Unsolved Mystery
Survival of the Synesthesia Gene: Why Do People Hear
Colors and Taste Words?
David Brang*, V. S. Ramachandran
Department of Psychology, University of California, San Diego, La Jolla, California, United States of America
Abstract: Synesthesia is a perceptual experience in
which stimuli presented through one modality will
spontaneously evoke sensations in an unrelated modality.
The condition occurs from increased communication
between sensory regions and is involuntary, automatic,
and stable over time. While synesthesia can occur in
response to drugs, sensory deprivation, or brain damage,
research has largely focused on heritable variants
comprising roughly 4% of the general population. Genetic
research on synesthesia suggests the phenomenon is
heterogeneous and polygenetic, yet it remains unclear
whether synesthesia ever provided a selective advantage
or is merely a byproduct of some other useful selected
trait. Progress in uncovering the genetic basis of
synesthesia will help us understand why synesthesia has
been conserved in the population.
Introduction
Synesthesia is a condition present in 2%–4% of the population
[1] in which a sensory stimulus presented to one modality elicits
concurrent sensations in additional modalities [2]. Synesthesia can
theoretically bind any two senses, but research has largely focused
on two of the most common variants in which auditory tones and
achromatic (colorless) numbers produce vivid and perceptually
salient colors. The specificity of these evoked colors remains stable
over time within any given individual [3], but the same tone or
grapheme doesn’t necessarily evoke the same color in different
people. Synesthesia has been of interest to scientists for nearly 200
years [4], and while familial linkage analyses show a strong genetic
component, the precise genes involved and reasons why synesthesia
has been conserved in the population remain unsolved
mysteries.
Neural Basis of Synesthesia
The neural substrate of synesthesia has been thoroughly studied
in grapheme-color synesthesia (in which numbers and letters evoke
colors) using both psychophysical tests and functional imaging.
Several groups have demonstrated that simple achromatic graphemes
activate both grapheme regions as well as color area V4 (a
region of visual cortex that shows a stronger response to colors
than to grayscale stimuli) in the brains of synesthetes, which is
consistent with the view that synesthetic colors are sensory in
nature (i.e., arise through a bottom-up processing stream) [5,6] as
opposed to being high-level cognitive associations, as has been
proposed [7]. Predicting this finding of ‘‘cross-activation’’ between
grapheme and color regions, Ramachandran and Hubbard [6]
proposed that synesthesia results from an excess of neural
connections between associated modalities, possibly due to decreased
neural pruning between (typically adjacent) regions that
are interconnected in the fetus. Consistent with this suggestion, a
number of studies have demonstrated anatomical differences in the
inferior temporal lobe near regions related to grapheme and color
processing in synesthetes, including increased fractional anisotropy
(reflecting increased white matter or coherence of white matter)
[8,9] and increased gray matter volume [9,10]; increased connectivity
has been found in other forms of synesthesia as well [11].
Furthermore, Brang and colleagues recently demonstrated that
color area V4 becomes active as early as 110 ms after viewing
achromatic letters and numbers, signifying that synesthetic colors
follow a similar time-course in the brain as colors evoked from the
retina [12–14].
Adding support to the sensory cross-activation hypothesis,
Ramachandran and Hubbard [6,15] demonstrated that synthetically
induced colors can lead to perceptual texture segregation;
recent results by Jamie Ward and colleagues [16] lend additional
empirical evidence for this view. Ramachandran and Brang also
noted [17] that the same number can take on multiple colors in
some synesthetes (e.g., the numbers 7 and 8 in Figure 1) or even
the visual appearance of textural qualities like metallic and smooth
[18], further suggesting that synesthesia is a bottom-up sensory
phenomenon. Nevertheless, top-down influences (e.g., attention,
context, etc.) must also play a significant role in synesthesia as first
shown by Ramachandran and Hubbard [15] using Navon figures;
that is, if the subject sees a large 5 made up of small 2 s, the evoked
color will change depending on whether the subject focuses on the
local or global image (i.e., the ‘‘trees’’ or ‘‘forest’’). How integration
of these bottom-up and top-down processing streams occurs is still
not known.
Heredity in Synesthesia
While a proven genetic basis for synesthesia remains elusive, the
phenomenon tends to run in families, as ,40% of synesthetes
report a first-degree relative with the condition [3,19]. Pedigree
analyses of synesthesia suggest high transmissibility from parent to
offspring (Figure 2), yet in at least one confirmed instance,
synesthesia is present in only one monozygotic twin [20]. At least
Citation: Brang D, Ramachandran VS (2011) Survival of the Synesthesia Gene:
Why Do People Hear Colors and Taste Words? PLoS Biol 9(11): e1001205.
doi:10.1371/journal.pbio.1001205
Published November 22, 2011
Copyright: ß 2011 Brang, Ramachandran. This is an open-access article
distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided
the original author and source are credited.
Funding: No specific funding was received for this article.
Competing Interests: The authors have declared that no competing interests
exist.
* E-mail: dbrang@ucsd.edu
Unsolved Mysteries discuss a topic of biological importance that is poorly
understood and in need of research attention.
PLoS Biology | www.plosbiology.org 1 November 2011 | Volume 9 | Issue 11 | e1001205
60 different forms of synesthesia have been documented (i.e.,
different combinations among the senses), reflecting the extreme
heterogeneity of the condition, and one could easily assume that
each type of synesthesia is caused by a unique gene or set of genes.
However, the specific form of synesthesia an individual expresses
can vary within families [19], suggesting the genetic undertones
impose a predisposition to synesthesia but not its expression.
Indeed, individuals with one type of synesthesia are much more
likely to have another as well, an observation that was adduced by
Ramachandran and Hubbard [15] as support for the idea that the
defective pruning gene or genes confer a general propensity to
linking unrelated sensations or even concepts. Further, while
individual synesthetes often display multiple forms of the phenomenon,
large-scale factor analyses suggest that some variants cooccur
with greater frequency within a single individual, suggesting
that some forms are more highly related (i.e., local ‘‘clustering’’ or
‘‘islands’’ of synesthesia types), which is suggestive of a common
origin [21]. However, non-clustering forms still co-occur with
greater frequency than predicted by prevalence rates in the
general population [22], significantly impeding theories of single
genetic markers and the notion of independence among different
forms of the condition.
Previous studies examining the prevalence of synesthesia found
a significant gender gap with a 6:1 ratio of female synesthetes to
males, leading to the suggestion that synesthesia was an X-linked
condition [23]. However, prevalence studies conducted using
random sampling have shown an even distribution of synesthesia
among the genders, suggesting the discrepancy was based on
methodological flaws and self-report biases in earlier studies.
Subsequent research on the genetics of synesthesia has unfortunately
not clarified which genes underlie the phenomenon. Examining
the relationship between synesthesia-like hallucinogenic
experiences and serotonin 2A receptor coding on chromosome 13,
Brang and Ramachandran [24] suggest that synesthesia might
occur from over-expression of this gene, producing higher receptor
density. However, direct investigations using a whole-genome
linkage scan [25] and a family-based linkage analysis [26] each
65/99
66%
26/65
40%
21/34
62%
3/17
18% 0%
100%
Incidence of Familial Heritability for
Auditory- and Grapheme-Color Synesthesias
ProbabilityofSynesthesia
Figure 2. Average familial pedigrees for synesthetes composed from data in references [3,18,19,23,25,48], demonstrating incidence of
heritable transmission from one synesthetic parent (top row) to either a female or male child (bottom row). Squares represent males
and circles females. Color intensity reflects probability of synesthesia pedigree taken from the numbers at the bottom, representing incidence of each
case.
doi:10.1371/journal.pbio.1001205.g002
Figure 1. Number-color associations for one of our synes-
thetes.
doi:10.1371/journal.pbio.1001205.g001
PLoS Biology | www.plosbiology.org 2 November 2011 | Volume 9 | Issue 11 | e1001205
localized distinct loci that overlapped neither with the region
suggested by Brang and Ramachandran [24] nor with one
another, suggesting either a lack of power from the derived sample
sizes or that the phenomenon is largely polygenic. A polygenic
origin is likely, as transmissibility is heterogenous and synesthetes
often possess multiple forms, as mentioned above [15,19]. In light
of these conflicting results, research into the genetics underlying
synesthesia remains in a nascent state and will require much larger
sample sizes and variants of the condition to understand the
underlying factors for transmission. Furthermore, evidence suggests
that synesthesia may in fact be a graded phenomenon in the
general population, creating the possibility that non-synesthetic
relatives of synesthetes show endophenotypes of the condition,
complicating the use of family linkage analyses.
Why Was the Gene Conserved?
Epiphenomenal
Before asking why a synesthesia gene might have been preserved
through evolution, one first must consider the possibility
that synesthesia may likely be merely epiphenomenal, and that the
gene(s) involved may have served some totally unrelated purpose.
It is also possible that the gene(s) may have been retained simply
because they did not incur a great enough cost to be purged by
selection, and could be an example of an evolutionary spandrel.
Another possible explanation is that synesthesia simply represents
the tail end of a normal distribution of cross-modality interactions
present in the general population [15,23]. Partial evidence supporting
this idea comes as sensory deprivation and deafferentation
(i.e., loss of sensory input through the destruction of sensory nerve
fibers) can lead to synesthetic-like experiences. For example, after
early visual deprivation due to retinitis pigmentosa, touch stimuli
can produce visual phosphenes [27], and after loss of tactile
sensation from a thalamic lesion, sounds can elicit touch sensations
[28]. More remarkably, arm amputees experience touch in the
phantom limb merely by watching another person’s hand being
touched [29]. Long-standing evidence has also demonstrated that
hallucinogenic drugs can cause synesthesia-like experiences (for a
review see [30]), suggesting the neural mechanism is present in all
or many individuals but is merely suppressed. However, no research
has yet established the relationship between these acquired
forms to the genetic variant and whether the same neural mechanism
is responsible for both.
Creativity and Metaphor
The question of whether the synesthesia gene(s) may have a
‘‘hidden agenda’’ like the sickle cell anemia gene has with malaria
resistance, and whether that agenda may be ‘‘creativity and
metaphor’’, was first raised by Ramachandran and Hubbard [15].
Subjectively, synesthetes report these experiences are largely
positive and engender facilitative benefits for creative aspects of
their lives. Studies have indeed confirmed the increased incidence
of synesthesia among artists [31] and, relative to controls, synesthetes
report spending more time engaged in creative activities
[32]. However, the nature of the link between synesthesia and
creativity (including metaphor) remains elusive given that
synesthesia involves arbitrarily connecting two unrelated things
(e.g., color and number), whereas there is a non-arbitrary
conceptual connection between, say, Juliet and the sun (of Romeo
and Juliet). One potential solution to this problem comes from
realizing that any given word has only a finite set of associations
(e.g., the sun is warm, nurturing, radiant, bright, etc.). The
overlapping region among halos of associations between two
words (e.g., Juliet and the sun; both are radiant, warm, and
nurturing)—the basis of metaphor—exists in all of us but is larger
and stronger in synesthesia as a result of the cross-activation gene;
in this formulation synesthesia is not synonymous with metaphor,
but only that the gene which produces synesthesia confers a
propensity towards metaphor. While the link between synesthesia
and creativity has received remarkable interest over the last
decade, research has not yet directly demonstrated any causal
relationship between the two and so the argument, at this point,
remains seductive and compelling but not conclusive.
Sensory Processing and Cognitive Abilities
Recently, research has confirmed numerous cognitive and
perceptual benefits that are associated with synesthesia, any of
which could be argued to produce a stronger basis for selection. As
extreme examples of these benefits, two well-characterized savants
have demonstrated remarkable memory abilities based on their
synesthesias: Daniel Tammet used his synesthesia to memorize pi
to 22,514 digits and Luria [33] described an individual (‘‘S’’) with
a prodigious memory based largely on using synesthetic associations
evoked by the items to be memorized. Such cases have led to
the suggestion that synesthesia may exist as a foundation for
savantism, and while Tammet and S are at the extreme end of the
spectrum, synesthetes as a group also have demonstrated improved
memories relative to controls, particularly for items related to their
synesthetic experiences (e.g., memory for phone numbers is aided
by number-color associations) [6,15,34,35].
Outside the realm of memory research there is accumulating
evidence of enhanced sensory processing in synesthesia as well.
Specifically, grapheme-color synesthetes show enhanced detection
of colors on a perceptually low-level visual test of parvocellular
processing (K. Wagner, D. Brang, V. Ramachandran, K. Dobkins,
unpublished data) paralleled by the finding of differences in early
visual processes to simple colors using visual-evoked potentials [36]
well before the time period in the brain in which synesthesia
engages. Furthermore, number-color synesthetes are also more
sensitive at discriminating very similar colors [37]. These early
perceptual effects suggest that synesthesia is associated with increased
processing of color information; however, it remains
possible that these differences in color processing are not due to
synesthesia itself but are merely caused by synesthetes’ excessive
experience with colors. Confirming these sensory enhancements in
a different form of the condition, Banissy and colleagues demonstrated
that mirror-touch synesthetes (individuals who experience
tactile sensations on their own body while watching someone else
being touched) possess increased tactile acuity [37]. Lastly, individuals
who experience auditory sounds evoked by visual motion
process rhythmic visual stimuli more accurately than controls and
in a manner similar to how non-synesthetes process auditory
information [38].
These demonstrations of enhanced processing of sensory information
suggest a provocative evolutionary hypothesis for synesthesia:
synesthetic experiences may serve as cognitive and
perceptual anchors to aid in the detection, processing, and retention
of critical stimuli in the world; in terms of memory benefits,
these links are akin to a method of loci association. In addition to
facilitating processes in individual sensory modalities, synesthetes
also show increased communication between the senses unrelated
to their synesthetic experiences, suggesting that benefits from
synesthesia generalize to other modalities as well, supporting their
ability to process multisensory information [39]. Furthermore,
others have argued that synesthesia is the direct result of enhanced
communication between the senses as a logical outgrowth of the
cross-modality interactions present in all individuals [40]. Taken
collectively, these data suggest that synesthesia may be associated
PLoS Biology | www.plosbiology.org 3 November 2011 | Volume 9 | Issue 11 | e1001205
Box 1. Remaining Questions
1. Beyond the vague assertion that synesthesia might enhance
sensory and intersensory processing (whether accidentally or
‘‘deliberately’’ selected for), can synesthesia actually enhance
sophisticated and abstract mental abilities? Ramachandran
and Hubbard [42] pointed out that many synesthetes with
visual-spatial number forms [2] claimed such enhancement
did occur. When a number-form synesthete imagines or
visualizes a number in front of him he always sees it occupying
a specific location in space; the numbers are arranged
sequentially along a number line that can be highly convoluted
in three dimensions—sometimes even doubling
back on itself. Many of them said the ‘‘kinks’’ in the line often
interfered with their ability to do simple arithmetic across the
kinks. Intriguingly some of them reported being able to ‘‘see
hidden relationships’’ from unusual vantage points geometrically
as a result of the numerical landscape, an effect which
could—and should—be measured quantitatively because of
the insight it may provide into mathematical computation in
normal people as well as savants [15]; indeed, Einstein often
remarked that even his ‘‘mathematical’’ thinking was spatial
in nature. Finally, we have noted that some number-color
synesthetes report difficulty with simple arithmetic because
they found the colors ‘‘distracting’’—an effect we are
currently investigating.
2. Synesthesia tends to be a unidirectional phenomenon such
that numbers evoke colors but colors won’t typically evoke
the concept of numbers [15]. This prospect of unidirectionality
should constrain theories on the types of anatomical and
functional connections that mitigate synesthetic experiences.
Presenting a particularly interesting test for the crossactivation
theory, research suggests that synesthesia may
be unconsciously bidirectional [43]. Future studies investigating
the types of anatomical and/or functional connections
that mitigate synesthesia will hopefully clarify this matter.
3. What is the relationship between inherited synesthesias
(e.g., grapheme-color synesthesia) and acquired conditions
and phenomena that produce similar experiences? Specifically,
what aspects of synesthesia are based on pharmacology
(intensity of the experience, number of different
forms of synesthesia within a single individual, or simply
possessing synesthesia in general), and how does altering
these neurotransmitters affect the experience of synesthesia
in the normal population as well as in synesthetes; i.e.,
does a synesthete who ingests LSD experience novel forms
of the condition and/or an enhancement of their current
synesthesia? Does a non-synesthete who takes LSD
multiple times experience any consistency in these
temporary synesthetic associations (e.g., does a 2,000-hz
tone elicit a consistent color across multiple sessions)?
While the ethical implications of such studies today impede
current testing, research from the mid-20th century has
provided preliminary evidence relating inherited synesthesia
to pharmacologically induced forms: Simpson and
McKellar [44] reported on two developmental synesthetes
who, under the influence of mescaline, experienced
increased vividness of their ‘‘natural’’ synesthetic experiences
and also new forms of the phenomenon as well.
4. Do the genes that predispose one to synesthesia independently
produce sensory or cognitive enhancements? The
specific types of the condition examined in this paper
suggest that synesthesia enhances sensory processing. The
claim that part of the reason why the phenomenon has
survived evolution would be supported if the same
benefits are found in all forms of synesthesia. Further,
one of the critical links missing from this picture is the
question of whether the synesthetic phenotype actually
causes these generalized sensory enhancements. This
problem can be partially addressed by testing whether
family members of synesthetes who themselves are not
synesthetic (i.e., carriers) show similar perceptual benefits
due to endophenotypes of the synesthesia gene. Additionally,
do these individuals show latent synesthetic
associations or an enhanced ability to make these
associations? No research has been published in this area
to date, but our group is currently testing these ideas.
5. Does synesthesia exist in animals? If synesthesia is a
phylogenetically old trait it may discount the notion that
synesthesia evolved to aid creativity and metaphor in the
population. Indeed, the criteria required to successfully
create an animal model of synesthesia can be debated as
synesthesia is defined by the conscious experience of
sensation. Nevertheless, mice with a mutation on a2d3 show
reduced pain sensitivity due to the failure of transmission
from the thalamus to the cortex, yet pain instead causes
activation of visual and auditory regions similar to the crossactivation
seen in synesthesia [45]. It remains to be seen
whether this gene is related to synesthesia in humans, but it
provides an interesting candidate for research.
6. The phenomena of number-form, weekday-form (each day
occupies a specific location in space), and month-form
(each month occupies a location in space) synesthesias
seem unrelated, yet some synesthetes display all three and
in many these sequences evoke colors as well. It remains
unclear whether these variants are due to interactions
between spatial maps in the parietal lobes and ordinality
mechanisms (ordered sequences such as numbers, months,
etc.) thought to originate in the vicinity of the angular
gyrus as suggested by Ramachandran and Hubbard [15].
Astonishingly, in some instances these spatial-forms
change predictably over time; e.g., in month-form synesthesia
the calendar will change shape and position to keep
the current month in a static position relative to the subject
[46]. There is nothing in synesthesia research that can
explain such oddities. They remind us both of the fact that
we have barely scratched the surface and that synesthesia
might give us insights into basic sensory codes used by the
brain to represent time and space, topics of which a great
deal has been written but nothing is known.
7. If synesthesia involves cross-domain interactions between
organized maps of color in V4 and the elementary
components of visual forms, and if the disposition of such
maps is not random, is there a correlation between the
overall shape of the grapheme and color (e.g., do curvy
shapes tend to be red and jagged shapes blue)? We have
observed that within an individual synesthete correlations
exist between shape similarity and color similarity [47], but
the question remains whether the layout of hue and shape
maps across all individuals predispose particular shape-color
correspondences in general. Analogously, are there phoneme
maps (depending on where the tongue hits the
palette: aspirations, labials, etc.) in cortical motor areas that
are non-randomly correlated with evoked colors? This can be
partly be tested using an artificially synthesized language like
Korean in which the alphabet was constructed based on the
position of the tongue on the palette; do letters corresponding
to similar tongue positions evoke more similar colors?
PLoS Biology | www.plosbiology.org 4 November 2011 | Volume 9 | Issue 11 | e1001205
with enhanced primary sensory processing as well as the
integration between the senses. However, to fully understand this
relationship, identification of the genetic component involved and
evidence of selection on these genes will be required to determine
whether synesthesia serves to enhance normal sensory processing.
Towards a Solution
Synesthesia is associated with a wide variety of conceptual and
perceptual benefits, suggesting that the gene(s) involved may have
been selected for because of a hidden agenda. Whether this is true,
and if so, what that agenda may be, beyond specific enhanced
cognitive and sensory benefits, remains to be explicated (For a
further exploration of the remaining scientific questions, please see
Box 1). The picture is complicated not only by the fact that there
appear to be many degrees and many variants of the phenomenon
(as there is in dyslexia, autism, etc.), but also by the extraordinary
phenomenological experiences of some synesthetes (e.g., ‘‘5 is not
only red but has a grainy texture to it’’). But it is precisely because
synesthesia seems to occupy that mysterious boundary zone
between elementary sensations on the one hand and higher level
abstractions (such as gender and personality, and even emotions;
e.g., sandpaper evoking the sensation of jealousy [41]) on the other
that the phenomenon intrigues us and provides an experimental
lever for investigating high-level mental processes. Indeed, Ramachandran
and Hubbard [15] pointed out that number personifications
in synesthesia (e.g., 5 is male, 7 is female, etc.) may reflect
an amplification of the universal human propensity to ‘‘binarize’’
the world to economize cognitive processing.
In summary, synesthesia is a highly heritable phenomenon that is
associated with numerous benefits to cognitive processing, potentially
underscoring a basis for why this condition has survived
evolutionary pressures. Research into synesthesia is now passing its
bicentennial anniversary in science, and understanding both the
mechanisms underlying the phenomenon and the reasons for its
selection are finally at a point in which synesthesia can inform our
understanding of cognitive and perceptual processes in the general
population. To appropriately understand this condition and its
relation to normal cognition will require both technically and
intellectually diverse contributions from all areas of biology. In sum,
this research suggests that synesthesia, far from being a ‘‘fringe’’
phenomenon as formerly believed (or that it is purely ‘‘conceptual’’
or associative in nature), can give us vital clues toward understanding
some of the physiological mechanisms underlying some of the
most elusive yet cherished aspects of the human mind.
References
1. Simner J, Sagiv N, Mulvenna C, Tsakanikos E, Witherby SA, et al. (2006)
Synaesthesia: the prevalence of atypical cross-modal experiences. Perception
35(8): 1024–1033.
2. Galton F (1883) Inquiries into human faculty and its development. London:
Dent & Sons.
3. Baron-Cohen S, Burt L, Smith-Laittan F, Harrison J, Bolton P (1996)
Synaesthesia: Prevalence and familiality. Perception 25(9): 1073–1079.
4. Sachs GTL (1812) Historiae naturalis duorum leucaetiopum: Auctoris ipsius et
sororis eius. Erlangen.
5. Hubbard EM, Arman AC, Ramachandran VS, Boynton G (2005) Individual
differences among grapheme-color synesthetes: brain-behavior correlations.
Neuron 45(6): 975–985.
6. Ramachandran VS, Hubbard EM (2001) Psychophysical investigations into the
neural basis of synaesthesia. Proc Biol Sci 268: 979–983.
7. Nikolic´ D, Ju¨rgens UM, Rothen N, Meier B, Mroczko A (2011) Swimming-style
synesthesia. Cortex 47(7): 874–879.
8. Rouw R, Scholte HS (2007) Increased structural connectivity in grapheme-color
synesthesia. Nat Neurosci 10: 792–797.
9. Jancke L, Beeli G, Eulig C, Hanggi J (2009) The neuroanatomy of graphemecolor
synesthesia. Eur J Neurosci 29: 1287–1293.
10. Weiss PH, Fink GR (2009) Grapheme-colour synaesthetes show increased grey
matter volumes of parietal and fusiform cortex. Brain 132: 65–70.
11. Ha¨nggi J, Beeli G, Oechslin MS, Ja¨ncke L (2008) The multiple synaesthete E.S.:
neuroanatomical basis of interval-taste and tone-colour synaesthesia. Neuroimage
43(2): 192–203.
12. Brang D, Hubbard EM, Coulson S, Huang MX, Song T, Ramachandran VS
(2010) Magnetoencepalography reveals early activation of V4 in grapheme color
synesthesia. Neuroimage 53(1): 268–274.
13. Brang D, Edwards L, Ramachandran VS, Coulson S (2008) Is the sky 2?
Contextual priming in grapheme-color synesthesia. Psychol Sci 19(5): 421–
429.
14. Brang D, Kanai S, Ramachandran VS, Coulson S (2011) Contextual priming in
grapheme-color synesthetes and yoked controls: 400 milliseconds in the life of a
synesthete. J Cognitive Neurosci 7: 1681–1696.
15. Ramachandran VS, Hubbard EM (2001) Synaesthesia: a window into
perception, thought and language. J Consciousness Stud 8(12): 3–34.
16. Ward J, Jonas C, Dienes Z, Seth A (2010) Grapheme-colour synaesthesia
improves detection of embedded shapes, but without pre-attentive ‘pop-out’ of
synaesthetic colour. Proc Biol Sci 277(1684): 1021–1026.
17. Ramachandran VS, Brang D (2008) Synesthesia; from molecules to metaphor.
Scholarpedia 3(6): 3981.
18. Eagleman DM, Goodale MA (2009) Why color synesthesia involves more than
color. Trends Cogn Sci 13(7): 288–292.
19. Barnett KJ, Finucane C, Asher JE, Bargary G, Corvin AP, et al. (2008) Familial
patterns and the origins of individual differences in synaesthesia. Cognition
106(2): 871–893.
20. Smilek D, Moffatt BA, Pasternak J, White BN, Dixon MJ, Merikle PM (2002)
Synaesthesia: a case study of discordant monozygotic twins. Neurocase 8(4):
338–342.
21. Novich SD, Cheng S, Eagleman D (2011) Is synesthesia one condition or many?
A large-scale analysis reveals subgroups. J Neuropsychol 5(2): 353–371.
22. Sagiv N, Simner J, Collins J, Butterworth B, Ward J (2006) What is the
relationship between synaesthesia and visuo-spatial number forms? Cognition
101(1): 114–128.
23. Ward J, Simner J (2005) Is synaesthesia an X-linked dominant trait with lethality
in males? Perception 34: 611–623.
24. Brang D, Ramachandran VS (2007) Psychopharmacology of synesthesia; the
role of serotonin S2a receptor activation. Med Hypotheses 70(4): 903–904.
25. Asher JE, Lamb JA, Brocklebank D, Cazier JB, Maestrini E, et al. (2009) A
whole-genome scan and fine-mapping linkage study of auditory-visual
synesthesia reveals evidence of linkage to chromosomes 2q24, 5q33, 6p12, and
12p12. Am J Hum Genet 84(2): 279–285.
26. Tomson SN, Avidan N, Lee K, Sarma AK, Tushe R, et al. (2011) The genetics
of colored sequence synesthesia: suggestive evidence of linkage to 16q and
genetic heterogeneity for the condition. Behav Brain Res 223(1): 48–52.
27. Armel KC, Ramachandran VS (1999) Acquired synesthesia in retinitis
pigmentosa. Neurocase 5(4): 293–296.
28. Ro T, Farne` A, Johnson RM, Weeden V, Chu Z, et al. (2007) Feeling sounds
after a thalamic lesion. Ann Neurol 62(5): 433–441.
29. Ramachandran VS, Brang D (2009) Sensations evoked in patients with
amputation from watching an individual whose corresponding intact limb is
being touched. Arch Neurol 66(10): 1281–1284.
30. Cytowic RE, Eagleman DM (2009) Wednesday is indigo blue: discovering the
brain of synesthesia. Cambridge (Massachusetts): The MIT Press.
31. Rothen N, Meier B (2010) Higher prevalence of synaesthesia in art students.
Perception 39(5): 718–720.
32. Ward J, Thompson-Lake D, Ely R, Kaminski F (2010) Synaesthesia, creativity
and art: What is the link? Brit J Psychol 99(1): 127–141.
33. Luria A (1968) The mind of a mnemonist. Cambridge (Massachusetts): Harvard
University Press.
34. Smilek D, Dixon MJ, Cudahy C, Merikle PM (2002) Synesthetic color
experiences influence memory. Psychol Sci 13(6): 548–552.
35. Yaro C, Ward J (2007) Searching for Shereshevskii: what is superior about the
memory of synaesthetes? Q J Exp Psychol 60: 681–695.
36. Barnett KJ, Foxe JJ, Molhom S, Kelly SP, Shalgi S, et al. (2008) Differences in
early sensory-perceptual processing in synaesthesia: a visual evoked potential
study. Neuroimage 43: 605–613.
37. Banissy MJ, Walsh V, Ward J (2009) Enhanced sensory perception in
synaesthesia. Exp Brain Res 196(4): 565–571.
38. Saenz M, Koch C (2008) The sound of change: visually-induced auditory
synesthesia. Curr Biol 18(15): R650–R651.
39. Brang D, Williams LE, Ramachandran VS (2011) Grapheme-color
synesthetes show enhanced crossmodal processing between auditory and
visual modalities. Cortex;E-pub ahead of print 22 June 2011. doi:10.1016/
j.cortex.2011.06.008.
40. Bien N, Ten Oever S, Goebel R, Sack AT (2012) The sound of size Crossmodal
binding in pitch-size synesthesia: a combined TMS, 2 EEG and psychophysics
study. Neuroimage 59(1): 663–672.
41. Ramachandran VS, Brang D (2008) Tactile-emotion synesthesia. Neurocase
14(5): 390–399.
42. Ramachandran VS, Hubbard EM (2006) Synesthesia: what does it tell us about
the emergence of qualia, metaphor, abstract thought, and language? In van
PLoS Biology | www.plosbiology.org 5 November 2011 | Volume 9 | Issue 11 | e1001205
Hemmen JL, Sejnowski TJ, eds. 23 problems in systems neuroscience Oxford
University Press USA. pp 432–473.
43. Knoch D, Gianotti LR, Mohr C, Brugger P (2005) Synesthesia: when colors
count. Cogn Brain Res 25(1): 372–374.
44. Simpson L, McKellar P (1955) Types of synaesthesia. Brit J Psychiat 101(422):
141.
45. Neely GG, Hess A, Costigan M, Keene AC, Goulas S, et al. (2010) A genomewide
Drosophila screen for heat nociception identifies a2d3 as an evolutionarily
conserved pain gene. Cell 143(4): 628–638.
46. Brang D, Teuscher U, Ramachandran VS, Coulson S (2010) Temporal
sequences, synesthetic mappings, and cultural biases: the geography of time.
Conscious Cogn 19: 311–320.
47. Brang D, Coulson S, Ramachandran VS (2011) Similarly shaped letters evoke
similar colors in grapheme-color synesthesia. Neuropsychologia 49: 1355–1358.
48. Cytowic RE (2002) Synesthesia: a union of the senses. New York: Springer-
Verlag.
PLoS Biology | www.plosbiology.org 6 November 2011 | Volume 9 | Issue 11 | e1001205