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

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...

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Main Authors: Juan Carlos Baldermann, Jan Niklas Petry-Schmelzer, Thomas Schüller, Lin Mahfoud, Gregor A. Brandt, Till A. Dembek, Christina van der Linden, Joachim K. Krauss, Natalia Szejko, Kirsten R. Müller-Vahl, Christos Ganos, Bassam Al-Fatly, Petra Heiden, Domenico Servello, Tommaso Galbiati, Kara A. Johnson, Christopher R. Butson, Michael S. Okun, Pablo Andrade, Katharina Domschke, Gereon R. Fink, Michael D. Fox, Andreas Horn, Jens Kuhn, Veerle Visser-Vandewalle, Michael T. Barbe
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-55242-6
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author Juan Carlos Baldermann
Jan Niklas Petry-Schmelzer
Thomas Schüller
Lin Mahfoud
Gregor A. Brandt
Till A. Dembek
Christina van der Linden
Joachim K. Krauss
Natalia Szejko
Kirsten R. Müller-Vahl
Christos Ganos
Bassam Al-Fatly
Petra Heiden
Domenico Servello
Tommaso Galbiati
Kara A. Johnson
Christopher R. Butson
Michael S. Okun
Pablo Andrade
Katharina Domschke
Gereon R. Fink
Michael D. Fox
Andreas Horn
Jens Kuhn
Veerle Visser-Vandewalle
Michael T. Barbe
author_facet Juan Carlos Baldermann
Jan Niklas Petry-Schmelzer
Thomas Schüller
Lin Mahfoud
Gregor A. Brandt
Till A. Dembek
Christina van der Linden
Joachim K. Krauss
Natalia Szejko
Kirsten R. Müller-Vahl
Christos Ganos
Bassam Al-Fatly
Petra Heiden
Domenico Servello
Tommaso Galbiati
Kara A. Johnson
Christopher R. Butson
Michael S. Okun
Pablo Andrade
Katharina Domschke
Gereon R. Fink
Michael D. Fox
Andreas Horn
Jens Kuhn
Veerle Visser-Vandewalle
Michael T. Barbe
author_sort Juan Carlos Baldermann
collection DOAJ
description 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.
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spelling doaj-art-23d92c8b4b434dd185bcd62d30325cb62025-08-20T02:31:51ZengNature PortfolioNature Communications2041-17232024-12-0115111510.1038/s41467-024-55242-6A critical role of action-related functional networks in Gilles de la Tourette syndromeJuan Carlos Baldermann0Jan Niklas Petry-Schmelzer1Thomas Schüller2Lin Mahfoud3Gregor A. Brandt4Till A. Dembek5Christina van der Linden6Joachim K. Krauss7Natalia Szejko8Kirsten R. Müller-Vahl9Christos Ganos10Bassam Al-Fatly11Petra Heiden12Domenico Servello13Tommaso Galbiati14Kara A. Johnson15Christopher R. Butson16Michael S. Okun17Pablo Andrade18Katharina Domschke19Gereon R. Fink20Michael D. Fox21Andreas Horn22Jens Kuhn23Veerle Visser-Vandewalle24Michael T. Barbe25Department of Psychiatry and Psychotherapy, Medical Center – University of Freiburg, Faculty of Medicine, University of FreiburgDepartment of Psychiatry and Psychotherapy, Medical Center – University of Freiburg, Faculty of Medicine, University of FreiburgDepartment of Neurology, Faculty of Medicine and University Hospital Cologne, University of CologneDepartment of Psychiatry and Psychotherapy, Medical Center – University of Freiburg, Faculty of Medicine, University of FreiburgDepartment of Psychiatry and Psychotherapy, Medical Center – University of Freiburg, Faculty of Medicine, University of FreiburgDepartment of Psychiatry and Psychotherapy, Medical Center – University of Freiburg, Faculty of Medicine, University of FreiburgDepartment of Psychiatry and Psychotherapy, Medical Center – University of Freiburg, Faculty of Medicine, University of FreiburgDepartment of Neurosurgery, Hannover Medical SchoolDepartment of Neurology, University of CalgaryDepartment of Psychiatry, Socialpsychiatry and Psychotherapy, Hannover Medical SchoolMovement Disorder Clinic, Edmond J. Safra Program in Parkinson’s Disease, Division of Neurology University of Toronto, Toronto Western HospitalDepartment of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinDepartment of Stereotactic and Functional Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of CologneNeurosurgical Department, IRCCS Istituto Ortopedico Galeazzi, MilanNeurosurgical Department, IRCCS Istituto Ortopedico Galeazzi, MilanNorman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, USA; Department of Neurology, University of FloridaNorman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, USA; Department of Neurology, University of FloridaNorman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, USA; Department of Neurology, University of FloridaDepartment of Stereotactic and Functional Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of CologneDepartment of Psychiatry and Psychotherapy, Medical Center – University of Freiburg, Faculty of Medicine, University of FreiburgDepartment of Psychiatry and Psychotherapy, Medical Center – University of Freiburg, Faculty of Medicine, University of FreiburgCenter for Brain Circuit Therapeutics, Department of Neurology, Brigham & Women’s Hospital, Harvard Medical SchoolCenter for Brain Circuit Therapeutics, Department of Neurology, Brigham & Women’s Hospital, Harvard Medical SchoolAlexianer Hospital Cologne, Alexianer Köln GmbHDepartment of Stereotactic and Functional Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of CologneDepartment of Neurology, Faculty of Medicine and University Hospital Cologne, University of CologneAbstract 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.https://doi.org/10.1038/s41467-024-55242-6
spellingShingle Juan Carlos Baldermann
Jan Niklas Petry-Schmelzer
Thomas Schüller
Lin Mahfoud
Gregor A. Brandt
Till A. Dembek
Christina van der Linden
Joachim K. Krauss
Natalia Szejko
Kirsten R. Müller-Vahl
Christos Ganos
Bassam Al-Fatly
Petra Heiden
Domenico Servello
Tommaso Galbiati
Kara A. Johnson
Christopher R. Butson
Michael S. Okun
Pablo Andrade
Katharina Domschke
Gereon R. Fink
Michael D. Fox
Andreas Horn
Jens Kuhn
Veerle Visser-Vandewalle
Michael T. Barbe
A critical role of action-related functional networks in Gilles de la Tourette syndrome
Nature Communications
title A critical role of action-related functional networks in Gilles de la Tourette syndrome
title_full A critical role of action-related functional networks in Gilles de la Tourette syndrome
title_fullStr A critical role of action-related functional networks in Gilles de la Tourette syndrome
title_full_unstemmed A critical role of action-related functional networks in Gilles de la Tourette syndrome
title_short A critical role of action-related functional networks in Gilles de la Tourette syndrome
title_sort critical role of action related functional networks in gilles de la tourette syndrome
url https://doi.org/10.1038/s41467-024-55242-6
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