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

摘要，项目 4 在 NREM 睡眠期间，大脑中会出现大量脑脊液 (CSF) 流动。神经慢波 比这些脑脊液流波早几秒钟，表明连贯的神经活动可以驱动脑脊液 通过诱导大规模神经血管耦合来流动。该项目将检验以下假设：时空 神经活动的动态调节脑脊液在人脑中的流动。我们将优化整合多个 新颖的 MR 技术可对心室和血管周围空间的脑脊液流动进行成像，同时 使用脑电图测量神经活动，使用功能磁共振成像测量血流动力学反应。在目标 1 中，我们将测试是否 时空模式的神经活动与脑脊液流量相关，在成熟的视觉任务中进行测量。 在目标 2 中，我们将测试睡眠期间自发神经活动的动态是否与脑脊液流量耦合 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如何， 释放去甲肾上腺素和乙酰胆碱，与连贯神经活动和脑脊液之间的关系有关 流动。这些目标将共同测试神经活动如何与睡眠和清醒状态下的脑脊液流量相关联。 人脑，从心室到血管周围空间。 项目 4 将通过确定神经活动和脑脊液之间的联系来促进 U19 的总体目标 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血管周围空间和大得多的心室中的脑脊液流动有关。 通过与项目 2 交互，我们基于脑电图的神经一致性测量将与细胞水平相关联 神经元活动的测量，我们的两个项目都测试了与血管周围空间中脑脊液流动的联系。我们的 与项目 3 的相互作用对于了解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会发生变化。最后，我们与 Project 的持续互动 1 对于确定需要哪些经验测量来完全指定模型至关重要， 然后更新模型以做出进一步的预测。

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.