Abstract
Differences in cerebellar structure have been identified in autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and developmental dyslexia. However, it is not clear if different cerebellar regions are involved in each disorder, and thus whether cerebellar anatomical differences reflect a generic developmental vulnerability or disorder-specific characteristics. To clarify this, we conducted an anatomic likelihood estimate (ALE) meta-analysis on voxel-based morphometry (VBM) studies which compared ASD (17 studies), ADHD (10 studies), and dyslexic (10 studies) participants with age-matched typically-developing (TD) controls. A second ALE analysis included studies in which the cerebellum was a region of interest (ROI). There were no regions of significantly increased gray matter (GM) in the cerebellum in ASD, ADHD, or dyslexia. Data from ASD studies revealed reduced GM in the inferior cerebellar vermis (lobule IX), left lobule VIIIB, and right Crus I. In ADHD, significantly decreased GM was found bilaterally in lobule IX, whereas participants with developmental dyslexia showed GM decreases in left lobule VI. There was no overlap between the cerebellar clusters identified in each disorder. We evaluated the functional significance of the regions revealed in both whole-brain and cerebellar ROI ALE analyses using Buckner and colleagues' 7-network functional connectivity map available in the SUIT cerebellar atlas. The cerebellar regions identified in ASD showed functional connectivity with frontoparietal, default mode, somatomotor, and limbic networks; in ADHD, the clusters were part of dorsal and ventral attention networks; and in dyslexia, the clusters involved ventral attention, frontoparietal, and default mode networks. The results suggest that different cerebellar regions are affected in ASD, ADHD, and dyslexia, and these cerebellar regions participate in functional networks that are consistent with the characteristic symptoms of each disorder.
Highlights
Our understanding of the human cerebellum has undergone substantial revision in the past 20 years
The whole brain analysis revealed significant gray matter (GM) reduction in cerebellar clusters in right Crus I, left lobule VIIIB, and vermis lobule IX in autism spectrum disorder (ASD) (Figure 2, Table 3; whole-brain results are available in Supplementary Table 1: the most significant cluster in the brain was in the left cuneus [BA 7], followed by the left cerebellar VIII cluster, the right Crus I cluster, and the midline IX cluster)
In the attention deficit hyperactivity disorder (ADHD) group, significant anatomic likelihood estimate (ALE) values indicating decreased GM were found in bilateral cerebellar lobule IX (Figure 4, Table 4; whole-brain results are reported in Supplementary Table 2)
Summary
Our understanding of the human cerebellum has undergone substantial revision in the past 20 years. The cerebellum forms closed-loop circuits with the majority of the cerebral cortex, with the cerebellar hemispheres projecting to the contralateral cerebral cortex This closed-loop circuitry, together with the crystalline structure of the cerebellar cortex, suggests that the cerebellum contains repeating modules (Apps and Garwicz, 2005), such that the function of a given region of the cerebellum depends on its inputs and outputs (for review, Ramnani, 2006). Supporting this concept, within the cerebellum different regions are involved in overt motor control vs cognitive and emotional processing (Stoodley and Schmahmann, 2009).
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