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Multivariate white matter alterations are associated with epilepsy duration

Lookup NU author(s): Dr Tom Owen, Dr Yujiang WangORCiD, Dr Peter TaylorORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2020 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd. Previous studies investigating associations between white matter alterations and duration of temporal lobe epilepsy (TLE) have shown differing results, and were typically limited to univariate analyses of tracts in isolation. In this study, we apply a multivariate measure (the Mahalanobis distance), which captures the distinct ways white matter may differ in individual patients, and relate this to epilepsy duration. Diffusion MRI, from a cohort of 94 subjects (28 healthy controls, 33 left-TLE and 33 right-TLE), was used to assess the association between tract fractional anisotropy (FA) and epilepsy duration. Using ten white matter tracts, we analysed associations using the traditional univariate analysis (z-scores) and a complementary multivariate approach (Mahalanobis distance), incorporating multiple white matter tracts into a single unified analysis. For patients with right-TLE, FA was not significantly associated with epilepsy duration for any tract studied in isolation. For patients with left-TLE, the FA of two limbic tracts (ipsilateral fornix, contralateral cingulum gyrus) were significantly negatively associated with epilepsy duration (Bonferonni corrected p <.05). Using a multivariate approach we found significant ipsilateral positive associations with duration in both left, and right-TLE cohorts (left-TLE: Spearman's ρ = 0.487, right-TLE: Spearman's ρ = 0.422). Extrapolating our multivariate results to duration equals zero (i.e., at onset) we found no significant difference between patients and controls. Associations using the multivariate approach were more robust than univariate methods. The multivariate Mahalanobis distance measure provides non-overlapping and more robust results than traditional univariate analyses. Future studies should consider adopting both frameworks into their analysis in order to ascertain a more complete understanding of epilepsy progression, regardless of laterality.

Publication metadata

Author(s): Owen TW, de Tisi J, Vos SB, Winston GP, Duncan JS, Wang Y, Taylor PN

Publication type: Article

Publication status: Published

Journal: European Journal of Neuroscience

Year: 2021

Volume: 53

Issue: 8

Pages: 2788-2803

Print publication date: 01/04/2021

Online publication date: 22/11/2020

Acceptance date: 15/11/2020

Date deposited: 26/07/2021

ISSN (print): 0953-816X

ISSN (electronic): 1460-9568

Publisher: John Wiley & Sons Ltd


DOI: 10.1111/ejn.15055

PubMed id: 33222308


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Funder referenceFunder name
105617/Z/14/ZWellcome Trust (closed comp)
208940/Z/17/ZWellcome Trust
210109/Z/18/ZWellcome Trust