Effects of Theta Burst Stimulation on the Brain, Behavior, and Clinical Symptoms in Adults With Bipolar Disorder

Study Overview
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Brief Summary
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Bipolar Disorder (BD) is a common and highly debilitating psychiatric disorder, however, the predisposing brain mechanisms are poorly understood. Here, the investigators aim to examine the immediate effect of transcranial brain stimulation (TBS) on brain activity and emotions in adults with and without BD as a first stage toward understanding the predisposing brain mechanisms of BD. The investigators hypothesize that TBS will reduce brain activity while playing a game with rewards in all adults, but the TBS will reduce brain activity more in the adults with BD compared to adults without BD. Furthermore, the investigators hypothesize that this reduced brain activity will be associated with reduced BD symptoms, such as negative emotions.

Detailed Description
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This study aims to examine the effects of noninvasive stimulation on brain activity as measured by functional magnetic resonance imaging (fMRI) in participants with and without Bipolar I Disorder. Eligible participants will undergo 5 study visits: a screening visit, a baseline MRI visit, and 3 cTBS visits. Participants will receive brain stimulation and undergo fMRI scanning at each of the 3 cTBS study visits, however, at one of the visits, the brain stimulation will be a sham. The research associates and participants will be blinded to when the sham occurs, which will be randomized beforehand. Certain information is withheld to protect the scientific integrity of the study design

Official Title
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Elucidating Neural Mechanisms of Hypo/Mania Using Theta Burst Stimulation

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Device: Continuous Theta Burst Stimulation (cTBS)
* Device: Sham Continuous Theta Burst Stimulation (Sham cTBS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All participants 18-35 years of age Scoring less than or equal to 8 on the Hamilton Rating Scale for Depression (HRSD) at screen visit Participants with Bipolar Disorder (BD) Diagnosis of Bipolar Disorder I/II (BDI/II) (DSM-5 criteria) in remission (euthymic for >2 months) or with mild-moderate hypomania <15 on the Young Mania Rating Scale Not psychotic <3 on delusions, hallucinations, unusual thought content, and conceptual disorganization items of the Positive and Negative Syndrome Scale (PANSS) Unmedicated or on any combination (except antidepressant monotherapy) 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 taken for >2 months, as these are commonly-prescribed medications for BD Participants without Bipolar Disorder No present or lifetime history of BD or psychiatric disorder other than anxiety or non BD mood disorders Not in a current depressive episode No family history of BD Exclusion Criteria: All participants History of head injury, neurological, pervasive developmental disorder (e.g. autism), systemic medical disease and treatment (medical records, participant report) Family history of epilepsy (TBS exclusion criterion) Use of substances with seizure risk (e.g., stimulants) in the past month, assessed as at screening, baseline, and before each fMRI-cTBS-fMRI session Mini-Mental State Examination score (cognitive state) <24 Premorbid National Adult Reading Test Intelligent Quotient estimate<85 Visual disturbance: <20/40 Snellen visual acuity Left/mixed handedness History of alcohol/substance use disorder (SUD; all substances, including 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 cTBS scan day, 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 criteria: metallic objects, e.g., surgical implants; claustrophobia; proneness; positive pregnancy test for females (performed at the MRRC) or self-report pregnancy Inability to understand English <18 years of age or >35 year of age SNRI antidepressants and bupropion will not be allowed, as they can elevate seizure risk, a contraindication for TBS Scoring greater than or equal to 8 on HRSD and in depressive episode is confirmed on SCID-5 at screen visit Scoring greater than or equal to 18 on HRSD at any visit In current depressive episode Participants with Bipolar Disorder BD diagnosis other than BDI/II More severe hypo/mania (YMRS>15) Psychosis Using psychotropic medications other than those allowed in inclusion criteria Participants without Bipolar Disorder Present/ lifetime history of any psychiatric disorder other than anxiety and non BD mood disorders Family history of of BD

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Left ventrolateral prefrontal cortex (vlPFC)/Left SS/Left vlPFC sham<br>A random number sequence will be generated for randomization of the 3 cTBS scan session order to which each participant is assigned: left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex) left SS cTBS (cTBS applied to the left somatosensory area) left vlPFC sham TBS (go through the motions of applying cTBS to the left ventrolateral prefrontal cortex but very low current is administered so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells) Participants will know that one session will be a sham, but they will be blinded to which session is the sham. | Device: Continuous Theta Burst Stimulation (cTBS)<br>* cTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely. 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<br>* Other names: Transcranial Magnetic Stimulation (TMS);Device: Sham Continuous Theta Burst Stimulation (Sham cTBS)<br>* Sham cTBS goes through the motions of applying cTBS to the brain but administers very low current so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells. Participants will know that one session will be a sham, but they will be blinded to which session is the sham<br>* Other names: Sham Transcranial Magnetic Stimulation (Sham TMS);|
| Experimental: Left vlPFC/Left vlPFC sham/Left SS<br>A random number sequence will be generated for randomization of the 3 cTBS scan session order to which each participant is assigned: left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex) left SS cTBS (cTBS applied to the left somatosensory area) left vlPFC sham TBS (go through the motions of applying cTBS to the left ventrolateral prefrontal cortex but very low current is administered so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells) Participants will know that one session will be a sham, but they will be blinded to which session is the sham. | Device: Continuous Theta Burst Stimulation (cTBS)<br>* cTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely. 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<br>* Other names: Transcranial Magnetic Stimulation (TMS);Device: Sham Continuous Theta Burst Stimulation (Sham cTBS)<br>* Sham cTBS goes through the motions of applying cTBS to the brain but administers very low current so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells. Participants will know that one session will be a sham, but they will be blinded to which session is the sham<br>* Other names: Sham Transcranial Magnetic Stimulation (Sham TMS);|
| Experimental: Left SS/Left vlPFC sham/Left vlPFC<br>A random number sequence will be generated for randomization of the 3 cTBS scan session order to which each participant is assigned: left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex) left SS cTBS (cTBS applied to the left somatosensory area) left vlPFC sham TBS (go through the motions of applying cTBS to the left ventrolateral prefrontal cortex but very low current is administered so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells) Participants will know that one session will be a sham, but they will be blinded to which session is the sham. | Device: Continuous Theta Burst Stimulation (cTBS)<br>* cTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely. 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<br>* Other names: Transcranial Magnetic Stimulation (TMS);Device: Sham Continuous Theta Burst Stimulation (Sham cTBS)<br>* Sham cTBS goes through the motions of applying cTBS to the brain but administers very low current so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells. Participants will know that one session will be a sham, but they will be blinded to which session is the sham<br>* Other names: Sham Transcranial Magnetic Stimulation (Sham TMS);|
| Experimental: Left SS/Left vlPFC/Left vlPFC sham<br>A random number sequence will be generated for randomization of the 3 cTBS scan session order to which each participant is assigned: left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex) left SS cTBS (cTBS applied to the left somatosensory area) left vlPFC sham TBS (go through the motions of applying cTBS to the left ventrolateral prefrontal cortex but very low current is administered so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells) Participants will know that one session will be a sham, but they will be blinded to which session is the sham. | Device: Continuous Theta Burst Stimulation (cTBS)<br>* cTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely. 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<br>* Other names: Transcranial Magnetic Stimulation (TMS);Device: Sham Continuous Theta Burst Stimulation (Sham cTBS)<br>* Sham cTBS goes through the motions of applying cTBS to the brain but administers very low current so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells. Participants will know that one session will be a sham, but they will be blinded to which session is the sham<br>* Other names: Sham Transcranial Magnetic Stimulation (Sham TMS);|
| Experimental: Left vlPFC sham/Left SS/Left vlPFC<br>A random number sequence will be generated for randomization of the 3 cTBS scan session order to which each participant is assigned: left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex) left SS cTBS (cTBS applied to the left somatosensory area) left vlPFC sham TBS (go through the motions of applying cTBS to the left ventrolateral prefrontal cortex but very low current is administered so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells) Participants will know that one session will be a sham, but they will be blinded to which session is the sham. | Device: Continuous Theta Burst Stimulation (cTBS)<br>* cTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely. 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<br>* Other names: Transcranial Magnetic Stimulation (TMS);Device: Sham Continuous Theta Burst Stimulation (Sham cTBS)<br>* Sham cTBS goes through the motions of applying cTBS to the brain but administers very low current so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells. Participants will know that one session will be a sham, but they will be blinded to which session is the sham<br>* Other names: Sham Transcranial Magnetic Stimulation (Sham TMS);|
| Experimental: Left vlPFC sham/Left vlPFC/Left SS<br>A random number sequence will be generated for randomization of the 3 cTBS scan session order to which each participant is assigned: left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex) left SS cTBS (cTBS applied to the left somatosensory area) left vlPFC sham TBS (go through the motions of applying cTBS to the left ventrolateral prefrontal cortex but very low current is administered so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells) Participants will know that one session will be a sham, but they will be blinded to which session is the sham. | Device: Continuous Theta Burst Stimulation (cTBS)<br>* cTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely. 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<br>* Other names: Transcranial Magnetic Stimulation (TMS);Device: Sham Continuous Theta Burst Stimulation (Sham cTBS)<br>* Sham cTBS goes through the motions of applying cTBS to the brain but administers very low current so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells. Participants will know that one session will be a sham, but they will be blinded to which session is the sham<br>* Other names: Sham Transcranial Magnetic Stimulation (Sham TMS);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reward expectancy-related left ventrolateral prefrontal cortex activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted blood oxygen level-dependent (BOLD) signal from the left ventrolateral prefrontal cortex to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Reward expectancy-related right ventrolateral prefrontal cortex activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the right ventrolateral prefrontal cortex to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Reward expectancy-related left ventral striatum activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the left ventral striatum to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Reward expectancy-related right ventral striatum activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the left ventral striatum to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Reward expectancy-related left orbitofrontal cortex activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the left orbitofrontal cortex to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Reward expectancy-related right orbitofrontal cortex activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the left orbitofrontal cortex to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Reward expectancy-related midline rostral anterior cingulate cortex (rACC) activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the midline rostral anterior cingulate cortex (rACC) to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Reward expectancy-related midline dorsal anterior cingulate cortex activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the midline dorsal anterior cingulate cortex to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Reward expectancy-related left amygdala activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the left amygdala to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Reward expectancy-related right amygdala activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal from the left amygdala to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Reward expectancy-related left ventrolateral prefrontal cortex-right ventrolateral prefrontal cortex functional connectivity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left and right ventrolateral prefrontal cortices to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Reward expectancy-related left ventrolateral prefrontal cortex-left ventral striatum functional connectivity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and left ventral striatum to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Reward expectancy-related left ventrolateral prefrontal cortex-right ventral striatum functional connectivity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and right ventral striatum to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Reward expectancy-related left ventrolateral prefrontal cortex-left orbitofrontal cortex functional connectivity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and left orbitofrontal cortex to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Reward expectancy-related left ventrolateral prefrontal cortex-right orbitofrontal cortex functional connectivity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and right orbitofrontal cortex to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Reward expectancy-related left ventrolateral prefrontal cortex-midline rostral anterior cingulate cortex functional connectivity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and midline rACC to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Reward expectancy-related left ventrolateral prefrontal cortex-midline dorsal anterior cingulate cortex functional connectivity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and midline dorsal anterior cingulate cortex to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Reward expectancy-related left ventrolateral prefrontal cortex-left amygdala functional connectivity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and left amygdala to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Reward expectancy-related left ventrolateral prefrontal cortex-right amygdala functional connectivity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and right amygdala to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reward expectancy-related left ventrolateral prefrontal cortex wholebrain functional connectivity | The difference in magnitude between pre and post cTBS for each cTBS condition of the extracted parameter estimate for functional connectivity between the left ventrolateral prefrontal cortex and the whole brain to the uncertain reward expectancy regressor during performance of the reward task | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Left ventrolateral prefrontal cortex activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the left ventrolateral prefrontal cortex to the contrast of possible win vs. neutral control conditions | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Right ventrolateral prefrontal cortex activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the right ventrolateral prefrontal cortex to the contrast of possible win vs. neutral control conditions | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Left ventral striatum activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the left ventral striatum to the contrast of possible win vs. neutral control conditions | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Right ventral striatum activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the right ventral striatum to the contrast of possible win vs. neutral control conditions | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Left orbitofrontal cortex activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the left orbitofrontal cortex to the contrast of possible win vs. neutral control conditions | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Right orbitofrontal cortex activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the right orbitofrontal cortex to the contrast of possible win vs. neutral control conditions | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Midline rostral anterior cingulate cortex activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the midline rostral anterior cingulate cortex to the contrast of possible win vs. neutral control conditions | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Midline dorsal anterior cingulate cortex activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the midline dorsal anterior cingulate cortex to the contrast of possible win vs. neutral control conditions | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Left amygdala activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the left amygdala to the contrast of possible win vs. neutral control conditions | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Right amygdala activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the right amygdala to the contrast of possible win vs. neutral control conditions | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Left ventral lateral prefrontal cortex-wholebrain functional connectivity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimates of functional connectivity between the left ventrolateral prefrontal cortex and the wholebrain to the contrast of possible win vs. neutral control conditions | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Prediction error-related left ventral striatum activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the left ventral striatum to the prediction error regressor | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Prediction error-related right ventral striatum activity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted BOLD signal in the right ventral striatum to the prediction error regressor | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Prediction error-related left ventral striatum-wholebrain functional connectivity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimates of resting state functional connectivity between the left ventral striatum and the wholebrian to the prediction error regressor | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 
| Prediction error-related right ventral striatum-wholebrain functional connectivity | The difference in magnitude between pre and post cTBS scans for each cTBS condition of the extracted parameter estimates of resting state functional connectivity between the right ventral striatum and the wholebrain | Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar Disorder, Magnetic Resonance Imaging, Transcranial Magnetic Stimulation