3.+Diagnosing+Synaesthesia

 **Individual Neurowiki by Amirah Momen as a part of the Synaesthesia group Neurowiki** toc
 * Diagnosing synaesthesia **

Synaesthesia is a neurological condition characterized by the perception of a given sensory modality upon stimulation of another, typically independent, sensory pathway. To date, as many as 60 distinct variations of synaesthesia have been documented with individuals reporting mixed perception of every imaginable sensory combination . The ability to identify and diagnose individuals with synaesthesia is critical to attaining a better understanding of both the prevalence and nature of this condition. Over time, research has equipped scientists and medical practitioners with increasingly sensitive tools for diagnosing and categorizing synaesthetes;  however, there is still no true ‘litmus test’ for identifying effected individuals . Efforts to further develop current diagnostic tools  are carried out in the hopes of discovering potential biomarkers for synaesthesia. Such biomarkers are critical not only in regards to characterizing atypical neurological functioning , but also  to our understanding of the mechanisms underlying sense and perception in the normal brain.

=1.1 Historical development of diagnostic tools =

The earliest approach to diagnosing individuals with synaesthesia relied on self-report, a method used by [|Sir Francis Galton] throughout his research of the condition in the 19th century. Galton stressed that to the individuals reporting synaesthetic experiences, they were very real; he also noted the highly subjective nature of synaesthesia along with the significant limitations associated with self-report. Many scientists were quick to dismiss claims of synaesthetic experiences as 'imagined events' due to the absence of external symptoms or any means for third-person observation. . Galton, a ‘pioneer’ of the mental testing movement, later abandoned his work with synaesthesia in favor of research that corresponded with the ‘[|behaviorist]’ movement of psychology; the ideas of behaviorism did not correspond with the self-report methods used to diagnose and study synaesthetes as they relied too heavily on the invisible inner workings of the mind, the so called ‘black box’. Research later carried out by Karwoski & Riggs relied on tests that made use of standard psychological principles of the times; these tests involved optical illusions and time latency measures to assess the nature of a given individual’s self-described 'sensory coupling'. Today, the diagnosis of synaesthesia is carried out with a more holistic approach that integrates tools developed by experts with backgrounds in the experimental, psychiatric and neurological foundations of the condition. [|Richard E. Cytowic] ** [3] **, a preeminent figure in the field of synaesthesia research, explains his commonly shared clinical approach to diagnosis of the condition as it conforms to the 'Cartesian' method. This method combines a person's history with neuropsychological tests that serve to **1. verify whether the criteria for the condition are met** and **2. to localize the level of the 'lesion'**. Patient history is of critical importance when considering whether an individual is truly a synaesthete; before any further testing is carried out, clinicians ask suspected synaesthetes about the following: 
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">family prevalence of synaesthesia ;
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">age of the earliest remembered synaesthetic experience ;
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">prior history of drug use;
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">prior history of temporal lobe epilepsy

<span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; font-size: 10pt;"> Fig1. Adapted from Baron-Cohen et al. [1996] Family pedigrees for six synaesthetes. Synaesthetes are shaded black; probands are indicated by arrows.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> Once a family history has been taken, the clinician will ask the patient to describe the nature of their percepts and will assess whether their descriptions match the standard criteria for synaesthesia. Finally, the clinician can move on to more objective means of diagnosis i.e. neuropsychological testing. Current efforts are underway to develop diagnostic tools that rely on biomarkers for the various types of synaesthesia, however current methods of diagnosis remain dependent on the Cytowic's clinical approach.

=<span style="font-family: Cambria,serif;">1.2 Determining which processes to test: Perception versus Cognition =

<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">Before the creation of any diagnostic tests, early pioneers in the field of synaesthesia research had to come to an agreement about whether synaesthesia was a sensory-perceptual based condition or a product of higher cognitive processes.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> Most of the evidence surfacing from this debate has supported the sensory-perceptual basis for synaesthesia. Such evidence includes observations of: <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> Many of the early experimental tasks used to settle the cognition versus sensory-perception debate have been developed into diagnostic tests for identifying synaesthetes. They are described below in section 2.2. =<span style="font-family: Cambria,serif;">2.1 Criteria for synaesthesia =
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">reduced percept vividness in accordance with lowered stimulus intensity.
 * <span style="color: #000000; font-family: 'Times New Roman',Times,serif; font-size: 10pt;">[|Ramachandran]'s 'pop-out' test shows grapheme-color synaesthetes better segregate amongst numbers due to their elicited color percepts. This supports the theory that cross-activation occurs early on in sensory processing. ** [2] **
 * <span style="color: #000000; font-family: 'Times New Roman',Times,serif; font-size: 10pt;">Synaesthetes can adapt to synaesthetic experiences. This is similar to how sensory input (in the form of a noisy room) can result in 'white noise', becoming part of an individual's unconscious sensory processing.
 * <span style="color: #000000; font-family: 'Times New Roman',Times,serif; font-size: 10pt;">percepts are not elicited by abstract ideas but rather, by discrete stimuli.
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">Brain imaging evidence in the form of ERPs.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt; line-height: 24px;">Synaesthesia is not listed in the [|DSM-IV] ( Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ) as it is not considered detrimental to the daily living of affected individuals. While there is no official 'universal criteria' for identifying true synaesthetes, the below criteria describing the characteristics of synaesthetic percepts ,as outlined by Richard Cytowic ** [3] **<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt; line-height: 24px;">, is widely used by clinicians and researchers alike.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> 1. Synaesthetic percepts are involuntary

<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> 2. Synaesthetic percepts are spatially extended, existing close to the body i.e. grapheme-color percepts are experienced as if projected onto a screen close to the body; not in the visual field exactly nor merely imagined (Note: this criterion has since been amended to account for the experiences of associator synaesthetes whose percepts are perceived within the 'mind's eye') <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> 3. Synaesthetic percepts are consistent over time i.e. sensory associations do not change with time. This is akin to the observation that synaesthesia shows 're-test reliability' over time

<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> 4. Synaesthetic percepts are discrete in nature in that they are composed of simple elements and not complex scenes. This characteristic is what distinguishes synaesthetic percepts from hallucinations

<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> 5. Synaesthesia is memorable. This characteristic is detected in sensory recall tests where synaesthetic associations often serve as memory aids <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> 6. Synaesthesia is emotional. Cytowic and Wood suggested that in all forms of synaesthesia, sensory integration occurs via the limbic system; this hypothesis is based on the affective nature of the condition.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> <span style="background-color: #ffffff; font-family: 'Times New Roman',Times,serif;"> Of the criteria outlined by Cytowic ** [3] **<span style="background-color: #ffffff; font-family: 'Times New Roman',Times,serif;">, the key characteristics of synaesthesia are that **1.** percepts are consistent over time such that the association of one given stimulus always elicits the same cross-modal sensation and **2.** that percepts are both involuntary and automatic in nature i.e. they are neither willfully suppressible nor inducible. In essence, a synaesthete will report experiencing specific and automatic cross-wired sense perceptions which are consistent and reproducible over a lifetime. In absence of these key characteristics, clinicians can rule out synaesthesia. <span style="font-family: 'Times New Roman',Times,serif;">Some conditions which may be confused with classical synaesthesia include drug-induced synaesthesia (LSD), sensory deprivation hallucinations, hallucinations induced by [|temporal lobe epilepsy], [|peduncular hallucinosis of Lhermitte] and hypermnesia. ** [3] **

<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> <span class="wiki_link_ext">media type="youtube" key="yS73PY90q_s?version=3" height="360" width="640" <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; font-size: 10pt;"> A depiction of the involuntary, automatic and consistent nature of synaesthetic percepts. Note how the same tone is continually associated with the same color. Even minute differences in tone can be distinguished based on consistent tone-color associations. =<span style="font-family: Cambria,serif;">2.2 Distinguishing among types: testing approaches =

<span style="font-family: Cambria,serif;">2.2a Associator versus projector synaesthesia
<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">One recent development in the field of synaesthesia includes the amendment to Cytowic's original criteria which stated that precepts are always spatially extended into the outside world. Over the past few years, researches have come to distinguish two broad forms of synaesthesia which render the spatial expansion principle correct for only one of the two forms. Today, synaesthetes are recognized as either lower synaesthetes termed 'projectors' or higher synaesthetes termed 'associators'. The terms 'higher' and 'lower' refer to the level of processing at which the sense-perceptions are crossed while the terms 'projector' and 'associator' refer to where the percept is sensed i.e. out in the world versus in the mind's eye. Dixon et al. ** [10] **<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> came up with a method for differentiating between these two types of synaesthetes which does not depend on purely descriptive measures. They used third-person objective testing in addition to self-report in order to develop standardized performance measures for distinguishing between these groups. Using **<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">color-naming **<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> and **<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">photism-naming Stroop **<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> tasks they were able to identify two different patterns of Stroop interference for projectors and associators. Using these tests, Dixon et al. identified whether synaesthetes' percepts were made up of early-stage 'perceptual' or late-stage 'conceptual' aspects of color. In doing so, they identified whether it was //form// or //meaning// that elicited synaesthetic experiences for any given synaesthete. Ramachandran and Hubbard ** [8] **<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> have proposed that associator grapheme-color synaesthetes have 'cross-wiring' in the angular gyrus where higher order functions are carried out while projector grapheme-color synaesthetes are expected to have cross-wiring in centers responsible for lower levels of sensory processing. It is suspected that the proportion of associators greatly outnumbers that of projectors, however researchers have yet to propose values to support this claim. Further development of objective diagnostic tools are necessary to come to any conclusions on the associator-to-projector ratio.

<span style="font-family: Cambria,serif;">2.2b Tests used: Stroop-effect based tests
<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> **Test of genuineness**: Developed in 1987 by Baron-Cohen et al. and later revised, the Test of Genuineness (TOG) provides an objective basis for diagnosing synaesthesia. The TOG measures the degree to which a suspected synaesthete's percepts adhere to the key criterion of //consistency over time//. Subjects are instructed to provide detailed descriptions of the percepts they experience in association with a series of test stimuli i.e. tone-color synaesthetes will be played different tones and are asked to describe the colors they elicit. They are later re-tested **<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">without warning **<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">using the same stimuli. Synaesthetes score with a consistency percentile between 70-90% across trials while non-synaesthetes are only 20-38% consistent. The delay between tests is usually within two weeks of the initial test however, true synaesthetes can usually score within the expected 'genuineness percentile' when the delay is on the order of months. ** [13] **<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> Merikle and Dixon **<span style="background-color: #ffffff; font-family: 'Times New Roman',Times,serif; font-size: 80%; vertical-align: super;">[10] **<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">have since developed an online version of the TOG that has improved upon the confounds of memory-effects and inconsistent test conditions.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> **Stroop Interference Tests**: these diagnostic measures test for the //involuntary and automatic nature of synaesthetic percepts//. During a standard [|Stroop test], non-synaesthetes will exhibit interference due to competition between two characteristics of a given stimuli on account of one characteristic being more automatically processed than the other; this is seen with the classic colored-word Stroop Test for which reading is the automatic process that interferes with naming the colors of words. Modified Stroop tests take advantage of the automaticity of the percept which is bound to the test stimuli. An example of this is when Dixon et al. ** [13] **<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">asked suspected synaesthetes to name the color of words which were themselves associated with synaesthetic color percepts. The time latency due to this additional interference is used to diagnose individuals as synaesthetes. Stroop interference tests have been developed to test for every kind of synaesthesia by tailoring task stimuli to correspond with the sense modality the suspected synaesthete associates with their percepts.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">

<span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; font-size: 10pt;"> **Fig. 2** Adapted from Palmeri et al. [2001] (a) This local versus global form image is used to test for differences in the synaesthetic experiences of projectors and associators (b) A 'cyclopean' numeral made using randomized dot stereoscopy is seen differently by synaesthetes and non-synaesthetes (c) A depiction of a number that is defined by motion. The number is defined by the direction of motion of the dots. Note that colors and shading are depicted only to illustrate how the task looks to synaesthetes. **Fig 3.** Adapted from Palmeri et al. [2001] (a) Visual search experiment display (b) The same search display depicted using the synaesthetic colors of WO, a lexical-color synaesthete. (c) and (d) indicate correct target-present response times as a function of display size for non-synaesthetes and for synaesthete WO, respectively. WO is able to differentiate between 2's and 5's faster than non-synaesthetes because of the different color percepts they evoke.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> Besides the TOG and Stroop Interference Tests there are a few other diagnostics which rely on similar principles. **Visual search tests** and Ramachandran and Hubbard's **Pop-out test** <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> ** [8] **<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">are notable examples. Individuals with synaesthesia perform better on tests which require them to discriminate between stimuli that appear indistinguishable to non-synaesthetes on account of their automatic percepts. Like with Ramachandran's pop-out tests, visual search tests rely on the consistency of percept associations as well as the automaticity evoked synaesthetic percepts. The association between two sensory modalities s erves to reinforce the subtle differences between image, sound, movement, taste and tactile test stimuli.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> media type="youtube" key="stwzvpnnlqA?version=3" height="360" width="640" <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; font-size: 10pt;"> <span class="wiki_link_ext">Diagnosing motion-sound synaesthesia.

=<span style="font-family: Cambria,serif;">2.3 The future of diagnosis: Biomarkers =

<span style="font-family: 'Times New Roman',Times,serif; font-size: 12pt;">Neuroimaging
<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">Current efforts to develop physiologically-based diagnostic tools for synaesthesia include the search for neuroanitomical substrates of the condition. Scientists are actively pursuing both structural and functional [|biomarkers] by imaging clinically diagnosed synaesthetes with such technologies as MRI, fMRI, DTI and PET imaging. Recently, research focused on color-grapheme synaesthesia has identified anatomical differences in the cortical thickness and volume of the V4 cortex ** [8] **<span style="font-family: 'Times New Roman',Times,serif;">. Besides biomarkers for specific forms of synaesthesia, it is conceivable that there may one day be markers for both associator and projector synaesthetes seeing as the difference in bottom-up and top-down processing associated with the two has been correlated with differences in functional connectivity. Scientists have also carried out imaging studies to explore the neural correlates of lesion-induced synaesthesia. One example of this is the study carried out by Naumer & Bosch who observed altered thalamocortical connectivity in touch-tone synaesthesia. It is important to note that anatomical or functional differences do not indicate causality; researches are not sure whether these observations are responsible for the synaesthesia phenotype or whether they are a result of a lifetime of synaesthetic experiences. If the former is the case, using these findings as diagnostic biomarkers will be complicated by idiosyncratic developmental changes and neuroplasticity.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 12pt;"> **Genetic Screens** <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">The apparent hereditary nature of synaesthesia has been recorded from as far back as the 19th century by Galton ** [2] **<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> however, without the proper molecular tools, little headway was made in the search for diagnostic genetic markers until recently. Family pedigrees composed by Baron-Cohen et al. ** [11] **<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">have served as incentive in the search to identify genetic markers of the various forms of synaesthesia. There is reason to believe that different forms of synaesthesia share the same genetic basis seeing as synaesthetes often report having first, second and third-degree relatives with some form of <span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">synaesthesia. <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> The notion that all forms of synaesthesia share a similar genetic basis suggests the potential for a universal diagnostic marker which can identify each form of the condition. Additionally, there has been evidence that genes on chromosomal positions 2q24, 5q33, 6p12, and 12p12 are linked to auditory-visual synaesthesia. Others have suggested that color-grapheme synaesthesia is an X-linked dominant trait. While the search for genetic markers of synaesthesia continues, certain conclusions can be drawn from these works: //**1.** the genetic basis of synaesthesia is complicated// //**2.** it is unlikely that there will be any single 'synaesthesia gene'// and //**3.** the nature of contributions made by the many implicated genes to the phenotype will be challenging to unravel.// =<span style="font-family: Cambria,serif;">3.1 Difficulties in diagnosing synaesthetes =

<span style="font-family: Cambria,serif;">3.1a Subjective nature of synaesthesia
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font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">The subjective nature of synaesthesia limits researchers and clinicians in regards to forming a cohesive clinical diagnostic criteria. It is not simply the lack of any external manifestations that poses the greatest challenge to diagnosis but, rather, it is both the inability of synaesthetes to agree on the nature of their percepts along with their heavy reliance on language capabilities to relay their experiences which remain the greatest barriers to accurate diagnosis. ** [3] **

<span style="font-family: Cambria,serif;">3.3b Individual differences among same-type synaesthetes
<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; 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font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; 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font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt; vertical-align: baseline;">Historically, synaesthesia research has been carried out under the false pretext that synaesthetes with the same 'type' of the condition are a homogenous group. This is incorrect. Hubbard et al. showed that grapheme-color synaesthetes tend to perform differently on cognitive tests and further, that these behavioral differences show similarly contrasting neural correlates. Such individual differences, even among same-type synaesthetes, further complicates the search for diagnostic tools. .<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> Additionally, recent findings suggests that the different subjective experiences of same-type synaesthetes are the result of distinct neural mechanisms.

<span style="font-family: Cambria,serif;">3.3c Confounds: globally altered networks mask cross-wiring
<span class="highlight" style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">The search for neurological biomarkers of synaesthesia is further complicated by findings which suggest that synaesthetic experiences are caused by globally altered brain networks as opposed to discrete, localized neurological changes. These findings suggest that identifying a synaesthete will not be as simple as looking for discrete changes in activity, but rather that the neuronal manifestations of synaesthetic experiences are composed of complicated changes in activation patterns across broad neural networks. It may also be the case that higher cognitive functions, such as language, mask the underlying neuronal basis of synaesthesia.