A Multiphase Program of Multimodal Computational Modeling and Hybrid Interventions Including EEG-Synchronized Transcranial Magnetic Stimulation and Cognitive Behavioral Therapy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Change in reaction time (RT) tasks - Incongruent Stimuli
研究概览
简要总结
In this research study, investigators examine how brain activity changes during tests of emotional processing, attention, and memory using multimodal neuroimaging methods including electroencephalography (EEG), functional magnetic resonance imaging (fMRI), and functional near-infrared spectroscopy (fNIRS). Transcranial magnetic stimulation (TMS) is used to probe and modulate brain networks related to cognitive flexibility and emotion regulation.
The study includes multiple related sub-studies involving healthy participants and participants with depression. Some study components focus on mechanistic modeling using non-therapeutic neurostimulation in healthy participants, while other components include interventional approaches such as individualized EEG-synchronized repetitive TMS (rTMS), cognitive tasks, and brief cognitive behavioral therapy (CBT) in participants with depression. Certain study components also evaluate CBT alone without TMS to assess behavioral intervention effects.
详细描述
Investigators aim to characterize and modulate brain networks underlying cognitive flexibility (CF) and emotion regulation (ER) using a multimodal, precision neuroscience approach. The central hypothesis is that functional coupling within CF and ER networks is indexed by the phase of the brain's alpha oscillations, and that targeted modulation of these networks through individualized neurostimulation can induce neuroplastic changes associated with improved clinical outcomes in depression and suicidality.
To test this hypothesis, investigators utilize a novel integrated system that enables simultaneous functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and transcranial magnetic stimulation (TMS) to identify individualized stimulation parameters associated with optimal network coupling. A complementary system using functional near-infrared spectroscopy (fNIRS), EEG, and TMS is also used to extend these findings in a more scalable and accessible format.
This protocol includes multiple related sub-studies (Studies 1-4) conducted under a single IRB approval. These sub-studies are parallel investigations with differing populations and interventions and are not randomized arms of a single trial.
Study 1 is a proof-of-principle mechanistic study conducted in healthy adult participants. In this study, single-pulse TMS is delivered during EEG and neuroimaging sessions as a non-therapeutic probe to assess cortical excitability and functional connectivity during cognitive flexibility and emotion regulation tasks.
Study 2 is a proof-of-principle interventional study in participants with depression. It incorporates individualized, EEG-synchronized repetitive transcranial magnetic stimulation (rTMS) designed to entrain neural oscillatory dynamics within CF and ER networks. Participants may receive rTMS alone or in combination with cognitive tasks and brief cognitive behavioral therapy (CBT), with the goal of enhancing neuroplasticity and improving clinical symptoms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Study 1 (Healthy Participants)
- •Inclusion Criteria:
- •Age 18-65 years
- •Medically and psychiatrically healthy with no history of psychiatric or neurological disorders
- •English-speaking
- •Capacity to provide informed consent
- •Willingness and ability to complete study procedures
- •Negative pregnancy test for participants of childbearing potential
排除标准
- •Any current or past psychiatric diagnosis
- •Neurological disorders or history of central nervous system disease
- •History of seizure or epilepsy or use of medications that lower seizure threshold
- •Significant head injury or loss of consciousness
- •Implanted metal or contraindications to MRI or TMS
- •Substance use disorder (excluding nicotine or caffeine)
- •Pregnancy or plans to become pregnant during study participation
- •Inability to complete study procedures
- •Studies 2, 3, and 4 (Participants With Depression)
- •Inclusion Criteria:
- •Age 18-65 years
- •Current diagnosis of Major Depressive Disorder (MDD)
- •Depression severity consistent with study criteria (e.g., HAM-D ≥17)
- •No history of psychotic or bipolar disorders
- •English-speaking
- •Capacity to provide informed consent
- •Willingness and ability to complete study procedures
- •Negative pregnancy test for participants of childbearing potential
- •Exclusion Criteria:
- •Neurological disorders or history of central nervous system disease
- •History of seizure or epilepsy or use of medications that lower seizure threshold
- •Significant head injury or loss of consciousness
- •Implanted metal or contraindications to MRI or TMS
- •Substance use disorder (excluding nicotine or caffeine)
- •Current participation in another interventional clinical trial
- •Pregnancy or plans to become pregnant during study participation
- •Any condition that would interfere with safe participation or completion of study procedures
研究组 & 干预措施
Healthy Participants (Study 1)
Healthy adult participants with no history of psychiatric or neurological illness who undergo mechanistic and modeling procedures, including multimodal neuroimaging, behavioral cognitive tasks, and nontherapeutic neurostimulation, to characterize brain networks underlying cognitive flexibility and emotion regulation.
干预措施: Cognitive Flexibility and Emotion Regulation Tasks (Behavioral)
Depressed Participants - EEG-Synchronized rTMS (Studies 2 and 3)
Participants with major depressive disorder who receive individualized, EEG-synchronized repetitive transcranial magnetic stimulation (rTMS), delivered alone or in combination with cognitive tasks and/or brief cognitive behavioral therapy (CBT), to modulate neural networks underlying cognitive flexibility and emotion regulation.
干预措施: Cognitive Behavioral Therapy (CBT) (Behavioral)
Healthy Participants (Study 1)
Healthy adult participants with no history of psychiatric or neurological illness who undergo mechanistic and modeling procedures, including multimodal neuroimaging, behavioral cognitive tasks, and nontherapeutic neurostimulation, to characterize brain networks underlying cognitive flexibility and emotion regulation.
干预措施: Single-Pulse Transcranial Magnetic Stimulation (Device)
Depressed Participants - Cognitive Behavioral Therapy Only (Study 4)
Participants with major depressive disorder who receive a course of cognitive behavioral therapy (CBT) along with MRI and behavioral assessments, without transcranial magnetic stimulation or EEG-based neurostimulation. This group allows evaluation of behavioral intervention effects independent of neurostimulation.
干预措施: Cognitive Behavioral Therapy (CBT) (Behavioral)
Depressed Participants - EEG-Synchronized rTMS (Studies 2 and 3)
Participants with major depressive disorder who receive individualized, EEG-synchronized repetitive transcranial magnetic stimulation (rTMS), delivered alone or in combination with cognitive tasks and/or brief cognitive behavioral therapy (CBT), to modulate neural networks underlying cognitive flexibility and emotion regulation.
干预措施: Single-Pulse Transcranial Magnetic Stimulation (Device)
Depressed Participants - EEG-Synchronized rTMS (Studies 2 and 3)
Participants with major depressive disorder who receive individualized, EEG-synchronized repetitive transcranial magnetic stimulation (rTMS), delivered alone or in combination with cognitive tasks and/or brief cognitive behavioral therapy (CBT), to modulate neural networks underlying cognitive flexibility and emotion regulation.
干预措施: EEG-Synchronized Repetitive Transcranial Magnetic Stimulation (rTMS) (Device)
Depressed Participants - EEG-Synchronized rTMS (Studies 2 and 3)
Participants with major depressive disorder who receive individualized, EEG-synchronized repetitive transcranial magnetic stimulation (rTMS), delivered alone or in combination with cognitive tasks and/or brief cognitive behavioral therapy (CBT), to modulate neural networks underlying cognitive flexibility and emotion regulation.
干预措施: Cognitive Flexibility and Emotion Regulation Tasks (Behavioral)
Depressed Participants - Cognitive Behavioral Therapy Only (Study 4)
Participants with major depressive disorder who receive a course of cognitive behavioral therapy (CBT) along with MRI and behavioral assessments, without transcranial magnetic stimulation or EEG-based neurostimulation. This group allows evaluation of behavioral intervention effects independent of neurostimulation.
干预措施: Cognitive Flexibility and Emotion Regulation Tasks (Behavioral)
结局指标
主要结局
Change in reaction time (RT) tasks - Incongruent Stimuli
时间窗: Day 1, Day 2, Day 3
Tasks will be used to see differences between incongruent emotional stimuli.
Change in reaction time (RT) tasks - Congruent Stimuli
时间窗: Day 1, Day 2, Day 3
Tasks will be used to see differences between congruent emotional stimuli.
Change in reaction time (RT) tasks and accuracy - Incongruent Stimuli
时间窗: Day 1, Day 2, Day 3
Tasks will be used to see differences between incongruent emotional stimuli.
Change in reaction time (RT) tasks and accuracy - Congruent Stimuli
时间窗: Day 1, Day 2, Day 3
Tasks will be used to see differences between congruent emotional stimuli.
Clinical Improvement
时间窗: Day 13, Day 18
25% reduction in Generalized Anxiety Disorder -7 Questionnaire (GAD7) as a meaningful treatment response.
Change in Patient Health Questionnaire-9 (PHQ-9) Score
时间窗: Baseline to Day 7
Change in self-reported depression severity measured using the Patient Health Questionnaire-9 (PHQ-9). Scores range from 0 to 27; higher scores indicate more severe depression.
Change in Suicidal Ideation Severity (Passive and Active Suicidal Ideation Scale [PASIS])
时间窗: Baseline to Day 7
Change in suicidal ideation severity measured using the Passive and Active Suicidal Ideation Scale (PASIS). Higher scores indicate greater severity of suicidal ideation.
Change in Hamilton Depression Rating Scale (HAM-D) Score
时间窗: Baseline to Day 7
hange in clinician-rated depression severity measured using the Hamilton Depression Rating Scale (HAM-D). Scores range from 0 to 52; higher scores indicate more severe depression.
Change in Suicide Cognitions (Brief Suicide Cognitions Scale [B-SCS])
时间窗: Baseline to Day 7
Change in suicide-related cognitions measured using the Brief Suicide Cognitions Scale (B-SCS). Higher scores indicate greater severity of maladaptive suicide-related cognitions.
次要结局
- Change in Reaction Time During Cognitive Flexibility Tasks(Baseline to Day 7)
- Change in Accuracy on Cognitive Flexibility Tasks(Baseline to Day 7)
- Change in Generalized Anxiety Disorder-7 (GAD-7) Score(Baseline to Day 7)
- Change in EEG Alpha Phase Synchronization(Baseline to Day 7)
- Change in Functional Connectivity Strength (fMRI)(Baseline to Day 7)
- Change in Functional Connectivity Strength (fNIRS)(Baseline to Day 7)
- Proportion of Participants With ≥50% Reduction in HAM-D Score(Day 28)
- Proportion of Participants With ≥50% Reduction in PASIS Score(Day 28)
- Proportion of Participants With ≥50% Change in Hamilton Depression Rating Scale (HAM-D) Score(Day 28)
- Proportion of Participants With ≥50% Change in Brief Suicide Cognitions Scale (B-SCS) Score(Day 28.)