Malformation of the human superior olive in autistic spectrum disorders

Autistic spectrum disorders (ASD) comprise a continuum of psychosocial disorders clinically characterized by social difficulties, impaired communication skills and repetitive behavioral patterns. Despite the prevalence of ASD, the neurobiology of this disorder is poorly understood. However, abnormalities in neuronal morphology, cell number and connectivity have been described throughout the autistic brain. Further, there is ample evidence that auditory dysfunction is a common feature of autism. Our preliminary investigation of neuronal morphology in the auditory brainstem of individuals with ASD focused on the medial superior olive (MSO) and revealed that neurons in this region were significantly smaller and rounder than in controls. In this report, we expand our investigation to examine all nuclei within the human superior olivary complex (SOC), an important auditory brainstem center. We examine neuronal morphology and neuronal number in four control (average age=15 years) and 9 autistic brains (average age=15 years). This detailed investigation supports our previous descriptions of the MSO, and also reveals significant dysmorphology in five other SOC nuclei. Moreover, we provide evidence of a consistent and significant decrease in the number of SOC neurons in the autistic brain. Our studies implicate an extensive malformation of the auditory brainstem in the hearing and language difficulties in individuals with ASD. The results from this investigation suggest that neonatal testing of auditory function may aid in the identification of individuals with ASD earlier than presently possible.