Intellectual disability and cerebellar hypoplasia in autism reported by associative learning

ObjectiveTo determine how impairments in associative learning in autism spectrum disorder (ASD) relate to intellectual disability (ID) and early-childhood cerebellar hypoplasia. MethodsTrace and long-delay eye blink conditioning (EBC) were performed in 62 children age 11.2 years having: 1) ASD with ID (ASD+ID); 2) ASD without ID (ASD-noID); or 3) typical development (TD). The sub-second timing of conditioned eye-blink responses (CRs) acquired to a tone paired with a corneal air puff was related to brain structure at age 2 years and clinical measures across ages 2-12 years. Because CR timing is influenced strongly by cerebellar function, EBC was used to test hypotheses relating cerebellar hypoplasia to ASD. ResultsChildren with ASD+ID showed early-onset CRs during trace EBC that were related to early-childhood hypoplasia of the cerebellum but not of the cerebral cortex, hippocampus, or amygdala. Children with ASD-noID showed early-onset CRs only during long-delay EBC without cerebellar hypoplasia. Using EBC measures, logistic regression detected ASD with 81% sensitivity and 79% specificity while linear discriminant analysis separated ASD subgroups based on ID but not ASD severity. MRI of additional 2-year-olds with ASD indicated that early-onset CRs during trace EBC revealed ASD+ID more readily than cerebellar hypoplasia, per se. ConclusionsEarly-childhood cerebellar hypoplasia occurs in children with ASD+ID that demonstrate early-onset CRs during trace EBC. Trace EBC reveals the relationship between cerebellar hypoplasia and ASD+ID likely by engaging cerebro-cerebellar circuits involved in intellect. We emphasize that the cerebellum optimizes sensory-motor processing at sub-second intervals, impairments of which may contribute to ID.