Establishing connectivity through microdissections of midbrain stimulation-related neural circuits

Author:

Skandalakis Georgios P12,Neudorfer Clemens345,Payne Caitlin A1,Bond Evalina1,Tavakkoli Armin D1,Barrios-Martinez Jessica6,Trutti Anne C7,Koutsarnakis Christos2,Coenen Volker A8910,Komaitis Spyridon11ORCID,Hadjipanayis Constantinos G6,Stranjalis George2,Yeh Fang-Cheng6,Banihashemi Layla1213,Hong Jennifer1ORCID,Lozano Andres M14,Kogan Michael15,Horn Andreas345,Evans Linton T1,Kalyvas Aristotelis14

Affiliation:

1. Section of Neurosurgery, Dartmouth Hitchcock Medical Center , Lebanon, NH 03756 , USA

2. Department of Neurosurgery, National and Kapodistrian University of Athens Medical School, Evangelismos General Hospital , Athens 10676 , Greece

3. Center for Brain Circuit Therapeutics Department of Neurology Brigham & Women’s Hospital, Harvard Medical School , Boston, MA 02115 , USA

4. MGH Neurosurgery & Center for Neurotechnology and Neurorecovery (CNTR) at MGH Neurology Massachusetts General Hospital, Harvard Medical School , Boston, MA 02114 , USA

5. Movement Disorder and Neuromodulation Unit, Department of Neurology, Department of Neurology, Charité—Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin , 10117 Berlin , Germany

6. Department of Neurological Surgery, University of Pittsburgh , Pittsburgh, PA 15213 , USA

7. Integrative Model-Based Cognitive Neuroscience Research Unit, University of Amsterdam , Amsterdam 15926 , The Netherlands

8. Department of Stereotactic and Functional Neurosurgery, Medical Center of the University of Freiburg , Freiburg 79106 , Germany

9. Medical Faculty of the University of Freiburg , Freiburg 79110 , Germany

10. Center for Deep Brain Stimulation, Medical Center of the University of Freiburg , Freiburg 79106 , Germany

11. Queens Medical Center, Nottingham University Hospitals NHS Foundation Trust , Nottingham NG7 2UH , UK

12. Department of Psychiatry, University of Pittsburgh , Pittsburgh, PA 15213 , USA

13. Department of Bioengineering, University of Pittsburgh , Pittsburgh, PA 15213 , USA

14. Division of Neurosurgery, University Health Network, University of Toronto , Toronto, ON M5T 1P5 , Canada

15. Department of Neurosurgery, University of New Mexico School of Medicine , Albuquerque, NM 87106 , USA

Abstract

Abstract Comprehensive understanding of the neural circuits involving the ventral tegmental area is essential for elucidating the anatomofunctional mechanisms governing human behaviour, in addition to the therapeutic and adverse effects of deep brain stimulation for neuropsychiatric diseases. Although the ventral tegmental area has been targeted successfully with deep brain stimulation for different neuropsychiatric diseases, the axonal connectivity of the region is not fully understood. Here, using fibre microdissections in human cadaveric hemispheres, population-based high-definition fibre tractography and previously reported deep brain stimulation hotspots, we find that the ventral tegmental area participates in an intricate network involving the serotonergic pontine nuclei, basal ganglia, limbic system, basal forebrain and prefrontal cortex, which is implicated in the treatment of obsessive–compulsive disorder, major depressive disorder, Alzheimer’s disease, cluster headaches and aggressive behaviours.

Publisher

Oxford University Press (OUP)

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