Peters-Founshtein Gregory, Gazit Lidor, Naveh Tahel, Domachevsky Liran, Korczyn Amos, Bernstine Hanna, Groshar David, Marshall Gad A, Arzy Shahar
The Computational Neuropsychiatry Lab, Department of Medical Neurobiology, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Department of Nuclear Medicine, Sheba Medical Center, Ramat-Gan, Israel.
bioRxiv. 2023 Jan 26:2023.01.25.525587. doi: 10.1101/2023.01.25.525587.
Orientation is a fundamental cognitive faculty, allowing the behaving self to link his/her current state to their internal representations of the external world. Once exclusively linked to knowledge of the current place and present time, in recent years, the concept of orientation has evolved to include processing of social, temporal, and abstract relations. Concordantly with the growing focus on orientation, spatial disorientation has been increasingly recognized as a hallmark symptom of Alzheimer's disease (AD). However, few studies have sought to explore disorientation along the AD continuum beyond the spatial domain. 51 participants along the AD continuum performed an orientation task in the spatial, temporal and social domains. Under functional magnetic resonance imaging (fMRI), participants determined which of two familiar places/events/people is geographically/ chronologically/ socially closer to them, respectively. A series of analyses revealed disorientation along the AD- continuum to follow a three-way association between (1) orientation domain, (2) brain region, and (3) disease stage. Specifically, participants with MCI exhibited impaired spatio-temporal orientation and reduced task-evoked activity in temporoparietal regions, while participants with AD dementia exhibited impaired social orientation and reduced task-evoked activity in frontoparietal regions. Furthermore, these patterns of hypoactivation coincided with Default Mode Network (DMN) sub-networks, with spatio-temporal orientation activation overlapping DMN-C and social orientation with DMN-A. Finally, these patterns of disorientation- associated hypoactivations coincided with patterns of fluorodeoxyglucose (FDG) hypometabolism and cortical atrophy characteristic to AD-dementia. Taken together, our results suggest that AD may constitute a disorder of orientation, characterized by a biphasic process as (1) early spatio-temporal and (2) late social disorientation, concurrently manifesting in task-evoked and neurodegenerative changes in temporoparietal and parieto-frontal brain networks, respectively. We propose that a profile of disorientation across multiple domains offers a unique window into the progression of AD.
定向是一种基本的认知能力，使行为主体能够将其当前状态与他们对外部世界的内部表征联系起来。曾经定向仅仅与对当前地点和当前时间的认知相关联，近年来，定向的概念已经发展到包括对社会、时间和抽象关系的处理。与对定向的关注度不断提高相一致，空间定向障碍越来越被认为是阿尔茨海默病（AD）的一个标志性症状。然而，很少有研究试图在空间领域之外探索AD连续体上的定向障碍。51名处于AD连续体上的参与者在空间、时间和社会领域执行了一项定向任务。在功能磁共振成像（fMRI）下，参与者分别确定两个熟悉的地点/事件/人物中哪一个在地理上/时间上/社会上离他们更近。一系列分析揭示，AD连续体上的定向障碍遵循（1）定向领域、（2）脑区和（3）疾病阶段之间的三元关联。具体而言，轻度认知障碍（MCI）参与者表现出时空定向受损，颞顶叶区域的任务诱发活动减少，而AD痴呆症参与者表现出社会定向受损，额顶叶区域的任务诱发活动减少。此外，这些低激活模式与默认模式网络（DMN）子网一致，时空定向激活与DMN-C重叠，社会定向与DMN-A重叠。最后，这些与定向障碍相关的低激活模式与氟脱氧葡萄糖（FDG）低代谢模式以及AD痴呆症特有的皮质萎缩模式一致。综上所述，我们的结果表明，AD可能构成一种定向障碍，其特征是一个双相过程：（1）早期的时空定向障碍和（2）晚期的社会定向障碍，分别同时表现在颞顶叶和额顶叶脑网络的任务诱发变化和神经退行性变化中。我们提出，跨多个领域的定向障碍概况为AD的进展提供了一个独特的窗口。
