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Published July 15, 2021 | Submitted + Published
Journal Article Open

Combining brain perturbation and neuroimaging in non-human primates


Brain perturbation studies allow detailed causal inferences of behavioral and neural processes. Because the combination of brain perturbation methods and neural measurement techniques is inherently challenging, research in humans has predominantly focused on non-invasive, indirect brain perturbations, or neurological lesion studies. Non-human primates have been indispensable as a neurobiological system that is highly similar to humans while simultaneously being more experimentally tractable, allowing visualization of the functional and structural impact of systematic brain perturbation. This review considers the state of the art in non-human primate brain perturbation with a focus on approaches that can be combined with neuroimaging. We consider both non-reversible (lesions) and reversible or temporary perturbations such as electrical, pharmacological, optical, optogenetic, chemogenetic, pathway-selective, and ultrasound based interference methods. Method-specific considerations from the research and development community are offered to facilitate research in this field and support further innovations. We conclude by identifying novel avenues for further research and innovation and by highlighting the clinical translational potential of the methods.

Additional Information

© 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Received 11 September 2020, Revised 7 March 2021, Accepted 22 March 2021, Available online 29 March 2021. This work was supported by NIH-MH112142 (V.F. and E.K.); California National Primate Research Center Base Grant (P51-OD011107) (A.F.); Fondation Bettencourt Schueller, France and Human Brain Project (B.J., L.U., J.T.); the Intramural Research Program of the NIMH (ZIA MH002918) (A.M.); Wellcome Trust (WT 110157/Z/15/Z) (A.S.M.); European Research Council (ERC StG, OptoVision, 637638) (M.C.S and M.O.R.); National Key R&D Program of China 2018YFA0701400 (A.W.R.); Chinese NSF (81430010 and 31627802) (A.W.R.); Zhejiang province 2020C03004 (A.W.R.); Chinese National R&D Program Grant 2015AA020515 (A.W.R.); IDEXLYON "IMPULSION 2020 grant (IDEX/IMP/2020/14) (J.S.); Howard Hughes Medical Institute (D.T.); KU Leuven grant C14/17/109 (W.V.); the National Eye Institute Intramural Research Program (ZIA EY000511) at the National Institutes of Health, U.S.A. (W.V.); Fonds Wetenschappelijk Onderzoek-Vlaanderen (FWO) G0D5817N, G0B8617N, G0C1920N, G0E0520N, VS02219N (W.V.); the European Union's Horizon 2020 Framework Programme for Research and Innovation under Grant Agreement No 945539 (Human Brain Project SGA3) (W.V.); Hermann and Lilly Schilling Foundation; German Research Foundation (DFG) grants WI 4046/1-1 and Research Unit GA1475-B4, KA 3726/2-1, Primate Platform of DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB) (M.W. and I.K.); Wellcome Trust (WT092606AIA) (C.I.P.); European Research Council Horizon 2020 (ERC CoG, MECHIDENT 724198) (C.I.P.); the Bettencourt Schueller Foundation (Ultrabrain project) (J.-F. A.); the French National Agency for Research (ANR-10-EQPX-15) (J.-F. A.):and the National Institutes of Health (with Matthew Howard III: R01-DC04290) (C.I.P.); All research discussed in this work was performed in accordance with institutional and nationally approved oversight, such as the NIH Guide for Care and Use of Laboratory Animals, the U.K. Animals (Scientific Procedures) Act, 1986, and European Directive 2010/63/EU. This paper does not contain original data or analysis. The authors declare no competing financial interests.

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Published - 1-s2.0-S1053811921002949-main.pdf

Submitted - Klink_etal_NeuroImage_R1_OSF.pdf


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August 22, 2023
December 22, 2023