A critical role of action-related functional networks in Gilles de la Tourette syndrome

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.

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Publication Details

Journal
Nature Communications
Published
2024-12-16
DOI
https://doi.org/10.1038/s41467-024-55242-6
Citations
19
Primary Topic
Obsessive-Compulsive Spectrum Disorders
Type
article
Field-Weighted Citation Impact
12.14

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article

A critical role of action-related functional networks in Gilles de la Tourette syndrome

Katharina Domschke, Veerle E. R. M. Visser-Vandewalle, Gereon R. Fink, Kirsten Müller‐Vahl et al.
19 citations
Nature Communications
Obsessive-Compulsive Spectrum Disorders
12.14
article

A critical role of action-related functional networks in Gilles de la Tourette syndrome

Katharina Domschke, Veerle E. R. M. Visser-Vandewalle, Gereon R. Fink, Kirsten Müller‐Vahl, Christos Ganos, Jens Kuhn, Bassam Al‐Fatly, Pablo Andrade, Christopher R. Butson, Christina van der Linden, Andreas Horn, Jan Niklas Petry‐Schmelzer, Domenico Servello, Till A. Dembek, Tommaso Francesco Galbiati, Kara A. Johnson, Michael S. Okun, Thomas Schüller, Natalia Szejko, Juan Carlos Baldermann, Michael T. Barbe, Michael Fox, Lin Mahfoud, Joachim K. Krauss, Gregor A. Brandt, Petra Heiden
article en
19 citations

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.

Nature CommunicationsVol. 15(1)
Brigham and Women's Hospital (US), Harvard University (US), University of Freiburg (DE), University of Calgary (CA), Forschungszentrum Jülich (DE), University of Cologne (DE), University of Toronto (CA), Medical University of Warsaw (PL), Toronto Western Hospital (CA), University of Florida Health (US), University Medical Center Freiburg (DE), University of Florida (US), Medizinische Hochschule Hannover (DE), Humboldt-Universität zu Berlin (DE), Massachusetts General Hospital (US), Circuit Therapeutics (United States) (US), IRCCS Ospedale Galeazzi - Sant'Ambrogio (IT), University Hospital Cologne (DE), Einstein Center for Neurosciences Berlin (DE), Freie Universität Berlin (DE), Charité - Universitätsmedizin Berlin (DE)
EU Joint Programme – Neurodegenerative Disease Research, Deutsche Forschungsgemeinschaft, Else Kröner-Fresenius-Stiftung, Universität zu Köln, National Institutes of Health
Good health and well-being
Openalex Percentile: Top 1%
Obsessive-Compulsive Spectrum Disorders
12.14
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