The Cerebellum and Neurodevelopmental Disorders

Abstract

Cerebellar dysfunction is evident in several developmental disorders, including autism, attention deficit-hyperactivity disorder (ADHD), and developmental dyslexia, and damage to the cerebellum early in development can have long-term effects on movement, cognition, and affective regulation. Early cerebellar damage is often associated with poorer outcomes than cerebellar damage in adulthood, suggesting that the cerebellum is particularly important during development. Differences in cerebellar development and/or early cerebellar damage could impact a wide range of behaviors via the closed-loop circuits connecting the cerebellum with multiple cerebral cortical regions. Based on these anatomical circuits, behavioral outcomes should depend on which cerebro-cerebellar circuits are affected. Here, we briefly review cerebellar structural and functional differences in autism, ADHD, and developmental dyslexia, and discuss clinical outcomes following pediatric cerebellar damage. These data confirm the prediction that abnormalities in different cerebellar subregions produce behavioral symptoms related to the functional disruption of specific cerebro-cerebellar circuits. These circuits might also be crucial to structural brain development, as peri-natal cerebellar lesions have been associated with impaired growth of the contralateral cerebral cortex. The specific contribution of the cerebellum to typical development may therefore involve the optimization of both the structure and function of cerebro-cerebellar circuits underlying skill acquisition in multiple domains; when this process is disrupted, particularly in early development, there could be long-term alterations of these neural circuits, with significant impacts on behavior.

Keywords: Attention deficit-hyperactivity disorder; Autism; Cerebellum; Cognition; Developmental disorder.

Figure 1. Cerebellum and developmental disorders

(Top, left) Schematic showing closed-loop cerebro-cerebellar circuit with the frontal cortex: the cerebellar cortex projects via the deep nuclei, synapses in the thalamus, and onward to the cerebral cortex; the cerebral cortex projects via the pons to the cerebellum. Figure adapted from (2), with permission. (Top, right) Cerebellar grey matter in ASD (6). The cluster in red shows the region in right Crus I where ASD children showed significantly reduced grey matter compared with a group of age-matched typically-developing children. Other clusters show regions where grey matter volume correlated with scores on the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview (ADI). Correlations between cerebellar grey matter and scores converged on right lobules VI and VII for ADOS Social (violet), ADOS Social-Communication (cyan), and ADOS Stereotyped Behaviors & Restricted Interests (green); ADI Social Interaction (blue) and ADI Restricted, Repetitive, & Stereotyped Behaviors (yellow) scores were associated with grey matter volume in the anterior cerebellum. (Bottom) Different cerebellar regions show grey matter reductions in ASD (red), ADHD (blue) and developmental dyslexia (green). Figure adapted from (3).