Characterizing the Relationship between Brain Electrophysiology, Delirium, and Cognitive Decline

摘要 精神错乱是一种常见且代价高昂的问题，影响多达一半的住院老年人，并导致 严重的发病率、认知能力下降、功能独立性的丧失和死亡率的增加。精神错乱是 尤其是在阿尔茨海默氏症患者中，他们有更高的精神错乱风险，而且在 精神错乱会加速认知衰退的速度。然而，我们对神经学基础的理解 对特定个体的精神错乱的风险和影响的了解仍然非常有限。该项目旨在解决 利用磁共振成像(MRI)引导(神经导航)实现这一重要的知识鸿沟 经颅磁刺激(TMS)与同步脑电(EEG)和 肌电(EMG)用于评估择期手术患者的皮质功能。在未来 我们将检查180名患者的大脑网络连通性降低和机制改变 TMS-EEG-EMG特征的皮质可塑性与术后发生风险相关 精神错乱。我们将记录TMS诱发电位(TEP)的背外侧前额叶皮质，顶下 间歇性电刺激(ITBS)前后小叶和初级运动皮质的变化。我们假设 基线脑电频谱功率和连接性、基于TMS的皮质反应性测量和 连接性，ITBS测量皮质可塑性的指标将在随后发展的患者中降低 精神错乱，脑电特征和TMS基线测量有较大异常的患者将 精神错乱发作后更严重的精神错乱和更大的短期认知能力下降。我们将相互关联 神经生理学测量与患者认知能力和随后认知功能减退的变化 有或没有精神错乱。我们假设脑电的阿尔法功率和连接性、TMS反应性、TEP 皮质连接性和皮质可塑性机制的有效性将显示出更大的下降 有妄想症的患者比没有的患者，并将与认知功能下降的幅度相关。最后，在 以前观察到的精神错乱发作的患者(在SAGE I中)，我们将比较那些有和没有A的患者 精神错乱的病史，以及皮质生理异常与长期认知相关的假设 精神错乱(复杂的精神错乱)后下降。最终，我们的结果将定义神经生理学特征 它可以识别大脑脆弱的个体，这些个体容易出现精神错乱和随后的认知能力下降， 将提供新的工具来有效评估干预措施的有效性，以帮助提高个人 大脑复原力和降低精神错乱的风险，并将指导治疗干预措施的发展 有助于使大脑功能正常化，并最大限度地减少精神错乱后的长期认知衰退。

ABSTRACT Delirium is a common and costly problem, affecting up to half of hospitalized older adults, and resulting in substantial morbidity, cognitive decline, loss of functional independence, and increased mortality. Delirium is particularly problematic in patients with Alzheimer's dementia who have an increased risk for delirium, and in whom delirium accelerates the rate of cognitive decline. However, our understanding of the neurological basis of the risk for and effects of delirium in a given individual remains very limited. This project seeks to address this important knowledge gap by utilizing magnetic resonance imaging (MRI)-guided (neuronavigated) transcranial magnetic stimulation (TMS) with simultaneous electroencephalography (EEG) and electromyography (EMG) to evaluate cortical function in patients undergoing elective surgery. In a prospective cohort of 180 patients we will examine whether decreased brain network connectivity and altered mechanisms of cortical plasticity as characterized by TMS-EEG-EMG are associated with the risk of developing post-operative delirium. We will record TMS-evoked potentials (TEP) from dorsolateral prefrontal cortex, inferior parietal lobule, and primary motor cortex, before and after intermittent theta-burst stimulation (iTBS). We hypothesize that baseline EEG spectral power and connectivity, TMS-based measures of cortical reactivity and connectivity, and iTBS measures of cortical plasticity will be decreased in patients who subsequently develop delirium, and that patients with greater abnormalities in EEG features and TMS measures at baseline will have greater delirium severity and greater short-term cognitive decline after an episode of delirium. We will correlate neurophysiologic measures with changes in cognitive performance and subsequent cognitive decline in patients with versus without delirium. We hypothesize that EEG alpha power and connectivity, TMS reactivity, TEP cortical connectivity, and efficacy of the mechanisms of cortical plasticity will show greater decreases in patients with delirium than in those without, and will correlate with the magnitude of cognitive decline. Finally, in patients with a previously observed episode of delirium (in SAGES I) we will compare those with and without a history of delirium, and hypothesize that cortical physiology abnormalities will correlate with long-term cognitive decline after delirium (complicated delirium). Ultimately, our results will define neurophysiologic characteristics that can identify individuals with a vulnerable brain susceptible to delirium and subsequent cognitive decline, will provide novel tools to efficiently assess the effectiveness of interventions to help increase individual cerebral resilience and reduce the risk of delirium, and will guide development of therapeutic interventions to help normalize cerebral dysfunction and minimize long-term cognitive decline after delirium.