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Left prefrontal impact links subthalamic stimulation with depressive symptoms

View ORCID ProfileFriederike Irmen, View ORCID ProfileAndreas Horn, View ORCID ProfilePhilip Mosley, View ORCID ProfileAlistair Perry, View ORCID ProfileJan Niklas Petry-Schmelzer, View ORCID ProfileHaidar S. Dafsari, Michael Barbe, View ORCID ProfileVeerle Visser-Vandewalle, Gerd-Helge Schneider, View ORCID ProfileNingfei Li, Dorothee Kübler, Gregor Wenzel, Andrea Kühn
doi: https://doi.org/10.1101/665976
Friederike Irmen
1Department of Neurology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
2Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Germany
3Department of Biological Psychology and Cognitive Neuroscience, Freie Universität Berlin, Germany
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  • For correspondence: friederike.irmen@charite.de
Andreas Horn
1Department of Neurology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
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Philip Mosley
4Systems Neuroscience Group, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
5Queensland Brain Institute, University of Queensland, St Lucia, Queensland, Australia
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Alistair Perry
6Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Max Planck Institute for Human Development, Berlin, Germany
7Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany
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Jan Niklas Petry-Schmelzer
8University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Neurology, Cologne, Germany
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Haidar S. Dafsari
8University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Neurology, Cologne, Germany
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Michael Barbe
8University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Neurology, Cologne, Germany
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Veerle Visser-Vandewalle
9Dep. of Stereotactic and Functional Neurosurgery, University Hospital Cologne, Cologne, Germany
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Gerd-Helge Schneider
10Department of Neurosurgery, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
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Ningfei Li
1Department of Neurology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
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Dorothee Kübler
1Department of Neurology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
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Gregor Wenzel
1Department of Neurology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
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Andrea Kühn
1Department of Neurology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
2Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Germany
11Deutsches Zentrum für Neurodegenerative Erkrankungen, Berlin, Germany
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Abstract

Objective Subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s Disease (PD) not only stimulates focal target structures but also affects distributed brain networks. The impact this network modulation has on non-motor DBS effects is not well characterized. By focusing on the affective domain, we systematically investigate the impact of electrode placement and associated structural connectivity on changes in depressive symptoms following STN-DBS which have been reported to improve, worsen or remain unchanged.

Methods Depressive symptoms before and after STN-DBS surgery were documented in 116 PD patients from three DBS centers (Berlin, Queensland, Cologne). Based on individual electrode reconstructions, the volumes of tissue activated (VTA) were estimated and combined with normative connectome data to identify structural connections passing through VTAs. Berlin and Queensland cohorts formed a training and cross-validation dataset used to identify structural connectivity explaining change in depressive symptoms. The Cologne data served as test-set for which depressive symptom change was predicted.

Results Structural connectivity was linked to depressive symptom change under STN-DBS. An optimal connectivity map trained on the Berlin cohort could predict changes in depressive symptoms in Queensland patients and vice versa. Furthermore, the joint training-set map predicted changes in depressive symptoms in the independent test-set. Worsening of depressive symptoms was associated with left prefrontal connectivity.

Interpretation Fibers linking the STN electrode with left prefrontal areas predicted worsening of depressive symptoms. Our results suggest that for the left STN-DBS lead, placement impacting fibers to left prefrontal areas should be avoided to maximize improvement of depressive symptoms.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 23, 2020.
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Left prefrontal impact links subthalamic stimulation with depressive symptoms
Friederike Irmen, Andreas Horn, Philip Mosley, Alistair Perry, Jan Niklas Petry-Schmelzer, Haidar S. Dafsari, Michael Barbe, Veerle Visser-Vandewalle, Gerd-Helge Schneider, Ningfei Li, Dorothee Kübler, Gregor Wenzel, Andrea Kühn
bioRxiv 665976; doi: https://doi.org/10.1101/665976
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Left prefrontal impact links subthalamic stimulation with depressive symptoms
Friederike Irmen, Andreas Horn, Philip Mosley, Alistair Perry, Jan Niklas Petry-Schmelzer, Haidar S. Dafsari, Michael Barbe, Veerle Visser-Vandewalle, Gerd-Helge Schneider, Ningfei Li, Dorothee Kübler, Gregor Wenzel, Andrea Kühn
bioRxiv 665976; doi: https://doi.org/10.1101/665976

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