Lotter Leon D, Saberi Amin, Hansen Justine Y, Misic Bratislav, Paquola Casey, Barker Gareth J, Bokde Arun L W, Desrivières Sylvane, Flor Herta, Grigis Antoine, Garavan Hugh, Gowland Penny, Heinz Andreas, Brühl Rüdiger, Martinot Jean-Luc, Paillère Marie-Laure, Artiges Eric, Papadopoulos Orfanos Dimitri, Paus Tomáš, Poustka Luise, Hohmann Sarah, Fröhner Juliane H, Smolka Michael N, Vaidya Nilakshi, Walter Henrik, Whelan Robert, Schumann Gunter, Nees Frauke, Banaschewski Tobias, Eickhoff Simon B, Dukart Juergen
Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre Jülich, Jülich, Germany.
Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
Nat Commun. 2024 Sep 12;15(1):7987. doi: 10.1038/s41467-024-52366-7.
Human brain morphology undergoes complex changes over the lifespan. Despite recent progress in tracking brain development via normative models, current knowledge of underlying biological mechanisms is highly limited. We demonstrate that human cortical thickness development and aging trajectories unfold along patterns of molecular and cellular brain organization, traceable from population-level to individual developmental trajectories. During childhood and adolescence, cortex-wide spatial distributions of dopaminergic receptors, inhibitory neurons, glial cell populations, and brain-metabolic features explain up to 50% of the variance associated with a lifespan model of regional cortical thickness trajectories. In contrast, modeled cortical thickness change patterns during adulthood are best explained by cholinergic and glutamatergic neurotransmitter receptor and transporter distributions. These relationships are supported by developmental gene expression trajectories and translate to individual longitudinal data from over 8000 adolescents, explaining up to 59% of developmental change at cohort- and 18% at single-subject level. Integrating neurobiological brain atlases with normative modeling and population neuroimaging provides a biologically meaningful path to understand brain development and aging in living humans.
人类大脑形态在整个生命周期中会经历复杂的变化。尽管最近通过规范模型在追踪大脑发育方面取得了进展，但目前对潜在生物学机制的了解仍然非常有限。我们证明，人类皮质厚度的发育和衰老轨迹沿着分子和细胞水平的脑组织模式展开，这种模式可以从群体水平追溯到个体发育轨迹。在儿童期和青少年期，多巴胺能受体、抑制性神经元、神经胶质细胞群体和脑代谢特征的全皮质空间分布能够解释与区域皮质厚度轨迹寿命模型相关的高达50%的方差。相比之下，成年期模拟的皮质厚度变化模式最好由胆碱能和谷氨酸能神经递质受体及转运体分布来解释。这些关系得到了发育基因表达轨迹的支持，并转化为来自8000多名青少年的个体纵向数据，在队列水平上解释了高达59%的发育变化，在单受试者水平上解释了18%的发育变化。将神经生物学脑图谱与规范建模和群体神经影像学相结合，为理解活体人类的大脑发育和衰老提供了一条具有生物学意义的途径。
