Mapping dysfunctional circuits in the frontal cortex using deep brain stimulation

Barbara Hollunder; Jill L Ostrem; Ilkem Aysu Sahin; Nanditha Rajamani; Simón Oxenford; Konstantin Butenko; Clemens Neudorfer; Pablo Reinhardt; Patricia Zvarova; Mircea Polosan; Harith Akram; Matteo Vissani; Chencheng Zhang; Bomin Sun; Pavel Navratil; Martin M Reich; Jens Volkmann; Fang-Cheng Yeh; Juan Carlos Baldermann; Till A Dembek; Veerle Visser-Vandewalle; Eduardo Joaquim Lopes Alho; Paulo Roberto Franceschini; Pranav Nanda; Carsten Finke; Andrea A Kühn; Darin D Dougherty; R Mark Richardson; Hagai Bergman; Mahlon R DeLong; Alberto Mazzoni; Luigi M Romito; Himanshu Tyagi; Ludvic Zrinzo; Eileen M Joyce; Stephan Chabardes; Philip A Starr; Ningfei Li; Andreas Horn

doi:10.1038/s41593-024-01570-1

Mapping dysfunctional circuits in the frontal cortex using deep brain stimulation

Nat Neurosci. 2024 Mar;27(3):573-586. doi: 10.1038/s41593-024-01570-1. Epub 2024 Feb 22.

Authors

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 Dembek^{5

19}, Veerle Visser-Vandewalle²⁰, Eduardo Joaquim Lopes Alho²¹, Paulo Roberto Franceschini²², Pranav Nanda⁶, Carsten Finke^{2

3

23}, Andrea A Kühn^{1

2

3

24}, Darin D Dougherty²⁵, R Mark Richardson⁶, Hagai Bergman^{26

27

28}, Mahlon R DeLong²⁹, Alberto Mazzoni^{13

14}, Luigi M Romito³⁰, Himanshu Tyagi^{11

31}, Ludvic Zrinzo^{11

12}, Eileen M Joyce^{11

31}, Stephan Chabardes^{8

9

32}, Philip A Starr³³, Ningfei Li^#³⁴, Andreas Horn^#^{35

36

37

38}

Affiliations

¹ Movement Disorders and Neuromodulation Unit, 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 and 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 Université Grenoble Alpes, Grenoble, France.
⁹ Inserm, U1216, Grenoble Institut des Neurosciences, Grenoble, France.
¹⁰ Department of Psychiatry, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France.
¹¹ Unit of Functional Neurosurgery, UCL Queen Square Institute of Neurology, London, UK.
¹² Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, 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 Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
²⁴ NeuroCure Cluster of Excellence, Charité - Universitätsmedizin Berlin, Berlin, Germany.
²⁵ Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
²⁶ Edmond and Lily Safra Center for Brain Sciences, The Hebrew University, Jerusalem, Israel.
²⁷ Department of Medical Neurobiology, Institute of Medical Research Israel-Canada, The Hebrew University, Hadassah Medical School, Jerusalem, Israel.
²⁸ Department of Neurosurgery, Hadassah Medical Center, Jerusalem, Israel.
²⁹ Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
³⁰ Parkinson and Movement Disorders Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
³¹ Department of Neuropsychiatry, The National Hospital for Neurology and Neurosurgery, London, UK.
³² Department of Neurosurgery, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France.
³³ Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
³⁴ Movement Disorders and Neuromodulation Unit, Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany. [email protected].
³⁵ Movement Disorders and Neuromodulation Unit, Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany. [email protected].
³⁶ Einstein Center for Neurosciences Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany. [email protected].
³⁷ Center for Brain Circuit Therapeutics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. [email protected].
³⁸ Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. [email protected].

^# Contributed equally.

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)functions remains largely elusive. We studied 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 segregated the frontal cortex into circuits that had become dysfunctional in each of them. Dysfunctional circuits were topographically arranged from occipital to frontal, ranging from interconnections with sensorimotor cortices in dystonia, 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 impairments in the human brain.

MeSH terms

Brain
Brain Mapping
Deep Brain Stimulation*
Humans
Motor Cortex* / physiology
Parkinson Disease* / therapy

Abstract

MeSH terms

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