Developmental Imaging and Psychopathology Laboratory, University of Geneva School of Medicine, Geneva, Switzerland; Medical Image Processing Laboratory, Neuro-X Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Developmental Imaging and Psychopathology Laboratory, University of Geneva School of Medicine, Geneva, Switzerland; Medical Image Processing Laboratory, Neuro-X Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 Sep;9(9):882-895. doi: 10.1016/j.bpsc.2024.05.008. Epub 2024 Jun 5.
Compared with conventional unimodal analysis, understanding how brain function and structure relate to one another opens a new biologically relevant assessment of neural mechanisms. However, how function-structure dependencies (FSDs) evolve throughout typical and abnormal neurodevelopment remains elusive. The 22q11.2 deletion syndrome (22q11.2DS) offers an important opportunity to study the development of FSDs and their specific association with the pathophysiology of psychosis.
Previously, we used graph signal processing to combine brain activity and structural connectivity measures in adults, quantifying FSD. Here, we combined FSD with longitudinal multivariate partial least squares correlation to evaluate FSD alterations across groups and among patients with and without mild to moderate positive psychotic symptoms. We assessed 391 longitudinally repeated resting-state functional and diffusion-weighted magnetic resonance images from 194 healthy control participants and 197 deletion carriers (ages 7-34 years, data collected over a span of 12 years).
Compared with control participants, patients with 22q11.2DS showed a persistent developmental offset from childhood, with regions of hyper- and hypocoupling across the brain. Additionally, a second deviating developmental pattern showed an exacerbation during adolescence, presenting hypocoupling in the frontal and cingulate cortices and hypercoupling in temporal regions for patients with 22q11.2DS. Interestingly, the observed aggravation during adolescence was strongly driven by the group with positive psychotic symptoms.
These results confirm a central role of altered FSD maturation in the emergence of psychotic symptoms in 22q11.2DS during adolescence. The FSD deviations precede the onset of psychotic episodes and thus offer a potential early indication for behavioral interventions in individuals at risk.
与传统的单模态分析相比，了解大脑功能和结构如何相互关联为神经机制提供了一种新的具有生物学相关性的评估方法。然而，功能-结构依存关系（FSD）在正常和异常神经发育过程中是如何演变的仍然难以捉摸。22q11.2 缺失综合征（22q11.2DS）为研究 FSD 的发展及其与精神病理生理学的具体关联提供了一个重要的机会。
之前，我们使用图信号处理将成年人的大脑活动和结构连接测量值结合起来，量化了 FSD。在这里，我们将 FSD 与纵向多元偏最小二乘相关相结合，以评估整个群体以及伴有和不伴有轻度至中度阳性精神病症状的患者之间的 FSD 变化。我们评估了 194 名健康对照参与者和 197 名缺失携带者（年龄 7-34 岁，数据收集跨度为 12 年）的 391 次重复静息状态功能和弥散加权磁共振图像。
与对照组相比，22q11.2DS 患者从童年开始就表现出持续的发育偏移，大脑中存在区域的超连接和低连接。此外，第二种偏离的发育模式在青春期表现出加剧，22q11.2DS 患者的额皮质和扣带回皮质出现低连接，颞叶区域出现高连接。有趣的是，观察到的青春期恶化主要是由有阳性精神病症状的患者驱动的。
这些结果证实了在青春期，22q11.2DS 中，异常 FSD 成熟在精神病症状的出现中起着核心作用。FSD 偏差先于精神病发作的发生，因此为处于风险中的个体提供了进行行为干预的潜在早期指标。
