Autism is a behavioral syndrome characterized by impairments in social interactions and communication and by repetitive, stereotyped behavior. To date there is no clear and consistently replicated neuroanatomic correlate. While specific, focal core neuroanatomic or cognitive deficits have been sought, this study will examine the syndrome's more pervasive features. The purpose of this study is to understand these pervasive abnormalities at the levels of brain structure and of structure-function relationships. The finding of large brains in autism suggest a pervasive abnormality of the brain and abnormal regulation of brain development whose distributed consequences cannot be fully characterized by focal studies. Moreover, the higher-level cognitive functions disordered in autism are likely to have distributed rather than strictly localized or modular neuroanatomical correlates. By using a novel, detailed neuroanatomically-based whole-brain morphometric method, we will be able for the first time to characterize pervasive, distributed brain volumetric abnormalities. The study will be performed on subjects from two NIH-funded projects, the Autism and Language Disorders Nosology Project, NINDS 20489; and the Language in Autism: Clinical and Basic Studies Project, NIDCD PO1 DC 03610.
The Specific Aims will be 1) to test the morphometric hypothesis that dysregulated brain development in autism will manifest in abnormalities in morphometric quantifiers of size, scaling, and profiles of variance, and 2) to test the developmental cognitive neuroscience hypothesis that key abnormal cognitive and linguistic functions in autism will correlate better with distributed morphometric abnormalities such as deviations in neuroanatomic scaling and profiles of variance than with localized deviations in size of neuroanatomic modular units. The system-oriented whole brain morphometric profiles should provide new classes of neuroanatomical correlates that are more appropriate for the widespread higher-level cognitive functions disordered in autism. The nature of developmental dysregulation and neural systems abnormalities in this disorder should thus become clearer.
| Herbert, M R; Ziegler, D A; Deutsch, C K et al. (2005) Brain asymmetries in autism and developmental language disorder: a nested whole-brain analysis. Brain 128:213-26 |
| Herbert, Martha R (2004) Neuroimaging in disorders of social and emotional functioning: what is the question? J Child Neurol 19:772-84 |
| Herbert, Martha R; Ziegler, David A; Makris, Nikos et al. (2004) Localization of white matter volume increase in autism and developmental language disorder. Ann Neurol 55:530-40 |
| Kennedy, David N; Haselgrove, Christian; McInerney, Sean (2003) MRI-based morphometric of typical and atypical brain development. Ment Retard Dev Disabil Res Rev 9:155-60 |
| Herbert, M R; Ziegler, D A; Deutsch, C K et al. (2003) Dissociations of cerebral cortex, subcortical and cerebral white matter volumes in autistic boys. Brain 126:1182-92 |
| Herbert, Martha R; Harris, Gordon J; Adrien, Kristen T et al. (2002) Abnormal asymmetry in language association cortex in autism. Ann Neurol 52:588-96 |
