Pamela Moses

Unusual brain growth patterns in early life in patients with autistic disorder An MRI study

Objective: To quantify developmental abnormalities in cerebral and cerebellar volume in autism. Methods: The authors studied 60 autistic and 52 normal boys (age, 2 to 16 years) using MRI. Thirty autistic boys were diagnosed and scanned when 5 years or older. The other 30 were scanned when 2 through 4 years of age and then diagnosed with autism at least 2.5 years later, at an age when the diagnosis of autism is more reliable. Results: Neonatal head circumferences from clinical records were available for 14 of 15 autistic 2- to 5-year-olds and, on average, were normal (35.1 ± 1.3 cm versus clinical norms: 34.6 ± 1.6 cm), indicative of normal overall brain volume at birth; one measure was above the 95th percentile. By ages 2 to 4 years, 90% of autistic boys had a brain volume larger than normal average, and 37% met criteria for developmental macrencephaly. Autistic 2- to 3-year-olds had more cerebral (18%) and cerebellar (39%) white matter, and more cerebral cortical gray matter (12%) than normal, whereas older autistic children and adolescents did not have such enlarged gray and white matter volumes. In the cerebellum, autistic boys had less gray matter, smaller ratio of gray to white matter, and smaller vermis lobules VI–VII than normal controls. Conclusions: Abnormal regulation of brain growth in autism results in early overgrowth followed by abnormally slowed growth. Hyperplasia was present in cerebral gray matter and cerebral and cerebellar white matter in early life in patients with autism.

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.

Cognitive development following early brain injury: evidence for neural adaptation.

Over the past few decades a large body of work from developmental neurobiology has shown that mammalian brain development is the product of dynamic and adaptive processes operating within highly constrained, but continually changing, biological and environmental contexts. The recent study of children with prenatal focal brain injury supports this dynamic view of development for humans. Childrens injuries often affect substantial portions of one cerebral hemisphere, resulting in damage that would compromise cognitive ability in adults. However, longitudinal behavioral studies of this population have revealed only mild deficits. It is suggested here that childrens capacity for adaptation reflects normal developmental processes operating against a backdrop of serious neural perturbation. Data from three behavioral domains--linguistics, spatial cognition and affective development--illustrate this complex profile of change.

Functional MRI of Global and Local Processing in Children

Functional magnetic resonance imaging was used to examine developmental change in hemispheric biases for globally and locally directed analysis of hierarchical forms. In a previous reaction time (RT) study, which presented hierarchical stimuli to the visual hemifields, children 7 to 14 years of age demonstrated an emerging pattern of hemispheric differences. Initially children analyzed local elements more slowly, without a strongly lateralized advantage for local or global level processing. With age, childrens development was marked by a left hemisphere advantage for local level processing that resembled an adults and a trend toward a right hemisphere advantage for global. In the current study, 20 children 12 to 14 years old were imaged during attend-global and attend-local conditions to determine whether the developmental change in cognitive measures corresponded to a change in distribution of functional activation. Children formed two groups based on their RT performance, immature-bilateral (IB) or mature-lateralized (ML). The volume of task-related activation within lateral temporo-occipital regions of interest was compared for global and local conditions between the two groups. The IB children showed greater activation overall for local level processing, comparable activation across the two hemispheres for the global condition, and a trend of right greater than left hemisphere activation for local. In contrast, the ML children displayed right greater than left hemisphere activation during global analysis and the opposite during local processing. Importantly these patterns of functional activation mirror the profiles of RT performance. Together they demonstrate a shift from undifferentiated, bilateral processing toward hemispheric lateralization.

Alternative brain organization after prenatal cerebral injury: convergent fMRI and cognitive data.

The current study presents both longitudinal behavioral data and functional activation data documenting the effects of early focal brain injury on the development of spatial analytic processing in two children, one with prenatal left hemisphere (LH) injury and one with right hemisphere (RH) injury. A substantial body of evidence has shown that adults and children with early, lateralized brain injury show evidence of spatial analytic deficits. LH injury compromises the ability to encode the parts of a spatial pattern, while RH injury impairs pattern integration. The two children described in this report show patterns of deficit consistent with the site of their injury. In the current study, their longitudinal behavioral data spanning the age range from preschool to adolescence are presented in conjunction with data from a functional magnetic resonance imaging (fMRI) study of spatial processing. The activation results provide evidence that alternative profiles of neural organization can arise following early focal brain injury, and document where in the brain spatial functions are carried out when regions that normally mediate them are damaged. In addition, the coupling of the activation with the behavioral data allows us to go beyond the simple mapping of functional sites, to ask questions about how those sites may have come to mediate the spatial functions.