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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要抑郁症是一种慢性、损害性的精神病理学形式，是世界上导致抑郁症的主要原因之一。残疾。关于抑郁症神经机制的大量文献记录了抑郁症神经机制的破坏作为抑郁症病理生理学的一部分，奖励回路中的功能。具体来说，额纹状体的功能是改变，腹侧纹状体（VS）反应较低，内侧前额叶皮层（mPFC）反应较大，并且两个区域之间的功能连通性更强。然而，针对抑郁症的神经调节方法还很少已针对该电路。无创神经调节技术，例如经颅磁刺激（TMS）已应用于抑郁症，并可以通过以下方式阐明这种疾病的病理生理学：重点关注额纹状体电路的功能。对于拟议的 R21 研究，我们将使用交错进行受试者内平衡研究功能性 MRI 和 TMS，用于检查 theta 突发刺激的急性影响（TBS，TMS 的简化形式）对 35 名患有抑郁症的年轻人（18-25 岁，50% 女性）进行 dmPFC 评估。每位参与者将经历2 间歇性和连续性 TBS 各一次，目的是增加或减少 dmPFC 分别作出回应。每次 TBS 之前和之后都会评估大脑功能、行为和情绪会议。总的来说，我们预测 dmPFC 的抑制性 TBS 将降低 dmPFC 功能和 dmPFC-VS 连接性。我们还将评估额纹状体回路的这种变化改变行为和行为的潜力。奖励功能的主观方面，例如积极情绪。拟议的研究采用基于电路的视角，并使用多层次的评估方法，其目标是识别情感精神病理学的生物标志物。其目标是操纵正价系统神经水平来理解它们的功能，并可能揭示与未来相关的异质性来源实验治疗学研究。其高水平的创新和早期的发展阶段使用这种方法了解该电路使其非常适合 R21 融资。