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[Preprint]. 2023 Aug 25:2023.03.07.23286766.

doi: 10.1101/2023.03.07.23286766.

Mapping Dysfunctional Circuits in the Frontal Cortex Using Deep Brain Stimulation

Barbara Hollunder^{1

2

3}, Jill L Ostrem⁴, Ilkem Aysu Sahin^{1

2}, Nanditha Rajamani¹, Simón Oxenford¹, Konstantin Butenko⁵, Clemens Neudorfer^{5

6}, Pablo Reinhardt⁷, Patricia Zvarova^{1

2}, Mircea Polosan^{8

9

10}, Harith Akram^{11

12}, Matteo Vissani^{6

13

14}, Chencheng Zhang¹⁵, Bomin Sun¹⁵, Pavel Navratil¹⁶, Martin M Reich¹⁶, Jens Volkmann¹⁶, Fang-Cheng Yeh¹⁷, Juan Carlos Baldermann^{18

19}, Till A Dembek¹⁹, Veerle Visser-Vandewalle²⁰, Eduardo Joaquim Lopes Alho²¹, Paulo Roberto Franceschini²², Pranav Nanda⁶, Carsten Finke^{1

2

3}, Andrea A Kühn^{1

2

3

23}, Darin D Dougherty²⁴, R Mark Richardson⁶, Hagai Bergman^{25

26

27}, Mahlon R DeLong²⁸, Alberto Mazzoni^{13

14}, Luigi M Romito²⁹, Himanshu Tyagi^{11

12}, Ludvic Zrinzo^{11

12}, Eileen M Joyce^{11

12}, Stephan Chabardes^{8

9

30}, Philip A Starr³¹, Ningfei Li¹, Andreas Horn^{1

2

5

6}

Affiliations

¹ Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
² Einstein Center for Neurosciences Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany.
³ Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany.
⁴ Movement Disorders and Neuromodulation Centre, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
⁵ Center for Brain Circuit Therapeutics, Department of Neurology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁸ Univ. Grenoble Alpes, Grenoble, France.
⁹ Inserm, U1216, Grenoble Institut des Neurosciences, Grenoble, France.
¹⁰ Psychiatry Department, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France.
¹¹ Department of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, UK.
¹² National Hospital for Neurology and Neurosurgery, University College London Queen Square Institute of Neurology, London, UK.
¹³ The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy.
¹⁴ Department of Excellence in Robotics and AI, Scuola Superiore Sant'Anna, Pisa, Italy.
¹⁵ Department of Neurosurgery, Rujin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
¹⁶ Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
¹⁷ Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁸ Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
¹⁹ Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
²⁰ Department of Stereotactic and Functional Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
²¹ Clinic of Pain and Functional Neurosurgery, São Paulo, Brazil.
²² Department of Neurology and Neurosurgery, University of Caxias do Sul, Rio Grande do Sul, Brazil.
²³ NeuroCure Cluster of Excellence, Charité - Universitätsmedizin Berlin, Berlin, Germany.
²⁴ Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
²⁵ The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University, Jerusalem, Israel.
²⁶ Department of Medical Neurobiology, Institute of Medical Research Israel-Canada, The Hebrew University, Hassadah Medical School, Jerusalem, Israel.
²⁷ Department of Neurosurgery, Hadassah Medical Center, Jerusalem, Israel.
²⁸ Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
²⁹ Parkinson and Movement Disorders Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
³⁰ Department of Neurosurgery, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France.
³¹ Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.

PMID: 36945497
PMCID: PMC10029043
DOI: 10.1101/2023.03.07.23286766

Free PMC article

Mapping Dysfunctional Circuits in the Frontal Cortex Using Deep Brain Stimulation

Barbara Hollunder et al. medRxiv. 2023.

Free PMC article

[Preprint]. 2023 Aug 25:2023.03.07.23286766.

doi: 10.1101/2023.03.07.23286766.

Authors

Affiliations

¹ Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
² Einstein Center for Neurosciences Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany.
³ Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany.
⁴ Movement Disorders and Neuromodulation Centre, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
⁵ Center for Brain Circuit Therapeutics, Department of Neurology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁸ Univ. Grenoble Alpes, Grenoble, France.
⁹ Inserm, U1216, Grenoble Institut des Neurosciences, Grenoble, France.
¹⁰ Psychiatry Department, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France.
¹¹ Department of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, UK.
¹² National Hospital for Neurology and Neurosurgery, University College London Queen Square Institute of Neurology, London, UK.
¹³ The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy.
¹⁴ Department of Excellence in Robotics and AI, Scuola Superiore Sant'Anna, Pisa, Italy.
¹⁵ Department of Neurosurgery, Rujin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
¹⁶ Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
¹⁷ Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁸ Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
¹⁹ Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
²⁰ Department of Stereotactic and Functional Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
²¹ Clinic of Pain and Functional Neurosurgery, São Paulo, Brazil.
²² Department of Neurology and Neurosurgery, University of Caxias do Sul, Rio Grande do Sul, Brazil.
²³ NeuroCure Cluster of Excellence, Charité - Universitätsmedizin Berlin, Berlin, Germany.
²⁴ Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
²⁵ The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University, Jerusalem, Israel.
²⁶ Department of Medical Neurobiology, Institute of Medical Research Israel-Canada, The Hebrew University, Hassadah Medical School, Jerusalem, Israel.
²⁷ Department of Neurosurgery, Hadassah Medical Center, Jerusalem, Israel.
²⁸ Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
²⁹ Parkinson and Movement Disorders Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
³⁰ Department of Neurosurgery, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France.
³¹ Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.

PMID: 36945497
PMCID: PMC10029043
DOI: 10.1101/2023.03.07.23286766

Update in

Mapping dysfunctional circuits in the frontal cortex using deep brain stimulation.
Hollunder B, Ostrem JL, Sahin IA, Rajamani N, Oxenford S, Butenko K, Neudorfer C, Reinhardt P, Zvarova P, Polosan M, Akram H, Vissani M, Zhang C, Sun B, Navratil P, Reich MM, Volkmann J, Yeh FC, Baldermann JC, Dembek TA, Visser-Vandewalle V, Alho EJL, Franceschini PR, Nanda P, Finke C, Kühn AA, Dougherty DD, Richardson RM, Bergman H, DeLong MR, Mazzoni A, Romito LM, Tyagi H, Zrinzo L, Joyce EM, Chabardes S, Starr PA, Li N, Horn A. Hollunder B, et al. Nat Neurosci. 2024 Mar;27(3):573-586. doi: 10.1038/s41593-024-01570-1. Epub 2024 Feb 22. Nat Neurosci. 2024. PMID: 38388734 Free PMC article.

Abstract

Frontal circuits play a critical role in motor, cognitive, and affective processing - and their dysfunction may result in a variety of brain disorders. However, exactly which frontal domains mediate which (dys)function remains largely elusive. Here, we study 534 deep brain stimulation electrodes implanted to treat four different brain disorders. By analyzing which connections were modulated for optimal therapeutic response across these disorders, we segregate the frontal cortex into circuits that became dysfunctional in each of them. Dysfunctional circuits were topographically arranged from occipital to rostral, ranging from interconnections with sensorimotor cortices in dystonia, with the primary motor cortex in Tourette's syndrome, the supplementary motor area in Parkinson's disease, to ventromedial prefrontal and anterior cingulate cortices in obsessive-compulsive disorder. Our findings highlight the integration of deep brain stimulation with brain connectomics as a powerful tool to explore couplings between brain structure and functional impairment in the human brain.

Keywords: Connectome; Deep Brain Stimulation (DBS); Dystonia; Obsessive-Compulsive Disorder (OCD); Parkinson’s disease (PD); Structural Connectivity; Subthalamic Nucleus (STN); Tourette’s syndrome (TS).

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Conflict of interest statement

Declaration of Competing Interests J.L.O. reports research grant support from Medtronic and Boston Scientific and is a consultant for Abbott, outside of the submitted work. M.M.R. reports grant support and honoraria for speaking from Medtronic and Boston Scientific, outside of the submitted work. J.V. reports grants and personal fees from Medtronic Inc., grants, and personal fees from Boston Scientific, personal fees from Abbott, outside of the submitted work. H.B. is consultant of Alpha-Omega, outside of the submitted work. S.C. is consultant for Medtronic and Boston Scientific, outside of the submitted work. A.H. is a consultant for FxNeuromodulation and Abbott, and reports lecture fees from Boston Scientific, outside of the submitted work. B.H., I.A.S., N.R., S.O., K.B., C.N., P.R., P.Z., M.P., H.A., M.V., C.Z., B.S., P.N., F.-C.Y., J.C.B., T.A.D., V.V.-V., E.J.L.A., P.R.F., C.F., A.A.K., P.N., D.D.D., R.M.R., M.R.D., A.M., L.M.R., H.T., L.Z., E.M.J., P.A.S., and N.L. report no competing interests.

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This is a preprint.

Mapping Dysfunctional Circuits in the Frontal Cortex Using Deep Brain Stimulation

Affiliations

Mapping Dysfunctional Circuits in the Frontal Cortex Using Deep Brain Stimulation

Authors

Affiliations

Update in

Abstract

Conflict of interest statement

Publication types

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources