Maisano Anna, Pia Ilaria
from the ancient Greek σύν [syn], "together", and αἴσθησις [aisthēsis], "sensation", is a perceptual experience in which stimuli presented through one modality will evoke an unusual experience in another unrelated modality.
"These additional exeperience often occur between modalities, such as seeing colours while listening to music or feeling tactile shapes while tasting foods" (Baron-Choen and Harrison, 1997 and Cytowic 1989).
For example looking at the letter E or the number 7 or hearing a particular word or note, may elicit coloured perception or special flavours.
An interesting thing about it is the fact that the same tone or grapheme doesn't necessary evoke the same colour in different people.
The trigger of the experience is called "the inducer", the additional experience evoked is called "the concurrent" (Grossenbacher and Lovelace, 2001).
About genetic components of synesthesia, early researches have demonstrated that synesthesia is a familial trait: 40% of synesthetes report a first-degree relative with this condition (Baron-Cohen et. Al., 1996 and Galton 1883).
In addition, it has been found that there is a significant gender gapwith a 6:1 of female synesthetes to males, leading to the suggestion that synesthesia is an X-linked condition.
Nevertheless other studies on monozygotic tweens that were discordant for synesthesia and data suggesting that it can skip a generation do not fit with the idea that it is a dominant character.
In sum, recent data suggest that the genetic mechanism underlying synesthesia may be more complex than the simple theory of the X-linked dominant account proposed before.
Survival of the Synesthesia Gene: Why Do People Hear Colors and Taste Words? Brang e Ramachandran, 2001
The prevalence of synesthesia might be as high as 1 in 20 across all forms and 1 in 100 for grapheme-colour synesthesia. These high prevalence suggest that it is a widespread phenomenon with neural basis of the mind and not only a "benign cognitive variant" as thought before by Ward and Mattingley (Ramachandran and Hubbard, 2001).
It is important to know that, if it is true that underneath the manifestation of synesthesia there is a genetic component, it is also true that its influence is not much about the expression of the symptoms but the genetic undertones only impose the predisposition to this condition. This idea comes from the observation that there are multiple forms of synesthesia (at least 60), and they do not always come from the expression of the same and unique set of genes, but a similar form of synestesia in two different people can be caused by different genes.
Many researchers have tried to define which genes were connected with this condition, but every study leaded to different conclusions. For example, Brang and Ramachandran suggest tha synesthesia might occur from over-expression og the gene coding for serotonin 2A receptor on chromosome 13 (this hypotesis is supported by the relationship observed between synesthesia-like hallucinogenic experiences and serotonin action on 2A receptor).
This different localizations of synesthesia genes' loci can be explained either by a lack of power from the derived sample sizes or by the idea that the phenomenon is the largely polygenic.
Another question about synesthesi genes is wheather they have been conservated for some reasons or, as an example on an evolutionary spandrel, if they have simply been kept pnly because their elimination represented a too high cost for evolution. In a relation to this idea, synesthesia may also be merely epiphenomenal, which means its genes might have been retained for no related purpose.
One of the first questions that researchers have asked themeselves is about wheather synesthesia arises from a failure in neural pruning during the formation of the neural system or if it derives from a dishinibition.
Many studies suggest that synesthesia can come from a form of crossactivation of different brain zones, a fact that can be related to the observation of prenatal connections between inferior temporal regions and area V4 (Kennedy et al., 1997 and Rodman and Moore, 1997).
As Hubbard and Ramachandran underline, it is important to note that it is the presence of connection between the two areas that makes the crossactivation possible, and not only their being adjacent "per se".
Neurocognitive Mechanisms of Synesthesia, Hubbard Em et al., 2005
Researchers have carried out studies using both psychophysical and functional imaging. It has been demonstrated that when simple achromtic graphemes are shown to a patient, in his brain both grapheme regions and color area V4 (a brain area that has a stronger response to colours than to grayscale stimuli) activate.
This fact supports the idea that colours are sensory in nature and they do not derive from high level cognitive associations. Knowing this particular activation of different brain areas in response to one stimulus, Ramachandran and Hubbard have proposed a theory that says synesthesia is the result of an excess of neural connections between associated modalities, which can possibly be due to a lack of neural pruning between adjacent and interconnected regions in the fetus.
On the other hand, other studies' results are more likely to support the theory of a disinhibiting feedback from a "multisensory nexus" such as the temporo-parietal-occipital junction. An example of this comes from a patient who, after becoming blind from retinitis pigmentosa, reported the experience of having the impression of seeing movements after receiving tactile stimuli; in addition, the intensity of the stimuli required to have this sensation was greater when his hand was held in front of him then behind, leading to the suggestion of some top-down multisensory activation perhaps mediated by parietal structures.
In conclusion it can be said that the two theories are not mutually exclusive: making a comparision with the phantom limb phenomenon, it appears how in some cases, when the sensation of the phantom limb is experienced few hours after the loss, the sensation comes from the unmusking of exsisting, previously inhibited connections (Borsook et al., 1998)
In other cases, expecially when the sensation occurs some time after the amputation, it is more likely to come from the development of neural connections (Ramachandran and Hirstein, 1998).
In addition to this fact, there are studies that have also demonstrated anatomical differences in the inferior temporal lobe of synesthetes, near regions that process grapheme and colour information; for example it has been seen an increased gray matter volume and an increased fractional anisotropy.
Brang and colleagues have then demonstrated that achromatic letters and numbers evoke an attivation in colour area V4 only 110 ms after they have been seen, just as colours evoked from the retina do; this finding can support the idea that synesthetic colours and real colours follow a similiar time-course in the brain.
THE ROLE OF 5-HT
One neurotransmitter suspected to be central to the perceptual changes is serotonin, which increases the excitability and connectedness of sensory brain regions. Excessive serotonin in the brain may cause many of the characteristics of psychedelic intoxication, it may also play a role in synesthesia acquired after brain injury and alterations in serotoninergic system may lead to developmental synesthesia that occurs in individuals with autism.
According to Grossenbacher and Lovelace (2001), there are three different types of synesthesia:
- Acquired synesthesia
- Developmental synesthesia
- Drug-induced synesthesia
It is a form of the condition that emerges after brain injury or disease or artificial technologies like sensory substitution that occurs from plasticity of the sensory systems resulting in increased connectivity.
This increased connectivity is probably caused by increased neurotransmitter activity in cortical regions adjacent to the affected site. In traumatic brain injury the cells shift to anaerobic glycolysis, resulting in an accumulation of lactic acid. The anaerobic metabolism is not powerful enough to mantain the energy levels, so ATP-stores are depleted and the membrane ion-pumps, which depend on ATP, fail. This leads to cell death (apoptosis) which results in excessive release of excitatory neurotransmitters, particularly serotonin and glutamate.
This excess in extracellular serotonin and glutamate availability affects neurons and astrocytes and results in over-stimulation of serotonin and glutamate receptors.
Initially this increase in excitatory neurotransmitter activity leads to lower excitability in local areas through negative feedback within weeks but this decreased activity in affected neural regions could lead to a disinhibitory enhancement of neural activity and connectivity in unaffected cortical regions. Alternatively, the early increase in serotonin levels could lead to the formation of unusual feature binding.
It is a form of the condition that has persisted since birth or early childhood that remains relatively stable over time.
About 30% of autistic individuals have a 25 to 70 % increase in blood levels of serotonin, also known hyperserotonemia. Serotonin cannot normally cross the blood-brain barrier in adults, so high blood levels of serotonin are not necessarily a good indicator of high extracellular serotonin in the brain.
High blood levels of serotonin, however, may indicate brain levels of serotonin in young children, as the blood-brain barrier is not fully developed until the age of two.
Serotonin synthesis is typically increased unilaterally in individuals with autism, about 15 percent of which are believed to experience synesthesia compared to about 4 percent population-wide. In terms of a potential mechanism, one possibility is that serotonin causes aberrant structural binding in the spared neural regions that are also responsible for the savant skills found in 10 percent of autistic individuals.
A whole-genome linkage scan and a family-linkage analysis in a sample of 43 multiplex families with auditory-visual synesthesia suggested that synesthesia may be traceable to a region on chromosome 2 (2q24.1) that has been implicated in autism (Newbury et al., 2009), indicating that there may be genetic link between developmental synesthesia and autism.
People exposed to a hallucinogen (psilocybin, LSD, mescaline) can also experience synesthesia.
This type of synesthesia is different from the others because it is usually limited to the most intense phases of intoxication, though in some cases it continues for weeks or months after exposure to the drug. It has been suggested that “serotonin S2a receptors are the ‘synesthesia receptors’ in the brain”; there are in fact some evidences:
- LSD produces synesthesia by selectively activating serotonin 5-HT2A receptors;
- Prozac (fluoxetine), a selective serotonin reuptake inhibitor that increases 5-HT1 receptor activity thereby inhibiting 5-HT2A, blocked synesthesia in two subjects;
- melatonin, a brain hormone derived from serotonin that can disinhibit 5-HT2A receptor activity, temporarily induced grapheme-color synesthesia in a subject with number-form synesthesia.
Though not all serotonin agonists elicit synesthetic experience, it is widely agreed that the mechanism of action for the class of serotonergic hallucinogens is through binding of serotonin to the 5-HT2A serotonin receptor (Presti and Nichols, 2004; González-Maeso et al., 2007).
The mechanism underlying drug-induced synesthesia plausibly involves serotonergic excitatory activity in layer V pyramidal neurons implicated in multisensory binding.
Serotonergic Hyperactivity as a Potential Factor in Developmental, Acquired and Drug-Induced Synesthesia, Berit Brogaard, 2013
In conclusion, even though synesthesia has been first investigated since 1800, it has first been treated more as a curiosity by psychologists and neuroscientists, and it has only recentely started to be considered under a more scientific level. It is now well known that synesthesia has a genetic component and that it involves aberrant structural and functional brain connectivity, so that adjacent brain regions do not work separately anymore, but they start to interact with direct projection or disinhibited feedback mechanisms, so that their information mix. It is still mostly unknown what causes the onset of synesthesia but some of the latest researches have found the presence of excessive levels of serotonin as a possible trigger for acquired, developmental and drug-induce cases of this experience.