Enlarged Cortical Surface Area In Autistic Infants

Background: Although overall brain enlargement has been reported in infants and toddlers with autism, studies directly measuring cortical surface area and comparing it to volumetric enlargement have yet to be undertaken. This comparison is of particular interest because recent evidence points to increased number of neurons as a possible mechanism underlying brain enlargement (Courchesne 2011). However, increased neuron number does not translate to proportionate overall brain weight increase (and thus overall brain volume enlargement) in autistic children, as it does in typically developing controls. The expected consequence of increased cell number is expanded cortical surface area (Chenn 2002). Therefore, a comparison of relative expansion of surface and other volumetric measures could prove useful in understanding the neural basis of brain enlargement in autism.

Objectives: This study aims to investigate brain enlargement in multiple measurement dimensions from a general population sample of simplex and multiplex autistic infants and toddlers and typically developing controls. We also sought to study the relationship between measures of brain enlargement and differential symptom severity within the autism group.

Methods: We measured gray and white matter volume and cortical surface area on 51 ASD and 45 control subjects between 12 and 48 months. Brain images were measured with algorithms from the software packages FSL and BrainVisa that were customized to more accurately segment and reconstruct the small size and tight sulci of the developing infant brain. A combination of longitudinal and cross-sectional data was analyzed to determine degree of enlargement and relative enlargement of volume and cortical surface area. We also evaluated the relationship between brain enlargement and impairment in reciprocal social interaction and developmental quotient as measured on the ADOS and Mullen Scales of Early Learning.

Results: We found increased gray matter and white matter volume as well as surface area in infants and toddlers with autism (p=0.05). We also found that female autistic subjects with greatest impairments in reciprocal social interaction and lowest developmental quotients had significantly larger surface area in the right hemisphere when compared to both controls (p=0.05) and autistic females with less impairment (p=0.0005). In males, there was a trend towards greater brain enlargement in subjects with greatest impairments in reciprocal social interaction and lowest developmental quotients. For a large cluster of autistic subjects, enlarged cortical surface area was also accompanied by deviant small white matter volume for age relative to gray matter volume for age.

Conclusions: In autistic infants, cortical surface area in combination with volumetric measures was shown to better identify and characterize brain enlargement in autistic subjects than volumetric measures alone. Increased surface area in the first few years of life supports the theory that increased neuron number drives brain enlargement in children with autism, and further investigation into expansion of the cortical surface in autism may be a more powerful way to detect early clinical and biological indicators of the disorder.