Department of Neurology, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV 89106, USA.
Department of Neurology, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV 89106, USA.
Neuroscience. 2024 Nov 1;559:8-16. doi: 10.1016/j.neuroscience.2024.08.031. Epub 2024 Aug 22.
Olfactory dysfunction is an early sign of such neurodegenerative diseases as Parkinson's (PD) and Alzheimer's (AD), and is often present in Mild Cognitive Impairment (MCI), a precursor of AD. Understanding neuro-temporal relationships, i.e., functional connectivity, between olfactory eloquent structures in such disorders, could shed light on their basic pathophysiology. To this end, we employed region-based analyses using resting-state functional magnetic resonance imaging (rs-fMRI) obtained from cognitively normal (CN), MCI, and PD patients with cognitive impairment (PD-CogImp). Using machine learning (linear and ensemble learning), we determined whether the identified functional patterns could classify abnormal function from normal function. Olfaction, as measured by objective testing, was found to be most strongly associated with diagnostic status, emphasizing the fundamental association of this primary sensory system with these conditions. Consistently lower functional connectivity was observed in the PD-CogImp cohort compared to the CN cohort among all identified brain regions. Differences were also found between PD-CogImp and MCI at the level of the orbitofrontal and cingulate cortices. MCI and CN subjects had different functional connectivity between the posterior orbitofrontal cortex and thalamus. Regardless of study group, males showed significantly higher connectivity than females in connections involving the orbitofrontal cortex. The logistic regression model trained using the top discriminatory features revealed that caudate was the most involved olfaction-related brain structure (accuracy = 0.88, Area under the Receiver operator characteristic curve of 0.90). In aggregate, our study demonstrates that resting functional connectivity among olfactory eloquent structures has potential value in better understanding the pathophysiology of several neurodegenerative diseases.
嗅觉功能障碍是帕金森病 (PD) 和阿尔茨海默病 (AD) 等神经退行性疾病的早期迹象，并且常常存在于轻度认知障碍 (MCI) 中，MCI 是 AD 的前兆。了解这些疾病中嗅觉相关结构的神经时间关系，即功能连接，可能有助于揭示它们的基本病理生理学。为此，我们使用基于区域的分析方法，利用来自认知正常 (CN)、MCI 和有认知障碍的 PD 患者 (PD-CogImp) 的静息状态功能磁共振成像 (rs-fMRI)。我们使用机器学习 (线性和集成学习) 来确定所识别的功能模式是否可以将异常功能与正常功能进行分类。通过客观测试测量的嗅觉与诊断状态的关联最密切，强调了这个主要感觉系统与这些疾病的基本关联。与 CN 队列相比，PD-CogImp 队列中所有识别出的大脑区域的功能连接均明显较低。在眶额皮层和扣带皮层水平，也发现了 PD-CogImp 与 MCI 之间的差异。MCI 和 CN 受试者的后眶额皮层和丘脑之间的功能连接不同。无论研究组如何，男性在涉及眶额皮层的连接中的连接性都明显高于女性。使用最佳鉴别特征训练的逻辑回归模型表明，尾状核是与嗅觉相关的最相关脑结构 (准确率 = 0.88，接收器操作特性曲线下面积为 0.90)。总之，我们的研究表明，嗅觉相关结构之间的静息功能连接在更好地理解几种神经退行性疾病的病理生理学方面具有潜在价值。
