Tomographic tract tracing and data driven approaches to unravel complex 3D fiber anatomy of DBS relevant prefrontal projections to the diencephalic-mesencephalic junction in the marmoset

Volker A. Coenen; Akiya Watakabe; Henrik Skibbe; Tetsuo Yamamori; Máté D. Döbrössy; Bastian E.A. Sajonz; Peter C. Reinacher; Marco Reisert

Brain Stimulation (Mar 2023)

Tomographic tract tracing and data driven approaches to unravel complex 3D fiber anatomy of DBS relevant prefrontal projections to the diencephalic-mesencephalic junction in the marmoset

Volker A. Coenen,
Akiya Watakabe,
Henrik Skibbe,
Tetsuo Yamamori,
Máté D. Döbrössy,
Bastian E.A. Sajonz,
Peter C. Reinacher,
Marco Reisert

Affiliations

Volker A. Coenen: Department of Stereotactic and Functional Neurosurgery, Medical Center of the University of Freiburg, Freiburg, Germany, Breisacher Straße 64, 79106, Freiburg Im Breisgau, Germany; Medical Faculty of the University of Freiburg, Breisacher Str. 153, 79110, Freiburg Im Breisgau, Germany; Center for Deep Brain Stimulation, Medical Center of the University of Freiburg, Germany; AG Stereotaxy and Interventional Neurosciences (SIN), Department of Stereotactic and Functional Neurosurgery, Medical Center of the University of Freiburg, Freiburg, Germany, Breisacher Straße 64, 79106, Freiburg Im Breisgau, Germany
Akiya Watakabe: Laboratory for Molecular Analysis of Higher Brain Function, RIKEN Center for Brain Science, Japan
Henrik Skibbe: Brain Image Analysis Unit, RIKEN Center for Brain Science, Japan
Tetsuo Yamamori: Laboratory for Molecular Analysis of Higher Brain Function, RIKEN Center for Brain Science, Japan
Máté D. Döbrössy: Department of Stereotactic and Functional Neurosurgery, Medical Center of the University of Freiburg, Freiburg, Germany, Breisacher Straße 64, 79106, Freiburg Im Breisgau, Germany; AG Stereotaxy and Interventional Neurosciences (SIN), Department of Stereotactic and Functional Neurosurgery, Medical Center of the University of Freiburg, Freiburg, Germany, Breisacher Straße 64, 79106, Freiburg Im Breisgau, Germany
Bastian E.A. Sajonz: Department of Stereotactic and Functional Neurosurgery, Medical Center of the University of Freiburg, Freiburg, Germany, Breisacher Straße 64, 79106, Freiburg Im Breisgau, Germany; Medical Faculty of the University of Freiburg, Breisacher Str. 153, 79110, Freiburg Im Breisgau, Germany
Peter C. Reinacher: Department of Stereotactic and Functional Neurosurgery, Medical Center of the University of Freiburg, Freiburg, Germany, Breisacher Straße 64, 79106, Freiburg Im Breisgau, Germany; Medical Faculty of the University of Freiburg, Breisacher Str. 153, 79110, Freiburg Im Breisgau, Germany; Fraunhofer Institute for Laser Technology (ILT), Aachen, Germany
Marco Reisert: Department of Stereotactic and Functional Neurosurgery, Medical Center of the University of Freiburg, Freiburg, Germany, Breisacher Straße 64, 79106, Freiburg Im Breisgau, Germany; Medical Faculty of the University of Freiburg, Breisacher Str. 153, 79110, Freiburg Im Breisgau, Germany; Department of Diagnostic and Interventional Radiology, Medical Physics, Medical Center – University of Freiburg, Killianstrasse 5a, 79106, Freiburg, Germany; Corresponding author. Department of Stereotactic and Functional Neurosurgery, Medical Center, University of Freiburg, Breisacher Straße 64, 79106, Freiburg, i.Br, Germany, .

Journal volume & issue: Vol. 16, no. 2
pp. 670 – 681

Abstract

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Background: Understanding prefrontal cortex projections to diencephalic-mesencephalic junction (DMJ), especially to subthalamic nucleus (STN) and ventral mesencephalic tegmentum (VMT) helps our comprehension of Deep Brain Stimulation (DBS) in major depression (MD) and obsessive-compulsive disorder (OCD). Fiber routes are complex and tract tracing studies in non-human primate species (NHP) have yielded conflicting results. The superolateral medial forebrain bundle (slMFB) is a promising target for DBS in MD and OCD. It has become a focus of criticism owing to its name and its diffusion weighted-imaging based primary description. Objective: To investigate DMJ connectivity in NHP with a special focus on slMFB and the limbic hyperdirect pathway utilizing three-dimensional and data driven techniques. Methods: We performed left prefrontal adeno-associated virus - tracer based injections in the common marmoset monkey (n = 52). Histology and two-photon microscopy were integrated into a common space. Manual and data driven cluster analyses of DMJ, subthalamic nucleus and VMT together, followed by anterior tract tracing streamline (ATTS) tractography were deployed. Results: Typical pre- and supplementary motor hyperdirect connectivity was confirmed. The advanced tract tracing unraveled the complex connectivity to the DMJ. Limbic prefrontal territories directly projected to the VMT but not STN. Discussion: Intricate results of tract tracing studies warrant the application of advanced three-dimensional analyses to understand complex fiber-anatomical routes. The applied three-dimensional techniques can enhance anatomical understanding also in other regions with complex fiber anatomy. Conclusion: Our work confirms slMFB anatomy and enfeebles previous misconceptions. The rigorous NHP approach strengthens the role of the slMFB as a target structure for DBS predominantly in psychiatric indications like MD and OCD.

Published in Brain Stimulation

ISSN: 1935-861X (Print); 1876-4754 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/brain-stimulation

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