Biology of variation in anatomical brain asymmetries
Guadalupe examined the potential relations between the anatomy of the cerebral cortex and handedness in the largest study to have been performed of this question to date (1960 right-handed and 106 left-handed subjects). Identifying anatomical brain correlates of handedness could provide clues to its ontogeny. In turn, by postulating specific ontogenetic mechanisms, these could guide further investigations on the overall genetic architecture, as well as clarify the relations of handedness with other forms of lateralized cognition, including the relationship between brain structure and function.
Although sex is often thought to be a driving factor underlying differences in brain asymmetry, there is currently no strong consensus regarding the morphological specificity of sex effects or their functional implications. Guadalupe set out to map sex differences in grey matter asymmetries over the entire cerebral cortex, initially in more than 2000 healthy adults. In collaboration with the University of Greifswald, a replication study solidified their conclusions regarding sexual dimorphisms in the adult brain. At the same time, this collaboration led to the first genome-wide analysis of a cortical brain asymmetry to date.
In line with evidence suggesting a possible subcortical origin in the development of brain asymmetries, Guadalupe also investigated volumetric asymmetries in 6 subcortical structures and the hippocampus. Due to the overall strong similarity between the left and right sides of these structures, the initial focus of his study was to determine the feasibility of automated measurement of subtle differences in volumetric asymmetry, applied to large datasets. Using data from 235 subjects who had undergone MRI twice, Guadalupe assessed inter-subject agreements between measures obtained at different time points, as well as the agreement between two automated methods. As the first comprehensive genetic association study for a subcortical human brain asymmetry, the insights gained are valuable for future and on-going consortium projects.
Guadalupe’s thesis also contains the first work by the Lateralization working group within the ENIGMA consortium (Enhancing Neuro Imaging Genetics through Meta-Analysis). ENIGMA is an international collaborative effort with the goal to perform large-scale analysis of brain morphology, assessed with MRI, and to identify influential genetic variants. In a meta-analysis of more than 15,000 human participants, unambiguous effects of sex and age on the asymmetries of some subcortical structures were established. This was one of the largest studies ever to have been performed in relation to any aspect of human brain variability.
Guadalupe discusses his findings in the context of their contributions to our understanding of brain asymmetry, including new directions that can now be pursued within the ENIGMA-Lateralization working group. As with previous investigations of other features of brain morphology, large-scale studies are necessary to disentangle the highly complex biology underlying brain asymmetries. Future studies may shed light on the relations between brain asymmetries and disorders such as schizophrenia, attention deficit hyperactivity disorder (ADHD), or obsessive-compulsive disorder (OCD).
- Tulio Guadalupe will defend his thesis on Thursday, February 2 at 12:30 in the Aula of the Radboud University.
- The thesis appears in the MPI Series (no 117).