Optimal deep brain stimulation sites and networks for stimulation of the fornix in Alzheimer’s disease

Ana Sofía Ríos, Simón Oxenford, Clemens Neudorfer, Konstantin Butenko, Ningfei Li, Nanditha Rajamani, Alexandre Boutet, Gavin J. B. Elias, Jurgen Germann, Aaron Loh, Wissam Deeb, Fuyixue Wang, Kawin Setsompop, Bryan Salvato, Leonardo Brito de Almeida, Kelly D. Foote, Robert Amaral, Paul B. Rosenberg, David F. Tang-Wai, David A. Wolk, Anna D. Burke, Stephen Salloway, Marwan N. Sabbagh, M. Mallar Chakravarty, Gwenn S. Smith, Constantine G. Lyketsos, Michael S. Okun, William S. Anderson, Zoltan Mari, Francisco A. Ponce, Andres M. Lozano and Andreas Horn ()
Additional contact information
Ana Sofía Ríos: Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Simón Oxenford: Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Clemens Neudorfer: Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Konstantin Butenko: Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Ningfei Li: Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Nanditha Rajamani: Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Alexandre Boutet: University Health Network and University of Toronto
Gavin J. B. Elias: University Health Network and University of Toronto
Jurgen Germann: University Health Network and University of Toronto
Aaron Loh: University Health Network and University of Toronto
Wissam Deeb: UMass Chan Medical School, Department of Neurology
Fuyixue Wang: Harvard Medical School, Massachusetts General Hospital
Kawin Setsompop: Harvard Medical School, Massachusetts General Hospital
Bryan Salvato: University of Florida Health Jacksonville
Leonardo Brito de Almeida: University of Florida
Kelly D. Foote: University of Florida
Robert Amaral: Cerebral Imaging Centre, Douglas Research Centre
Paul B. Rosenberg: School of Medicine, Johns Hopkins University
David F. Tang-Wai: University of Toronto
David A. Wolk: University of Pennsylvania
Anna D. Burke: Barrow Neurological Institute
Stephen Salloway: Alpert Medical School of Brown University
Marwan N. Sabbagh: Barrow Neurological Institute
M. Mallar Chakravarty: Cerebral Imaging Centre, Douglas Research Centre
Gwenn S. Smith: School of Medicine, Johns Hopkins University
Constantine G. Lyketsos: School of Medicine, Johns Hopkins University
Michael S. Okun: University of Florida
William S. Anderson: Johns Hopkins School of Medicine
Zoltan Mari: Johns Hopkins School of Medicine
Francisco A. Ponce: Barrow Neurological Institute
Andres M. Lozano: University Health Network and University of Toronto
Andreas Horn: Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract Deep brain stimulation (DBS) to the fornix is an investigational treatment for patients with mild Alzheimer’s Disease. Outcomes from randomized clinical trials have shown that cognitive function improved in some patients but deteriorated in others. This could be explained by variance in electrode placement leading to differential engagement of neural circuits. To investigate this, we performed a post-hoc analysis on a multi-center cohort of 46 patients with DBS to the fornix (NCT00658125, NCT01608061). Using normative structural and functional connectivity data, we found that stimulation of the circuit of Papez and stria terminalis robustly associated with cognitive improvement (R = 0.53, p

Date: 2022
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DOI: 10.1038/s41467-022-34510-3

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