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; Andreas Horn

doi:10.1038/s41467-022-34510-3

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. WolkAnna 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, Andreas Horn

School of Medicine

Research output: Contribution to journal › Article › peer-review

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 < 0.001). On a local level, the optimal stimulation site resided at the direct interface between these structures (R = 0.48, p < 0.001). Finally, modulating specific distributed brain networks related to memory accounted for optimal outcomes (R = 0.48, p < 0.001). Findings were robust to multiple cross-validation designs and may define an optimal network target that could refine DBS surgery and programming.

Original language	English (US)
Article number	7707
Journal	Nature communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-34510-3
State	Published - Dec 2022

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-022-34510-3

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Ríos, A. S., Oxenford, S., Neudorfer, C., Butenko, K., Li, N., Rajamani, N., Boutet, A., Elias, G. J. B., Germann, J., Loh, A., Deeb, W., Wang, F., Setsompop, K., Salvato, B., Almeida, L. B. D., Foote, K. D., Amaral, R., Rosenberg, P. B., Tang-Wai, D. F., ... Horn, A. (2022). Optimal deep brain stimulation sites and networks for stimulation of the fornix in Alzheimer’s disease. Nature communications, 13(1), Article 7707. https://doi.org/10.1038/s41467-022-34510-3

Ríos, AS, Oxenford, S, Neudorfer, C, Butenko, K, Li, N, Rajamani, N, Boutet, A, Elias, GJB, Germann, J, Loh, A, Deeb, W, Wang, F, Setsompop, K, Salvato, B, Almeida, LBD, Foote, KD, Amaral, R, Rosenberg, PB, Tang-Wai, DF, Wolk, DA, Burke, AD, Salloway, S, Sabbagh, MN, Chakravarty, MM, Smith, GS , Lyketsos, CG, Okun, MS, Anderson, WS, Mari, Z, Ponce, FA, Lozano, AM & Horn, A 2022, 'Optimal deep brain stimulation sites and networks for stimulation of the fornix in Alzheimer’s disease', Nature communications, vol. 13, no. 1, 7707. https://doi.org/10.1038/s41467-022-34510-3

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abstract = "Deep brain stimulation (DBS) to the fornix is an investigational treatment for patients with mild Alzheimer{\textquoteright}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 < 0.001). On a local level, the optimal stimulation site resided at the direct interface between these structures (R = 0.48, p < 0.001). Finally, modulating specific distributed brain networks related to memory accounted for optimal outcomes (R = 0.48, p < 0.001). Findings were robust to multiple cross-validation designs and may define an optimal network target that could refine DBS surgery and programming.",

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T1 - Optimal deep brain stimulation sites and networks for stimulation of the fornix in Alzheimer’s disease

AU - Ríos, Ana Sofía

AU - Oxenford, Simón

AU - Neudorfer, Clemens

AU - Butenko, Konstantin

AU - Li, Ningfei

AU - Rajamani, Nanditha

AU - Boutet, Alexandre

AU - Elias, Gavin J.B.

AU - Germann, Jurgen

AU - Loh, Aaron

AU - Deeb, Wissam

AU - Wang, Fuyixue

AU - Setsompop, Kawin

AU - Salvato, Bryan

AU - Almeida, Leonardo Brito de

AU - Foote, Kelly D.

AU - Amaral, Robert

AU - Rosenberg, Paul B.

AU - Tang-Wai, David F.

AU - Wolk, David A.

AU - Burke, Anna D.

AU - Salloway, Stephen

AU - Sabbagh, Marwan N.

AU - Chakravarty, M. Mallar

AU - Smith, Gwenn S.

AU - Lyketsos, Constantine G.

AU - Okun, Michael S.

AU - Anderson, William S.

AU - Mari, Zoltan

AU - Ponce, Francisco A.

AU - Lozano, Andres M.

AU - Horn, Andreas

PY - 2022/12

Y1 - 2022/12

N2 - 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 < 0.001). On a local level, the optimal stimulation site resided at the direct interface between these structures (R = 0.48, p < 0.001). Finally, modulating specific distributed brain networks related to memory accounted for optimal outcomes (R = 0.48, p < 0.001). Findings were robust to multiple cross-validation designs and may define an optimal network target that could refine DBS surgery and programming.

AB - 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 < 0.001). On a local level, the optimal stimulation site resided at the direct interface between these structures (R = 0.48, p < 0.001). Finally, modulating specific distributed brain networks related to memory accounted for optimal outcomes (R = 0.48, p < 0.001). Findings were robust to multiple cross-validation designs and may define an optimal network target that could refine DBS surgery and programming.

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

Abstract

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