Cerebral lobes in autism: early hyperplasia and abnormal age effects

Metabolic, functional, behavioral, and histologic studies suggest that the structure of the cerebrum may be abnormal in autism. In a previous cross-sectional study we found abnormal enlargement of cerebral cortex and cerebral white matter volumes in autistic 2- and 3-year-olds and abnormally slow rates of volume change across later ages. In the present study, we assessed whether these volume abnormalities are limited to particular cerebral regions or are pervasive throughout the cerebrum. We used magnetic resonance imaging (MRI) to quantify volumes of cerebral lobes (frontal, temporal, parietal, and occipital regions), using classic sulcal boundaries to define regions. We examined 38 boys with autism and 39 normal control boys between the ages of 2 and 11 years. Several regions showed signs of gray matter and white matter hyperplasia in 2- and 3-year-old patients (as much as 20% enlargement), but there appeared to be an anterior to posterior gradient in the degree of hyperplasia. The frontal lobe showed the greatest enlargement while the occipital lobe was not significantly different from normal. Gray and white matter differences were not found in the older children. By examining the relationships between regional volumes and subject age, we found that frontal, temporal, and parietal white matter volumes, as well as frontal and temporal gray matter volumes, changed at significantly slower rates in autism patients than in controls across the 2- to 11-year-age range. For example, frontal lobe white matter volume increased by about 45% from 2-4 years of age to 9-11.5 years, but by only 13% in autistic patients. Mechanisms that might account for early hyperplasia are discussed as they might relate to the regional differences in degree of abnormality. For instance, possible influences of neurotrophic factors, or of abnormal afferent activity from other affected brain regions are considered.