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

项目摘要 唤醒调节系统在广泛的精神和神经系统疾病中被破坏， 令人惊讶的是，我们对大脑网络的基本机制知之甚少。 睡眠和觉醒状态。侵入性动物研究已经证明了几个脑深部的因果作用， 包括脑干和丘脑的核团在内的区域在睡眠中被唤醒，最近，人类功能 磁共振成像（fMRI）研究唤醒暗示这些脑深部区域作为关键贡献者。 虽然我们知道大脑节律，连接和行为的变化伴随着觉醒状态的转变， 在这种状态变化期间，在这些关键区域中展开的全脑动态仍然未知。先前 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 发生在觉醒时侵入性研究受到它们可以同时记录的区域数量的限制， 并且传统的非侵入性方法缺乏捕获快速动态所必需的时间分辨率 发生在觉醒时我们的新方法将使用脑电图（EEG）和行为反应来检测 唤醒状态的变化结合同时快速fMRI（采样率< 1秒）在7特斯拉测量深， 脑干的核团、丘脑的单个核团、基底神经节区域和皮质的脑活动 人类从睡眠中觉醒的区域。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的显著时间差异。我们假设激活 脑干的蓝斑，其次是一个独特的激活序列，在丘脑核和 基底前脑，将先于唤醒，皮层区域的失活将随之而来。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 这将是必要的，以最终了解如何唤醒调节系统的动力学改变的障碍。 使用功能磁共振成像描绘这种时间网络动态将提供一个更精确的理解， 大脑在认知状态之间切换，通过允许我们将数十个皮层下核团的活动联系起来， 同步在人类中识别这些网络机制也将为未来的研究提供机会。 研究，以确定精细尺度的差异，在神经精神疾病，这是以前不可能的。

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.