Reassessing associations between white matter and behaviour with multimodal microstructural imaging

Alberto Lazari; Piergiorgio Salvan; Michiel Cottaar; Daniel Papp; Olof Jens van der Werf; Ainslie Johnstone; Zeena-Britt Sanders; Cassandra Sampaio-Baptista; Nicole Eichert; Kentaro Miyamoto; Anderson Winkler; Martina F Callaghan; Thomas E Nichols; Charlotte J Stagg; Matthew F S Rushworth; Lennart Verhagen; Heidi Johansen-Berg

doi:10.1016/j.cortex.2021.08.017

Reassessing associations between white matter and behaviour with multimodal microstructural imaging

Cortex. 2021 Dec:145:187-200. doi: 10.1016/j.cortex.2021.08.017. Epub 2021 Oct 8.

Authors

Alberto Lazari¹, Piergiorgio Salvan², Michiel Cottaar², Daniel Papp², Olof Jens van der Werf³, Ainslie Johnstone⁴, Zeena-Britt Sanders², Cassandra Sampaio-Baptista², Nicole Eichert², Kentaro Miyamoto⁵, Anderson Winkler⁶, Martina F Callaghan⁷, Thomas E Nichols⁸, Charlotte J Stagg⁹, Matthew F S Rushworth⁵, Lennart Verhagen¹⁰, Heidi Johansen-Berg¹¹

Affiliations

¹ Wellcome Centre for Integrative Neuroimaging, FMRIB, Nu_eld Department of Clinical Neurosciences, University of Oxford, UK. Electronic address: [email protected].
² Wellcome Centre for Integrative Neuroimaging, FMRIB, Nu_eld Department of Clinical Neurosciences, University of Oxford, UK.
³ Section Brain Stimulation and Cognition, Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands; Maastricht Brain Imaging Centre (MBIC), Maastricht University, Maastricht, the Netherlands.
⁴ Wellcome Centre for Integrative Neuroimaging, FMRIB, Nu_eld Department of Clinical Neurosciences, University of Oxford, UK; Department of Clinical and Movement Neuroscience, Institute of Neurology, University College London, UK.
⁵ Wellcome Centre for Integrative Neuroimaging, Department of Experimental Psychology, University of Oxford, UK.
⁶ National Institute of Mental Health, National of Health, Bethesda, MD, USA.
⁷ Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology, UCL, London, UK.
⁸ Oxford Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nu_eld Department of Population Health, University of Oxford, UK.
⁹ Wellcome Centre for Integrative Neuroimaging, FMRIB, Nu_eld Department of Clinical Neurosciences, University of Oxford, UK; Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging, Department of Psychiatry, University of Oxford, UK; MRC Brain Network Dynamics Unit, University of Oxford, Oxford, UK.
¹⁰ Wellcome Centre for Integrative Neuroimaging, Department of Experimental Psychology, University of Oxford, UK; Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, the Netherlands.
¹¹ Wellcome Centre for Integrative Neuroimaging, FMRIB, Nu_eld Department of Clinical Neurosciences, University of Oxford, UK. Electronic address: [email protected].

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.

Keywords: Bimanual coordination; Cognitive control; Microstructural imaging; Multimodal imaging; Myelin; White matter.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anisotropy
Brain / diagnostic imaging
Diffusion Tensor Imaging
Humans
Magnetic Resonance Imaging
White Matter* / diagnostic imaging

Abstract

Publication types

MeSH terms

Grants and funding