Dept. Medical Biophysics, University of Toronto, Toronto, Canada.
Neurosciences & Mental Health, Hospital for Sick Children, Toronto, Canada.
Transl Psychiatry. 2024 Apr 3;14(1):173. doi: 10.1038/s41398-024-02857-4.
The cerebellum, through its connectivity with the cerebral cortex, plays an integral role in regulating cognitive and affective processes, and its dysregulation can result in neurodevelopmental disorder (NDD)-related behavioural deficits. Identifying cerebellar-cerebral functional connectivity (FC) profiles in children with NDDs can provide insight into common connectivity profiles and their correlation to NDD-related behaviours. 479 participants from the Province of Ontario Neurodevelopmental Disorders (POND) network (typically developing = 93, Autism Spectrum Disorder = 172, Attention Deficit/Hyperactivity Disorder = 161, Obsessive-Compulsive Disorder = 53, mean age = 12.2) underwent resting-state functional magnetic resonance imaging and behaviour testing (Social Communication Questionnaire, Toronto Obsessive-Compulsive Scale, and Child Behaviour Checklist - Attentional Problems Subscale). FC components maximally correlated to behaviour were identified using canonical correlation analysis. Results were then validated by repeating the investigation in 556 participants from an independent NDD cohort provided from a separate consortium (Healthy Brain Network (HBN)). Replication of canonical components was quantified by correlating the feature vectors between the two cohorts. The two cerebellar-cerebral FC components that replicated to the greatest extent were correlated to, respectively, obsessive-compulsive behaviour (behaviour feature vectors, r = -0.97; FC feature vectors, r = -0.68) and social communication deficit contrasted against attention deficit behaviour (behaviour feature vectors, r = -0.99; FC feature vectors, r = -0.78). The statistically stable (|z| > 1.96) features of the FC feature vectors, measured via bootstrap re-sampling, predominantly comprised of correlations between cerebellar attentional and control network regions and cerebral attentional, default mode, and control network regions. In both cohorts, spectral clustering on FC loading values resulted in subject clusters mixed across diagnostic categories, but no cluster was significantly enriched for any given diagnosis as measured via chi-squared test (p > 0.05). Overall, two behaviour-correlated components of cerebellar-cerebral functional connectivity were observed in two independent cohorts. This suggests the existence of generalizable cerebellar network differences that span across NDD diagnostic boundaries.
小脑通过与大脑皮层的连接，在调节认知和情感过程中发挥着重要作用，其功能失调可能导致与神经发育障碍 (NDD) 相关的行为缺陷。在患有 NDD 的儿童中识别小脑-大脑功能连接 (FC) 图谱，可以深入了解常见的连接图谱及其与 NDD 相关行为的相关性。来自安大略省神经发育障碍 (POND) 网络的 479 名参与者（正常发育=93 名，自闭症谱系障碍=172 名，注意缺陷/多动障碍=161 名，强迫症=53 名，平均年龄=12.2 岁）接受了静息态功能磁共振成像和行为测试（社交沟通问卷、多伦多强迫症量表和儿童行为检查表-注意力问题子量表）。使用典型相关分析识别与行为相关性最大的 FC 成分。然后通过重复对来自独立 NDD 队列（健康大脑网络 (HBN)）的 556 名参与者的调查来验证结果。通过比较两个队列的特征向量来量化典型成分的复制。复制程度最高的两个小脑-大脑 FC 成分分别与强迫症行为（行为特征向量，r=-0.97；FC 特征向量，r=-0.68）和社交沟通缺陷相对于注意力缺陷行为（行为特征向量，r=-0.99；FC 特征向量，r=-0.78）相关。通过 bootstrap 重采样测量的 FC 特征向量的统计稳定（|z|>1.96）特征主要包括小脑注意力和控制网络区域与大脑注意力、默认模式和控制网络区域之间的相关性。在两个队列中，对 FC 加载值进行谱聚类导致受试者聚类混合在不同的诊断类别中，但通过卡方检验（p>0.05），没有一个聚类显著富集任何特定的诊断。总体而言，在两个独立的队列中观察到两个与行为相关的小脑-大脑功能连接成分。这表明存在可跨 NDD 诊断边界推广的一般性小脑网络差异。
