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

January 15, 2026 updated by: Mary Phillips, MD MD (Cantab)

Elucidating Neural Mechanisms of Hypo/Mania Using Theta Burst Stimulation

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
146

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Simona Graur, MSW, LCSW
  • Phone Number: 412-256-8693
  • Email: impres@upmc.edu

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 35 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. 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

  2. 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

  3. 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:

  1. 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

  2. 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

  3. Participants without Bipolar Disorder

    • Present/ lifetime history of any psychiatric disorder other than anxiety and non BD mood disorders
    • Family history of of BD

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Left ventrolateral prefrontal cortex (vlPFC)/Left SS/Left vlPFC sham

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)
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
Other Names:
  • Transcranial Magnetic Stimulation (TMS)
Device: Sham Continuous Theta Burst Stimulation (Sham cTBS)
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
Other Names:
  • Sham Transcranial Magnetic Stimulation (Sham TMS)
Experimental: Left vlPFC/Left vlPFC sham/Left SS

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)
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
Other Names:
  • Transcranial Magnetic Stimulation (TMS)
Device: Sham Continuous Theta Burst Stimulation (Sham cTBS)
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
Other Names:
  • Sham Transcranial Magnetic Stimulation (Sham TMS)
Experimental: Left SS/Left vlPFC sham/Left vlPFC

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)
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
Other Names:
  • Transcranial Magnetic Stimulation (TMS)
Device: Sham Continuous Theta Burst Stimulation (Sham cTBS)
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
Other Names:
  • Sham Transcranial Magnetic Stimulation (Sham TMS)
Experimental: Left SS/Left vlPFC/Left vlPFC sham

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)
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
Other Names:
  • Transcranial Magnetic Stimulation (TMS)
Device: Sham Continuous Theta Burst Stimulation (Sham cTBS)
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
Other Names:
  • Sham Transcranial Magnetic Stimulation (Sham TMS)
Experimental: Left vlPFC sham/Left SS/Left vlPFC

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)
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
Other Names:
  • Transcranial Magnetic Stimulation (TMS)
Device: Sham Continuous Theta Burst Stimulation (Sham cTBS)
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
Other Names:
  • Sham Transcranial Magnetic Stimulation (Sham TMS)
Experimental: Left vlPFC sham/Left vlPFC/Left SS

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)
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
Other Names:
  • Transcranial Magnetic Stimulation (TMS)
Device: Sham Continuous Theta Burst Stimulation (Sham cTBS)
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
Other Names:
  • Sham Transcranial Magnetic Stimulation (Sham TMS)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Reward expectancy-related left ventrolateral prefrontal cortex activity
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Reward expectancy-related left ventrolateral prefrontal cortex wholebrain functional connectivity
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Left ventrolateral prefrontal cortex-wholebrain resting state functional connectivity
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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 ventrolateral prefrontal cortex and the wholebrain
Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Left ventrolateral prefrontal cortex-right ventrolateral prefrontal cortex resting state functional connectivity
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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 and right ventrolateral prefrontal cortices
Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Left ventrolateral prefrontal cortex-left ventral striatum resting state functional connectivity
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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 ventrolateral prefrontal cortex and the left ventral striatum
Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Left ventrolateral prefrontal cortex-right ventral striatum resting state functional connectivity
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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 ventrolateral prefrontal cortex and the right ventral striatum
Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Left ventrolateral prefrontal cortex-left orbitofrontal cortex resting state functional connectivity
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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 ventrolateral prefrontal cortex and the left orbitofrontal cortex
Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Left ventrolateral prefrontal cortex-right orbitofrontal cortex resting state functional connectivity
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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 ventrolateral prefrontal cortex and the right orbitofrontal cortex
Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Left ventrolateral prefrontal cortex-midline rostral anterior cingulate cortex resting state functional connectivity
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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 ventrolateral prefrontal cortex and the midline rostral anterior cingulate cortex
Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Left ventrolateral prefrontal cortex-midline dorsal anterior cingulate cortex resting state functional connectivity
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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 ventrolateral prefrontal cortex and the midline dorsal anterior cingulate cortex
Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Left ventrolateral prefrontal cortex-left amygdala resting state functional connectivity
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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 ventrolateral prefrontal cortex and the left amygdala
Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
Left ventrolateral prefrontal cortex-right amygdala resting state functional connectivity
Time Frame: Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)
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 ventrolateral prefrontal cortex and the right amygdala
Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mary Phillips, MD MD (Cantab)

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Mental Health (NIMH)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mary Phillips, MD, MD, University of Pittsburgh
  • Principal Investigator: Fabio Ferrarelli, MD, PhD, University of Pittsburgh

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 6, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 24, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 24, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 18, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 4, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 6, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 20, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 15, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STUDY20060322
  • R01MH122990 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The investigators will complete and submit a National Data Archive (NDA) Data Sharing Agreement within 6 months of the Notice of Award Issue date. Study staff will upload data dictionary to the NDA website, and will review the NDA data definition for the measures collected and define the project's data definition harmonized to that standard. For measures not yet defined, project staff will work with the NDA staff to define the measure following NDA best practices. Informed consent will be collected from study participants that allows for broad sharing of participants' de-identified data. Study staff will use participants' personally identifiable information to generate NDA Global Unique Identifier (GUID) numbers for study participants.

All data will be identified by GUID numbers only prior to submission to the NDA database. Data transfer procedures will be in accordance with all Institutional Review Board guidelines and federal regulations including HIPAA.

IPD Sharing Time Frame

Raw data and data from descriptive/raw measures will be submitted on a semi-annual basis by July 15 and January 15 or the next business day. We also agree to submit to NDA the analyzed data yielded in our project (i.e., 12 months after accomplishment of each primary aim or objective, or immediately upon publication of the project's primary results, whichever occurs first). The PIs reserve the right to publish on the stated aims in a timely manner during the period of the award. Data will be available for addressing other research questions (i.e. which are not described in funded/pending grants) as soon as the data have been checked for accuracy (a period which will be no later than one year after the completion of each assessment). After the award has ended, the study investigators will continue to test the stated aims, but will also continue to solicit collaborations with outside researchers and to consider data requests in a timely manner.

IPD Sharing Access Criteria

Outside investigators must submit a 1)proposal of the study aims, hypotheses, variables/constructs, analytic approach, and estimated duration of the proposed research; 2)resume, qualifications, source of financial support, and conflict of interest statement; 3)sign a data-sharing agreement and confidentiality statement that stipulates using the data for the stated research purposes only, securing the data using appropriate computer technology, not manipulating the data in order to identify participants, acknowledging the grant that supported data collection and management in publications/presentations, and destroying or returning the data after analyses are complete; 4)obtain approval from their Institutional Review Board, and along with other staff members who have access to the data, submit certificates of the University of Pittsburgh Education and Certification Program in Research Practice Fundamentals or provide written documentation pf similar human subjects protection training.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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