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Merlin M. Weeda, Ilanah J. Pruis, Aimee S. R. Westerveld, Iman Brouwer, Barbara Bellenberg, Frederik Barkhof, Hugo Vrenken, Carsten Lukas, Ruth Schneider, Petra J. W. Pouwels

• \(\bf Background:\) In early multiple sclerosis (MS), thalamus atrophy and decreased integrity of the thalamocortical white matter (WM) tracts have been observed. \(\bf Objective:\) To investigate the temporal association between thalamus volume and WM damage in the thalamocortical tract in subjects with early MS. \(\bf Methods:\) At two time points, 72 subjects with early MS underwent T1, FLAIR and diffusion tensor imaging. Thalamocortical tracts were identified with probabilistic tractography using left and right thalamus as seed regions. Regression analysis was performed to identify predictors of annual percentage change in both thalamus volumes and integrity of the connected tracts. \(\bf Results:\) Significant atrophy was seen in left and right thalamus (\(\it p\) < 0.001) over the follow-up period (13.7 \(\pm\) 4.8 months), whereas fractional anisotropy (FA) and mean diffusivity (MD) changes of the left and right thalamus tracts were not significant, although large inter-subject variability was seen. Annual percentage change in left thalamus volume was significantly predicted by baseline FA of the left thalamus tracts (\(\it F\)(1.71) = 4.284, (\(\it p\) = 0.042; while no such relation was found for the right thalamus. Annual percentage change in FA or MD of the thalamus tracts was not predicted by thalamus volume or any of the demographic parameters. \(\bf Conclusion:\) Over a short follow-up time, thalamus atrophy could be predicted by decreased integrity of the thalamic tracts, but changes in the integrity of the thalamic tracts could not be predicted by thalamus volume. This is the first study showing directionality in the association between thalamus atrophy and connected WM tract damage. These results need to be verified over longer follow-up periods.