{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:09:38Z","timestamp":1791583778222,"version":"4.3.4"},"reference-count":95,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"866","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-AG070135"],"award-info":[{"award-number":["R01-AG070135"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19-NS128613"],"award-info":[{"award-number":["U19-NS128613"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000872","name":"McKnight Endowment Fund for Neuroscience","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000872","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000875","name":"Pew Charitable Trusts","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000875","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000879","name":"Alfred P. Sloan Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000879","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000893","name":"Simons Foundation","doi-asserted-by":"publisher","award":["811231"],"award-info":[{"award-number":["811231"]}],"id":[{"id":"10.13039\/100000893","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Corundum Convergence Institute"},{"name":"PanasonicWELL"},{"name":"MIT EECS Transformative Research Fund"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,9,9]]},"abstract":"<jats:p>Cerebrospinal fluid (CSF) is a key component of healthy brain function, constantly circulating to maintain brain homeostasis. Large waves of CSF flow appear in nonrapid eye movement (NREM) sleep, and these CSF flow waves are associated with neural slow waves in the electroencephalogram (EEG). Whether neural slow waves are causally linked to CSF flow, and whether this flow can be enhanced, is not yet established. We developed a technique for performing closed-loop auditory stimulation of sleep slow waves with simultaneous magnetic resonance imaging (MRI) using real-time denoising and a neural network\u2013based strategy for stimulus targeting. We first established that our technique could increase EEG slow waves during sleep inside the MRI scanner in healthy adults. We then found that closed-loop auditory stimulation during sleep caused increased CSF flow waves. Furthermore, this CSF flow effect was phase dependent and only apparent when auditory stimuli were aligned with slow-wave peaks. Widespread hemodynamic waves were also elicited by the stimulus, suggesting a brain-wide modulation contributing to this CSF flow effect. This work demonstrates that closed-loop slow-wave neurofeedback causes waves of CSF flow and provides a technique for simultaneous modulation and imaging of CSF flow during sleep that can next be explored as a potential translational tool in clinical populations.<\/jats:p>","DOI":"10.1126\/scitranslmed.aea5469","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:58:12Z","timestamp":1788976692000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Closed-loop auditory stimulation in phase with slow waves during sleep enhances cerebrospinal fluid flow in humans"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2510-1989","authenticated-orcid":true,"given":"Joshua","family":"Levitt","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Boston University, Boston, MA, USA."},{"name":"Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4859-9055","authenticated-orcid":true,"given":"Xiangjian","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zinong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA."},{"name":"Graduate Program in Neuroscience, Boston University, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4783-1368","authenticated-orcid":true,"given":"Leandro P. L.","family":"Jacob","sequence":"additional","affiliation":[{"name":"Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4003-0277","authenticated-orcid":true,"given":"Laura D.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA."},{"name":"Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA."},{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA."},{"name":"Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-8454-5-10"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1592-13.2013"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1241224"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.10.014"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2024.09.017"},{"key":"e_1_3_2_7_2","first-page":"1743","article-title":"Decoupling between brain activity and cerebrospinal fluid movement in neurological disorders","volume":"60","author":"Liu X.","year":"2024","unstructured":"X. Liu, Decoupling between brain activity and cerebrospinal fluid movement in neurological disorders. J. Magn. Reson. Imaging 60, 1743\u20131752 (2024).","journal-title":"J. Magn. Reson. Imaging"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax5440"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","unstructured":"S. M. Bailes S. D. Williams B. Ashenagar J. Licata M. Y. Bosli B. J. Dormes H. J. Yun D. Zimmerman A. H. Moyers D. H. Salat L. D. Lewis The aging human brain exhibits reduced cerebrospinal fluid flow during sleep due to both neural and vascular factors. bioRxiv 639649 [Preprint] (2025); https:\/\/doi.org\/10.1101\/2025.02.22.639649.","DOI":"10.1101\/2025.02.22.639649"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001233"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14296"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12930"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002035"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07132-6"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-024-00701-z"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aav5447"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07108-6"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.13735"},{"key":"e_1_3_2_19_2","first-page":"63","article-title":"Can slow-wave sleep enhancement improve memory? A review of current approaches and cognitive outcomes","volume":"92","author":"Zhang Y.","year":"2019","unstructured":"Y. Zhang, R. Gruber, Can slow-wave sleep enhancement improve memory? A review of current approaches and cognitive outcomes. Yale J. Biol. Med. 92, 63\u201380 (2019).","journal-title":"Yale J. Biol. Med."},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsaa296"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci10050300"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.13385"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.03.006"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3133-14.2015"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2015.10.016"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsx003"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0306-19.2019"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.13818"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2024.11.009"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2017.00109"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.14179"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.14316"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.622719"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.1998.0361"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2000.0599"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2023.1123014"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2013.08.039"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.10.064"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2023.120353"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2023.120092"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-024-00607-8"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2022.119362"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1088\/1741-2552\/ab8683"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-025-02098-8"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2015.11.007"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.3390\/s21155169"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1109\/TBME.2022.3157468"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910360219"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.09.088"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1162\/IMAG.a.9"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsz315"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsab204"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abi8375"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2022.118888"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.25961"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0901435106"},{"key":"e_1_3_2_57_2","first-page":"zsz218","article-title":"Functional MRI of arousals in nonrapid eye movement sleep","volume":"43","author":"Zou G.","year":"2020","unstructured":"G. Zou, J. Xu, S. Zhou, J. Liu, Z. H. Su, Q. Zou, J.-H. Gao, Functional MRI of arousals in nonrapid eye movement sleep. Sleep 43, zsz218 (2020).","journal-title":"Sleep"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33010-8"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsab125"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2019.04.002"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2010.07543.x"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afad228"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02170-3"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.12.1746"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1169626"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.14152"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2019.08.070"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.02.025"},{"key":"e_1_3_2_69_2","first-page":"75","article-title":"Sleep spindles and auditory sensory gating: Two measures of cerebral inhibition in preschool-aged children are strongly correlated","volume":"2","author":"Wei P.-P.","year":"2017","unstructured":"P.-P. Wei, S. K. Hunter, R. G. Ross, Sleep spindles and auditory sensory gating: Two measures of cerebral inhibition in preschool-aged children are strongly correlated. Colo. J. Psychiatry Psychol. 2, 75\u201383 (2017).","journal-title":"Colo. J. Psychiatry Psychol."},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19076-2"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00042.2018"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1159\/000108735"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01101.2003"},{"key":"e_1_3_2_74_2","doi-asserted-by":"crossref","unstructured":"S. Leach S. Fattinger E. Krugliakova J. Skorucak G. Sousouri S. Snipes S. Sch\u00fchle M. L. Ferster G. D. Poian W. Karlen R. Huber Local modulation of sleep slow waves depends on timing between auditory stimuli. bioRxiv 641406 [Preprint] (2025); https:\/\/doi.org\/10.1101\/2025.03.05.641406.","DOI":"10.1101\/2025.03.05.641406"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.03.008"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.12.012"},{"key":"e_1_3_2_77_2","first-page":"zsz197","article-title":"Acoustic slow wave sleep enhancement via a novel, automated device improves executive function in middle-aged men","volume":"43","author":"Diep C.","year":"2020","unstructured":"C. Diep, S. Ftouni, J. E. Manousakis, C. L. Nicholas, S. P. A. Drummond, C. Anderson, Acoustic slow wave sleep enhancement via a novel, automated device improves executive function in middle-aged men. Sleep 43, zsz197 (2020).","journal-title":"Sleep"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2018.09.006"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.11.027"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.243521"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.5082"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-025-02073-3"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46329-1"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.13676"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.10778"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1163\/156856897X00366"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1163\/156856897X00357"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2007.03.024"},{"key":"e_1_3_2_89_2","first-page":"1","article-title":"Application of the hierarchical bootstrap to multi-level data in neuroscience","volume":"3","author":"Saravanan V.","year":"2020","unstructured":"V. Saravanan, G. J. Berman, S. J. Sober, Application of the hierarchical bootstrap to multi-level data in neuroscience. Neuron. Behav. Data Anal. Theory 3, 1\u201325 (2020).","journal-title":"Neuron. Behav. Data Anal. Theory"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.12.025"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.22361"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.23097"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.01.021"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2008.10.055"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.06.060"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.116231"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.aea5469","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:58:36Z","timestamp":1788976716000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.aea5469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":95,"journal-issue":{"issue":"866","published-print":{"date-parts":[[2026,9,9]]}},"alternative-id":["10.1126\/scitranslmed.aea5469"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.aea5469","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]},"assertion":[{"value":"2025-07-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaea5469"}}