By school age, the rate of normal human brain growth declines sharply, but these final phases are especially critical to the maturation of motor, linguistic, cognitive and social aptitudes in the acquisition of adaptive behaviors. These growth rates reflect a delicate balance of normal progressive and regressive histogenic mechanisms. The developmental disorders can be a model for study of anomalous brain development, in particular autistic disorder (AD), which is characterized by deficits in socialization, attention, concept formation, verbal and non-verbal communication, and ritualistic, perseverative behaviors. The investigator's prior MRI-based morphometric analysis in children with AD, developmental language disorders (DLD), non-autistic low IQ (NILIQ), and normal children have shown that both AD and DLD brains are unexpectantly larger in volume and controls which is due to excessive white matter disproportionately localized to the temporal and posterior parietal region, including the angular gyrus, superior parietal lobule, and visual/association regions. These results point to maldevelopment of neocortical systems and are consistent with some of the classic neocortical localization theories. The investigators propose: 1) To recruit three new cohorts of children in early adolescence, aged 10.0 through 15.11, N=30 in each: a) autistic disorder, divided into high IQ (nonverbal IQ70) and low (nonverbal IQ<70) AD cohort; b) nonautistic low IQ (nonverbal IQ<70); c) normal control volunteers are children with headaches, with normal birth, development, and medical histories, and normal, cognitive, linguistic and behavioral function (nonverbal IQ<70); 2) To replicate the investigator's previous morphometric findings of localized anomalous white matter volumes in the AD cohorts by performing the first of two sequential high-resolution three dimensional (3D) gradient echo T(1) - weighted MRI scans. Complete morphometric analysis will include computation of volume for whole brain, individual substructures, and hemisphere gradients. A new method of cortical localization and parcellation will then be applied to these MRI scans, reference to the Brodnann architectonic map and compatible with the Mesulem scheme of neurosystems hierarchy; 3) To test the hypothesis that the anomalous dysfunctional neurosystems are related to linguistic and neurobehavioral deficits in AD, independent of nonverbal IQ; and 4) To further investigate the effects of puberty on brain development in AD by performing a second of two sequential MRI scans three years later with repeated morphometric and cortical parcellation analysis on these AD and control cohorts.
| Filipek, Pauline A; Juranek, Jenifer; Nguyen, Minh T et al. (2004) Relative carnitine deficiency in autism. J Autism Dev Disord 34:615-23 |
| Filipek, Pauline A; Juranek, Jenifer; Smith, Moyra et al. (2003) Mitochondrial dysfunction in autistic patients with 15q inverted duplication. Ann Neurol 53:801-4 |
