Quantifying the Brain Metabolism Underlying Task-Based BOLD Imaging

项目摘要/摘要 最近的证据表明，代谢功能障碍是精神疾病的一个关键的跨诊断风险因素。 功能磁共振成像(FMRI)测量与大脑代谢变化相关的血液动力学变化，并可以 弥合精神疾病的生物标记物与人类经验和行为之间的关键差距；然而， 血流动力学反应背后的代谢过程仍然知之甚少。在我们可以 了解精神疾病中的大脑代谢障碍，我们首先需要了解大脑代谢过程中 健康的认知功能。一个特别的争议点是对感官信号的大胆反应和 认知活动与葡萄糖消耗的大幅增加相吻合，与氧气的增加无关 新陈代谢。这个过程被称为有氧糖酵解。它的功能仍然存在争议。我们已经开发出一种 来自神经生理学证据汇合线的假说，阐明了有氧糖酵解如何服务于 神经元通讯中的自适应功能。拟议的研究将通过以下方式为基础科学做出贡献 提出测量和解释基于任务的脑代谢动力学所需的方法和理论。我们 结合功能PET成像(FPET)和双校准fMRI的技术创新，以同时 测量区域葡萄糖和氧气代谢的绝对速率和基于任务的相对变化。目标1 评估混合PET/fMRI方法在扫描阶段内和跨扫描阶段的可靠性，并与先前的PET- 派生估计值。Aim 2测试了一个关于有氧糖酵解在信息中的作用的新假说 变速箱。我们假设有氧糖酵解为不可预测的交流补充能量。 感觉信号，即预测误差。为了测试这一点，我们将使用一个简单的行为任务来操作 听觉和视觉刺激的可预测性，与感官流之间的注意力操纵相交叉。 目标1代表了我们测量大脑代谢动力学能力的关键进步，正如先前的研究所做的那样 仅限于执行独立的PET会议。Aim 2在更广泛的理论中测试了一个关键预测 框架，这有可能大幅重新框架对现有功能磁共振研究的解释， 在显性信息和代谢中重新设置血流动力学反应和“脑激活”的语境 条款。

Project Summary/Abstract Recent evidence suggests that metabolic dysfunction is a crucial transdiagnostic risk factor for mental illness. Functional MRI (fMRI) measures hemodynamic changes related to metabolic shifts in the brain and could bridge a critical gap between biomarkers for mental illness and human experience and behavior; however, metabolic processes underlying the hemodynamic response have remained poorly understood. Before we can understand brain metabolic dysfunction in mental illness, we first need to understand brain metabolism during healthy cognitive function. A particular point of controversy is that the BOLD response to sensory signals and cognitive activity coincides with a substantial increase in glucose consumption, decoupled from increases in O2 metabolism. This process is called aerobic glycolysis. and its function remains disputed. We have developed a hypothesis from converging lines of neurophysiological evidence that clarifies how aerobic glycolysis serves an adaptive function in neuronal communication. The proposed research will contribute to basic science by advancing the methods and theory needed to measure and interpret task-based brain metabolic dynamics. We combine technical innovations in functional PET imaging (fPET) and dual-calibrated fMRI, to simultaneously measure absolute rates and task-based relative changes in regional glucose and O2 metabolism. Aim 1 evaluates the reliability of hybrid PET/fMRI method, within and across scan sessions, and against prior PET- derived estimates. Aim 2 tests a novel hypothesis about the role aerobic glycolysis plays in information transmission. We hypothesize that aerobic glycolysis supplements energy for communicating unpredictable sensory signals, i.e., prediction error. To test this, we will use a simple behavioral task, manipulating the predictability of auditory and visual stimuli, crossed with an attention manipulation between sensory streams. Aim 1 represents a critical advance in our ability to measure brain metabolic dynamics, as prior research has been limited to performing independent PET sessions. Aim 2 tests a key prediction in a broader theoretical framework, which has the potential to significantly reframe interpretations of existing fMRI research, recontextualizing the hemodynamic response and “brain activation” in explicit informational and metabolic terms.