Structural connectivity in the asymmetric brain: Genetic and nongenetic influences

Abstract

By combining fMRI and DTI, this thesis conducted three experiments exploring the relationship between functional hemispheric specialization and structural connectivity within and between the hemispheres. In Experiment 1, the hemispheric dominance pattern for language and spatial processing was related to the efficacy of callosal connectivity. Individuals with a right-sided language network or crowding of functions to one hemisphere showed high anisotropic diffusion through the corpus callosum, suggesting that unusual hemispheric dominance is associated with enhanced interhemispheric connectivity. Experiment 2 assessed the hypothesis of whether hemispheric language dominance might be achieved through callosal pruning by assessing structural-functional covariations in 35 monozygotic twin pairs. On the basis of genetic models of handedness and language dominance, twin pairs were classified according to their likelihood of carrying the right-shift (RS) allele, which is thought to introduce a bias towards right-handedness and left-cerebral language dominance. Twin pairs with a high probability of carrying the putative RS+ allele showed a connectivity pattern characterized by a genetically controlled, low anisotropic diffusion over the whole corpus callosum. In contrast, the high connectivity pattern exhibited by twin pairs more likely to lack the RS+ allele was under significantly less genetic influence. In Experiment 3, the arcuate fasciculus was reconstructed in the same set of monozygotic twin pairs in order to assess whether asymmetry in the intrahemispheric language pathway corresponds to the functional laterality indices for language derived from fMRI. Results revealed a close relationship between functional and structural asymmetries with the more left-cerebrally dominant twin also showing a more leftward asymmetry of the arcuate fasciculus than his or her less left-cerebrally dominant co-twin. Because monozygotic twin pairs share the same genotype, the results indicate a strong nongenetic component in arcuate fasciculus asymmetry. Taken together, my results suggest that the asymmetric distribution of functional networks might rely on dense intrahemispheric pathways in the dominant hemisphere, allowing efficient information transfer. Interhemispheric connectivity, on the other hand, might play a key role in the development of hemispheric specialization, possibly through a genetically controlled process of axonal pruning.