Age-related differences in the functional topography of the locus coeruleus: implications for cognitive and affective functions.
Age-related differences in the functional topography of the locus coeruleus: implications for cognitive and affective functions.
复制标题
蓝斑功能地形的年龄相关差异：对认知和情感功能的影响。
DOI：
10.1101/2023.02.25.23286442
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Pereira,JoanaB
中科院分区：
文献类型：
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作者：
Veréb,Dániel;Mijalkov,Mite;Canal-Garcia,Anna;Chang,Yu-Wei;Gomez-Ruis,Emiliano;Gerboles,BlancaZufiria;Kivipelto,Miia;Svenningsson,Per;Zetterberg,Henrik;Volpe,Giovanni;Betts,MathewJ;Jacobs,Heidi;Pereira,JoanaB
蓝斑核（LC）是一个重要的去甲肾上腺素能核团，由于其在认知和精神疾病中的作用，最近引起了人们的广泛关注。虽然以前的组织学研究表明，LC具有异质性连接和细胞特征，但还没有研究评估其在体内的功能拓扑结构，这种异质性如何随着年龄的增长而变化，以及它是否与认知和情绪有关。在此，我们采用基于梯度的方法，在年龄从18岁到88岁的人群队列（剑桥老龄化和神经科学中心队列，n= 618）中使用3T静息态fMRI来表征LC随年龄增长的组织功能异质性。我们发现LC沿其纵轴沿着表现出喙尾功能梯度，这在一个独立的数据集（Human Connectome Project [HCP] 7T数据集，n= 184）中得到了复制。虽然这个梯度的主要喙尾方向是一致的年龄组，其空间特征随年龄的增长，情绪记忆和情绪调节。更具体地说，失去喙状连接，更集群的功能地形，和更大的不对称之间的右和左LC梯度与更高的年龄和更差的行为表现。此外，医院焦虑和抑郁量表（HADS）评分高于正常的参与者也表现出梯度的变化，表现为更大的不对称性。这些结果提供了一个在体内帐户的LC的功能地形如何随着年龄的增长而变化，并意味着该组织的空间特征的LC相关的行为措施和精神病理学的相关标志物。
The locus coeruleus (LC) is an important noradrenergic nucleus that has recently attracted a lot of attention because of its emerging role in cognitive and psychiatric disorders. Although previous histological studies have shown that the LC has heterogeneous connections and cellular features, no studies have yet assessed its functional topography in vivo, how this heterogeneity changes over aging, and whether it is associated with cognition and mood. Here, we employ a gradient-based approach to characterize the functional heterogeneity in the organization of the LC over aging using 3T resting-state fMRI in a population-based cohort aged from 18 to 88 years of age (Cambridge Centre for Ageing and Neuroscience cohort, n= 618). We show that the LC exhibits a rostro-caudal functional gradient along its longitudinal axis, which was replicated in an independent dataset (Human Connectome Project [HCP] 7T dataset, n= 184). Although the main rostro-caudal direction of this gradient was consistent across age groups, its spatial features varied with increasing age, emotional memory, and emotion regulation. More specifically, a loss of rostral-like connectivity, more clustered functional topography, and greater asymmetry between right and left LC gradients was associated with higher age and worse behavioral performance. Furthermore, participants with higher-than-normal Hospital Anxiety and Depression Scale (HADS) ratings exhibited alterations in the gradient as well, which manifested in greater asymmetry. These results provide an in vivo account of how the functional topography of the LC changes over aging, and imply that spatial features of this organization are relevant markers of LC-related behavioral measures and psychopathology.