Regional and hemispheric determinants of language laterality: implications for preoperative fMRI

Abstract

Language is typically a function of the left hemisphere but the right hemisphere is also essential in some healthy individuals and patients. This inter-subject variability necessitates the localization of language function, at the individual level, prior to neurosurgical intervention. Such assessments are typically made by comparing left and right hemisphere language function to determine "language lateralization" using clinical tests or fMRI. Here, we show that language function needs to be assessed at the region and hemisphere specific level, because laterality measures can be misleading. Using fMRI data from 82 healthy participants, we investigated the degree to which activation for a semantic word matching task was lateralized in 50 different brain regions and across the entire cortex. This revealed two novel findings. First, the degree to which language is lateralized across brain regions and between subjects was primarily driven by differences in right hemisphere activation rather than differences in left hemisphere activation. Second, we found that healthy subjects who have relatively high left lateralization in the angular gyrus also have relatively low left lateralization in the ventral precentral gyrus. These findings illustrate spatial heterogeneity in language lateralization that is lost when global laterality measures are considered. It is likely that the complex spatial variability we observed in healthy controls is more exaggerated in patients with brain damage. We therefore highlight the importance of investigating within hemisphere regional variations in fMRI activation, prior to neuro-surgical intervention, to determine how each hemisphere and each region contributes to language processing.

Figure 1

A: Main effect of semantic matching on words relative to perceptual matching on unfamiliar greek letters (random‐effect analysis over 82 subjects, at P < 0.001 uncorrected). Significant effects are shown in red‐to‐yellow color coding and projected on an individual T1‐weighted image in neurological convention. B: Consistent effect of laterality at the voxel level (random‐effect analysis on the LM maps over 82 subjects, at P < 0.001 uncorrected). C: laterality indices (LI) of our 82 subjects. For display purposes, individual LI values are sorted from weak to strong left‐lateralization. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 2

Relationship between global LI values and the parameter estimates of each voxel for the contrast “semantic word matching versus perceptual matching on unfamiliar greek letters.” Positive (red) and negative (blue) relationships are shown in neurological convention on axial slices (top) and 3D‐rendering volume (bottom). Significant effects are shown at P < 0.05 corrected (for height or size). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 3

A: Multidimensional scaling projection of the distance between the 50 clusters (numbered from 1 to 50). The regions belonging to the most distant clusters (clusters 45 and 49) are displayed on axial slices. B: Scatter‐plot of the negative correlation between laterality in the angular gyrus (cluster 45) and ventral precentral gyrus (cluster 49). Each subject is shown by a circle‐dot shape. C: Effect size of left and right angular and ventral precentral gyri during semantic matching on words and pictures. This displays the mean parameter estimates over all subjects that code the differences in activation signal during semantic versus perceptual matching. SW, semantic word matching; SP, semantic picture matching; PM, perceptual matching on unfamiliar stimuli.