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While a proven genetic basis for synesthesia remains elusive, the phenomenon tends to run in families, as ∼40% of synesthetes report a first-degree relative with the condition. How integration of these bottom-up and top-down processing streams occurs is still not known.
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Nevertheless, top-down influences (e.g., attention, context, etc.) must also play a significant role in synesthesia as first shown by Ramachandran and Hubbard using Navon figures that is, if the subject sees a large 5 made up of small 2 s, the evoked color will change depending on whether the subject focuses on the local or global image (i.e., the “trees” or “forest”). Ramachandran and Brang also noted that the same number can take on multiple colors in some synesthetes (e.g., the numbers 7 and 8 in Figure 1) or even the visual appearance of textural qualities like metallic and smooth, further suggesting that synesthesia is a bottom-up sensory phenomenon. Īdding support to the sensory cross-activation hypothesis, Ramachandran and Hubbard, demonstrated that synthetically induced colors can lead to perceptual texture segregation recent results by Jamie Ward and colleagues lend additional empirical evidence for this view. Furthermore, Brang and colleagues recently demonstrated that color area V4 becomes active as early as 110 ms after viewing achromatic letters and numbers, signifying that synesthetic colors follow a similar time-course in the brain as colors evoked from the retina –. Consistent with this suggestion, a number of studies have demonstrated anatomical differences in the inferior temporal lobe near regions related to grapheme and color processing in synesthetes, including increased fractional anisotropy (reflecting increased white matter or coherence of white matter), and increased gray matter volume, increased connectivity has been found in other forms of synesthesia as well. Predicting this finding of “cross-activation” between grapheme and color regions, Ramachandran and Hubbard proposed that synesthesia results from an excess of neural connections between associated modalities, possibly due to decreased neural pruning between (typically adjacent) regions that are interconnected in the fetus. Several groups have demonstrated that simple achromatic graphemes activate both grapheme regions as well as color area V4 (a region of visual cortex that shows a stronger response to colors than to grayscale stimuli) in the brains of synesthetes, which is consistent with the view that synesthetic colors are sensory in nature (i.e., arise through a bottom-up processing stream), as opposed to being high-level cognitive associations, as has been proposed. The neural substrate of synesthesia has been thoroughly studied in grapheme-color synesthesia (in which numbers and letters evoke colors) using both psychophysical tests and functional imaging.