Journal Article

FZJ-2025-00564

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A critical role of action-related functional networks in Gilles de la Tourette syndrome

Baldermann, J. C. (Corresponding author) ; Petry-Schmelzer, J. N. ; Schüller, T. ; Mahfoud, L. ; Brandt, G. A. ; Dembek, T. A. ; van der Linden, C. ; Krauss, J. K. ; Szejko, N. ; Müller-Vahl, K. R. ; Ganos, C. ; Al-Fatly, B. ; Heiden, P. ; Servello, D. ; Galbiati, T. ; Johnson, K. A. ; Butson, C. R. ; Okun, M. S. ; Andrade, P. ; Domschke, K. ; Fink, G. R.FZJ* ; Fox, M. D. ; Horn, A. ; Kuhn, J. ; Visser-Vandewalle, V. ; Barbe, M. T.

2024
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41467-024-55242-6  doi:10.34734/FZJ-2025-00564

Abstract: Gilles de la Tourette Syndrome (GTS) is a chronic tic disorder, characterized by unwanted motor actions and vocalizations. While brain stimulation techniques show promise in reducing tic severity, optimal target networks are not well-defined. Here, we leverage datasets from two independent deep brain stimulation (DBS) cohorts and a cohort of tic-inducing lesions to infer critical networks for treatment and occurrence of tics by mapping stimulation sites and lesions to a functional connectome derived from 1,000 healthy participants. We find that greater tic reduction is linked to higher connectivity of DBS sites (N = 37) with action-related functional resting-state networks, i.e., the cingulo-opercular (r = 0.62; p < 0.001) and somato-cognitive action networks (r = 0.47; p = 0.002). Regions of the cingulo-opercular network best match the optimal connectivity profiles of thalamic DBS. We replicate the significance of targeting cingulo-opercular and somato-cognitive action network connectivity in an independent DBS cohort (N = 10). Finally, we demonstrate that tic-inducing brain lesions (N = 22) exhibit similar connectivity to these networks. Collectively, these results suggest a critical role for these action-related networks in the pathophysiology and treatment of GTS.

Note: Open Access funding enabled and organized by Projekt DEAL.This study was funded by the German Research Foundation (CRC-1451,Project 431549029-C07, to J.C.B. and V.V.V.) and the Else Kröner-Fresenius-Stiftung (grant number 2022_EKES.23 to J.C.B.). A.H. wassupported by the German Research Foundation (Deutsche Forschungsgemeinschaft, 424778381 – TRR 295), Deutsches Zentrum für Luft- undRaumfahrt (DynaSti grant within the EU Joint Programme NeurodegenerativeDisease Research, JPND), the National Institutes of Health (R0113478451, 1R01NS127892-01, 2R01 MH113929 & UM1NS132358), and theNew Venture Fund (FFOR Seed Grant). JNPS was funded by the CologneClinician Scientist Program (CCSP) / Faculty of Medicine / University ofCologne, funded by theGerman Research Foundation (DFG, FI 773/15-1).

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Contributing Institute(s):

1. Kognitive Neurowissenschaften (INM-3)

Research Program(s):

1. 5251 - Multilevel Brain Organization and Variability (POF4-525) (POF4-525)
2. SFB 1451 C07 - Neuronale Grundlagen der Bildung und Unterdrückung motorischer Tics (C07) (458687122) (458687122)

Appears in the scientific report 2024

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