Joint Anatomical, Histological, and Imaging Investigation of the Midbrain Target Region for Superolateral Medial Forebrain Bundle Deep Brain Stimulation

Volker Arnd Coenen; Jana Maxi Zielinski; Bastian Elmar Alexander Sajonz; Peter Christoph Reinacher; Annette Thierauf-Emberger; Johanna Wessolleck; Maximilian Frosch; Björn Spittau; Thomas Eduard Schläpfer; Juan Carlos Baldermann; Dominique Endres; Wolf Lagrèze; Máté Daniel Döbrössy; Marco Reisert

doi:10.1159/000541834

Joint Anatomical, Histological, and Imaging Investigation of the Midbrain Target Region for Superolateral Medial Forebrain Bundle Deep Brain Stimulation

Stereotact Funct Neurosurg. 2024 Nov 11:1-13. doi: 10.1159/000541834. Online ahead of print.

Authors

Volker Arnd Coenen^{1

2

3

4}, Jana Maxi Zielinski¹, Bastian Elmar Alexander Sajonz^{1

2}, Peter Christoph Reinacher^{1

2

5}, Annette Thierauf-Emberger^{2

6}, Johanna Wessolleck^{2

7}, Maximilian Frosch^{2

8}, Björn Spittau^{9

10}, Thomas Eduard Schläpfer^{2

11}, Juan Carlos Baldermann^{2

12}, Dominique Endres^{2

12}, Wolf Lagrèze^{2

13}, Máté Daniel Döbrössy^{2

4

7

14}, Marco Reisert^{1

2

15}

Affiliations

¹ Department of Stereotactic and Functional Neurosurgery, Medical Center of Freiburg University, Freiburg, Germany.
² Medical Faculty of Freiburg University, Freiburg, Germany.
³ Center for Deep Brain Stimulation, Medical Center of Freiburg University, Freiburg, Germany.
⁴ Center for Basics in Neuromodulation, Medical Faculty of Freiburg University, Freiburg, Germany.
⁵ Fraunhofer Institute for Laser Technology (ILT), Aachen, Germany.
⁶ Institute of Forensic Medicine, Medical Center of Freiburg University, Freiburg, Germany.
⁷ Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, Medical Center of Freiburg University, Freiburg, Germany.
⁸ Institute of Neuropathology, Medical Center of Freiburg University, Freiburg, Germany.
⁹ Medical School OWL, Anatomy and Cell Biology, Bielefeld University, Freiburg, Germany.
¹⁰ Department of Molecular Embryology, Institute for Anatomy and Cell Biology, Faculty of Medicine, Freiburg University, Freiburg, Germany.
¹¹ Division of Interventional Biologial Psychiatry, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Freiburg, Germany.
¹² Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Freiburg, Germany.
¹³ Department of Opthalmology, Medical Center - University of Freiburg, Freiburg, Germany.
¹⁴ Faculty of Biology, University of Freiburg, Freiburg, Germany.
¹⁵ Department of Diagnostic and Interventional Radiology, Medical Physics, Medical Center - University of Freiburg, Freiburg, Germany.

PMID: 39527932
DOI: 10.1159/000541834

Abstract

Introduction: Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (slMFB) is currently being researched in clinical trials and open case series as a therapeutic option for treatment-resistant major depressive disorder and treatment-resistant obsessive-compulsive disorder (TR-OCD). There are numerous publications describing stimulation in such proximity to the ventral tegmental area (VTA) and open questions remain concerning the stimulation target and its functional environment. As of right now, we are not aware of any publications that compare the typical electrode placements with the histologically supported tractographic depiction of the target structure.

Methods: We used three cadaver midbrain samples with presumed unaltered anatomy. After fixation, staining and slicing, the histological samples were warped to the Montreal Neurological Institute (MNI) big brain environment. Utilizing a tractographic atlas, a qualitative analysis of the typical slMFB stimulation site in the lateral VTA utilizing a subset of clinically implanted DBS electrodes in n = 12 patients, successfully implanted for TR-OCD was performed.

Results: A joint qualitative overlay analysis of predominantly tyrosine hydroxylase stained histology at different resolutions in an anatomical common space was achieved. Localization of the DBS lead bodies was found in the typical positions in front of the red nuclei in the lateral VTA. DBS lead tip region positions explained the oculomotor side effects of stimulation related to paranigral or parabrachial pigmented sub-nuclei of the VTA, respectively. The location of active electrode contacts suggests downstream and antidromic effects on the greater VTA related medial forebrain bundle system.

Conclusion: This is the first dedicated joint histopathological overlay analysis of DBS electrodes targeting the slMFB and lateral VTA in a common anatomical space. This analysis might serve to better understand the DBS target region for this procedure.

Keywords: Deep brain stimulation; Major depressive disorder; Midbrain; Obsessive-compulsive disorder; Superolateral medial forebrain bundle; Ventral tegmental area.