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

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Volker Arnd CoenenDepartment of Stereotactic and Functional Neurosurgery, Medical Center of Freiburg University, Freiburg, Germany.

Jana Maxi ZielinskiDepartment of Stereotactic and Functional Neurosurgery, Medical Center of Freiburg University, Freiburg, Germany.

Bastian Elmar Alexander SajonzDepartment of Stereotactic and Functional Neurosurgery, Medical Center of Freiburg University, Freiburg, Germany.

Peter Christoph ReinacherDepartment of Stereotactic and Functional Neurosurgery, Medical Center of Freiburg University, Freiburg, Germany.

Annette Thierauf-EmbergerMedical Faculty of Freiburg University, Freiburg, Germany.

Johanna WessolleckMedical Faculty of Freiburg University, Freiburg, Germany.

Maximilian FroschMedical Faculty of Freiburg University, Freiburg, Germany.

Björn SpittauMedical School OWL, Anatomy and Cell Biology, Bielefeld University, Freiburg, Germany.

Thomas Eduard SchläpferMedical Faculty of Freiburg University, Freiburg, Germany.

Juan Carlos BaldermannMedical Faculty of Freiburg University, Freiburg, Germany.

Dominique EndresMedical Faculty of Freiburg University, Freiburg, Germany.

Wolf LagrèzeMedical Faculty of Freiburg University, Freiburg, Germany.

Máté Daniel DöbrössyMedical Faculty of Freiburg University, Freiburg, Germany.

Marco ReisertDepartment of Stereotactic and Functional Neurosurgery, Medical Center of Freiburg University, Freiburg, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionDeep 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.

methodsWe 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.

resultsA 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.

conclusionThis 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.

introductionDeep 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.

methodsWe 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.

resultsA 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.

conclusionThis 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.

Indexed as

Deep Brain StimulationMedial Forebrain BundleMesencephalonObsessive-Compulsive DisorderAdultCadaverElectrodes, ImplantedFemaleHumansMaleMiddle AgedVentral Tegmental AreaDeep brain stimulationMajor depressive disorderMidbrainObsessive-compulsive disorderSuperolateral medial forebrain bundleVentral tegmental area