Novel fMRI Strategy to Assess Consciousness in Brain-Injured Patients

多项研究表明，一些在严重脑损伤后行为反应迟钝的患者可以根据命令调整他们的大脑活动。然而，其他患者对命令遵循范例缺乏反应不能被视为意识缺失的证据。因此，迫切需要一种神经成像工具，能够在不依赖任务的情况下诊断行为反应迟钝的受试者的隐蔽意识。以往对意识神经相关(NCC)的神经成像研究大多利用状态间范式(例如，清醒与睡眠)或基于报告的对比，将支持意识的大脑活动的差异与支持行为或任务反应的大脑活动的差异混为一谈。为了解决这些局限性，我的赞助人(朱利奥·托诺尼博士)开发了一种状态内、无报告的范例，它使用连续唤醒来对比睡眠中的意识状态和无意识状态，这是一种生理上的无反应状态。使用高密度脑电(EEG)，他的研究小组已经证明，睡眠中做梦意识的出现与枕叶、顶叶和颞叶皮质后部皮质热区的增量活动(睡眠慢波)减少有关。为了进行临床应用，现在有必要使用联合EEG-fMRI(功能磁共振成像)来确认和扩展这些发现。为此，在一项重要的新发展中，Tononi博士和他的合作者最近证明，通过fMRI中明显的高频(~0.17赫兹)血氧水平依赖(BOLD)振荡，有可能准确地跟踪睡眠期间的EEG慢波活动。这一发现为以高空间分辨率研究睡眠中的NCC提供了前所未有的机会，避免了EEG源建模的潜在陷阱，并可以不受限制地访问皮质下结构。利用这些新的发现，在这个项目中，我建议将睡眠慢波的新颖功能磁共振特征与序列唤醒范式相结合来定位睡眠中的NCC。具体地说，我将收集40名健康受试者从睡眠中醒来约1,080次的fMRI-EEG数据，并调查有无做梦意识的神经关联(目标1)。我假设，与无梦睡眠相比，追踪睡眠慢波的高频大胆振荡会显示出做梦时特定皮质后部区域的区域性减少。在目标2中，我将使用基于高频粗体强度和常规粗体幅度的单变量和多变量建模方法来识别特定梦境内容(例如，面孔的存在)和复杂性的NCC。如果成功，拟议中的实验将成为在行为无反应状态下识别维持意识及其内容的大脑区域的重要一步。这些结果可以为改善DOC患者的临床护理开辟新的途径，并为评估麻醉受试者的术中意识提供信息。

Multiple studies have shown that some patients who remain behaviorally unresponsive after severe brain damage can modulate their brain activity in response to command. A lack of response to the command- following paradigm in other patients, however, cannot be taken as evidence that consciousness is absent. There is thus an urgent need for neuroimaging tools that are able to diagnose covert consciousness in behaviorally unresponsive subjects without relying on a task. Previous neuroimaging studies of the neural correlates of consciousness (NCCs) have mostly utilized between-state paradigms (e.g., wakefulness vs. sleep) or report-based contrasts, which conflate differences in brain activity supporting consciousness with differences in brain activity supporting behavior or task response. To address these limitations, my sponsor (Dr. Giulio Tononi) has developed a within-state, no-report paradigm that uses serial awakenings to contrast states of consciousness versus unconsciousness during sleep, a physiological unresponsive state. Using high density electroencephalography (EEG), his group has shown that the occurrence of dreaming consciousness during sleep is associated with a reduction of delta activity (sleep slow waves) in a posterior cortical ‘hot zone’ encompassing occipital, parietal and temporal cortices. To proceed towards clinical applications, it is now essential to confirm and extend these findings using combined EEG-fMRI (functional magnetic resonance imaging). To this effect, in an important new development, Dr. Tononi and collaborators have recently shown that it is possible to faithfully track EEG slow wave activity during sleep by means of a high-frequency (~0.17 Hz) blood-oxygenation level dependent (BOLD) oscillation evident in fMRI. This finding provides an unprecedented opportunity to investigate the NCCs during sleep with high spatial resolution, avoiding potential pitfalls of EEG source modeling, and with unrestricted access to subcortical structures. Taking advantage of these new findings, in this project, I propose to combine the novel fMRI signature of sleep slow waves with a serial awakenings paradigm to locate the NCCs during sleep. Specifically, I will acquire fMRI-EEG data during ~1,080 awakenings from sleep across 40 healthy subjects and investigate the neural correlates of the presence versus absence of dreaming consciousness (Aim 1). I hypothesize that high-frequency BOLD oscillation—which tracks sleep slow-waves—will show regional decreases in specific posterior cortical areas during dreaming compared to dreamless sleep. In Aim 2, I will use univariate and multivariate modeling approaches based on high-frequency BOLD power and conventional BOLD amplitude to identify the NCCs of specific dream contents (e.g., presence of faces) and complexity. If successful, the proposed experiments will constitute an important step forward in identifying brain regions that sustain consciousness and its contents during behaviorally unresponsive states. These results can open new avenues to improve clinical care in patients with a DOC and inform the assessment of intraoperative awareness in anesthetized subjects.