cTBS | Brain Activity (Beta Power) in Other RNet and CEN Regions | Immediate Choice (small immediate reward) (dorsal anterior cingulate cortex) | 928.72 Percentage of change post versus pre | Standard Deviation 2473.59 |
| Left SS cTBS | Brain Activity (Beta Power) in Other RNet and CEN Regions | Delayed Choice (larger reward in the future) (posterior parietal cortex) | 142.64 Percentage of change post versus pre | Standard Deviation 444.57 |
| Left SS cTBS | Brain Activity (Beta Power) in Other RNet and CEN Regions | Delayed Choice (larger reward in the future)(dorsal anterior cingulate cortex) | 41.73 Percentage of change post versus pre | Standard Deviation 335.39 |
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre) (dorsal anterior cingulate cortex). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.86107891t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre) (dorsal anterior cingulate cortex). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.62228799t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre) (dorsal anterior cingulate cortex). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.79477883t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre) (dorsal anterior cingulate cortex). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.12634435t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre) (dorsal anterior cingulate cortex). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.79477883t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre) (dorsal anterior cingulate cortex). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.12634435t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre) (posterior parietal cortex). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.62461968t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre) (posterior parietal cortex). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.51324793t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre) (posterior parietal cortex). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.60543603t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre) (posterior parietal cortex). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.75565448t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre) (posterior parietal cortex). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.60543603t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre) (posterior parietal cortex). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.75565448t-test, 2 sided
Secondary
Functional Connectivity Among Other RNet and CEN Regions
The difference in functional connectivity (a measure of interactions between 2 brain regions) among other RNet and CEN regions from pre TBS to post TBS. Higher numbers indicate more functional connectivity after TBS, while lower numbers indicate less functional connectivity after TBS.
Time frame: Change in magnitude of functional connectivity immediately before and immediately after each TBS condition at EEG/TBS visits (15-30 mins)
Population: Initially, 10 main outcome measures were stated based on the assumption that 25 participants with bipolar disorder (BD) would be recruited and all data (neuroimaging and behavioral) would be collected from at least 20 participants. However, all data was collected from only 12 BD participants. As such, to not jeopardize the power for the 10 main outcome measures, statistical analyses were performed on only 4 of the 10 outcome measures.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Left vLPFC cTBS | Functional Connectivity Among Other RNet and CEN Regions | Delayed Choice (larger reward in the future)(Left vLPFC and Posterior Parietal Cortex) | 2.45 Percentage of change post versus pre | Standard Deviation 4.33 |
| Left vLPFC cTBS | Functional Connectivity Among Other RNet and CEN Regions | Immediate Choice (small immediate reward) (Left vLPFC and Posterior Parietal Cortex) | 2.33 Percentage of change post versus pre | Standard Deviation 9.95 |
| Right dlPFC iTBS | Functional Connectivity Among Other RNet and CEN Regions | Delayed Choice (larger reward in the future)(Left vLPFC and Posterior Parietal Cortex) | -2.10 Percentage of change post versus pre | Standard Deviation 7.23 |
| Right dlPFC iTBS | Functional Connectivity Among Other RNet and CEN Regions | Immediate Choice (small immediate reward) (Left vLPFC and Posterior Parietal Cortex) | 3.83 Percentage of change post versus pre | Standard Deviation 13.52 |
| Left SS cTBS | Functional Connectivity Among Other RNet and CEN Regions | Delayed Choice (larger reward in the future)(Left vLPFC and Posterior Parietal Cortex) | 1.18 Percentage of change post versus pre | Standard Deviation 4.97 |
| Left SS cTBS | Functional Connectivity Among Other RNet and CEN Regions | Immediate Choice (small immediate reward) (Left vLPFC and Posterior Parietal Cortex) | 1.27 Percentage of change post versus pre | Standard Deviation 7.24 |
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.09266386t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.53980185t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.30223686t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.39166649t-test, 2 sided
Comparison: Paired t-test examining delayed choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.30223686t-test, 2 sided
Comparison: Paired t-test examining immediate choices on the delay discounting task (post versus pre). One participant was excluded from the EEG data analysis due to lack of immediate choices on the delay discounting taskp-value: 0.39166649t-test, 2 sided
Secondary
Immediate Choices Made on the Delay Discounting Task
The sum (overall total) of the immediate choices (choosing to receive a small immediate reward) made on the delay discounting task
Time frame: 15-30 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Left vLPFC cTBS | Immediate Choices Made on the Delay Discounting Task | -18.47 percentage of immediate choices changes | Standard Deviation 29.74 |
| Right dlPFC iTBS | Immediate Choices Made on the Delay Discounting Task | -9.78 percentage of immediate choices changes | Standard Deviation 29.74 |
| Left SS cTBS | Immediate Choices Made on the Delay Discounting Task | -26.28 percentage of immediate choices changes | Standard Deviation 27.38 |
Comparison: Paired t-test (post versus pre)p-value: 0.0265t-test, 2 sided
Comparison: Paired t-test (post versus pre)p-value: 0.1053t-test, 2 sided
Comparison: Paired t-test (post versus pre)p-value: 0.0033t-test, 2 sided