Synesthesia: Genetic Insights and Implications
By Hansub Kim
To most, the senses used to perceive the world are distinct and differentiable; experiences can be compartmentalized into the sensory paths into which they are received, whether auditory, visual, or a clearly defined combination of both. The senses are well tied with abstract concepts and intangible entities created by experience, but do not associate with each other, due to the discrepancies in how different things are interpreted via different senses. Listening to a powerful song evokes emotion; tasting a tea-soaked Madeleine may evoke long lost memories, but it is absurd to think that the color green sounds like 7, or that Tuesday tastes purple. To a certain group, however, this seemingly unfathomable cross-sensory perception is ubiquitous.
Synesthesia, quite literally “sensing together,” is an intriguing neurological phenomenon – in the mind of a synesthete, cognitive pathways are not distinct, but instead blend together – smells can lead to sudden, inherent and involuntary associations with sound; colors can have textures and personality; words take the form of shapes. Long unknown throughout history, synesthesia has recently come to light over the last century, as many artists, writers, and scientists have stepped into the scientific community as self-proclaimed synesthetes including Richard Feynman, Wassily Kandinsky, and Vladimir Nabokov (2). Over 80 different forms of synesthesia exist, many of which can manifest themselves together in one individual. The most common form, grapheme-color synesthesia, is present in over 86% of synesthetes, who associate words or phrases with certain colors. Time-color synesthesia follows at 62%, then music-color type, at 41% (3). Although not ubiquitous, musical synesthesia is especially relevant to the neuroscientific scene because almost all audio/visual synesthesia types, as well as genetic musical phenomena such as absolute pitch, exhibit uncanny genotypic overlaps with each other – findings that could provide insight into neuroauditory connectivity and a long-sought answer for the elusive mechanism behind synesthesia.
Tone-color, or tone-chromatic synesthesia has recently been found to be a biological hotspot that carries many genetic implications, and exhibits significant connectivity with absolute pitch. (9) Absolute pitch is a rare, congenital auditory ability that allows an individual to determine the pitch of a note or series of notes without a second reference note. These abilities are accompanied by the reliable detection of pitch class, in which tones recur within a set octave. In a study published in Human Molecular Genetics in February 2013 at the Boas Center for Genomics and Human Genetics, genetic linkage analysis and sequencing of relevant exons of subjects with synesthesia, absolute pitch (AP), both conditions revealed that specific exons on chromosome 6 of subjects showed strong linkage with those on EPHA7, a genetic locus involved in brain development, CNR1, a cannabinoid receptor which plays a role in cortical brain development, and GABRR1/2, GABA receptors that could potentially facilitate expression of synesthetic behavior via disinhibition. (1) Since EPHA7 is specifically related to the formation and development of the auditory cortex in relation to cortical thalamic connectivity, levels of expression of ephrin, the enzyme that is produced in the EPHA7 locus, are highly regulated. (1) As a result, differently regulated or deviant variants of EPHA7 could lead to the formation of cognitive phenotypes such as AP and synesthesia. (1)
Research conducted at the Department of Neurology at the Beth Israel Deaconess Medical Center in 2013 showed that white matter content and composition differed significantly in the IFOF (interior fronto-occipital fasculus) of tone-color synesthetes, a white matter pathway that connects the visual and auditory cortexes (4). The study also showed that the white matter content of both the fusiform gyrus, a part of the temporal lobe that plays a role in color association and the IFOF in both APs and synesthetes showed a correlation with scores in the audiovisual portion of the Synesthesia Battery, a psychological test created to determine the presence of synesthetic symptoms and qualities. (4). Synesthesia and AP also seemed to point to a second biological junction point at the superior temporal gyrus (STG), which displays drastically enhanced activity when listening or playing music. The bilateral lingual gyrus (BLG) and inferior temporal gyrus (ITG) also showed further activation among synesthetes, strengthening the hypothesized link between tone-color synesthesia and cortical activity. Additionally, deletions of specific exons on chromosome 6 are responsible for differences in patterning of white matter, further suggesting that the genetic mechanisms behind AP and synesthetic symptoms are highly connected. These underlying biological connections can provide further insight into the genetic subtleties of synesthesia and highlight important mechanisms of musical connectivity in the human brain.
Synesthesia, especially tone-color synesthesia, can also be viewed as a disorder or mental syndrome, rather than a genetic boon. Recent research shows that in rare instances, synesthesia can be acquired by the modification of the thalamus during a stroke or neurodegenerative brain disorder. Communication between the thalamus and the cerebellar cortex is so dynamic and complex that the specific pathways and alterations that give rise to synesthetic symptoms are not well understood – however, the source of the synesthesia resulting from stroke is probably the left posterior section of the lateral thalamus, as this area exercises control over hemivisual, olfactory, and auditory senses. (11) Neural plasticity during recovery may have also altered cognitive pathways connecting the thalamus, the cortical areas, and cerebellar cortex. (11)
More fascinating is that occurrence of both synesthesia and absolute pitch are significantly higher in the autistic population. This statistic is hypothesized to be the result of a third subtle syndrome, savant syndrome, prevalent in individuals with autism or Asperger’s syndrome, that shows marked genetic overlap with both synesthesia and absolute pitch. (7) Savant syndrome is characterized by highly superior intelligence and ability in certain cognitive areas, and a markedly lacking ability in others. The mechanisms behind all three of these attributes are fundamentally rooted in the thalamus and cortical areas of the brain, as seen in savants such as Daniel Tammet, a writer and public speaker who possesses tone-color synesthesia as well as several forms of grapheme synesthesia, giving him the profound ability to learn languages within a matter of days. (11) Another mental condition, Williams Syndrome, is at the crossroads of research of musical phenomena and neurological conditions. In these patients, increased activity of the left auditory cortex may lead to contested, but possible phenotypical development of synesthesia and absolute pitch. (12). Approaching synesthesia from the perspective of mental illness and brain injury sheds light on the neurological mechanisms behind recovery and abnormal development, and how the thalamus and cortical areas of the brain play critical roles in shaping perception.
All in all, neuroscience is a mostly uncharted but dynamic, complex field in which symptoms, syndromes, and neurological phenomena are difficult to elucidate individually without branching connections into other conditions and subtleties. Tone-color synesthesia, a fascinating anomaly of neural connectivity and thalamic activity, remains the subject of burgeoning interest, as a deeper understanding of the biological mechanisms behind synesthesia would provide considerable implications into other cognitive activity in the brain.
- Gregersen, P. K., & Kowalsky, E. (2013, February 12). Absolute pitch exhibits phenotypic and genetic overlap with synesthesia. Retrieved September/October, 2016, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707203/pdf/ddt059.pdf
- Vladimir Nabokov. (2012). Retrieved September/October, 2016, from http://sdl.granthazard.com/exhibits/show/famous-synesthetes/famous-synesthetes-closer-look/vladimir-nabokov
- Cytowic, R. E., & Eagleman, D. (2009). Wednesday is indigo blue: Discovering the brain of synesthesia. Cambridge, MA: MIT Press.
- Zamm, A., & Schlaug, G. (2013, July 1). Pathways to Seeing Music: Enhanced Structural Connectivity in Colored-Music Synesthesia. Retrieved September/October, 2016, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3643691/pdf/nihms-460245.pdf
- Loui, P., Zamm, A., & Schlaug, G. (2012). Absolute Pitch and Synesthesia: Two Sides of the Same Coin? Shared and Distinct Neural Substrates of Music Listening. Retrieved September/October, 2016, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596158/pdf/nihms415660.pdf
- Hubbard, E. M., & Ramachandran, V. S. (2005, November 3). Neurocognitive Mechanisms of Synesthesia. Retrieved September/October, 2016, from http://www.cell.com/neuron/pdf/S0896-6273(05)00835-4.pdf
- Bouvet, L., & Donnadieu, S. (2014, February 18). Veridical mapping in savant abilities, absolute pitch, and synesthesia: An autism case study. Retrieved September/October, 2016, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927080/pdf/fpsyg-05-00106.pdf
- Brang, D., & Ramachandran, V. S. (2011, November). Survival of the Synesthesia Gene: Why Do People Hear Colors and Taste Words? Retrieved September/October, 2016, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3222625/pdf/pbio.1001205.pdf
- Ramachandran, V. S. (2011). The tell-tale brain: A neuroscientist’s quest for what makes us human. New York: W.W. Norton.
- Goller, A. I., & Otten, L. J. (2008). Seeing Sounds and Hearing Colors: An Event-related Potential Study of Auditory–Visual Synesthesia. Retrieved September/October, 2016, from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn.2009.21134
- Fornazzari, L., & Fischer, C. E. (2011, November 24). “Blue is music to my ears”: Multimodal synesthesias after a thalamic stroke. Retrieved September/October, 2016, from http://www.tandfonline.com/doi/abs/10.1080/13554794.2011.608362
- Mitchell, K. (2010, August 27). Coloured hearing in Williams Syndrome. Retrieved September/October, 2016, from http://www.wiringthebrain.com/2010/08/coloured-hearing-in-williams-syndrome.html