Approaches to measuring language lateralisation: an exploratory study comparing two fMRI methods and functional transcranial Doppler ultrasound

Abstract In this exploratory study we compare and contrast two methods for deriving a laterality index (LI) from functional magnetic resonance imaging (fMRI) data: the weighted bootstrapped mean from the widely-used Laterality Toolbox (toolbox method), and a novel method that uses subtraction of activations from homologous regions in left and right hemisphere to give an array of difference scores (mirror method). Data came from 31 individuals who had been selected to include a high proportion of people with atypical laterality when tested with functional transcranial Doppler ultrasound (fTCD), and who had fMRI data for two tasks, word generation and semantic matching, which were selected as likely to activate different brain regions. In general, the mirror method gave better agreement with fTCD laterality than the toolbox method, both for individual regions of interest, and for a large region corresponding to the middle cerebral artery. LI estimates from this method had much smaller CIs than those from the toolbox method; with the mirror method, most participants were reliably lateralised to left or right, whereas with the toolbox method, a higher proportion were categorised as bilateral (i.e. the CI for the LI spanned zero). Reasons for discrepancies between fMRI methods are discussed: one issue is that the toolbox method averages the LI across a wide range of thresholds. Furthermore, examination of task-related t-statistic maps from the two hemispheres showed that language lateralisation is evident in regions characterised by deactivation, and so key information may be lost by ignoring voxel activations below zero, as is done with conventional estimates of the LI.