Age-related differences in the functional topography of the locus coeruleus and their implications for cognitive and affective functions.
Age-related differences in the functional topography of the locus coeruleus and their implications for cognitive and affective functions.
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DOI：
10.7554/elife.87188
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发表时间：
2023-08-31
期刊：
影响因子：
7.7
通讯作者：
Pereira JB
中科院分区：
文献类型：
--
作者：
Veréb D;Mijalkov M;Canal-Garcia A;Chang YW;Gomez-Ruiz E;Gerboles BZ;Kivipelto M;Svenningsson P;Zetterberg H;Volpe G;Betts M;Jacobs HIL;Pereira JB
蓝斑核（locus coeruleus， LC）是一种重要的去肾上腺素能核，近年来因其在认知和精神疾病中的作用而受到广泛关注。虽然之前的组织学研究表明LC具有异质性连接和细胞特征，但尚未有研究评估其在体内的功能地形，这种异质性如何随年龄变化，以及它是否与认知和情绪有关。在这里，我们采用基于梯度的方法，利用3T静息状态功能磁共振成像技术，对年龄在18岁至88岁之间的人群队列（剑桥老龄化和神经科学中心队列，n=618）中LC组织的功能异质性进行表征。我们发现，LC沿其纵轴呈现出一个直立-尾端功能梯度，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。虽然该梯度的主要方向在各年龄组中是一致的，但其空间特征随着年龄、情绪记忆和情绪调节的增加而变化。更具体地说，喙状连通性的丧失，更多的聚集功能地形，以及左右LC梯度之间更大的不对称性与年龄的增长和更差的行为表现有关。此外，医院焦虑和抑郁量表（HADS）评分高于正常水平的参与者也表现出梯度的变化，这表现出更大的不对称性。这些结果提供了LC的功能地形如何随年龄变化的体内解释，并暗示该组织的空间特征是LC相关行为测量和精神病理的相关标记。
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.