Data underlying y-axis of S3 Fig.

The human brain is organized as segregation and integration units and follows complex developmental trajectories throughout life. The cortical manifold provides a new means of studying the brain’s organization in a multidimensional connectivity gradient space. However, how the brain’s morphometric organization changes across the human lifespan remains unclear. Here, leveraging structural magnetic resonance imaging scans from 1,790 healthy individuals aged 8 to 89 years, we investigated age-related global, within- and between-network dispersions to reveal the segregation and integration of brain networks from 3D manifolds based on morphometric similarity network (MSN), combining multiple features conceptualized as a “fingerprint” of an individual’s brain. Developmental trajectories of global dispersion unfolded along patterns of molecular brain organization, such as acetylcholine receptor. Communities were increasingly dispersed with age, reflecting more disassortative morphometric similarity profiles within a community. Increasing within-network dispersion of primary motor and association cortices mediated the influence of age on the cognitive flexibility of executive functions. We also found that the secondary sensory cortices were decreasingly dispersed with the rest of the cortices during aging, possibly indicating a shift of secondary sensory cortices across the human lifespan from an extreme to a more central position in 3D manifolds. Together, our results reveal the age-related segregation and integration of MSN from the perspective of a multidimensional gradient space, providing new insights into lifespan changes in multiple morphometric features of the brain, as well as the influence of such changes on cognitive performance.

人类大脑以分离与整合单元的形式组织，并在整个生命周期中遵循复杂的发育轨迹。皮层流形（cortical manifold）为在多维连接梯度空间中研究大脑组织模式提供了新的手段。然而，大脑的形态计量组织如何在人类整个生命周期中发生变化，目前仍不明确。本研究利用1790名年龄在8至89岁的健康个体的结构磁共振成像（structural magnetic resonance imaging）扫描数据，结合被概念化为个体大脑“指纹”的多特征，探究了与年龄相关的全局、网络内及网络间离散度，以基于形态计量相似性网络（MSN）的三维流形视角揭示大脑网络的分离与整合机制。全局离散度的发育轨迹沿大脑分子组织模式展开，例如乙酰胆碱受体（acetylcholine receptor）。脑网络模块的离散度随年龄增长而增加，反映出模块内部的形态计量相似性特征愈发呈现异配性模式。初级运动皮层与联合皮层的网络内离散度增加，介导了年龄对执行功能认知灵活性的影响。本研究还发现，在衰老过程中，次级感觉皮层与其余皮层的离散度逐渐降低，这可能表明人类生命周期中次级感觉皮层在三维流形空间中的位置从极端位置转向了更核心的位置。综上，本研究从多维梯度空间的视角揭示了MSN随年龄变化的分离与整合模式，为大脑多种形态计量特征的生命周期变化以及此类变化对认知表现的影响提供了全新的研究视角。