Neural from a neurobiological point of view.

Neural Activity of Synesthesia between Genders    Synesthesia is a rare condition where one sensory modality consistently triggers concurrent precepts in another modality. This condition occurs in 1-4% of the population. These additional experiences include seeing colors when listening to music or feeling shapes while tasting foods. Synesthetes usually report lifelong synesthetic perceptions and describe these experiences as automatic and involuntary even when they try to suppress them. Auditory-visual synesthesia is the most reported form of synesthesia, in which auditory stimulation triggers visual input. Current neurophysiological models of synesthesia mainly hypothesize the brains are hyperconnected but differ in the direction of signal transmission. It is clear that synesthesia causes structural and functional differences in the brain which provides evidence of synesthetic perception. One key question is whether how common synesthesia is and if it affects men and women differently. Past studies have shown that this condition is very strongly female dominant. However, it is worth exploring how synesthetic experiences affect males and females differently from a neurobiological point of view. I hypothesize that imaging studies will show a greater neural activation in females than in males.    There are primarily two different models that are used to explain the neurophysiological underpinnings of all types of synesthesia which include the two-stage cross-activation/hyper-binding model and the disinhibited feedback model. The two-stage cross-activation/hyper-binding model was proposed on the basis of fMRI studies conducted with grapheme-color synesthetes, where one associates colors with numbers, and mostly relies on the physical closeness between the involved processing areas. According to these models, the grapheme and color processing areas are strongly interconnected both functionally and anatomically. For color-hearing synesthesia, it would imply that there is a strong anatomical and/or functional connections between auditory and visual areas. The disinhibited feedback model is based on studies demonstrating specific forms of synesthesia rather than brain imaging data. The disinhibited feedback model suggests that synesthesia results from disinhibited feedback from higher level cortical areas. Based on the cross-activation/hyperbinding model proposes simultaneous activation of the brain regions involved in processing the inducer and the concurrent. On the contrary, the disinhibition model proposes that the neural activation connected with the processing of the inducer should precede that connected with the processing of the concurrent. A study was conducted using EEG techniques in the context of a pre-attentive mismatch negativity (MMN), it was shown that the connection of tones and color in color-hearing synesthetes is associated with increased MMN amplitudes in response to deviant tones that were aiming to induce the novel concurrent color perceptions. The increased MMN amplitudes revealed in the synesthetes were associated with stronger intracerebral current densities starting from the auditory cortex, parietal cortex, and the ventral visual areas. This can imply that the automatic binding of tones and colors in color-hearing synesthetes accompanied by an early pre-attentive process recruiting the auditory cortex, inferior a superior parietal lobes, as well as the ventral occipital areas (Jancke et al. 2012).    Though there are theories of synesthesia regarding hyperbinding and disinhibited feedback between modality-specific processing regions as mechanisms as underlying synesthetic perception. Conflicting evidence made it difficult to be certain which model provided the more accurate description of synesthesia or if the mechanisms of hyperconnectivity and disinhibited feedback are mutually exclusive. In one study, the amount of white matter was measured in people with color-music synesthetes. Using diffusion tensor imaging to trace the white matter tracts in the temporal and occipital lobe regions in ten synesthetes and ten non-synesthete controls. Their study showed that synesthetes possessed different hemispheric patterns of fractional anisotropy in the fronto-occipital fasciculus which is a major white matter pathway that connects the visual and auditory association regions to the frontal regions. White matter integrity within the synesthetes was correlated with the scores received on audiovisual tests. This shows the white matter substrate of color music synesthesia and suggests that the higher amount of white matter connectivity is connected with the enhanced cross-modal associations (Zamm, 2013).    In auditory-visual synesthesia, electrical brain activity was recorded from adult synesthetes and control participants who were played brief tones and were required to monitor for an infrequent auditory target. The synesthetes were directed to attend to either the auditory or to the visual dimension of the tone while the controls were told to attend the auditory dimensions only. In result, there were clear differences between the synesthetes and the controls including that the differences in deflections of the auditory-evoked potential rather than the presence of an additional posterior deflection. The differences happened irrespective of what the synesthetes attended to. It was shown that significant electrophysiological differences between synesthetes and the controls presented with unimodal auditory stimuli in which the auditory tone is reliably associated with a visual experience in the synesthetes but not the controls (Goller, 2008). The results suggest that the differences between synesthetes and others occur early in time and that synesthesia is qualitatively different from similar effects found in infants and certain auditory induced visual illusions in adults.    Electric brain tomography with high temporal resolution in color hearing synesthetes and non-synesthetic controls during auditory verbal stimulation was conducted. The auditory-stimuli potentials to words and letters were different between synesthetes and controls at the N1 and P2 components, showing longer latencies and lower amplitudes in synesthetes. The intracerebral sources of these components were estimated with lower resolution brain electromagnetic tomography and that showed stronger activation in synesthetes in left posterior inferior temporal regions, the color area in the fusiform gyrus, and in the orbitofrontal brain regions (Beeli, 2007). These findings were also similarly reported in earlier experiments with functional magnetic resonance imaging and positron emission tomography in color-hearing synesthesia.     Another study focused on the directionality of signal transmission. To test the different models of synesthesia, they estimated local current density, directed and undirected connectivity patterns in the intracranial space during two minutes of resting state EEG in 11 color hearing synesthetes and eleven non-synesthetes. The synesthetes showed increased parietal theta, alpha, and lower beta current density than the non synesthetes. The color hearing synesthetes were characterized by increased top-down signal transmission from the superior parietal lobe to the left color processing area V4 in the upper beta frequency band. Analyses of undirected connectivity revealed a global, synesthesia-specific connectivity in the alpha frequency band (Brauchli, 2017). The neural activity of the superior parietal lobe even during the resting period indicates its strong role in color hearing synesthesia.     A number of past studies have suggested that synesthesia is a condition more often found in women than men, with up to six times more synesthetes than males. However, it is possible that this female bias is because women synesthetes are simply more likely to self-refer for study. A study was conducted assuming that there is no extreme female bias in synesthesia. They studied this by re-analyzing past reports of large female biases to show that they most likely were because of self-referral or other logistical issues. They also presented the largest published prevalence study to date on grapheme-color synesthesia their prevalence is similar to their earlier estimates where there was no significant female bias. After individually screening 3893 participants, of which, 2135 were female and 1758 were male, they were each screened for grapheme-color synesthesia. They found that 33 of the 2135 females and 21 out of 1758 males had grapheme-color synesthesia. This was a ratio of 1.3: 1, female to male synesthetes was non-significant (Simner, 2015).    Though Simner’s study has noted that synesthesia is not favored amongst women, it did not look at the neurobiological aspects between the genders. The other studies discussed within this paper clearly sees that synesthetes have more activity within brain regions including the parietal lobe, occipital lobe, and ventral visual areas as well as higher connectivity of white matter. However, there were no studies conducted to compare the neural activity of synesthetes that are males versus females. Although female synesthetes are not more common than males, they could perhaps have more intense experiences or be more aware of these experiences. This could play a role as to why females are more like to self-refer themselves for studies. However, there is no data to support this question. For future studies, it would be interesting to test a large group of female synesthetes and male synesthetes and compare their two-stage cross-activation/hyper-binding model and the disinhibited feedback model as well as their fMRI, EEG, electric brain tomography, and the amount of white matter connectivity. 

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