Medical Research Council Cognition and Brain Sciences Unit, University of Cambridge, Cambridge CB2 7EF, United Kingdom.
Department of Neurology, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A. 2023 Oct 17;120(42):e2307508120. doi: 10.1073/pnas.2307508120. Epub 2023 Oct 10.
Neural phenotypes are the result of probabilistic developmental processes. This means that stochasticity is an intrinsic aspect of the brain as it self-organizes over a protracted period. In other words, while both genomic and environmental factors shape the developing nervous system, another significant-though often neglected-contributor is the randomness introduced by probability distributions. Using generative modeling of brain networks, we provide a framework for probing the contribution of stochasticity to neurodevelopmental diversity. To mimic the prenatal scaffold of brain structure set by activity-independent mechanisms, we start our simulations from the medio-posterior neonatal rich club (Developing Human Connectome Project, = 630). From this initial starting point, models implementing Hebbian-like wiring processes generate variable yet consistently plausible brain network topologies. By analyzing repeated runs of the generative process (>10 simulations), we identify critical determinants and effects of stochasticity. Namely, we find that stochastic variation has a greater impact on brain organization when networks develop under weaker constraints. This heightened stochasticity makes brain networks more robust to random and targeted attacks, but more often results in non-normative phenotypic outcomes. To test our framework empirically, we evaluated whether stochasticity varies according to the experience of early-life deprivation using a cohort of neurodiverse children (Centre for Attention, Learning and Memory; = 357). We show that low-socioeconomic status predicts more stochastic brain wiring. We conclude that stochasticity may be an unappreciated contributor to relevant developmental outcomes and make specific predictions for future research.
神经表型是概率发育过程的结果。这意味着随机性是大脑自我组织的固有方面,因为它是在一个漫长的时期内自我组织的。换句话说,虽然基因组和环境因素都塑造了发育中的神经系统,但另一个重要的——尽管常常被忽视的——贡献因素是概率分布所带来的随机性。我们使用大脑网络的生成模型,为研究随机性对神经发育多样性的贡献提供了一个框架。为了模拟由非活动依赖性机制设定的大脑结构的产前支架,我们从中脑后部新生儿丰富俱乐部(发育人类连接组计划,n=630)开始我们的模拟。从这个初始起点开始,实现类赫布式布线过程的模型生成可变但始终合理的大脑网络拓扑结构。通过分析生成过程的重复运行(>10 次模拟),我们确定了随机性的关键决定因素和影响。具体来说,我们发现,当网络在较弱的约束下发展时,随机变化对大脑组织的影响更大。这种增加的随机性使大脑网络更能抵抗随机和有针对性的攻击,但更经常导致非规范的表型结果。为了通过经验检验我们的框架,我们使用一组神经多样性儿童(注意力、学习和记忆中心;n=357)评估了早期生活剥夺经历是否会导致随机性变化。我们发现,低社会经济地位预示着大脑布线的随机性更高。我们得出的结论是,随机性可能是相关发育结果的一个未被充分认识的贡献因素,并为未来的研究提出了具体的预测。