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Size always matters : an investigation of the influence of connection length on the organization of white-matter in typical development and in autism

  • Author(s): Lewis, John D.
  • et al.
Abstract

Across species, increases in white matter volume outpace increases in gray-matter volume, but increases in gray- matter volume outpace increases in the size of the corpus callosum. This dissertation explores the hypothesis that this hyposcaling of the callosum stems from the impact of the conduction delays and cellular costs of the long- distance connections on normal developmental mechanisms. Neuroanatomy research to date has only indirectly examined this relation, using measures such as brain volume. The research in this dissertation uses diffusion tensor imaging to more directly measure the relation between the length of the interhemispheric connections and the degree of connectivity -- the ratio of between-area connections to total projection neurons in the areas connected. Using tractography to detail the patterns of interhemispheric connectivity and to determine the length of the connections, and formulae based on histological results to estimate degree of connectivity, we show that, across normal young adult males, connection length is significantly negatively correlated with degree of connectivity in the anterior, posterior, and body of the callosum. Using the same methodology, in typically developing boys a significant relation between connection length and degree of connectivity was found only in the posterior of the callosum. The combined results indicate that the relation between connection length and degree of connectivity develops during childhood and adolescence. Children with autism are known to have enlarged brains during the first years of life. This is predicted to lead to decreased long-distance connectivity. To explore this prediction, neural networks which modeled inter- hemispheric interaction were grown at the rate of either typically developing children or children with autism. By 2 years of simulated age, the networks that modeled autistic growth showed a reduced reliance on long-distance connections, performance reductions, and reductions in structural connectivity. Using the same methodology as with the adults and children, the relation between connection length and degree of connectivity in adults with autism was examined. Connection length and degree of connectivity showed the typical negative relation, but with a reduced degree of connectivity in anterior regions -- the locus of development during the period of maximal brain overgrowth, and where axon diameters are smallest

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