Inside a synesthete's head: a functional connectivity analysis with grapheme-color synesthetes

Grapheme-color synesthesia is a condition in which letters are perceived with an additional color dimension. To identify brain regions involved in this type of synesthesia and to analyze functional connectivity of these areas, 18 grapheme-color synesthetes and 18 matched controls were stimulated with letters and pseudo-letters presented in black and color in an event-related fMRI experiment. Based on the activation-differences between synesthetes and non-synesthetic controls regions of interest were defined. In a second analysis step functional connectivity was calculated using beta series correlation analysis for these seed regions. First we identified one seed region in the left inferior parietal (IPL) cortex (BA7) showing activation differences between grapheme-color synesthetes and controls. Furthermore, we found activation differences in brain areas involved in processing of letters and pseudo-letters, in particular the right IPL cortex (BA7), but also two more clusters in the right hemispheric BA 18 and BA 40. Functional connectivity analysis revealed an increased connectivity between the left IPL seed region and primary/secondary visual areas (BA 18) in synesthetes. Also the right BA 7 showed a stronger connectivity with primary/secondary visual areas (BA 18) in grapheme-color synesthetes. The results of this study support the idea that the parietal lobe plays an important role in synesthetic experience. The data suggest furthermore that the information flow in grapheme-color synesthetes was already modulated at the level of the primary visual cortex which is different than previously thought. Therefore, the current models of grapheme-color synesthesia have to be refined as the unusual communication flow in synesthetes is not restricted to V4, fusiform cortex and the parietal lobe but rather involves a more extended network.