Abstract
Handedness and language lateralization are the most investigated phenotypes among functional hemispheric asymmetries, i.e. differences in function between the left and the right half of the human brain. Both phenotypes are left hemisphere-dominant, while investigations of the molecular factors underlying right hemisphere-dominant phenotypes are less prominent. In the classical line bisection task, healthy subjects typically show a leftward attentional bias due to a relative dominance of the right hemisphere for visuospatial attention. Based on findings of variations in dopamine-related genes affecting performance in the line bisection task, we first tested whether DNA methylation in non-neuronal tissue in the promoter regions of DBH, SLC6A3, and DRD2 are associated with line bisection deviation. We replicated the typical behavioral pattern and found an effect of DNA methylation in the DBH promoter region on line bisection deviation in right-aligned trials. A second exploratory analysis indicated that an overall DNA methylation profile of genes involved in dopamine function predicts line bisection performance in right-aligned trials. Genetic variation in dopamine-related genes has been linked to attention deficit hyperactivity disorder (ADHD), a neurodevelopmental trait associated with rightward attentional bias. Overall, our findings point towards epigenetic markers for functional hemispheric asymmetries in non-neuronal tissue not only for left hemisphere-dominant, but also for right hemisphere-dominant phenotypes.
Highlights
Like most of our inner organs, human brain and behavior are asymmetrically organized[1]
The first aim of the present study was to investigate the effect of DNA methylation in the promoter regions of three dopamine candidate genes on attentional bias in the line bisection task
In previous studies conducted on buccal cells, we have shown an association of DNA methylation in promoter regions of respective candidate genes with handedness[12] and attentional modulation of language lateralization[13]
Summary
Like most of our inner organs, human brain and behavior are asymmetrically organized[1]. In line with lesion studies, fMRI studies in healthy subjects revealed activation in right-hemispheric posterior parietal areas during visuospatial attention tasks[14,21]. Due to an involvement of the superior occipitofrontal fasciculus, it was concluded that the parietal cortex, and communication between the parietal and frontal cortex is crucial for visuospatial attention and neglect[23] This conclusion was confirmed in a subsequent DTI study[24]. Among genetic variations affecting attentional bias, several candidate genes affecting dopaminergic pathways have been investigated This selection of candidate genes is based on a direct role of dopamine and noradrenaline in lateralized visuospatial attention that has been concluded from research in animals and humans. Suppression or reversal of pseudoneglect has been reported in normal aging and associated with age-related loss of dopamine[30]
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