Principal Investigator: Dr Clyde Francks
Department: Language and Genetics
Max Planck Institute for Psycholinguistics, Language and Genetics, Wundlaan 1, Nijmegen 6525XD, NetherlandsTags: 16066, asymmetry, Brain, cognition, disorder, dyslexia, language
Lead Collaborators: Dr Fabrice Crivello
Collaborating Institutions and Addresses: University of Bordeaux, Neurofunctioning Imaging Group, UMR 5296 – CNRS CEA, 146 rue Léo Saignat CS 61292, Bordeaux 33076, France
Funding body: National Initiative Brain and Cognition, Netherlands Organisation for Scientific Research.
1a: Left-right asymmetry is an important feature of the human brain. One prominently asymmetric brain network underlies the uniquely human ability to speak and understand language. A lack of brain asymmetry is associated with variation in human cognitive abilities linked to language, and also susceptibility to cognitive disorders including language impairment and dyslexia. The genetic basis of human brain asymmetry is unknown, while links between asymmetric anatomy and function are poorly understood. It is likely that genes involved in brain asymmetry contain variants in the population that influence cognitive performance and cognitive disorders.
1b: We will test whether certain genetic profiles affect asymmetric brain structure and function particularly for regions involved in speaking and listening. We will also test whether these same genetic variations affect susceptibility to language-related disorders including dyslexia and Specific Language Impairment. Both can be severe disorders with lifelong impacts on achievement and mental health. Dyslexia is identified as a disability in the UK’s Equality Act 2010. According to the British Dyslexia Association, roughly 4% of the population has severely impaired reading ability. Each illiterate pupil, by age 37, is estimated to cost taxpayers an extra roughly 50,000GBP.
1c: Some brain regions are asymmetrical and important for speech and language. We will use Biobank brain imaging data in combination with genetic data to identify genomic profiles linked to the thickness, surface area and volumes of these regions. If possible, we will also do a similar analysis with Biobank MRI data that measures how active the language regions are during rest. We will follow up the findings in other cohorts of people with brain imaging and genetic data, and language-related disorders and genetic data. We are leading members of scientific consortia that study these questions with meta-analysis.
1d: Data will be used from all Biobank participants who have done MRI scans (roughly 5000 at the time of writing, September 2015). We will also need the genotype data of as many of these participants as possible. The larger the available dataset, the more statistical power there is to detect and measure the individual and pooled effects of genomic variants on brain anatomy and function.
Project extension text:
This request concerns functional brain imaging data (fMRI), as we would like to investigate the functional asymmetry of task-invoked activations. This fits clearly with the rest of our approved project, which focuses on mapping brain asymmetry and exploring the underlying genetic factors. Similar to structural and intrinsic functional measures, considerable hemispheric asymmetries have been revealed in task-invoked activation (e.g., leftward language activation and rightward face processing). One task fMRI with well-known lateralization (Corballis, 1991) was included in the UK Biobank imaging protocol, the Hariri faces/shapes task. This functional asymmetry has been shown to be reliable within individuals (Yovel et al., 2008), heritable (Polk et al., 2007), and to interact with handedness (Willems et al., 2010). Using General Linear Modelling, we will map the asymmetry of functional activation and extract activation asymmetry phenotypes. Downstream analyses, including genetics, will proceed as described in our main project.
Project extension March 2018:
“As outlined in the project application, we are interested in left-right asymmetry of the human brain.
A functional reflection of brain asymmetry is hand preference. In twin studies, hand preference was shown to have a heritability of ~ 25%, while SNP-heritability in the UK-biobank data was 3%.
It seems clear both genetic and environmental factors influence hand preference.
Like other aspects of brain asymmetry, atypical handedness has been found to be associated with neurocognitive disorders, such as autism or schizophrenia.
In addition to genetic factors underlying brain asymmetry, which we also study in other parts of application 16066, we are interested in environmental correlates.
Hand preference has received a lot of attention in both scientific and popular literature. Preference gets established before or shortly after birth.
Previous studies have found various perinatal factors to be associated with the probability of being right or left handed, such as birth weight, being a twin, maternal smoking or having been breastfed and others.
One difficulty is that many of these factors are interrelated to some extent, but not all have necessarily been measured in any given study, or else the range of variation available across these various factors has been too limited or biased by sample selection in order to disentangle them.
The large, and thoroughly characterised, population-based cohort of the UK Biobank allows multiple potential factors to be considered together, while providing statistical power to begin to disentangle them.
We propose to study hand preference in relation to the available ‘Early life factors’ breastfed as a baby, adopted as a child, part of a multiple birth, maternal smoking around birth and birth weight, as well as month of birth to better understand this behavioural aspect of brain asymmetry.
As some of these factors are heritable themselves, we will also test whether genetic co-variation with hand preference can be detected.”