Multimodal principal component analysis to identify major features of white matter structure and links to reading

Abstract

The role of white matter in reading has been established by diffusion tensor imaging (DTI), but DTI cannot identify specific microstructural features driving these relationships. Neurite orientation dispersion and density imaging (NODDI), inhomogeneous magnetization transfer (ihMT) and multicomponent driven equilibrium single-pulse observation of T1/T2 (mcDE-SPOT) can be used to link more specific aspects of white matter microstructure and reading due to their sensitivity to axonal packing and fiber coherence (NODDI) and myelin (ihMT and mcDESPOT). We applied principal component analysis (PCA) to combine DTI, NODDI, ihMT and mcDESPOT measures (10 in total), identify major features of white matter structure, and link these features to both reading and age. Analysis was performed for nine reading-related tracts in 46 neurotypical 6-16 year olds. We identified three principal components (PCs) which explained 79.5% of variance in our dataset. PC1 probed tissue complexity, PC2 described myelin and axonal packing, while PC3 was related to axonal diameter. Mixed effects regression models did not identify any significant relationships between principal components and reading skill. Bayes factor analysis revealed that the absence of relationships was not due to low power. Increasing PC1 in the left arcuate fasciculus with age suggest increases in tissue complexity, while increases of PC2 in the bilateral arcuate, inferior longitudinal, inferior fronto-occipital fasciculi, and splenium suggest increases in myelin and axonal packing with age. Multimodal white matter imaging and PCA provide microstructurally informative, powerful principal components which can be used by future studies of development and cognition. Our findings suggest major features of white matter undergo development during childhood and adolescence, but changes are not linked to reading during this period in our typically-developing sample.

White matter properties underlying reading abilities differ in 8-year-old children born full term and preterm

“…Our finding suggests that myelin content is unlikely to be driving the associations between FA and reading in FT children. While myelin content may be associated with maturity and transmission efficiency, it appears not to be the principal factor associated with individual differences in reading in FT born individuals, based on the results in this study and those in related work (Geeraert et al, 2020). These findings are consistent with studies that report negative associations of FA and reading (Dougherty et al, 2007;Odegard et al, 2009;Travis et al, 2016), because myelin content is likely to cause positive FA associations, not negative ones.…”

“…Our team has reported that values of R1 in the cerebellar peduncles were related to reading abilities in FT children (Bruckert et al, 2020). A recent study showed, however, that two brain imaging metrics of myelin content in cerebral tracts were associated with age but not with reading abilities in typically developing FT children (Geeraert et al, 2020). A gap in the literature is whether reading abilities in FT and PT children would show similar or different patterns of associations with metrics sensitive to myelin content in cerebral white matter pathways, as they do with diffusion metrics.…”

“…Second, we wanted to assess the associations between reading abilities and R1 of the same pathways. Based on a previous study that found no associations between reading abilities and two myelin-sensitive metrics in their FT participants (Geeraert et al, 2020), we hypothesized that we would not observe associations between reading and R1 in the FT group. Given that the encephalopathy of prematurity (white matter injury and dysmaturity) seen in PT children results from injury to the myelin producing oligodendrocyte precursor cells (Back, 2017;Volpe, 2009), we hypothesized a positive association between reading and the myelin-sensitive metric (R1) in the PT group.…”

Multi-tract multi-symptom relationships in pediatric concussion

“…Interestingly, our PCA yielded combinations of diffusion measures that differed from those of two prior studies that have used this approach. 30,47 These prior studies used samples of typically-developing children without neurological insults and found similar PCs. To the extent that the PCs reported in these prior studies reflect healthy neurotypical brains, our PCs suggest that our concussed sample was not as similar in white matter structure to healthy controls as expected.…”

In Vivo Cortical Microstructure: A Proxy for Tauopathy and Cognitive impairment in the Elderly with and without MCI/Dementia

“…While we observed significant univariate associations of tau to NDI and ODI, these indices’ contribution was minimized when considered in a multivariate context. This, however, may not be the case for healthy younger adults or when only considering a sample of healthy aging individuals where pathology is less salient, though it remains unclear since multivariate multimodal imaging is not yet routinely applied to NODDI outputs(though see 53 ) and future studies are warranted.…”