Abstract
Several studies have established specific relationships between White Matter (WM) and behaviour. However, these studies have typically focussed on fractional anisotropy (FA), a neuroimaging metric that is sensitive to multiple tissue properties, making it difficult to identify what biological aspects of WM may drive such relationships. Here, we carry out a pre-registered assessment of WM-behaviour relationships in 50 healthy individuals across multiple behavioural and anatomical domains, and complementing FA with myelin-sensitive quantitative MR modalities (MT, R1, R2∗).Surprisingly, we only find support for predicted relationships between FA and behaviour in one of three pre-registered tests. For one behavioural domain, where we failed to detect an FA-behaviour correlation, we instead find evidence for a correlation between behaviour and R1. This hints that multimodal approaches are able to identify a wider range of WM-behaviour relationships than focusing on FA alone.To test whether a common biological substrate such as myelin underlies WM-behaviour relationships, we then ran joint multimodal analyses, combining across all MRI parameters considered. No significant multimodal signatures were found and power analyses suggested that sample sizes of 40–200 may be required to detect such joint multimodal effects, depending on the task being considered.These results demonstrate that FA-behaviour relationships from the literature can be replicated, but may not be easily generalisable across domains. Instead, multimodal microstructural imaging may be best placed to detect a wider range of WM-behaviour relationships, as different MRI modalities provide distinct biological sensitivities. Our findings highlight a broad heterogeneity in WM's relationship with behaviour, suggesting that variable biological effects may be shaping their interaction.
Highlights
The past decade has shown that White Matter (WM), and in particular the myelinated structures that dominate it, have more varied functions than previously thought, from trophic support of axons (Funfschilling et al, 2012; Nave, 2010) to active regulation of physiological and behavioural processes (Kaller et al, 2017; Lazari et al, 2018; Steadman et al, 2019)
No relationships were found between behaviour and fractional anisotropy (FA) within tracts of interest for either Temporal order judgement (TOJ) or Digit symbol substitution test (DSST) (TOJ: peak pcorr 1⁄4 .08; DSST: peak pcorr 1⁄4 .49)
No relationships were found between behaviour and multimodal Magnetic Resonance Imaging (MRI) metrics within tracts of interest for either TOJ or Alternating Finger Tapping (AFT) (TOJ: peak pcorr 1⁄4 .339; or AFT: peak pcorr 1⁄4 .09)
Summary
The past decade has shown that White Matter (WM), and in particular the myelinated structures that dominate it, have more varied functions than previously thought, from trophic support of axons (Funfschilling et al, 2012; Nave, 2010) to active regulation of physiological and behavioural processes (Kaller et al, 2017; Lazari et al, 2018; Steadman et al, 2019). Much evidence on the role of WM has come from a large body of studies linking behaviour to diffusiontensor-based metrics such as fractional anisotropy (FA), a metric derived from diffusion weighted imaging that is sensitive to features of WM microstructure (Boekel et al, 2015; Johansen-Berg, 2010; Lazari & Lipp, 2021; Roberts et al, 2013). While these studies have provided seminal evidence for a link between WM and human behaviour, questions remain about the generalizability and interpretation of these effects. While other tensor-based metrics can be derived from diffusionweighted imaging, it is unclear whether they differ from FA in their biological sensitivity (Lazari & Lipp, 2021)
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