Multi-parametric MRI Assessment of Brain Connectivity and Spectroscopic Biomarkers in Patients with a Substance Use Disorder

药物滥用障碍患者大脑连接性和光谱生物标志物的多参数 MRI 评估

• 批准号: 10685347
• 负责人: Brian Allen Taylor
• 金额: $ 19.02万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10685347
• 关键词: Amygdaloid structure; Animals; Anterior; Attention; Biological Markers; Biology; Board Certification; Brain; Brain region; Centers for Disease Control and Prevention (U.S.); Cessation of life; Clinical; Cocaine use disorder; Corpus striatum structure; Coupling; Cues; Data; Development; Diagnosis; Disease; Drug usage; Ethics; Extinction; Functional Magnetic Resonance Imaging; Glutamates; Goals; Heroin Users; Hippocampus; Human; Image; Insula of Reil; Intake; Knowledge; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurable; Measures; Medical; Mentors; Methods; Modality; Modeling; Nature; Neurons; Neurosciences; Neurotransmitters; Opioid; Oxycodone; Pathway interactions; Patients; Pharmaceutical Preparations; Physics; Physiological; Physiology; Prediction of Response to Therapy; Prefrontal Cortex; Reaction Time; Relapse; Reporting; Research; Research Personnel; Rodent; Self Administration; Serotonin Agonists; Services; Societies; Stimulus; Substance Use Disorder; Techniques; Training; Training Programs; United States; Work; addiction; attentional bias; causal model; cingulate cortex; craving; cue reactivity; design; drug craving; gamma-Aminobutyric Acid; imaging study; indicated prevention; mortality; multimodality; neural circuit; neuroimaging; neuromechanism; neuronal circuitry; opioid use; opioid use disorder; public health emergency; relapse prediction; research study; response; social; substance use; targeted treatment; theories; tool; visual stimulus

Opioid use disorder (OUD) has been declared as a public health emergency in the United States. Data from the Centers for Disease Control and Prevention indicate a fivefold increase in the number of deaths due to opioids from 1999 to 2016. Neuroimaging is a powerful tool in understanding the neurocircuitry and physiology of OUD in order to target treatments for patients suffering from this disorder. This K23 application presents a training program for a board-certified clinical medical physicist, who specializes in magnetic resonance imaging (MRI), in order to receive training in the neuroscience of substance use disorders and to become an independent investigator. The goals set in this application will build on the candidate’s imaging physics background by (1) developing a foundational knowledge of brain function and neurocircuitry in substance use disorders in order to design, optimize, and interpret advanced neuroimaging techniques for addiction research; (2) acquiring training in professional development to become an independent investigator, mentor and educator; and (3) receiving additional training in the responsible and ethical conduct of scientific research. The overall training program will involve a research study focused on (1) brain effective connectivity (i.e., directional connectivity) of neural circuits in OUD, and (2) magnetic resonance spectroscopic quantification of neurotransmitters related to these circuits. In this proposed work, we will employ fMRI-based dynamic causal modeling of effective connectivity with guided expertise from mentors in order to identify neurocircuits underlying drug craving and attentional bias to dug cues. In addition, we will use MR spectroscopy to investigate the neurotransmitters gamma-aminobutyric acid (GABA) and glutamate in OUD and their relation to drug craving and attentional bias, and to explore the association of these neurotransmitters with brain effective connectivity.

阿片类药物使用障碍（OUD）已被宣布为美国的公共卫生紧急情况。数据从 美国疾病控制和预防中心表示，死亡人数增加了五倍， 从1999年到2016年的阿片类药物。神经影像学是了解神经回路和生理学的有力工具 OUD，以便针对患有这种疾病的患者进行治疗。此K23应用程序提供了一个 一个专门从事磁共振成像的委员会认证的临床医学物理学家的培训计划 (MRI)，以便接受药物使用障碍神经科学方面的培训，并成为一名 独立调查员在这个应用程序中设置的目标将建立在候选人的成像物理 通过（1）发展物质使用中大脑功能和神经回路的基础知识 疾病，以设计，优化和解释先进的神经成像技术成瘾研究; (2)获得专业发展培训，成为独立调查员，导师， 教育工作者;（3）在科学研究的负责任和道德行为方面接受额外的培训。的 整个训练计划将涉及集中于（1）大脑有效连接（即，定向 （2）OUD中神经回路的磁共振光谱定量， 与这些回路相关的神经递质。在这项拟议的工作中，我们将采用基于fMRI的动态因果 利用导师的指导专业知识对有效连接进行建模，以识别神经回路 潜在的药物渴望和对挖掘线索的注意力偏差。此外，我们还将使用MR光谱， 探讨OUD中神经递质γ-氨基丁酸（GABA）和谷氨酸（Glu）的变化及其相互关系 药物渴求和注意偏向，并探讨这些神经递质与大脑 有效连接。