Short-term Mentored Career Development Award: Iron Metabolism, Brain Energetics,

说明(申请人提供)：缺铁(ID)是一种非常普遍的微量营养素缺乏症，影响到世界上很大一部分人口。在ID的众多影响中，最近开始受到系统关注的一类是对知觉和认知表现的影响，以及伴随而来的对大脑结构和功能的关注。这项研究记录了与ID相关的大量缺陷，以及铁补充对知觉和认知表现的实质性恢复作用。这也增加了我们对铁的消耗和补充对大脑新陈代谢和功能的影响的认识。然而，目前文献中缺少的是一种系统和机械地将铁的枯竭和再枯竭对大脑状态以及知觉和认知表现的影响联系起来的方法。数学和计算建模提供了将这些不同级别的分析(身体、大脑和行为)联系起来的方法。理想情况下，对这类复杂关系的建模最好是在多学科协作中进行，而创建成功的跨学科协作的一个关键是关于研究问题核心元素的共享知识集。我在实验心理学、数学建模和电生理学(EEG)方面的培训和经验使我能够围绕铁耗竭和耗竭的感知和认知影响的建模开发出一套初步的合作方案。然而，由于我缺乏铁生理学知识以及用于评估其后遗症的实验方法和措施，我完全参与这些合作的能力受到限制。因此，我请求一年的支持，以便在这些领域得到两位国际公认的ID专家的指导。这个项目的近期目标是三个：(A)获得了解铁生理学所需的基础生物化学和生理和代谢测量知识，以及测量铁耗竭和再利用的影响。(B)将这些基础知识与该领域新的和正在进行的研究结合起来。(C)将所获得的所有知识应用于一个研究问题，该问题将身体、大脑和行为这三个层面的分析联系起来，以开发铁的枯竭和再枯竭对知觉和认知的影响的机制模型。长期目标是为铁在大脑功能以及知觉和认知行为中的机械作用开发可实验验证的数学模型。 与公共健康相关：拟议的项目将调查在缺铁的情况下使用脑电模式来估计大脑能量消耗和能量效率的可能性。这项工作将促进我们对铁在受损和健康大脑的功能中的作用，以及铁补充可以改善大脑功能的方式的理解。

DESCRIPTION (provided by applicant): Iron deficiency (ID) is a highly-prevalent micronutrient deficiency, affecting a large proportion of the world's population. Of the numerous effects of ID, a class that has recently begun to receive systematic attention has been the impact on perceptual and cognitive performance, with a concomitant concern for brain structure and function. This research has documented both substantial deficits associated with ID and substantial restorative effects of iron repletion on perceptual and cognitive performance. It has also increased our knowledge of the effects of iron depletion and repletion on brain metabolism and function. However, what is currently missing in the literature is a means of systematically and mechanistically relating the effects of iron depletion and repletion on changes in brain states and perceptual and cognitive performance. Mathematical and computational modeling offers the means for relating these disparate levels of analysis (body, brain, and behavior). Ideally, modeling these kinds of complex relations is best done in multi-disciplinary collaborations, and one key to creating successful cross-disciplinary collaborations is a shared set of knowledge about the core elements of the research question. My training and experience in experimental psychology, mathematical modeling, and electrophysiology (EEG) has allowed me to develop an initial set of collaborations around the modeling of perceptual and cognitive effects of iron depletion and repletion. However, my ability to fully participate in these collaborations is limited by my lack of knowledge of iron physiology and the experimental methods and measures used to assess its sequelae. As such, I am requesting one year of support in order to be mentored in these areas by two internationally-recognized experts in ID. The immediate goals for this project are three: (a) Acquire knowledge of the foundational biochemistry and physiological and metabolic measurements needed for an understanding of iron physiology and the measurement of the effects of iron depletion and repletion. (b) Integrate this foundational knowledge with new and ongoing research in the field. (c) Apply all of the knowledge gained to a research question linking the three levels of analysis-body, brain, and behavior- needed for developing mechanistic models of the effects of iron depletion and repletion on perception and cognition. The long-term goal is to develop experimentally-testable mathematical models for the mechanistic role of iron in brain function and perceptual and cognitive behaviors. PUBLIC HEALTH RELEVANCE: The proposed project will investigate the potential for using patterns of EEG to estimate brain energy expenditures and energetic efficiency in the context of iron deficiency. This work will advance our understanding of the role of iron in the functioning of both compromised and healthy brains, and the ways in which iron repletion can improve brain function.