Neuroinflammation and Executive Function in Bipolar Disorder: A PET-fMRI Study

双相情感障碍的神经炎症和执行功能：PET-fMRI 研究

基本信息

批准号：
10521262
负责人：
Amy Peters
金额：
$ 19.98万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-15 至 2025-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10521262
关键词：
Active Biological Transport Adult Afferent Pathways Age Attention Attenuated Autopsy Basal Ganglia Behavior Binding Bipolar Disorder Brain Brain imaging Clinical Cognition Cognitive Cognitive deficits Consultations Data Development Disinhibition Encephalitis Ensure Executive Dysfunction Exhibits Functional Magnetic Resonance Imaging Functional disorder Funding Future Goals Imaging Device Imaging technology Immune Immunologic Markers Immunology Immunotherapy Impulsivity Individual Inflammation Inflammatory Investigational Therapies Link Magnetic Resonance Imaging Measurement Measures Mental Depression Mentors Mentorship Methodology Mood Disorders National Institute of Mental Health Neurobehavioral Manifestations Neurobiology Neuroglia Neuroimmune Neurons Organ Participant Performance Peripheral Positron-Emission Tomography Prefrontal Cortex Productivity Proteins Psychoneuroimmunology Radiopharmaceuticals Research Research Project Grants Rest Role Scanning Schizophrenia Self Destructive Behavior Specificity Training Unemployment Visualization Work brain circuitry brain dysfunction career career development clinical translation clinically significant cognitive performance cognitive testing cytokine density executive function experience follow-up glial activation human imaging imaging study immune activation improved in vivo indexing inflammatory marker innovation knowledge base mind control molecular imaging multimodality neural neural circuit neuroimaging neuroimmunology neuroinflammation neuroregulation novel programs radioligand receptor response statistics success suicidal tool translational scientist

项目摘要

Individuals with bipolar disorder (BD) experience severe and persistent difficulties with executive functions, such as inhibitory control. Inhibitory control difficulties in BD could be related to inflammation via its effects on brain functioning. However, direct measurement of brain inflammation markers (i.e. glial activation) in BD is limited and further understanding of how glial activation contributes to inhibitory brain dysfunction in BD is needed. The goal of this proposal is to study the neuroinflammatory basis of inhibitory control and identify novel neuroimmune treatment targets for executive dysfunction in mood disorders. To this end, the candidate proposes: (1) training objectives to establish expertise in the use of simultaneous PET-MRI as a research tool, an interdisciplinary knowledge base in psychoneuroimmunology, and full independence with fMRI methodology, which together will further career development into an expert clinical translational researcher in bipolar disorder; (2) a research objective to examine glial activation as a mechanism of inhibitory control brain dysfunction and cognitive performance in BD; (3) a team of mentors and advisors to ensure the candidate’s success, with expertise in bipolar disorder (Dr. Andrew Nierenberg), multi-modal psychiatric neuroimaging (Dr. Darin Dougherty), molecular imaging and simultaneous PET-fMRI (Dr. Jacob Hooker), psychiatric neuroimmunology (Dr. Beth Stevens), fMRI inhibitory control paradigms (Dr. Scott Langenecker), and neuroimaging statistics (Dr. Mark Vangel). The rationale for the proposed project is that despite evidence for inflammatory alterations in BD, interrogation of brain inflammatory markers in-vivo and their role in executive functioning is limited. Human imaging with novel radiopharmaceuticals to visualize glial activation and its role in inhibitory brain function is needed. The central hypothesis of the proposal is that glial activation adversely impacts frontostriatal brain circuitry and, in turn, inhibitory control in BD. The proposed specific aims are to determine the: (1) difference in glial activation between BD (n = 20) and healthy controls (HC; n = 20); (2) association between glial activation and inhibitory control neural circuitry in BD; (3) association between glial activation and inhibitory control performance on cognitive testing in BD. This proposed research is innovative for examining markers of brain inflammation as a novel mechanism of the understudied burden of executive function in BD using cutting edge simultaneous PET- fMRI technology. The proposed research is significant because it could yield novel neuroimmune treatment targets and crucial pilot data towards the use of PET-fMRI for understanding the unmet clinical problem of inhibitory dysfunction in BD. Overall, this project and training plan will promote the candidate’s career development by facilitating an independent program of program of research at the interface of psychiatric neuroimaging and neuroimmunology. This is a critical first step in furthering the candidate’s career goals to study the neuroinflammatory basis of cognition and to identify novel neuroimmune targets for future experimental therapeutics in mood disorders.

双相情感障碍（BD）的个体具有执行功能的严重和持续的差异，例如作为抑制性控制。但是，功能，直接测量脑炎症标记（即glial激活）需要进一步了解神经胶质激活如何导致BD中的脑功能障碍该提案的目标是研究继承控制的神经炎症基础并识别Novy Neuroumune 候选人提出的治疗目标是情绪障碍的执行功能障碍。建立在使用同时使用PET-MRI作为ASREARZEREARZ工具（跨学科）的目标方面建立专业知识的目标 fMRI方法论的心理肌免疫学和完全独立性的知识基础，将会将会将会在躁郁症（2）研究中，将职业发展成为一种经验的宗教研究员目的检查神经胶质激活作为抑制控制脑的机制和认知的机制 BD的表现；（3）一组导师和候选人的顾问躁郁症（Andrew Nierenberg博士），多模式精神神经影像学（博士成像和同时发生PET-FMRI（Jacob Hooker博士），精神神经免疫学（Beth Stevens博士），fMRI 抑制控制范例（Scott Languenecker博士）和神经影像统计（Mark Vangel博士）拟议项目的基本原理是，尽管有证据表明BD炎症改变，但对脑部炎症标志物在体内及其在执行功能中的作用是有限的。需要放射性药物来可视化胶质化，并且需要在Hivitor中的作用该提案的假设是神经胶质激活不利影响额叶脑电路，而反过来又反过来又反过来。 BD中的抑制性控制。在BD（n = 20）和健康对照之间（HC; n = 20）之间；控制BD中的神经回路； BD中的认知测试。使用前沿同时使用PET- FMRI技术。目标和至关重要的试点数据用于使用PET-FMRI来理解Unment的临床可能性 BD的抑制功能障碍。通过促进精神病学计划的发展神经影像学和神经免疫学。研究认知的神经炎症基础，并确定未来实验的Novy Neuromune靶标情绪障碍的治疗学。