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CLAS of slow oscillation up\u2010states in sleep is becoming a popular tool to study and enhance sleep's functions, as it increases slow oscillations, evokes sleep spindles and enhances memory consolidation of certain tasks. However, few studies have examined the specific neurophysiological mechanisms involved in CLAS, in part because of practical limitations to available tools. To evaluate evidence for possible models of how sound stimulation during brain up\u2010states alters brain activity, we simultaneously recorded electro\u2010 and magnetoencephalography in human participants who received auditory stimulation across sleep stages. We conducted a series of analyses that test different models of pathways through which CLAS of slow oscillations may affect widespread neural activity that have been suggested in literature, using spatial information, timing and phase relationships in the source\u2010localized magnetoencephalography data. The results suggest that auditory information reaches ventral frontal lobe areas via non\u2010lemniscal pathways. From there, a slow oscillation is created and propagated. We demonstrate that while the state of excitability of tissue in auditory cortex and frontal ventral regions shows some synchrony with the electroencephalography (EEG)\u2010recorded up\u2010states that are commonly used for CLAS, it is the state of ventral frontal regions that is most critical for slow oscillation generation. Our findings advance models of how CLAS leads to enhancement of slow oscillations, sleep spindles and associated cognitive benefits and offer insight into how the effectiveness of brain stimulation techniques can be improved.<\/jats:p>","DOI":"10.1111\/ejn.16132","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T06:21:34Z","timestamp":1694067694000},"page":"613-640","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["The neurophysiology of closed\u2010loop auditory stimulation in sleep: A magnetoencephalography study"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5004-101X","authenticated-orcid":false,"given":"Hugo R.","family":"Jourde","sequence":"first","affiliation":[{"name":"Concordia University  Montreal Quebec Canada"},{"name":"International Laboratory for Brain, Music and Sound Research (BRAMS)  Montreal Quebec Canada"},{"name":"Centre for Research on Brain, Language and Music (CRBLM)  Montreal Quebec Canada"},{"name":"Quebec Bio\u2010Imaging Network (QBIN)  Sherbrooke Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rapha\u00eblle","family":"Merlo","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Brooks","sequence":"additional","affiliation":[{"name":"Concordia University  Montreal Quebec Canada"},{"name":"International Laboratory for Brain, Music and Sound Research (BRAMS)  Montreal Quebec Canada"},{"name":"Centre for Research on Brain, Language and Music (CRBLM)  Montreal Quebec Canada"},{"name":"Quebec Bio\u2010Imaging Network (QBIN)  Sherbrooke Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith","family":"Rowe","sequence":"additional","affiliation":[{"name":"McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8249-7396","authenticated-orcid":false,"given":"Emily B. 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