The Tell-Tale Brain: A Neuroscientist's Quest for What Makes Us Human

The fact that we see various types of synesthesia provides additional evidence for cross-wiring. Perhaps the mutant gene expresses itself to a greater degree, in more brain regions, in some synesthetes than in others. But how exactly does the mutation cause cross-wiring? We know that the normal brain does not come ready-made with neatly packaged areas that are clearly delineated from each other. In the fetus there is an initial dense overproliferation of connections that get pruned back as development proceeds. One reason for this extensive pruning process is presumably to avoid leakage (signal spread) between adjacent areas, just as Michelangelo whittled away excess marble to produce David. This pruning is largely under genetic control. It’s possible that the synesthesia mutation leads to incomplete pruning between some areas that lie close to each other. The net result would be the same: cross-wiring.

However, it is important to note that anatomical cross-wiring between brain areas cannot be the complete explanation for synesthesia. If it were, how could you account for the commonly reported emergence of synesthesia during the use of hallucinogenic drugs such as LSD? A drug can’t suddenly induce sprouting of new axon connections, and such connections would not magically vanish after the drug wore off. Thus it must be enhancing the activity of preexisting connections in some way—which is not inconsistent with the possibility that synesthetes have more of these connections than the rest of us. David Brang and I also encountered two synesthetes who temporarily lost their synesthesia when they started taking antidepressant drugs called selective serotonin reuptake inhibitors (SSRIS), a drug family that famously includes Prozac. While subjective reports cannot entirely be relied on, they do provide valuable clues for future studies. One person was able to switch her synesthesia on or off by starting or stopping her drug regimen. She detested the antidepressant Wellbutrin because it deprived her of the sensory magic that synesthesia provided; the world looked drab without it.

I have been using the word “cross-wiring” somewhat loosely, but until we know exactly what’s going on at the cellular level, the more neutral term “cross-activation” might be better. We know, for instance, that adjacent brain regions often inhibit each other’s activity. This inhibition serves to minimize crosstalk and keeps areas insulated from one other. What if there were a chemical imbalance of some kind that reduces this inhibition—say, the blocking of an inhibitory neurotransmitter, or a failure to produce it? In this scenario there would not be any extra “wires” in the brain, but the synesthete’s wires would not be properly insulated. The result would be the same: synesthesia. We know that, even in a normal brain, extensive neural connections exist between regions that lie far apart. The normal function of these is unknown (as with most brain connections!), but a mere strengthening of these connections or a loss of inhibition might lead to the kind of cross-activation I suggest.

In light of the cross-activation hypothesis we can now also start to guess why Francesca had such powerful emotional reactions to mundane textures. All of us have a primary touch map in the brain called the primary somatosensory cortex, or S1. When I touch you on the shoulder, touch receptors in your skin detect the pressure and send a message to your S1. You feel the touch. Similarly when you touch different textures, a neighboring touch map, S2, is activated. You feel the textures: the dry grain of a wooden deck, the slippery wetness of a bar of soap. Such tactile sensations are fundamentally external, originating from the world outside your body.