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

摘要 谵妄是一种常见且昂贵的问题，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、功能独立性丧失和死亡率增加。谵妄是 在患有阿尔茨海默氏痴呆症的患者中尤其成问题，这些患者具有增加的谵妄风险， 精神错乱会加速认知能力的下降然而，我们对神经基础的理解 在特定个体中谵妄的风险和影响仍然非常有限。该项目旨在解决 利用磁共振成像（MRI）引导（神经导航） 经颅磁刺激（TMS）与同步脑电图（EEG）， 肌电图（EMG），以评估接受择期手术的患者的皮质功能。一项前瞻性 我们将研究180名患者的队列是否减少了大脑网络连接和改变了 以TMS-EEG-EMG为特征的皮层可塑性与术后发展的风险相关 精神错乱我们将记录背外侧前额叶皮层、顶叶下皮层和颞叶下皮层的经颅磁刺激诱发电位（TEP）。 小叶和初级运动皮层，之前和之后的间歇θ-突发刺激（iTBS）。我们假设 基线EEG频谱功率和连通性，基于TMS的皮质反应性测量， 在随后发展为神经性疾病的患者中， 谵妄，并且基线时EEG特征和TMS测量异常更大的患者将有 更严重的谵妄和更大的短期认知能力下降谵妄发作后。我们将相互关联 神经生理学指标与患者认知能力的变化和随后的认知下降 有无谵妄我们假设EEG α功率和连通性，TMS反应性，TEP 皮质连接性和皮质可塑性机制的功效将显示出更大的降低， 谵妄患者比那些没有谵妄，并将与认知能力下降的幅度。最后在 之前观察到谵妄发作的患者（在SAGES I中），我们将比较有和没有谵妄发作的患者 谵妄病史，并假设皮质生理异常与长期认知功能相关 谵妄后下降（复杂性谵妄）。最终，我们的结果将定义神经生理学特征， 它可以识别出大脑脆弱的个体，这些个体容易出现谵妄和随后的认知能力下降， 将提供新的工具，以有效地评估干预措施的有效性，以帮助提高个人 大脑恢复力和减少谵妄的风险，并将指导治疗干预措施的发展， 帮助大脑功能障碍正常化，并最大限度地减少谵妄后长期认知能力下降。

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.