Structural and Functional Aberrations of the Auditory Brainstem in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with difficulties in the social, communicative, and behavioral domains. Most cases of ASD arise from an unknown etiologic process, but there are numerous risk factors, including comorbidities and maternal exposures. Although it is not part of the diagnostic criteria, hearing difficulties ranging from deafness to hyperacusis are present in the majority of persons with ASD. High-functioning children with ASD have been found to have significantly slower and asymmetric auditory brainstem reflexes. Additionally, histopathological studies of postmortem brainstems in decedents who had ASD have consistently revealed significantly fewer neurons in auditory nuclei compared with those in people who did not have ASD. The authors review the literature implicating auditory dysfunction in ASD along with results from human study participants and postmortem human brain tissue. Together, these results implicate significant structural and functional abnormalities in the auditory brainstem in ASD and support the utility of auditory testing to screen for ASD.

Quantification of the stapedial reflex reveals delayed responses in autism.

Autism is a developmental disorder characterized, in part, by sensory abnormalities. It is well established that most if not all patients with autism have problems with auditory processing, ranging from deafness to hyperacusis, and physiological testing of auditory function (i.e. auditory brain stem responses) implicates brain stem dysfunction in autism. Additionally, previous research from this lab has revealed significantly fewer auditory brain stem neurons in autistic subjects as young as 2 years of age. These observations have led us to hypothesize that objective, noninvasive measures of auditory function can be used as an early screening tool to identify neonates with an elevated risk of carrying a diagnosis of autism. Here, we provide a detailed quantitative investigation of the acoustic stapedial reflex (ASR), a three- or four-neuron brain stem circuit, in young autistic subjects and normal developing controls. Indeed, we find significantly lower thresholds, responses occurring at significantly longer latency and right-left asymmetry in autistic subjects. The results from this investigation support deficits in auditory function as a cardinal feature of autism and suggest that individuals with autism can be identified by their ASR responses.

Malformation of the superior olivary complex in an animal model of autism.

Autism is a neurodevelopmental disorder characterized by social difficulties, impaired communication skills and repetitive behavioral patterns. Additionally, there is evidence that auditory deficits are a common feature of the autism spectrum disorders. Despite the prevalence of autism, the neurobiology of this disorder is poorly understood. However, abnormalities in neuronal morphology, cell number and connectivity have been described throughout the autistic brain. Indeed, we have demonstrated significant dysmorphology in the superior olivary complex (SOC), a collection of auditory brainstem nuclei, in the autistic brain. Prenatal exposure to valproic acid (VPA) in humans has been associated with autism and in rodents prenatal VPA exposure produces many neuroanatomical and behavioral deficits associated with autism. Thus, in an effort to devise an animal model of the autistic auditory brainstem, we have investigated neuronal number and morphology in animals prenatally exposed to valproic acid (VPA). In VPA exposed rats, we find significantly fewer neurons and significant alterations in neuronal morphology. Thus, prenatal VPA exposure in rats appears to produce similar dysmorphology as we have reported in the autistic human brain.

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.