Theta Burst Stimulation of Frontostriatal Reward Circuitry in Young Adults with Depression

年轻抑郁症患者额纹状体奖赏回路的 Theta 爆发刺激

• 批准号: 9766893
• 负责人: Erika E Forbes
• 金额: $ 17.72万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9766893
• 关键词: Acute; Address; Adolescence; Affect; Affective; Anhedonia; Behavior; Behavior assessment; Behavioral; Biological Markers; Brain; Cessation of life; Chronic; Clinical; Complement; Corpus striatum structure; Development; Disease; Effectiveness; Etiology; Exploratory/Developmental Grant; Female; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Goals; Heterogeneity; Human; Impairment; Investigational Therapies; Literature; Measures; Medial; Mediating; Mental Depression; Methods; Moods; Motivation; Neurosciences; Nucleus Accumbens; Participant; Patient Self-Report; Pattern; Positive Valence; Prefrontal Cortex; Protocols documentation; Psychopathology; Reporting; Research; Rewards; Rodent; Source; Standardization; System; Techniques; Testing; Time; Transcranial magnetic stimulation; Work; base; brain circuitry; cognitive control; design; disability; emerging adult; experience; innovation; motivated behavior; neglect; neuroimaging; neuromechanism; neuroregulation; novel; optogenetics; positive mood; relating to nervous system; response; reward circuitry; young adult

Project Summary/Abstract Depression is a chronic, impairing form of psychopathology that is one of the world's leading causes of disability. An extensive literature on the neural mechanisms of depression has documented the disruption of function in reward circuitry as part of the pathophysiology of depression. Specifically, frontostriatal function is altered, with lower ventral striatal (VS) response, greater medial prefrontal cortex (mPFC) response, and stronger functional connectivity between the two regions. Yet few neuromodulatory approaches to depression have targeted this circuitry. Noninvasive neuromodulatory techniques such as transcranial magnetic stimulation (TMS) have been applied to depression and can elucidate the pathophysiology of this disorder by focusing on function in frontostriatal circuitry. For the proposed R21 study, we will conduct a within-subject, counterbalanced study using interleaved functional MRI and TMS to examine the acute effects of theta-burst stimulation (TBS, a briefer form of TMS) to dmPFC in 35 young adults (18-25 years, 50% female) with depression. Each participant will undergo 2 sessions, one each of intermittent and continuous TBS, with the goal of increasing or decreasing dmPFC responding, respectively. Brain function, behavior, and mood will be assessed before and after each TBS session. Broadly, we predict that inhibitory TBS of the dmPFC will reduce dmPFC function and dmPFC-VS connectivity. We will also assess the potential for such change in frontostriatal circuitry to alter behavioral and subjective aspects of reward function, such as positive mood. The proposed study takes a circuit-based perspective and uses a multi-level assessment approach with the goal of identifying biomarkers of affective psychopathology. Its goal is to manipulate positive valence systems at the neural level to understand their function, and potentially reveal a source of heterogeneity relevant to future research in experimental therapeutics. Its high level of innovation and early stage of development for understanding this circuit using this method make it ideally suited for R21 funding.

项目摘要/摘要 抑郁症是一种慢性，损害的心理病理学形式，是世界上主要的原因之一 残疾。关于抑郁症神经机制的广泛文献证明了破坏 作为抑郁症病理生理学的一部分，奖励电路的功能。具体而言，额叶功能是 随着腹侧纹状体（VS）反应的较低，内侧前额叶皮层（MPFC）反应改变，并且 两个区域之间的功能连接更强。但是很少有神经调节方法用于抑郁症 已经针对此电路了。无创神经调节技术，例如经颅磁 刺激（TMS）已应用于抑郁症，可以通过 专注于额叶电路中的功能。 对于拟议的R21研究，我们将使用交织 功能性MRI和TMS检查theta-Burst刺激的急性影响（TBS，TMS的Briefer形式） 在35名年轻人（18-25岁，女性50％）中，DMPFC患有抑郁症。每个参与者将经历2 会议，每次间歇性和连续的TBS，其目标是增加或减少DMPFC 分别做出回应。在每个TBS之前和之后，将评估大脑功能，行为和情绪 会议。从广义上讲，我们预测DMPFC的抑制性TBS将降低DMPFC功能和DMPFC-VS 连接性。我们还将评估额叶电路中这种变​​化的可能性，以改变行为和 奖励功能的主观方面，例如积极的情绪。 拟议的研究采用基于电路的视角，并采用多层次评估方法 识别情感心理病理学的生物标志物。它的目标是操纵正价系统 神经层次了解其功能，并有可能揭示与未来相关的异质性的来源 实验治疗学研究。其高水平的创新和发展的早期阶段 使用此方法了解此电路使其非常适合R21资金。