Lutz Gretchen, Smerconish Simon, Roalf David, Neale Michael C, Schmitt J Eric
Department of Radiology, Division of Neuroradiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Psychiatry, Brain Behavior Laboratory, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Hum Brain Mapp. 2025 Aug 1;46(11):e70300. doi: 10.1002/hbm.70300.
The cerebellum, traditionally associated with motor control, is increasingly recognized for its involvement in higher-order cognitive functions. However, the role of cerebellar subregions in cognition remains underexplored, as are the roles of genetic factors on cerebellar structure and brain-behavioral associations. The primary goal of this study was to investigate the relationship between cerebellar subregion volumes and cognitive performance. A secondary aim was to quantify the genetic contributions to cerebellar structure and determine the degree to which any brain-behavior associations were genetically mediated. 3T anatomic MRI data from N = 932 typically developing individuals from the Human Connectome Project were used for this study. Twenty-seven cerebellar regions of interest (ROIs) were automatically parcellated using CerebNet. Three additional lobar-level ROIs were derived from smaller measures. Nine functional domains (six cognitive and three motor) related to known or suspected cerebellar function were selected. Linear regression analyses were conducted to identify correlations between cerebellar volumes and cognitive outcomes, adjusting for age, sex, and overall brain volume. Univariate and bivariate quantitative genetic modeling was then performed in OpenMx. There were numerous statistically significant phenotypic associations between cognitive measures and cerebellar lobar and lobular volumes, particularly in the IPL, AL, bilateral cortices, left lobule V, right lobule VI, vermis, and vermis lobule VIII, each meeting the threshold of p < 0.02 across at least four out of nine cognitive domains. The vermis and vermis lobule VIII were of particular note, showing even stronger associations (p < 0.0009 across three domains). Cognitive measures were modestly heritable, and cerebellar ROIs were highly heritable. Quantitative genetic models suggested that brain-behavior associations are largely driven by shared environmental factors. Our findings identify novel associations between specific cerebellar subregions and cognitive performance, highlighting the vermis as a critical structure. We also provide a detailed map of the quantitative genetics of human cerebellar structure. Future studies are warranted.
传统上认为小脑与运动控制相关，但现在人们越来越认识到它也参与高阶认知功能。然而，小脑亚区域在认知中的作用仍未得到充分研究，遗传因素对小脑结构和脑-行为关联的作用也同样如此。本研究的主要目标是调查小脑亚区域体积与认知表现之间的关系。次要目标是量化遗传因素对小脑结构的贡献，并确定任何脑-行为关联在多大程度上是由遗传介导的。本研究使用了来自人类连接体项目的N = 932名典型发育个体的3T解剖MRI数据。使用CerebNet自动分割出27个小脑感兴趣区域（ROI）。从较小的测量值中得出另外三个叶级ROI。选择了九个与已知或疑似小脑功能相关的功能域（六个认知域和三个运动域）。进行线性回归分析以确定小脑体积与认知结果之间的相关性，并对年龄、性别和全脑体积进行校正。然后在OpenMx中进行单变量和双变量定量遗传建模。认知测量与小脑叶和小叶体积之间存在许多具有统计学意义的表型关联，特别是在顶下小叶、前叶、双侧皮质、左小叶V、右小叶VI、蚓部和蚓小叶VIII，在九个认知域中的至少四个中，每个区域的p值均满足p < 0.02的阈值。蚓部和蚓小叶VIII尤其值得注意，在三个域中显示出更强的关联（p < 0.0009）。认知测量具有适度的遗传性，而小脑ROI具有高度遗传性。定量遗传模型表明，脑-行为关联在很大程度上由共同环境因素驱动。我们的研究结果确定了特定小脑亚区域与认知表现之间的新关联，突出了蚓部作为关键结构的重要性。我们还提供了人类小脑结构定量遗传学的详细图谱。未来的研究很有必要。
