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Lookup NU author(s): Harry Clifford, Dr Sonja Fenske, Dr Jonathan Horsley, Callum Simpson, Nathan Evans, Professor Yujiang WangORCiD, Dr Tiago da Silva Costa, Dr Rhys ThomasORCiD, Professor Peter TaylorORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.Vagus nerve stimulation (VNS) reduces seizure frequency and severity in some, but not all, individuals with epilepsy. The hippocampus has been implicated in VNS response, but is yet to be studied structurally using T1-weighted (T1w) magnetic resonance imaging (MRI). In this study we hypothesized greater hippocampal abnormality in VNS non-responders. Using hippocampal morphometrics, we extracted the volumes of four hippocampal regions from T1w MRI across three groups; VNS responders ((Formula presented.)), non-responders ((Formula presented.)), and healthy controls ((Formula presented.)). We first calculated the multivariate Mahalanobis distance using z-scores from all four hippocampal regions to measure abnormality relative to controls. We then compared traditional univariate measures to the Mahalanobis distance. Response to VNS was defined as having a (Formula presented.) seizure reduction 2 years post-implantation. Hippocampal morphometrics were significantly more abnormal in non-responders than responders ((Formula presented.)) using the multivariate Mahalanobis distance. Univariate approaches did not differ significantly between responders and non-responders ((Formula presented.)). At the group level, non-responders to VNS had greater structural hippocampal abnormality when using the multivariate approach. Conversely, this effect was lost with the univariate analysis. This suggests that abnormality is likely present in different parts of the hippocampus in different individuals. Future studies should incorporate multivariate, and potentially multi-modal, information to better characterize the mechanisms of VNS response.
Author(s): Clifford HJ, Fenske S, Horsley J, Simpson C, Evans N, Wang Y, da Silva Costa T, Thomas RH, Iqbal S, Elliott CA, Duncan JS, Taylor PN
Publication type: Article
Publication status: Published
Journal: Epilepsia
Year: 2025
Pages: epub ahead of print
Online publication date: 03/10/2025
Acceptance date: 15/09/2025
Date deposited: 20/10/2025
ISSN (print): 0013-9580
ISSN (electronic): 1528-1167
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1111/epi.18658
DOI: 10.1111/epi.18658
Data Access Statement: Anonymized data and code to reproduce the findings of this study are at the following location https://github.com/cnnp-lab/mahal-vns.
PubMed id: 41042256
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