Elucidating Neural Mechanisms of Hypo/Mania Using Theta Burst Stimulation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 146
- 试验地点
- 1
- 主要终点
- Reward expectancy-related left orbitofrontal cortex activity
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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, 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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Sham Continuous Theta Burst Stimulation (Sham cTBS) (Device)
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.
干预措施: Continuous Theta Burst Stimulation (cTBS) (Device)
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.
干预措施: Sham Continuous Theta Burst Stimulation (Sham cTBS) (Device)
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.
干预措施: Continuous Theta Burst Stimulation (cTBS) (Device)
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.
干预措施: Sham Continuous Theta Burst Stimulation (Sham cTBS) (Device)
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.
干预措施: Continuous Theta Burst Stimulation (cTBS) (Device)
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.
干预措施: Sham Continuous Theta Burst Stimulation (Sham cTBS) (Device)
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.
干预措施: Continuous Theta Burst Stimulation (cTBS) (Device)
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.
干预措施: Continuous Theta Burst Stimulation (cTBS) (Device)
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.
干预措施: Sham Continuous Theta Burst Stimulation (Sham cTBS) (Device)
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.
干预措施: Continuous Theta Burst Stimulation (cTBS) (Device)
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.
干预措施: Sham Continuous Theta Burst Stimulation (Sham cTBS) (Device)
结局指标
主要结局
Reward expectancy-related left orbitofrontal cortex activity
时间窗: 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
Reward expectancy-related right amygdala activity
时间窗: 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
Reward expectancy-related left ventrolateral prefrontal cortex-left ventral striatum functional connectivity
时间窗: 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
Reward expectancy-related left ventrolateral prefrontal cortex-right orbitofrontal cortex functional connectivity
时间窗: 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
Reward expectancy-related left ventrolateral prefrontal cortex-midline rostral anterior cingulate cortex functional connectivity
时间窗: 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
Reward expectancy-related right ventrolateral prefrontal cortex activity
时间窗: 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
Reward expectancy-related left ventral striatum activity
时间窗: 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
Reward expectancy-related right ventral striatum activity
时间窗: 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
Reward expectancy-related midline rostral anterior cingulate cortex (rACC) activity
时间窗: 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
Reward expectancy-related midline dorsal anterior cingulate cortex activity
时间窗: 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
Reward expectancy-related left ventrolateral prefrontal cortex-right ventrolateral prefrontal cortex functional connectivity
时间窗: 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
Reward expectancy-related left ventrolateral prefrontal cortex-right ventral striatum functional connectivity
时间窗: 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
Reward expectancy-related right orbitofrontal cortex activity
时间窗: 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
Reward expectancy-related left amygdala activity
时间窗: 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
Reward expectancy-related left ventrolateral prefrontal cortex-midline dorsal anterior cingulate cortex functional connectivity
时间窗: 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
Reward expectancy-related left ventrolateral prefrontal cortex activity
时间窗: 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
Reward expectancy-related left ventrolateral prefrontal cortex-left orbitofrontal cortex functional connectivity
时间窗: 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
Reward expectancy-related left ventrolateral prefrontal cortex-left amygdala functional connectivity
时间窗: 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
Reward expectancy-related left ventrolateral prefrontal cortex-right amygdala functional connectivity
时间窗: 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
次要结局
- Right ventrolateral prefrontal cortex activity(Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins))
- Right orbitofrontal cortex activity(Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins))
- Right ventral striatum activity(Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins))
- Left amygdala activity(Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins))
- Left ventrolateral prefrontal cortex activity(Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins))
- Right amygdala activity(Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins))
- Midline dorsal anterior cingulate cortex activity(Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins))
- Prediction error-related left ventral striatum activity(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(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(Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins))
- Reward expectancy-related left ventrolateral prefrontal cortex wholebrain functional connectivity(Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins))
- Left ventral striatum activity(Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins))
- Left orbitofrontal cortex activity(Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins))
- Midline rostral anterior cingulate cortex activity(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(Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins))
- Prediction error-related right ventral striatum activity(Change in magnitude immediately before and immediately after each cTBS condition at scan visits (30-60 mins))
研究者
Mary Phillips, MD MD (Cantab)
Professor
University of Pittsburgh