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 抑郁症是一种慢性的精神病理形式，是世界上导致抑郁症的主要原因之一 残疾。一篇关于抑郁症神经机制的广泛文献记录了抑郁症的破坏 作为抑郁症病理生理学的一部分，在奖赏回路中发挥作用。具体地说，额纹状体功能 改变，腹侧纹状体(VS)反应较低，内侧前额叶皮质(MPFC)反应较大，以及 两地功能联通更加紧密。然而，很少有治疗抑郁症的神经调节方法 已经瞄准了这条线路。经颅磁等非侵入性神经调节技术 刺激(TMS)已被应用于抑郁症，并可通过以下方式阐明这种疾病的病理生理学 专注于额纹状体回路的功能。 对于拟议的R21研究，我们将使用交织进行受试者内的平衡研究 功能磁共振成像和TMS检查电刺激的急性效应(TBS，TMS的一种简写形式) 对35例青壮年抑郁症患者(18~25岁，女性占50%)进行dmPFC检测。每位参与者将接受2次 会话，间歇性和连续性TBS各一次，目标是增加或减少dmPFC 分别作出回应。大脑功能、行为和情绪将在每次TBS之前和之后进行评估 会议。广义地，我们预测抑制dmPFC的TBS将降低dmPFC功能和dmPFC-VS 连通性。我们还将评估这种额纹状体回路改变的可能性，以改变行为和 奖励功能的主观方面，如积极情绪。 拟议的研究采取了基于电路的观点，并使用了具有以下目标的多层次评估方法 识别情感精神病的生物标记物。它的目标是操纵正价系统在 神经水平，以了解它们的功能，并可能揭示与未来相关的异质性来源 实验治疗学的研究。其高水平的创新和早期的开发 使用这种方法了解这个电路，使其非常适合R21资助。