Development of Human Cerebral Cortex in Health and Disease

Background:  

Cerebral cortex is the dominant structure of the human brain, and abnormalities in cortical circuitry are implicated in autism as well as many other brain disorders.  In order to interpret disease-related abnormalities, it is important to gain a deeper understanding of normal brain circuitry, its variability across individuals, and its pattern of development. 

Much of human cortical development occurs prenatally.  During the second trimester, cortical neurons are born and migrate to form a thin and smooth cortical sheet.  During the third trimester, the cortex expands dramatically in surface area, becomes highly convoluted, and differentiates into a mosaic that contains hundreds of anatomically and functionally distinct cortical areas.  Complex but highly specific long-distance connections are established between nearby and distant cortical areas during this period via axonal fiber bundles in the white matter that underlies the cortical sheet. Mechanical tension generated by these axons may contribute to cortical folding, by bringing strongly connected regions more closely together.

Premature birth can impede the normal maturation of brain structure and function, resulting in a wide range of childhood behavioral and learning disorders, including autism.  Magnetic resonance imaging (MRI) provides a powerful tool for studying brain structure and function in premature infants.  Such approaches will hopefully lead to insights that help in diagnosing and treating the effects of abnormal brain maturation.

Healthy infants born at term have a brain that is only one-third its adult size.  Many aspects of cortical maturation occur postnatally, including a three-fold expansion in cortical surface area that allows cortical circuits to be heavily shaped by postnatal experience.  Interestingly, postnatal cortical expansion is regionally non-uniform, with the greatest expansion occurring in regions implicated in higher cognitive functions.

MRI-based methods for studying human brain structure, function, and connectivity have improved dramatically in recent years, including major advances driven by the Human Connectome Project (HCP).  A consortium of HCP investigators led by Washington University, the University of Minnesota, and Oxford University is using these methods to study brain circuits in healthy adult twins and their non-twin siblings.  Advanced analysis methods, including novel approaches to brain parcellation, are enabling characterization of functionally distinct parcels in individual subjects and in the overall population.  Comparisons across individuals are beginning to reveal aspects of brain circuitry that are related to specific behavioral capacities.  Data from the HCP are made freely available to the neuroscience community for extensive data mining via a user-friendly informatics platform.  Insights gained using HCP-generated datasets and future application of such approaches to autism should accelerate progress in understanding, diagnosis, and treatment of this serious brain disorder.  

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