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. 2023 Sep 28;13:16279. doi: 10.1038/s41598-023-43618-5

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© The Author(s) 2023, corrected publication 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Trajectory curves for earlier onset (A) versus simultaneous onset (B). Estimation of Progressive Brain Tissue Loss (PBTL) in two individuals with MS (Panels A and B). The solid yellow line represents the individual MS subjects’ thalamic volume trajectories (95% CI = dashed yellow lines). The solid blue line represents the thalamic volume trajectory for a hypothetical normal aging individual with same demographic characteritics and baseline thalamic volume as the MS patient (their digital twin). 95% CI = dashed blue lines. The point at which the MS subjects’ trajectory deviates from their digital twin is defined as the onset of PBTL, denoted with the green dot (95% CI from bootstrapping in green). The red dot denotes the age of clinical onset. Black diamonds represent MS subjects’ observed thalamic volumes over time. A High-resolution version of this Figure can be found in Supplementary Information 2.