Increased resting state network connectivity in synesthesia: evidence for a neural basis of synesthetic consistency.

Studying individual differences in conscious awareness can potentially lend fundamental insights into the neural bases of binding mechanisms and consciousness (Cohen Kadosh and Henik, 2007). Partly for this reason, considerable attention has been devoted to the neural mechanisms underlying grapheme– color synesthesia, a healthy condition involving atypical brain activation and the concurrent experience of color photisms in response to letters, numbers, and words. For instance, the letter C printed in black on a white background may elicit a yellow color photism that is perceived to be spatially colocalized with the inducing stimulus or internally in the “mind’s eye” as, for instance, a visual image. Synesthetic experiences are involuntary, idiosyncratic, and consistent over time (Rouw et al., 2011). To date, neuroimaging research on synesthesia has focused on brain areas activated during the experience of synesthesia and associated structural brain differences. However, activity patterns of the synesthetic brain at rest remain largely unexplored. Moreover, the neural correlates of synesthetic consistency, the hallmark characteristic of synesthesia, remain elusive. Functional imaging studies suggest that grapheme– color synesthesia is associated with activation of brain regions specific to relevant visual processes and binding processes (i.e., occipitotemporal, parietal, and frontal brain regions) (for review, see Rouw et al., 2011). A popular view is that grapheme– color synesthesia arises in the fusiform gyrus—more specifically, from cross-activation between the visual word form area and the color area V4 (for an overview, see Hubbard et al., 2011). A recent study refined this view and showed that V4 is activated via functional pathways from the superior parietal lobe for synesthetes who experience color photisms in the mind’s eye but from the letter shape area in the fusiform gyrus for those who experience color photisms as spatially colocalized with the inducing stimulus (van Leeuwen et al., 2011). Structural imaging studies complement the functional studies and suggest morphometric differences in similar brain regions: synesthetes exhibit increased gray and white matter density in the fusiform gyrus (including V4) and parietal and primary visual cortices (Rouw et al., 2011). However, on the basis of functional and structural imaging results, Hupé and colleagues (2012) have questioned the role of regional activations and structural changes in the experience of synesthesia and proposed that synesthesia may arise from subtle and distributed neural coding. This is in line with the recent finding that synesthesia is associated with marked differences in global structural brain networks (Hänggi et al., 2011). In a recent article published in The Journal of Neuroscience, Dovern and colleagues (2012) investigated intrinsic (resting) network connectivity and its relationship to color consistency in grapheme–color synesthesia. Using resting-state functional magnetic resonance imaging (rs-fMRI), they sought to identify network differences that would discriminate demographically matched groups of synesthetes and controls. Synesthetes exhibited strong consistency when retested on color associations for more than 120 items after a 6-month period. The rs-fMRI data were analyzed using independent component analysis (ICA). To identify relevant network connections at rest [i.e., intrinsic connectivity networks (ICNs)], independent components were regressed against brain templates containing synesthesia-specific regions of interest consisting of visual cortex, auditory cortex, and intraparietal cortex. Validation of the ICNs was obtained when ICAs were run separately in each group. Spatial brain maps obtained from the combined group ICA were then used to analyze group differences within ICNs. Finally, the authors calculated correlations between the time course of blood oxygenation level dependent (BOLD) signal changes of synesthesiarelevant ICNs to measure functional network connectivity (FNC). Received July 26, 2012; revised Aug. 14, 2012; accepted Aug. 15, 2012. This work was supported by the Holcim Foundation for the Advancement of Scientific Research and the Dr. Mortimer and Theresa Sackler Foundation (N.R.), and the Cogito Foundation (D.B.T.). Correspondence should be addressed to Nicolas Rothen, School of Psychology, Sackler Centre for Consciousness Science, University of Sussex, Falmer, Brighton, BN1 9QH, United Kingdom. E-mail: [email protected]. DOI:10.1523/JNEUROSCI.3577-12.2012 Copyright©2012theauthors 0270-6474/12/3213641-03$15.00/0 The Journal of Neuroscience, October 3, 2012 • 32(40):13641–13643 • 13641