Microstructural and functional gradients are increasingly dissociated in transmodal cortices

While the role of cortical microstructure in organising neural function is well established, it remains unclear how structural constraints can give rise to more flexible elements of cognition. While nonhuman primate research has demonstrated a close structure–function correspondence, the relationship between microstructure and function remains poorly understood in humans, in part because of the reliance on post mortem analyses, which cannot be directly related to functional data. To overcome this barrier, we developed a novel approach to model the similarity of microstructural profiles sampled in the direction of cortical columns. Our approach was initially formulated based on an ultra-high–resolution 3D histological reconstruction of an entire human brain and then translated to myelin-sensitive magnetic resonance imaging (MRI) data in a large cohort of healthy adults. This novel method identified a system-level gradient of microstructural differentiation traversing from primary sensory to limbic regions that followed shifts in laminar differentiation and cytoarchitectural complexity. Importantly, while microstructural and functional gradients described a similar hierarchy, they became increasingly dissociated in transmodal default mode and fronto–parietal networks. Meta-analytic decoding of these topographic dissociations highlighted involvement in higher-level aspects of cognition, such as cognitive control and social cognition. Our findings demonstrate a relative decoupling of macroscale functional from microstructural gradients in transmodal regions, which likely contributes to the flexible role these regions play in human cognition.尽管大脑皮层微结构在组织神经功能中的作用已得到广泛证实，但结构约束如何催生认知中更具灵活性的要素，目前仍不明确。尽管非人灵长类动物研究已证明结构与功能间存在紧密的对应关系，但人类大脑微结构与功能的关联机制仍知之甚少，部分原因在于过往研究依赖死后分析，而这类分析无法与功能数据直接关联。为突破这一局限，我们开发了一种全新方法，用于建模沿大脑皮层柱方向采样的微结构特征的相似性。该方法最初基于全脑超高分辨率三维组织学重建构建，随后被推广应用于大样本健康成人的髓鞘敏感磁共振成像（myelin-sensitive magnetic resonance imaging, MRI）数据。该全新方法揭示了一套系统级的微结构分化梯度，该梯度从初级感觉区域延伸至边缘系统区域，且与皮层分层分化和细胞构筑复杂度的变化相一致。值得注意的是，尽管微结构梯度与功能梯度呈现出相似的层级结构，但在跨模态默认模式网络与额顶网络中，二者的关联程度逐渐减弱。对这些地形学分离现象的元分析解码结果显示，这些区域涉及认知控制与社会认知等高级认知功能。我们的研究结果表明，跨模态区域的宏观功能梯度与微结构梯度存在相对解耦现象，这或许正是这些区域在人类认知中发挥灵活作用的重要基础。