Neural basis of synesthesia
Encyclopedia
Synesthesia
Synesthesia
Synesthesia , from the ancient Greek , "together," and , "sensation," is a neurologically based condition in which stimulation of one sensory or cognitive pathway leads to automatic, involuntary experiences in a second sensory or cognitive pathway...

is a neurological
Neurology
Neurology is a medical specialty dealing with disorders of the nervous system. Specifically, it deals with the diagnosis and treatment of all categories of disease involving the central, peripheral, and autonomic nervous systems, including their coverings, blood vessels, and all effector tissue,...

 condition in which two or more bodily sense
Sense
Senses are physiological capacities of organisms that provide inputs for perception. The senses and their operation, classification, and theory are overlapping topics studied by a variety of fields, most notably neuroscience, cognitive psychology , and philosophy of perception...

s are coupled. For example, in a form of synesthesia known as Grapheme → color synesthesia
Grapheme-color synesthesia
Grapheme → color synesthesia is a form of synesthesia in which an individual's perception of numbers and letters is associated with the experience of colors. Like all forms of synesthesia, grapheme → color synesthesia is involuntary, consistent, and memorable...

, letters or numbers may be perceived as inherently colored. In another, called number → form synesthesia
Number form
A number form is a mental map of numbers, which automatically and involuntarily appears whenever someone who experiences number-forms thinks of numbers. Numbers are mapped into distinct spatial locations and the mapping may be different across individuals. Number forms were first documented and...

, numbers are automatically and consistently associated with locations in space. In yet another form of synesthesia, called ordinal linguistic personification
Ordinal linguistic personification
Ordinal-linguistic personification is a form of synesthesia in which ordered sequences, such as ordinal numbers, days, months and letters are associated with personalities...

, numbers, days of the week and months of the year evoke personalities. In other forms of synesthesia, music and other sounds may be perceived as colored or having particular shapes. Recent research has begun to explore the neural basis of these experiences, drawing both on neuroscientific principles and on functional neuroimaging data.

Based on these data, two major theories have been proposed concerning the neural basis of synesthesia. Both theories start from the observation that there are dedicated regions of the brain that are specialized for certain functions. For example, the part of the human brain involved in processing visual input, called the visual cortex
Visual cortex
The visual cortex of the brain is the part of the cerebral cortex responsible for processing visual information. It is located in the occipital lobe, in the back of the brain....

 can be further subdivided into regions that are preferentially involved in color processing (the fourth visual area, V4) or with motion processing, called V5 or MT. Based on this notion of specialized regions, some researchers have suggested that increased cross-talk between different regions specialized for different functions may account for different types of synesthesia.

Cross-activation

Since regions involved in the identification of letters and numbers lie adjacent to a region involved in color processing (V4), the additional experience of seeing colors when looking at graphemes might be due to "cross-activation" of V4 . This cross-activation may arise due to a failure of the normal developmental process
Neural development
Neural development comprises the processes that generate, shape, and reshape the nervous system, from the earliest stages of embryogenesis to the final years of life. The study of neural development aims to describe the cellular basis of brain development and to address the underlying mechanisms...

 of pruning, which is one of the key mechanisms of synaptic plasticity
Synaptic plasticity
In neuroscience, synaptic plasticity is the ability of the connection, or synapse, between two neurons to change in strength in response to either use or disuse of transmission over synaptic pathways. Plastic change also results from the alteration of the number of receptors located on a synapse...

, in which connections between brain regions are partially eliminated with development. Similarly, lexical → gustatory synesthesia may be due to increased connectivity between adject regions of the insula
Insular cortex
In each hemisphere of the mammalian brain the insular cortex is a portion of the cerebral cortex folded deep within the lateral sulcus between the temporal lobe and the frontal lobe. The cortical area overlying it towards the lateral surface of the brain is the operculum...

 in the depths of the lateral sulcus
Lateral sulcus
-External links:* * * http://www.uams.edu/radiology/education/residency/diagnostic/pdf/sylvian_cistern_RSNA2003.pdf...

 involved in taste processing that lie adjacent to temporal lobe
Temporal lobe
The temporal lobe is a region of the cerebral cortex that is located beneath the Sylvian fissure on both cerebral hemispheres of the mammalian brain....

 regions involved in auditory processing. Similarly, taste → touch synesthesia may arise from connections between gustatory regions and regions of the somatosensory system
Somatosensory system
The somatosensory system is a diverse sensory system composed of the receptors and processing centres to produce the sensory modalities such as touch, temperature, proprioception , and nociception . The sensory receptors cover the skin and epithelia, skeletal muscles, bones and joints, internal...

 involved in processing touch. However, not all forms of synesthesia are easily explained by adjacency.

Disinhibited feedback

Alternatively, synesthesia may arise through "disinhibited feedback" or a reduction in the amount of inhibition along feedback pathways . It is well established that information not only travels from the primary sensory areas
Primary sensory areas
The primary sensory areas are the main cerebral areas that receive sensory information from thalamic nerve projections.Though some areas of the human brain that receive primary sensory information remain poorly defined, each of the five sensory modalities has been recognized to relate to specific...

 to association areas such as the parietal lobe
Parietal lobe
The parietal lobe is a part of the Brain positioned above the occipital lobe and behind the frontal lobe.The parietal lobe integrates sensory information from different modalities, particularly determining spatial sense and navigation. For example, it comprises somatosensory cortex and the...

 or the limbic system
Limbic system
The limbic system is a set of brain structures including the hippocampus, amygdala, anterior thalamic nuclei, septum, limbic cortex and fornix, which seemingly support a variety of functions including emotion, behavior, long term memory, and olfaction. The term "limbic" comes from the Latin...

, but also travels back in the opposite direction, from "higher order" cortical regions to early sensory areas. Normally, the balance of excitation and inhibition are maintained. However, if this feedback were not adequately inhibited, then signals coming from later stages of processing might influence earlier stages of processing, such that tones would activate visual cortical areas in synesthetes more than in non-synesthetes. In this case, it might be possible to temporarily have synesthetic experiences after taking drugs like LSD
LSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...

 or mescaline
Mescaline
Mescaline or 3,4,5-trimethoxyphenethylamine is a naturally occurring psychedelic alkaloid of the phenethylamine class used mainly as an entheogen....

. Indeed, some psychedelic drug users report synesthesia-like experiences, although the exact degree of similarity between these drug induced experiences and congenital synesthesia is still unclear.

Neurophysiological substrates

Given that synesthesia is known to run in families, it has been suggested that a genetic difference, or single-nucleotide polymorphisms (SNPs, pronounced "SNiPs") might be responsible for either decreased pruning or decreased inhibition in the synesthete brain, leading to increased activation. These theories are not mutually exclusive. It may be that both mechanisms are possible causes of synesthesia, but that one or the other is present in differing degrees between different synesthetes, or for different types of synesthesia.

Functional neuroimaging studies

Functional neuroimaging
Functional neuroimaging
Functional neuroimaging is the use of neuroimaging technology to measure an aspect of brain function, often with a view to understanding the relationship between activity in certain brain areas and specific mental functions...

 studies using positron emission tomography
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...

 (PET) and functional magnetic resonance imaging (fMRI) have demonstrated significant differences between the brains of synesthetes and non-synesthetes. The first such study used PET to demonstrate that some regions of the visual cortex (but not V4) were more active when auditory word → color synesthetes listened to words compared to tones . More recent studies using fMRI have demonstrated that V4 is more active in both word → color and grapheme → color synesthetes . However, these neuroimaging studies do not have the spatial and temporal resolution to distinguish between the pruning and disinhibited feedback theories. Future research will continue to examine these questions using not only fMRI but also diffusion tensor imaging (DTI), which allows researchers to directly investigate neural connectivity in the human brain and magnetic resonance spectroscopy (MRS) which allows researchers to measure the amounts of different neurotransmitters in the brain.
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