Explaining function with anatomy: language lateralization and corpus callosum size.

The anatomy of the corpus callosum (CC) has been advocated as a potential marker for functional lateralization because its size is supposedly proportional to the number of fibers connecting the hemispheres. Previous morphometric studies of this relationship have compared CC size in groups of subjects who are more or less likely to show differences in their lateralization (e.g., left vs right handers). The findings, however, have been inconsistent, and to our knowledge, no previous study has directly compared CC size with lateralization assessed by functional imaging data. We therefore combined anatomical measurements of CC size with left versus right hemisphere language activation in 74 normal subjects. After controlling for perceptual and motor output effects, as well as for global white-matter volume, handedness, gender and age, we found that subjects who had a larger CC showed more left lateralization for language in posterior temporal and inferior frontal regions. Examination of these effects revealed that, as CC size increased, stronger lateralization resulted from more left hemisphere activation in both regions as well as reduced right hemisphere activation in the posterior temporal region. Our observations provide the first clear evidence in normal subjects that the midsagittal surface area of the CC contributes to the degree to which language is functionally lateralized. We discuss the complex interhemispheric processes that might underlie this effect.