The phenomenon of synesthesia. A review

Synesthesia is a greek word (syn=together + aisthesis=perception) and means the physical experience of a cross-modal association. That is, the stimulation of one sensory modality reliably causes a perception in one or more different senses. Its phenomenology clearly distinguishes it from metaphor, literary tropes, sound symbolism, and deliberate artistic contrivances that sometimes employ the term "synesthesia" to describe their multisensory joinings. An unexpected demographic and cognitive constellation co-occurs with synesthesia: females and non-right-handers predominate, the trait is familial, and memory is superior while math and spatial navigation suffer. Synesthesia appears to be a left-hemisphere function that is not cortical in the conventional sense.

Synesthesia runs in families in a pattern consistent with either autosomal or X-linked dominant transmission. Perhaps the most famous family case is that of the Russian novelist Valdimir Nabokov. Mother, son and the son of her son were synesthetic but also the wife of her son as well. Women synesthetes predominate. It was found in the U.S. a ratio of 3:1 while in the U.K. 8:1. Synesthetes are preponderantly non-right-handed. Synesthetes are normal in the conventional sense. They appear bright, and hail from all walks of life. The impression that they are inherently "artistic" seems to be a sampling bias, given that famous synesthetes such as Valdimir Nabokov, Olivier Messiaen, David Hockney, and Alexander Scriabin are well-known because of their art rather than their synesthesia. Clinically, synesthetes seem mentally balanced. Their MMPIs are unremarkable except for non-stereotypical male-female scales. Standard neurological exams are also normal.

Synesthesia is involuntary but elicited, usually is projected. Synesthetic perceptions are durable and generic, never pictorial or elaborated. Synesthesia is emotional. The experience is accompanied by a sense of certitude and a conviction that what synesthetes perceive is real and valid. Synesthesia is memorable. It was Luria's The Mind of A Mnemonist (1968) that first suggested a link between synesthesia and hypermnesia. The apparently limitless memory of his subject, S, seemed due to the synesthesia that accompanied his every experience. During recall, S described a replay of somatic feelings and "an overall sensation" during which "the thing remembers itself." By this, S meant that "he" exerted no effort to retrieve the desired information.

The synesthesia that occasionally occurs with lysergic acid diethyl-amide (LSD) and other antiserotoninergics is relevant here because of the drug's effect on visual perception and CNS integration. The colored visions themselves seem paradoxical in view of increased thresholds for axonal response beyond thalamic synapses until one appreciates the facilitating effect of sensory input from other modalities on the perception of visual hallucinations-i.e., synesthesia.

Almost all measures of color perception are affected in humans given LSD. LSD has a differential action on central synapses: Facilitation of primary evoked responses and inhibition of the recruiting. LSD facilitates the primary afferent axosomatic synapses while inhibiting corticocortical association and nonspecific mesodiencephalic axodendritic pathways. This may provide a basis for the intellectual and behavioral disorganization so clearly seen clinically, inasmuch as LSD inhibits human cortical dendritic potentials in a manner similar to that recorded in cats.

In trying to fathom the brain basis of synesthesia, it is perhaps useful to first examine the phenomenon to which synesthesia is most similar. These include drug-induced synesthesia, eidetic imagery and other forms of hypermnesia, and release hallucinations.

Inhibition of only the excitatory serotonin receptors have been implicated in the serotonin behavioral syndrome. Increased dopamine in the face of decreased serotonin, however, may also be important. The negative action of increased brain serotonin in interfering with learning, and in disrupting memory consolidation, dream recall, and novel task performance, might be entertained to account for the memorability of the synesthetic perception.

Additional support for decreased cortical function comes from studies relating hallucinations to reduction of cortical blood flow, which is known to be closely coupled with neuronal metabolism. Cortical blood flow is also decreased during synesthetic performance.

The performance of synesthetic subjects may be seen as involving a suppression of rich corticocortical associations, which leaves the more unelaborated sensory percept (synesthesia, eidetic image, hallucination) to be directly associated at some lower level.

Synesthesia is "abnormal" only in being statistically rare. It is, in fact, a normal brain process that is prematurely displayed to consciousness in a minority of individuals.

Key words: Synesthesia, memory, perception, neurobiological substrate.