PECASE: Using Control Systems to Quantify Limbic Dysregulation for Neurobiologically-Based Diagnoses of Psychiatric Disabilities

PECASE：使用控制系统量化边缘系统失调，以进行基于神经生物学的精神障碍诊断

• 批准号: 0954643
• 负责人: Lilianne Mujica-Parodi
• 金额: $ 42.63万
• 依托单位: SUNY at Stony Brook
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0954643&HistoricalAwards=false
• 关键词: PECASE; Using; Control; Systems; Quantify

PI: Mujica-Parodi, LilianneProposal Number: 0954643PROJECT SUMMARYIntellectual Merit: For this proposal, we will develop and test computational methods for quantifying dysregulation between the excitatory and inhibitory components of the negative feedback loops in the brain that control homeostatic regulation of emotional arousal. This work conceptually integrates systems neuroscience with techniques originally developed for physics and engineering (power spectrum scale invariance, Shannon entropy) that have been successfully applied towards characterizing autonomic regulation via heart-rate variability analysis. Historically, neuroimaging has focused on measuring the amplitude of activation-levels in different regions of interest for some specific task. While in the past few years newer connectivity methods such as structural equation modeling, Granger causality, and dynamic causal modeling are important advances in investigating the temporal components of the time-series, these techniques are designed to investigate the strength of connections between node pairs. In contrast, our approach builds upon this work to answer a completely different type of question: to what degree does the system as a whole respond efficiently to perturbation in its maintenance of homeostasis? Our approach is explicitly motivated by the fact that many diseases-from diabetes to cancer to Cushing's disease-are dysregulatory in nature. As such, one technique that has enjoyed much diagnostic success is to "perturb" the system and then measure dynamic features of its return to baseline. In this proposal, we measure dysregulation of the limbic circuit, with neural timeseries obtained first from functional MRI and then near-infrared spectroscopy, in developing a neurobiologically-based instrument for objective and quantitative diagnosis of mental illness. The three patient groups with whom we will optimize our methods will include generalized anxiety disorder, major depression, and their comorbidity. These diagnostic choices provide a rational extension of our previous research on limbic dysregulation as a marker for individual variability in trait anxiety within the healthy population. Moreover, the symptoms associated with anxiety and depression have clearly-defined excitatory and inhibitory components with respect to physiological and behavioral arousal, and therefore will allow us to test dissociation between groups. The development of engineering techniques to assist individuals with psychiatric illness qualifies this proposal for consideration in the RAPD category as it advances innovation beyond the frontiers of current knowledge in disability-related research of mental illness. Given that psychiatric illnesses are currently diagnosed solely by clinicians' assessment of patients' self-reported moods, and therefore are highly subjective and wholly dependent upon patient compliance, the broad societal impact of this research lies in the potential ability to harness the functional neuroimaging technologies for applications that could be revolutionary in the diagnosis of mental health disorders, providing objective and quantifiable criteria for assessing prodromal risk, treatment efficacy, and identifying clean phenotypes for genetic research. This CAREER award would permit me, over the next five years, to collect the necessary data and to iteratively develop and adapt the computational engineering tools necessary to lead development in this critical evolving area of research.Broader Impact: In 2007, the National Academy of Science, National Academy of Engineering, andInstitute of Medicine were charged by Congress to form a committee to address the challenges associated with maintaining scientific innovation and economic competitiveness within an increasingly global economy. For this CAREER award, I will focus on addressing two specific recommendations made by this committee. One action item was to strengthen children's K-12 preparation in science and technology by enhancing the science and engineering education of the science teachers themselves. A second action item was to increase the total number of individuals qualified and motivated to pursue postgraduate study in science and engineering. This CAREER award will directly address both of these action items. The first action item will be addressed in three parts: (1) through the development of a fun and intellectually engaging hands-on 7th grade curriculum in "systems-based thinking" using STELLA software; (2) through training science teachers to use the curriculum during summer workshops; and, (3) through dissemination of the curriculum and workshop materials by posting them on our website and follow-up assessment to measure the curriculum's efficacy. The second action item will be addressed by setting up a collaborative program with the Georgia Institute of Technology Department of Biomedical Engineering to recruit minority biomedical engineers into our Biomedical Engineering Ph.D. program: first as summer-research undergraduates, and then as full-time students. By training students in the lab to exploit the benefits of thinking in terms of systems in their own research, and then training them to teach teachers and by extension junior high school students the same conceptual tools at a more basic level, we are able to integrate our research and educational goals to the fullest extent possible.

主要研究者：Mujica-Parodi，LilianneProposal Number：0954643项目概要智力优点：对于这个提案，我们将开发和测试计算方法，用于量化大脑中控制情绪唤醒的稳态调节的负反馈回路的兴奋性和抑制性成分之间的失调。这项工作在概念上将系统神经科学与最初为物理学和工程学开发的技术（功率谱标度不变性，香农熵）相结合，这些技术已成功应用于通过心率变异性分析来表征自主调节。从历史上看，神经影像学一直专注于测量某些特定任务的不同感兴趣区域的激活水平的幅度。虽然在过去的几年中，较新的连接方法，如结构方程模型，格兰杰因果关系，动态因果模型是重要的进展，在调查的时间序列的时间组成部分，这些技术的目的是调查节点对之间的连接强度。相比之下，我们的方法建立在这项工作的基础上，以回答一个完全不同类型的问题：在多大程度上系统作为一个整体有效地响应扰动，在其维持稳态？ 我们的方法是明确的事实，从糖尿病到癌症到库欣氏病，许多疾病是失调的性质。因此，有一种技术在诊断上取得了很大的成功，那就是“扰动”系统，然后测量其返回基线的动态特征。 在这个建议中，我们测量边缘回路的失调，首先从功能性MRI，然后近红外光谱获得的神经时间序列，在开发一个基于神经生物学的仪器，用于客观和定量诊断精神疾病。我们将优化我们的方法的三个患者群体将包括广泛性焦虑症，重性抑郁症及其合并症。 这些诊断的选择提供了一个合理的扩展，我们以前的研究边缘功能失调作为一个标志，在健康人群中的特质焦虑的个体差异。此外，与焦虑和抑郁相关的症状在生理和行为唤醒方面具有明确的兴奋和抑制成分，因此将允许我们测试群体之间的分离。工程技术的发展，以帮助个人与精神疾病资格这一建议，考虑在RAPD类，因为它的进步创新超越了目前的知识前沿，在残疾相关的研究精神疾病。鉴于精神疾病目前仅通过临床医生对患者自我报告的情绪进行评估来诊断，因此具有高度主观性，完全取决于患者的依从性，因此这项研究的广泛社会影响在于利用功能性的潜在能力神经成像技术的应用可能在精神健康障碍的诊断方面具有革命性，为评估前驱风险、治疗效果和为遗传研究鉴定干净的表型提供客观和可量化的标准。这个职业奖将允许我在未来五年内收集必要的数据，并迭代开发和调整必要的计算工程工具，以领导这一关键不断发展的研究领域的发展。2007年，美国国家科学院、国家工程院、美国国会授权美国医学研究所成立一个委员会，以应对在日益全球化的经济中保持科学创新和经济竞争力的挑战。对于这个职业奖，我将重点讨论这个委员会提出的两个具体建议。一个行动项目是通过加强科学教师本身的科学和工程教育，加强儿童在科学和技术方面的K-12准备。第二个行动项目是增加有资格和有动力攻读科学和工程学研究生课程的总人数。这个职业奖将直接解决这两个行动项目。第一个行动项目将分三个部分处理：（1）通过使用STELLA软件开发一个有趣和智力参与的“系统思维”七年级实践课程;（2）通过培训科学教师在暑期讲习班中使用该课程;及（三）透过网页发放课程及工作坊资料，并进行跟进评估，以衡量课程的成效。第二个行动项目将通过与格鲁吉亚理工学院生物医学工程系建立合作计划来解决，以招募少数民族生物医学工程师进入我们的生物医学工程博士学位。课程：首先是夏季研究本科生，然后是全日制学生。通过在实验室中训练学生在自己的研究中利用系统思维的好处，然后训练他们在更基本的层面上向教师和初中生教授相同的概念工具，我们能够最大限度地整合我们的研究和教育目标。