Skilled reading relies on coordinated processing across a widespread network of cortical areas. The white matter tracts connecting these areas play a key role in facilitating rapid signal transmission across the reading network. White matter properties can be studied noninvasively using diffusion-weighted imaging (DWI), which yields, among others, the fractional anisotropy (FA) index, a quantitative measure of the directionality of water diffusion used to characterize white matter organization.
There is ample evidence consolidating the involvement of white matter organization in relation to reading. Several DWI studies provide evidence of significant associations between white matter properties (as measured by FA) and reading ability in adults (for a review see Vandermosten et al. 2012b). Although a converging finding seems to be positive correlations in left frontal and temporo-parietal white matter (Lebel et al. 2013), studies have also reported negative associations between FA and reading measures (Yeatman et al. 2012). In addition, evidence from studies in pre-reading children suggests that an early link between literacy-related skills and white matter is present before the onset of reading acquisition (Vanderauwera et al. 2018; Walton et al. 2018). There is also strong evidence to support a link between white matter and reading throughout development (Yeatman et al. 2012), as well as predictive power of early white matter organization for later reading-related skills (Vanderauwera et al. 2017; Zuk et al. 2021).
What factors or processes might be driving the observed relationships between diffusion properties such as FA and reading? One of the original hypotheses put forward is myelination (Klingberg et al. 2000), a critical component of human white matter with a known role in cognitive functions and plasticity (Kaller et al. 2017). While early experiments have shown that anisotropy is primarily influenced by axonal membranes, including the density (packing) and diameter of axons, there is evidence that it is to a certain extent also modulated by myelination (Beaulieu 2009). Indeed, FA is sensitive to both microscopic and macroscopic aspects of tissue properties, but has demonstrably low specificity for any single neurobiological process (Jones et al. 2013), and therefore cannot inform us on the specific role of myelin-related processes. Myelin water imaging (MWI) is an approach that allows a more specific in vivo investigation of myelin, relying on the principles of varying T2 relaxation in the different cell compartments (reviewed in MacKay and Laule 2016). A quantitative index of MWI is myelin water fraction (MWF), which can be used as a proxy measure of cortical myelination. This measure represents a quantification of myelin water, based on the short relaxation rate of water trapped within the myelin bilayer (Whittall et al. 1997). Previous histology and imaging studies have validated the use of MWF as an indirect, yet specific measure of brain myelin using both qualitative and quantitative methods (Moore et al. 2000; Laule et al. 2006).
Few studies have investigated the link between MRI myelin measures and reading. Kraft et al. (2016) reported higher T1 intensities, interpreted as reduced myelin concentration, in the left anterior arcuate fasciculus of preliterate children at familial risk for developing dyslexia compared to children without a risk. Notably, the opposite pattern was reported in adults, whereby increased myelinated cortical thickness ratio is observed in the auditory cortex of dyslexic compared to typical readers (Skeide et al. 2018). To date, only one study has directly investigated the relationship between MWF and reading ability. In a sample of 20 participants aged 10-18 years old, Beaulieu et al. (2020) reported positive correlations between reading and MWF, as well as lower MWF in poor (n=7) compared to good readers (n=11) in several regions including bilateral thalamus, centrum semiovale, anterior and posterior limbs of the internal capsule and splenium of the corpus callosum. This study offers new insights into the relationship between myelin water and reading, however replication of these findings is warranted given the small sample size, the wide age range and the selection of regions which are not typically considered part of the core reading circuitry.
An important factor in interpreting associations between white matter and cognitive measures, is our understanding of how MWF relates to conventional DWI metrics such as FA. While some studies report an overall positive relationship between FA and MWF (Mädler et al. 2008; Friedrich et al. 2020), others find little evidence for shared variance between the two (Bells et al. 2011; Billiet et al. 2015). Notably, Mädler et al. (2008) reported that the relationship between FA and MWF differed across regions of interest. This finding is further corroborated by De Santis et al. (2014), who showed that the correlation between FA and MWF was only significant when regions with single fiber populations were considered, as compared to regions with multiple fiber populations. Altogether, these divergent findings suggest that a positive relationship between FA and MWF may exist, but is rather dependent on the underlying fiber architecture and potentially influenced by other microstructural factors as well. Importantly, most of the aforementioned studies were conducted using adult data. Given that white matter development is still ongoing throughout childhood and adolescence (Lebel and Beaulieu 2011), it is important to uncover whether the observed relations in adults also hold in children. In children, one study reported no significant correlation between MWF and FA (Morris et al. 2020), however the literature here is very limited.
The goal of the present work is to elucidate the relationship between white matter microstructure and reading ability in children. First, we extend previous work on the relationship between FA and the MWI-derived myelin water fraction (MWF) index, in order to better understand the shared relationship between the two metrics in our sample. Second, we investigate the relationship between MWF and reading in school-aged children. We focus on bilateral white matter tracts involved in reading processes, such as the dorsal direct temporo-parietal segment of the AF (AFdirect), dorsal anterior fronto-parietal segment of the AF (AFanterior) and the ventral inferior fronto-occipital fasciculus (IFOF).