|Figure 1. Synesthetic Experience|
|What letters may seem like to a
Synesthia is a specialized phenomenon in which activation in one sensory modality leads to the activation of another sensory modality. Multiple combinations of different modalities lead to a diverse range of synesthesic possibilities. The first reported case of synesthesia was over 200 years ago, but the mechanisms as to how it occurs is still under debate today. Several opposing theories have been proposed to try and explain the mechanisms as to how these individuals can experience these unique sensations. The two most prominent theories are the cross activation theory and the disinhibited feedback theory and each have different pieces of evidence supporting their claims. Recently due to the advent of new technology, researchers have also been able to discover genes that are thought to contribute to how synesthesia occurs. However for those that are not fortunate enough to have the genes involved with synesthesia, acquired forms of synesthesia such as learned synesthesia as well as other forms of drug induced and injury induced synesthesia have been reported, which further adds to the debate over the mechanisms of synesthesia.
Table of Contents
1. Prominent Theories
1.1 Cross Activation Theory
|Figure 2. Cross Activation Theory|
|Representation of the cross activation theory.
Input to the grapheme area with the letter A leads to activation of area V4 via
this increase in connection and the experience of seeing the colour red.
The cross-activation theory as proposed by Ramachandran and Hubbard suggests that synesthesia occurs due to an increase in neural connection caused by a decrease in pruning between the two sensory modalities in a synesthete brain (See Figure 2). Their theory stems from the observation that the brain areas involved in grapheme-colour synesthesia (e.g., the letter A leading to seeing the colour red) are in close proximity to each other in the brain. As shown in Figure 3 below, the grapheme area shown in green and the V4 area (the area of the brain responsible for colour perception) shown in red are adjacent to each other in the fusiform gyrus. They suggested that because these regions are in such close proximity to each other, they could very well be residual connections that were not pruned between these areas. They hypothesized that through this neuronal connection, neurons activated by the inducer (e.g., the letter A) could quickly activate neurons responsible for the concurrent (e.g., the colour red). Thus the cross-activation theory suggests the synesthete brain is different anatomically than a non-synesthete brain due to these hyper-connections.
1.1.1 Supporting Evidence
Evidence for the cross-activation theory first stem from fMRI studies. Hubbard, et al. attempted to compare activity in the V4 area in 6 grapheme-colour synesthetes to those of 6 control subjects when viewing grapheme stimuli. Results showed that activity in V4 was significantly greater in synesthetes in comparison to control subjects, and this increase in activity was specific in V4, as activity in earlier brain regions such as V1 or V2 showed no significant difference between synesthetes and controls supporting the increased connection between the grapheme area and area V4.
|Figure 3. Grapheme and V4 area in the brain|
|Green depicts the grapheme area and red depicts area V4 in the brain.
As shown, the two areas are in close proximity in the brain.
(Image adapted from Hubbard & Ramachandran, 2011).
Another source of evidence supporting cross-activation theory comes from diffusion tensor imaging (DTI). Rouw and Scholte sampled 18 synesthetes with the grapheme-coloured form of synesthesia. They hypothesized that if there was an increase in connection between the two modalities due to a decrease in pruning, we should see greater fractional anisotropy (FA) in a synesthete brain as a result of an increase in white matter. Indeed they were able to show that there was an increase in FA in the synesthetes, suggesting a difference in the white matter tracts. Specifically, they showed an increase in FA in the right inferior temporal cortex (where the fusiform gyrus and subsequently the grapheme and V4 area are). They were also able to show that there was a correlation between how intense the synesthete subjects’ experiences were and the FA measured in the fusiform gyrus, supporting the use of these white matter tracts in causing synesthesia. In addition to differences in white matter, Weiss and Fink were also able to demonstrate anatomical differences in the synesthete brain by the volume of grey matter near area V4.
Magnetoencephalographic (MEG) studies are known for their temporal acuity. The cross-activation theory proposes that activity in the V4 area after seeing a grapheme in a grapheme-colour synesthete should be almost simultaneous, as activation would travel quickly through the residual connection between the two modalities. Brang, et al. were of the first to attempt to use MEG to study the synesthete brain. They showed that there were no differences in activity of the graphme area between synesthetes and control participants which is expected as both groups are viewing the same letters. However, there were significant increases in activity in the V4 area in the synesthete compared to the control. Furthermore, this increase in activity reached significance only 5 ms after activity in the grapheme area. This near simultaneous activity supports the increase in neural connection in a synesthete brain as proposed by cross-activation theory.
1.2 Disinhibited Feedback Theory
The disinhibited feedback theory suggests an opposing mechanism to the cross-activation theory. The major difference is that the cross-activation theory emphasizes that a synesthete brain is anatomically different than a normal brain in that these is an increase in connection that is not present in non-synesthetes. However, the disinhibited feedback theory proposes that there is nothing that distinguishes a synesthete brain from a normal brain but instead synesthesthic sensations arise via disinhibited feedback. Normally, input from multiple regions of the brain are sent to a central processing area that binds the information together. Because there is input from multiple regions, input from one region may lead to feedback from the central processor down to other regions that were not initially activated (See Figure 4). For example, seeing a grapheme stimulus “A” would send signals up to the central processor, and the central processor would then send feedback down to the colour region and activate the colour red. This theory suggests that in a non-synesthete individual this feedback is present but normally inhibited. However, in a synesthete brain, this feedback is disinhibited and so the usually inhibited feedback from the central processor can now travel down to other regions of the brain and activate them.
1.2.1 Supporting Evidence
Neufeld, et al. recently performed a study in which 14 auditory-visual synesthestes were recruited. This particular type of synesthesia is caused by hearing a tone and leading to seeing a coloured shape moving in space. They measured connectivity in these synesthetes in three particular brain regions: the auditory cortex, the visual cortex, and the left inferior parietal cortex (IPC). They found no increase in connectivity between the auditory cortex and the visual cortex, as would be hypothesized by the cross-activation theory if there was a decrease in pruning between the two modalities. Instead, they found greater connectivity from the left IPC to both the auditory cortex and the visual cortex. This is precisely what the disinhibited feedback theory would predict, as the left IPC has been shown to be important for multi-sensory perception along with processing synesthetic sensations. Thus the left IPC may be the central processor as suggested by the disinhibited feedback theory, and through increased feedback to the auditory and visual cortex from this region subsequently led to an increase in connectivity in synesthetes as compared to control subjects. Importantly, all individuals have this feedback connection from the IPC, therefore it is not a formation of a novel connection as suggested by cross-activation theory, but rather a strengthening of an old connection that all individuals have.
|Figure 5. Famlilal Trend of Synesthesia|
|Chances of having Synesthesia depending on whether your
parents have it as well. Suggests a genetic basis to synesthesia.
(Image adapted from Brang & Ramachandran, 2011)
Researchers have recognized a familial trend to synesthesia, such that it appears to be much more prominent in families. This observation was first noted by Francis Galton in 1883, and several studies afterwards have confirmed this familial trend. This suggests that genetics may play a role in developing synesthesia. A genetic factor can explain why a person that has one form of synesthesia are likely to have another form, as the genes would be expressed throughout the whole brain and affect multiple modalities. A genetic factor would also lend further evidence to the cross-activation theory, as a gene that results in decreased pruning would cause an increased connection between two areas of the brain in synesthetes, and those that do not have the gene would not see a decrease in pruning and become non-synesthetes.
Asher, et al. conducted one of the few genetic studies done on synesthesia to date. By surveying 43 families that had synesthesia, they found four different loci that were thought to play a role in affecting brain development. Importantly, one of the roles the genes affect may be important for neuronal migration and pruning, which fits well with the cross-activation hypothesis of a decrease in pruning between two sensory areas. However, a study done more recently by Tomson, et al. found a different loci than was reported by Asher, et al., which may suggest that synesthesia is not due to the activity of a single gene but perhaps several genes working in tandem.
2.1 Why the gene has survived
One benefit of having synesthesia is the enhanced memory abilities synesthetes seem to have based on their sensations such as the well known case of Daniel Tammet and his ability to remember more than 22,000 digits of Pi. Other cases include case study C, who had number-colour synesthesia and had remarkable memory of digits even after 48 hours versus control subjects whose performance deteriorated dramatically after 48 hours. In addition, synesthetes also seem to have enhanced sensory processing. Evidence of this comes from greater amplitudes of early visual-evoked potentials in synesthetes compared to control subjects as well as the ability of number-colour synethetes to differentiate between colours that are nearly identical. Taken together these results suggest that individuals with the genes of synesthesia had advantages over non-synesthetes in both memory and sensory processing, and this may have resulted for the selection of the synesthetic genes to be passed on by the process of natural selection.
|Daniel Tammet, a well know synesthete, explains
how he is able to memorize 22,000 digits of Pi due to his synesthesia.
3. Acquired Synesthesia
3.1 Drug Induced Synesthesia
|Figure 6. Gustatory-Colour Synesthesia|
|Some individuals after taking drugs report feeling synesthetic
like sensations such as tasting colours or seeing colours.
Cases of drug induced synesthesia due to methamphetamine, lysergic acid diethylamide (LSD), and other hallucinogens have been reported such that users of these drugs often experience synesthesia like sensations. These cases of drug induced synesthesia would lend support to the disinhibited feedback theory, as it suggests a regular individual with no anatomically distinct brain is able to acquire synesthesia by simply taking a drug. The cross-activation theory would not predict drug induced synesthesia to be possible, as these individuals do not have the increase in connection between modalities suggested to be responsible for causing synesthesia. However, scientists have called into question whether drug induced synesthesia is the same phenomenon as actual synesthesia. For example, one criteria for actual synesthesia is the fact that associations must remain the same over time (e.g., an A will always be red, and will not turn into a blue A later on in life). However, drug induced synesthesia appears to produce different associations each time, thereby calling into question how genuine it is and whether these cases are valid.
3.2 Injury Induced Synesthesia
Injury induced synesthesia is another form of acquired synesthesia that have appeared. One case of injury induced synesthesia is reported by Ro, et al. in which a woman with lesions in the ventrolateral nucleus of the thalamus developed auditory-tactile synesthesia after the lesions, such that hearing a tone produced a touch sensation. It was suggested that the synesthesia may have developed due to neuroplasticity following the lesion resulting in rewiring of the brain, and subsequently greater connections between the auditory area and the sommatosensory area. This rewiring may have occurred due to the fact that pathways travelling through the ventrolateral nucleus no longer transmit signals, leaving the brain to have to find new ways to transmit information. This explanation of acquired synesthesia would support the cross-activation theory, as new connections being formed between sensory modalities are responsible for causing the synesthetic sensations. The disinhibited feedback model would not be able to explain synesthesia due to this plasticity. However, several differences between injury induced synesthesia and regular synesthesia have also been pointed out, such that injury induced synesthesia seems not to be automatic, as patient who acquired synesthesia after injury only appeared to experience the sensations approximately 80% of the time, whereas regular synesthetes who were born with synesthesia experience these associations all the time.
3.3 Learned Synesthesia
|Figure 7. Learning Synesthesia|
|Reaction time and accuracy on a modified stroop task before and after participants
read from coloured books. There was both an increase in accuracy and a decrease in reaction
for congruent trials after reading from the books and a decrease in accuracy and increase in
reaction time for incongruent trials post reading. (Image adapted from Colizoli et al., 2012)
One study published recently have attempted to observe if normal individuals can learn synesthesia by reading a book filled with colored letters (e.g., apple) over a two to four week period. Participants read over 100,000 words during this time span. They measured participants accuracy and reaction time to a modified Stroop task, such that participants were required to name the colour of the letter that is presented. In prior experiments, it has been shown that synesthetes are more accurate and faster to respond when the colour of the letter was congruent to their perceptual experience (e.g., a red A) versus when it is incongruent with their experience (e.g., a blue A).
Participants performed this modified Stroop task before and after reading the coloured books. Prior to reading, there were no observable differences between congruent letters and incongruent letters in terms of response time and accuracy as seen in Figure 7. However after reading, participants were both faster and more accurate when the letters were congruent with the letter colours in the book, and slower and less accurate when the letters were incongruent with the letter colours in the book. If participants were not experiencing colours after reading, there should be no difference between congruent and incongruent colours as colours should not be associated with a particular letter. Participants’ subjective experiences were also recorded, and it was found those who answered highly on whether or not they experienced colour as they saw the letters also showed the strongest Stroop effect. However it is not certain whether participants are performing better on congruent Stroop tasks because they are experiencing synesthesia, or whether it is merely a strong learned association due to prolonged reading of the books .