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仍然没有行为反应的患者可以调节他们的大脑活动以响应命令。然而，其他病人对命令遵循范式缺乏反应，不能被视为意识缺失的证据。因此，有一个迫切需要的神经成像工具，能够诊断在行为反应迟钝的主体，而不依赖于一个任务的隐蔽意识。先前对意识的神经相关物（NCC）的神经成像研究主要利用状态间范式（例如，清醒与睡眠）或基于报告的对比，其将支持意识的大脑活动的差异与支持行为或任务响应的大脑活动的差异合并。为了解决这些局限性，我的赞助商（朱利奥·托诺尼博士）开发了一种状态内，无报告范式，使用连续唤醒来对比睡眠期间的意识状态和无意识状态，这是一种生理无反应状态。利用高密度脑电图（EEG），他的研究小组已经表明，睡眠期间做梦意识的发生与包括枕叶、顶叶和颞叶皮质在内的后皮质“热区”中δ活动（睡眠慢波）的减少有关。为了进一步走向临床应用，现在必须使用组合EEG-fMRI（功能性磁共振成像）来确认和扩展这些发现。为此，在一项重要的新进展中，Tononi博士及其合作者最近表明，通过功能磁共振成像中明显的高频（~0.17 Hz）血氧水平依赖（BOLD）振荡，可以忠实地跟踪睡眠期间的EEG慢波活动。这一发现提供了一个前所未有的机会，调查NCC在睡眠期间的高空间分辨率，避免潜在的陷阱EEG源建模，并与不受限制的访问皮层下结构。利用这些新的发现，在这个项目中，我建议结合联合收割机睡眠慢波的新功能磁共振成像签名与一个串行唤醒范例，以定位NCC在睡眠期间。具体来说，我将在40名健康受试者的约1，080次睡眠觉醒期间获取fMRI-EEG数据，并研究存在与不存在做梦意识的神经相关性（目标1）。我假设，与无梦睡眠相比，高频BOLD振荡（跟踪睡眠慢波）将显示做梦时特定后皮层区域的区域性减少。在目标2中，我将使用基于高频BOLD功率和常规BOLD幅度的单变量和多变量建模方法来识别特定梦境内容的NCC（例如，的存在）和复杂性。如果成功的话，拟议中的实验将在确定在行为无反应状态下维持意识及其内容的大脑区域方面迈出重要的一步。这些结果可以为改善DOC患者的临床护理开辟新的途径，并为麻醉受试者术中意识的评估提供信息。

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.