Data_Sheet_1_Topographic organization of the human caudate functional connectivity and age-related changes with resting-state fMRI.docx

The striatum is postulated to play a central role in gating cortical processing during goal-oriented behavior. While many human neuroimaging studies have treated the striatum as an undivided whole or several homogeneous compartments, some recent studies showed that its circuitry is topographically organized and has more complex relations with the cortical networks than previously assumed. Here, we took a gradient functional connectivity mapping approach that utilizes the entire anatomical space of the caudate nucleus to examine the organization of its functional relationship with the rest of the brain and how its topographic mapping changes with age. We defined the topography of the caudate functional connectivity using three publicly available resting-state fMRI datasets. We replicated and extended previous findings. First, we found two stable gradients of caudate connectivity patterns along its medial-lateral (M-L) and anterior-posterior (A-P) axes, supporting findings from previous tract-tracing studies of non-human primates that there are at least two main organizational principles within the caudate nucleus. Second, unlike previous emphasis of the A-P topology, we showed that the differential connectivity patterns along the M-L gradient of caudate are more clearly organized with the large-scale neural networks; such that brain networks associated with internal vs. external orienting behavior are respectively more closely linked to the medial vs. lateral extent of the caudate. Third, the caudate's M-L organization showed greater age-related reduction in integrity, which was further associated with age-related changes in behavioral measures of executive functions. In sum, our analysis confirmed a sometimes overlooked M-L functional connectivity gradient within the caudate nucleus, with its lateral longitudinal zone more closely linked to the frontoparietal cortical circuits and age-related changes in cognitive control. These findings provide a more precise mapping of the human caudate functional connectivity, both in terms of the gradient organization with cortical networks and age-related changes in such organization.

纹状体（striatum）被认为在目标导向行为期间的皮层加工门控过程中发挥核心作用。尽管诸多人类神经影像学研究将纹状体视为一个不可分割的整体或数个同质亚区，但近期部分研究表明，其环路具有拓扑组织特性，且与皮层网络的关联比此前设想的更为复杂。本研究采用梯度功能连接映射方法，利用尾状核（caudate nucleus）的全部解剖空间，探究其与全脑其余区域的功能关联组织模式，以及该拓扑映射随年龄的变化情况。我们基于三套公开可用的静息态功能磁共振成像（resting-state fMRI）数据集定义了尾状核功能连接的拓扑结构，并复现、拓展了既往研究结论。首先，我们发现尾状核连接模式沿内侧-外侧（M-L）和前-后（A-P）轴存在两条稳定梯度，这支持了非人类灵长类动物示踪研究的结论，即尾状核内至少存在两种主要组织原则。其次，与既往对前-后拓扑结构的侧重不同，我们发现尾状核沿内侧-外侧梯度的差异化连接模式与大规模神经网络的组织关联更为清晰：与内部定向行为、外部定向行为相关的脑网络分别更紧密地连接于尾状核的内侧与外侧区域。第三，尾状核的内侧-外侧组织模式表现出更显著的年龄相关连接完整性下降，且该变化与执行功能行为测量指标的年龄相关改变存在关联。综上，本研究证实了尾状核内一条常被忽视的内侧-外侧功能连接梯度，其外侧纵向亚区与额顶叶皮层环路及认知控制的年龄相关变化联系更为紧密。本研究结果为人类尾状核功能连接提供了更为精准的映射，既涵盖其与皮层网络的梯度组织模式，也包含该组织模式随年龄的变化情况。