Advanced neuroimaging of arousal-state transition network dynamics in the human brain

项目总结 唤醒调节系统在广泛的精神和神经障碍中被扰乱，但 令人惊讶的是，我们对潜在的大脑网络机制知之甚少 睡眠和唤醒--状态。侵袭性动物研究已经证明了几个深部大脑的因果作用 从睡眠中觉醒的脑干和丘脑等区域，以及最近人类功能 对唤醒的磁共振成像(FMRI)研究表明，大脑深部区域是关键因素。 虽然我们知道大脑节奏、连通性和行为的变化伴随着觉醒状态的转换，但 在这种状态变化期间，整个大脑的动态变化在这些关键区域展开--目前尚不清楚。上一首 研究一直受到捕捉全脑网络动态所需的时空分辨率的限制 在觉醒时发生的。侵入性研究受到它们可以同时记录的区域数量的限制， 而传统的非侵入性方法缺乏捕捉快速动态所需的时间分辨率 在觉醒时发生的。我们的新方法将使用脑电(EEG)和行为反应来检测 唤醒状态变化结合同步快速功能磁共振成像(采样率1 S)在7特斯拉测量深度- 脑干核团、丘脑单个核团、基底节区和皮质的脑活动 在人类从睡眠中唤醒时的区域。初步数据表明，这种功能磁共振成像采集方法可以检测到 感兴趣区域之间的活动特征存在显著的时间差异。我们假设激活 脑干蓝斑，随后是丘脑核团和 基底前脑，将在觉醒之前，皮质区域将随之失活。我们的目标是建立一个 对支持人类觉醒-状态转换的基本网络机制的基本理解 这将是最终理解兴奋调节系统动态是如何在紊乱中改变的必要的。 使用功能磁共振成像描绘这种时间网络动力学将提供更准确的理解 大脑通过允许我们连接数十个皮质下核团的活动来在认知状态之间切换 同时。识别人类的这些网络机制也将为未来提供机会 研究确定神经精神障碍的细微差别，这在以前是不可能的。

PROJECT SUMMARY Arousal regulatory systems are disrupted in a wide range of psychiatric and neurological disorders, yet we know surprisingly little about the fundamental brain network mechanisms underlying transitions between the sleep and wake arousal-states. Invasive animal studies have demonstrated the causal role of several deep-brain regions including nuclei of the brainstem and thalamus in arousal from sleep, and recently, human functional magnetic resonance imaging (fMRI) studies of arousal implicated such deep-brain regions as key contributors. While we know shifts in brain rhythms, connectivity, and behavior accompany arousal-state transitions, how brain-wide dynamics unfold across such key regions during this state-change remains unknown. Previous studies have been limited by the spatiotemporal resolution necessary to capture whole-brain network dynamics occurring at arousal. Invasive studies are limited by the number of regions they can record from simultaneously, and traditional non-invasive methods lack the temporal resolution necessary to capture the fast dynamics occurring at arousal. Our novel method will use encephalography (EEG) and behavioral response to detect arousal-state changes combined with simultaneous fast fMRI (sample rate < 1 s) at 7 Tesla to measure deep- brain activity in nuclei of the brainstem, individual nuclei of the thalamus, basal ganglia regions, and cortical regions during human arousal from sleep. Preliminary data suggests that this fMRI acquisition method can detect significant temporal differences in activity signatures between regions of interest. We hypothesize that activation of the brainstem’s locus coeruleus, followed by a distinct activation sequence across thalamic nuclei and the basal forebrain, will precede arousal, and deactivation of cortical regions will follow. We aim to build a fundamental understanding of the basic network mechanisms supporting arousal-state transitions in humans that will be necessary to ultimately understand how arousal regulatory system dynamics are altered in disorders. Delineating such temporal network dynamics using fMRI will provide a more precise understanding of how the brain switches between cognitive states by allowing us to link activity across dozens of subcortical nuclei simultaneously. Identifying these network mechanisms in humans will also provide the opportunity for future studies to identify fine-scale differences in neuropsychiatric disorders that was not previously possible.