Project 4: Linking neural, hemodynamic, and multiscale cerebrospinal fluid flow measures in humans

摘要，项目4 在NREM睡眠期间，脑中出现脑脊髓液（CSF）流动的大波浪。神经慢波 在这些CSF流波之前几秒钟，这表明连贯的神经活动可以驱动CSF 通过诱导大规模神经血管耦合来实现血流。这个项目将检验时空 神经活动的动力学调节CSF如何在人脑中流动。我们将优化和整合多个 新的MR技术可以对脑室和血管周围空间中的CSF流动进行成像，同时 使用EEG测量神经活动，使用fMRI测量血液动力学反应。在目标1中，我们将测试 时空模式化的神经活动与CSF流量有关，在公认的视觉任务期间测量。 在目标2中，我们将测试睡眠期间自发神经活动的动力学是否与CSF流量相耦合 在多个空间尺度上。在目标3中，我们将确定基底前脑和蓝斑的活动， 释放去甲肾上腺素和乙酰胆碱，与相干神经活动和CSF之间的关系有关 流总之，这些目标将测试神经活动如何与睡眠和觉醒中的CSF流动相关联。 从脑室到血管周围空间。 项目4将通过确定神经活动和CSF之间的联系，为U19的总体目标做出贡献。 在多个空间尺度上流动。通过对人类进行全脑成像，我们可以测试局部和 整体神经动力学与微小的血管周围空间和大得多的脑室中的CSF流动有关。 通过与项目2的互动，我们基于EEG的神经连贯性测量将与细胞水平相关联。 我们的两个项目都测试了与血管周围空间中CSF流动的联系。我们 与项目3的相互作用将是至关重要的，以告知神经调节剂如何塑造血管动力学，以及如何 神经血管耦合在睡眠和清醒时发生改变。最后，我们与项目的持续互动 1将是必不可少的，以确定需要哪些经验测量来完全指定模型， 然后更新模型以进行进一步的预测。

Abstract, Project 4 During NREM sleep, large waves of cerebrospinal fluid (CSF) flow appear in the brain. Neural slow waves precede these CSF flow waves by several seconds, suggesting that coherent neural activity could drive CSF flow by inducing large-scale neurovascular coupling. This project will test the hypothesis that the spatiotemporal dynamics of neural activity regulate how CSF flows in the human brain. We will optimize and integrate multiple novel MR technologies to image CSF flow in the ventricles and in perivascular spaces, with simultaneous measures of neural activity using EEG, and hemodynamic responses using fMRI. In Aim 1, we will test whether spatiotemporally patterned neural activity is linked to CSF flow, measured during well-established visual tasks. In Aim 2, we will test whether the dynamics of spontaneous neural activity during sleep are coupled to CSF flow at multiple spatial scales. In Aim 3, we will identify how activity in basal forebrain and locus coeruleus, which release norepinephrine and acetylcholine, is linked to the relationship between coherent neural activity and CSF flow. Together, these Aims will test how neural activity is linked to CSF flow across sleep and wakefulness in the human brain, from ventricles down to perivascular spaces. Project 4 will contribute to the overall U19 goals by determining the link between neural activity and CSF flow at multiple spatial scales. By performing whole-brain imaging in humans, we can test how both local and global neural dynamics are linked to CSF flow in the tiny perivascular spaces and in the much-larger ventricles. By interacting with Project 2, our EEG-based measures of neural coherence will be linked to cellular-level measures of neuronal activity, with both our projects testing the link to CSF flow in the perivascular space. Our interactions with Project 3 will be critical to inform how neuromodulators shape vascular dynamics, and how neurovascular coupling is altered across sleep and wakefulness. Finally, our continuous interactions with Project 1 will be essential in order to determine which empirical measurements are needed to fully specify the model, and then update the model to make further predictions.