Atypical cortical regional homogeneity observed in grapheme-colour synaesthesia and its subtypes

Synaesthesia is a perceptual phenomenon in which the stimulation of one sensory or cognitive pathway leads to automatic and involuntary experiences in another (Simner, 2011). Synaesthetic experiences are varied and are categorised into distinct clusters, including language-colour synaesthesia (Jarick et al., 2009), sequence-space synaesthesia (Eagleman, 2009), and hearing-motion synaesthesia (Saenz & Koch, 2008), among others. Till date, over 60 types of synaesthesia have been identified (Day, 2013), with estimates suggesting the possibility of more than a hundred subtypes, many of which have not been clearly defined (Eagleman & Cytowic, 2009).

One of the most well-documented forms under the language-colour synaesthesia is grapheme-colour synaesthesia, where individuals associate specific letters or numbers with consistent colours (Ward & Simner, 2022). Two predominant subtypes of grapheme-colour synaesthesia have been identified in the current literature: projectors, who experience colours as externally projected onto graphemes, and associators, who perceive the colours internally, as part of their conceptual representation of the grapheme (Dixon et al., 2004). While extensive research has been conducted to define synaesthetic experiences and classifying different synaesthetic types (Novich et al., 2011; Ward & Simner, 2022), the underlying neurobiological systems of synaesthetes and their associated biological features however are yet to be fully understood.

Neuroimaging studies on grapheme–colour synaesthesia have focused on whole-brain differences between synaesthetes and controls, with many structural and functional differences found in occipital and temporal regions (Hubbard et al., 2005; O'Hanlon et al., 2013; Rouw & Scholte, 2007, 2010; van Leeuwen et al., 2010). Comparing the different grapheme-colour synaesthesia experiences, projector subtypes are also often found to have higher fractional anisotropy in the inferior temporal region (Rouw & Scholte, 2007). The finding by Rouw and Scholte also supports the idea that greater structural connectivity between different brain regions involved in categorising shape and colour experiences contributes to colour experiences that closely resemble “real” sensory perception. Contrastingly, associator synaesthetes exhibit an increased activity in structures relating to spatial perception and body part localisation, such as the left superior parietal lobule (van Leeuwen et al., 2010). These findings point to synaesthesia as not only a sensory anomaly but a complex neurobiological phenomenon.

Previous studies have linked grapheme-colour synaesthesia to differences in brain structure and function, particularly in regions associated with perception, memory, and executive function through structural and functional scans (Dovern et al., 2012; Rouw et al., 2011). Nevertheless, no studies have directly examined the role of local synchrony, such as through regional homogeneity, in relation to synaesthesia. Local synchrony, the temporal coordination of neural activity among neighbouring brain regions, is thought to play a critical role in the integration of sensory information (Jiang & Zuo, 2015), and atypical local connectivity may underlie the perceptual associations characteristic of synaesthesia, as seen in studies with other neurodivergent populations (An et al., 2013; Di Martino et al., 2014; Jiang et al., 2015). ReHo provides a reliable and sensitive measure of local synchrony by quantifying the similarity of the time series of each voxel with those of its immediate neighbours (Zang et al., 2004) and depending on the functional and structural context of each region, lower scores typically indicate reduced regional specialisation, greater functional flexibility or impaired function within the small region (Jiang & Zuo, 2015). Understanding differences in local synchrony in synaesthesia through ReHo can thus provide a novel perspective to understanding the etiology of the phenomenon. Furthermore, given evidence for distinct neural mechanisms underlying projector and associator experiences (Rouw & Scholte, 2007, 2010; van Leeuwen et al., 2010), distinguishing between subtypes is crucial to accurately characterise the cognitive and neural correlates of synaesthesia and to avoid obscuring important subtype-specific effects.

Additionally, while some behavioural studies suggest that synaesthetes differ in emotional and cognitive traits such as imagery vividness, emotional reactivity, and sensory sensitivity (Banissy et al., 2013; Ward, 2021b), these traits are rarely investigated in relation to neural markers. Measures like the Plymouth Sensory Imagery Questionnaire (PSI-Q) (Andrade et al., 2014) and the Impact of Event Scale - Revised (IES-R) (Weiss & Marmar, 1997) offer promising tools to link cognitive and affective traits to underlying brain function, but their integration into neuroimaging research on synaesthesia remains limited.

Currently, some mechanisms have been proposed in current literature to explain the etiology of synaesthesia, namely the cross activation theory (Ramachandran & Hubbard, 2001a, 2001b), the disinhibited feedback theory (Grossenbacher & Lovelace, 2001; Neufeld et al., 2012), the conceptual mediation theory (Chiou & Rich, 2014) and the stochastic resonance model of synaesthesia (Lalwani & Brang, 2019). While these theories have been well established, there lacks a consensus as to which theory best explains the neurobiological bases of synaesthesia (Hupé & Dojat, 2015). Under these theories of synaesthesia etiology, different predictions could be made about local neural synchrony, which can be probed using ReHo. The cross-activation theory suggests enhanced communication between adjacent sensory regions, which may potentially translate to atypical ReHo in occipital and inferior temporal cortices where grapheme and colour processing converge. The disinhibited feedback theory proposes reduced inhibitory control from frontal regions, predicting lower ReHo in executive and regulatory cortices that ordinarily constrain sensory associations. The conceptual mediation theory emphasises the role of higher-order semantic and parietal regions, anticipating reduced ReHo in the superior parietal lobule and related association cortices, reflecting conceptually driven concurrents. Finally, the stochastic resonance model posits that neural “noise” can amplify weak cross-modal signals, predicting variable ReHo alterations across networks, with reduced stability but increased sensitivity in regions where weak sensory inputs are transformed into conscious concurrents.

Building on these theoretical perspectives, this study aims to address gaps in synaesthesia literature by examining regional homogeneity (ReHo) in an open-access MRI dataset of grapheme-colour synaesthetes (Racey et al., 2023), focusing on how ReHo abnormalities are associated with synaesthesia and its projector and associator subtypes. Additionally, we will also investigate how ReHo in key brain regions correlates with cognitive and emotional traits as measured by the PSI-Q and IES-R. Based on prior evidence, we hypothesise that synaesthetes would show atypical regional homogeneity (ReHo) in brain regions supporting perception, memory, and executive functions, compared to controls. More specifically, we expected projector synaesthetes to exhibit reduced ReHo in perceptual regions such as the inferior temporal and occipital cortices, resulting in their vivid, perceptually grounded experiences. In contrast, we anticipated that associator synaesthetes would show reduced ReHo in higher-order parietal, including the superior parietal lobule, consistent with their heightened spatial perception. We further hypothesise that the identified regions would correlate with individual differences in sensory imagery and emotional sensitivity.

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