Revisiting Geschwind's hypothesis on brain lateralisation: a functional MRI study of digit ratio (2D:4D) and sex interaction effects on spatial working memory.

The Geschwind-Behan-Galaburda (GBG) hypothesis links cerebral lateralisation with prenatal testosterone exposure. Digit ratio measures in adults have been established as potential markers of foetal sex hormonal milieu. The aim of the study was to evaluate the sex-dependent interaction of digit ratio measures and cerebral lateralization as well as their neurohemodynamic correlates using functional MRI (fMRI). Digit ratio measures-ratio of index finger (2D) length to ring finger (4D) length (2D:4D) and difference between 2D:4D of two hands, i.e., right minus left (DR-L)-were calculated using high resolution digital images in 70 right-handed participants (42 men) based on reliable and valid method. fMRI was acquired during the performance of a spatial working memory task in a subset of 25 individuals (14 men), and analysed using Statistical Parametric Mapping 8 (SPM8) and the Laterality Index toolbox for SPM8. Men had significantly less bilateral 2D:4D than women. There was a significant negative correlation between right 2D:4D and 2-Back task accuracy (2BACC) in women. A significant sex-by-right 2D:4D interaction was observed in left parahippocampal gyrus activation. Additionally, sex-by-DR-L interaction was observed in left IPL activation. DR-L showed a significant positive correlation with the whole brain Laterality Index (LI), and LI, in turn, demonstrated a significant negative correlation with 2BACC. Our study observations suggest several novel sex-differential relationships between 2D:4D measures and fMRI activation during spatial working memory task performance. Given the pre-existing background data supporting digit ratio measures as putative indicator of prenatal sex hormonal milieu, our study findings add support to the Geschwind-Behan-Galaburda (GBG) hypothesis.