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外2019青少年和老年人工作记忆中的在线重复经颅磁刺激:一项随机的被试内比较
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RESEARCH ARTICLE Online repetitive transcranial magnetic stimulation during working memory in younger and older adults: A randomized within-subject comparison L. BeynelID1*, S. W. Davis2,3, C. A. Crowell1,3, S. A. Hilbig1, W. Lim1, D. Nguyen1, H. Palmer1, A. Brito1, A. V. PeterchevID1,4,5,6, B. Luber7, S. H. Lisanby7, R. Cabeza3,8, L. G. Appelbaum1 1 Department of Psychiatry and Behavioral Science, Duke University School of Medicine, Durham, North Carolina, United States of America, 2 Department of Neurology, Duke University School of Medicine, Durham, North Carolina, United States of America, 3 Center for Cognitive Neuroscience, Duke University, Durham, North Carolina, United States of America, 4 Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America, 5 Department of Electrical and Computer Engineering, Duke University, Durham, North Carolina, United States of America, 6 Department of Neurosurgery, Duke University School of Medicine, Durham, North Carolina, United States of America, 7 National Institute of Mental Health, Bethesda, Maryland, United States of America, 8 Department of Psychology & Neuroscience, Duke University, Durham, North Carolina, United States of America These authors contributed equally to this work. These authors also contributed equally to this work. * lysianne.beynel@duke.edu Abstract Working memory is the ability to perform mental operations on information that is stored in a flexible, limited capacity buffer. The ability to manipulate information in working memory is central to many aspects of human cognition, but also declines with healthy aging. Given the profound importance of such working memory manipulation abilities, there is a concerted effort towards developing approaches to improve them. The current study tested the capac- ity to enhance working memory manipulation with online repetitive transcranial magnetic stimulation in healthy young and older adults. Online high frequency (5Hz) repetitive tran- scranial magnetic stimulation was applied over the left dorsolateral prefrontal cortex to test the hypothesis that active repetitive transcranial magnetic stimulation would lead to signifi- cant improvements in memory recall accuracy compared to sham stimulation, and that these effects would be most pronounced in working memory manipulation conditions with the highest cognitive demand in both young and older adults. Repetitive transcranial magnetic stimulation was applied while participants were performing a delayed response alphabetization task with three individually-titrated levels of difficulty. The left dorsolateral prefrontal cortex was identified by combining electric field modeling to individualized func- tional magnetic resonance imaging activation maps and was targeted during the experiment using stereotactic neuronavigation with real-time robotic guidance, allowing optimal coil placement during the stimulation. As no accuracy differences were found between young and older adults, the results from both groups were collapsed. Subsequent analyses revealed that active stimulation significantly increased accuracy relative to sham PLOS ONE | https://doi.org/10.1371/journal.pone.0213707 March 22, 2019 1 / 19 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Beynel L, Davis SW, Crowell CA, Hilbig SA, Lim W, Nguyen D, et al. (2019) Online repetitive transcranial magnetic stimulation during working memory in younger and older adults: A randomized within-subject comparison. PLoS ONE 14(3): e0213707. https://doi.org/10.1371/journal. pone.0213707 Editor: Berthold Langguth, University of Regensburg, GERMANY Received: August 10, 2018 Accepted: February 26, 2019 Published: March 22, 2019 Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Data Availability Statement: The data are held in a public repository: Open Science Framework with the following link: https://osf.io/zwk86/. Funding: This research was funded by grant U01 AG050618 from the National Institute of Aging (https://www.nia.nih.gov/) and in part by the Intramural Research Program of the National Institute of Mental Health (https://www.nimh.nih. gov/index.shtml). Authors who received the funding: SWD, SHL, BL, LGA and RC. The funders

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