Autism is a disorder of social, intellectual and language functioning. Until recently, few clues to the anatomical basis of autism existed. In 1985, we proposed that a highly probable site of pathology in autism is the neocerebellum. We then tested and confirmed this hypothesis by showing with magnetic resonance (MR) technology that the neocerebellar vermis in autism was statistically significantly reduced in size in 30 adolescents and adults with autism relative to 30 normal controls. We also reported that the cerebellar hemispheres are significantly smaller in autistic subjects. Based on the site and the morphology of the vermian abnormalities, we proposed that these abnormalities are due to early developmental damage that could mark the onset of autism. We now propose to study neuroanatomical development in autism in far greater detail; our findings may have a major impact on the understanding of the etiology, neuroanatomy and neurophysiology of autism. The following issues will be addressed: 1. Are cerebellar abnormalities present at the time of the appearance of the earliest detectable behavioral symptoms of autism (age 2-4 years)? 2. If the cerebellar abnormalities have an early onset, do these abnormalities change with age, or do they remain stable throughout development? 3. If cerebellar abnormalities have a late onset, what is the developmental time-course of these abnormalities? 4. Are there abnormalities of other brain structures present in autism? I so, what are the onset times and developmental time-course of damage within these structures? The structures of greatest interest are: the frontal, temporal, parietal and occipital lobes; the hippocampus; he ventricular system; the basal ganglia; the corpus callosum; the thalamus; and the brainstem. Using MR, we propose to measure the cerebellum and additional CNS structures of greatest interest in groups of retarded and non-retarded autistic children and adolescents of ages 2-4, 6-7, 10-11 and 14-16 years. We will measure the same structures in non-sedated, normal volunteers of comparable age; in-depth comparisons will be performed; longitudinal data will be obtained by re-imaging the three younger groups of autistic abnormal subjects at a later age. Age-related effects will be analyzed.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Neurology A Study Section (NEUA)
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Rady Children's Hospital-San Diego
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Courchesne, Eric; Campbell, Kathleen; Solso, Stephanie (2011) Brain growth across the life span in autism: age-specific changes in anatomical pathology. Brain Res 1380:138-45
Schumann, Cynthia M; Bloss, Cinnamon S; Barnes, Cynthia Carter et al. (2010) Longitudinal magnetic resonance imaging study of cortical development through early childhood in autism. J Neurosci 30:4419-27
Schumann, Cynthia Mills; Barnes, Cynthia Carter; Lord, Catherine et al. (2009) Amygdala enlargement in toddlers with autism related to severity of social and communication impairments. Biol Psychiatry 66:942-9
Akshoomoff, Natacha; Farid, Nikdokht; Courchesne, Eric et al. (2007) Abnormalities on the neurological examination and EEG in young children with pervasive developmental disorders. J Autism Dev Disord 37:887-93
Redcay, Elizabeth; Kennedy, Daniel P; Courchesne, Eric (2007) fMRI during natural sleep as a method to study brain function during early childhood. Neuroimage 38:696-707
Bloss, Cinnamon S; Courchesne, Eric (2007) MRI neuroanatomy in young girls with autism: a preliminary study. J Am Acad Child Adolesc Psychiatry 46:515-23
Akshoomoff, Natacha (2006) Use of the Mullen Scales of Early Learning for the assessment of young children with Autism Spectrum Disorders. Child Neuropsychol 12:269-77
Belmonte, Matthew K; Carper, Ruth A (2006) Monozygotic twins with Asperger syndrome: differences in behaviour reflect variations in brain structure and function. Brain Cogn 61:110-21
Courchesne, Eric; Redcay, Elizabeth; Morgan, John T et al. (2005) Autism at the beginning: microstructural and growth abnormalities underlying the cognitive and behavioral phenotype of autism. Dev Psychopathol 17:577-97
Courchesne, Eric; Pierce, Karen (2005) Brain overgrowth in autism during a critical time in development: implications for frontal pyramidal neuron and interneuron development and connectivity. Int J Dev Neurosci 23:153-70

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