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Neural Eng."],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Objective.<\/jats:italic>\n                    Impaired hippocampal slow gamma oscillations and CA3-CA1 dysfunction may contribute to spatial memory deficits in early Alzheimer\u2019s disease (AD). This study examined whether phase-locked closed-loop transcranial ultrasound stimulation (TUS) could modulate CA3-CA1 activity and improve memory.\n                    <jats:italic>Approach.<\/jats:italic>\n                    A closed-loop TUS system was developed that uses the phase of endogenous slow gamma (30\u201345 Hz) rhythms in CA3 local field potentials as a trigger. Acute experiments were performed to assess phase-dependent neural responses. Normal rats received 14 d of stimulation to examine circuit connectivity and behavior. APP\/PS1 mice received 14 d of peak-phase stimulation to test behavioral and electrophysiological effects.\n                    <jats:italic>Main results.<\/jats:italic>\n                    Acute experiments showed that both stimulation phase and stimulation number jointly modulated neural responses. Peak-phase and random-phase stimulation increased slow gamma power and cross-frequency coupling, while peak-phase stimulation also decreased sample entropy and increased CA3-CA1 coherence. In normal rats, behavioral performance did not differ among groups after 14 d, but task-related CA3-CA1 slow gamma coherence was higher in the peak-phase group. In APP\/PS1 mice, peak-phase stimulation improved Y-maze spontaneous alternation and novel object location discrimination, alongside increased CA1 power, CA3-CA1 coherence, cross-frequency coupling, and spike-field coherence, all of which were positively correlated with behavioral scores.\n                    <jats:italic>Significance.<\/jats:italic>\n                    These findings indicate that phase-locked closed-loop ultrasound stimulation modulates hippocampal slow gamma activity and CA3-CA1 connectivity in a phase-dependent manner and improves spatial memory in an AD mouse model, supporting oscillation-guided noninvasive neuromodulation as a potential intervention strategy.\n                  <\/jats:p>","DOI":"10.1088\/1741-2552\/aeb075","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:53:02Z","timestamp":1791240782000},"page":"056050","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Phase-locked closed-loop ultrasound stimulation of hippocampal slow gamma modulates CA3-CA1 coherence and improves spatial memory in APP\/PS1 mice"],"prefix":"10.1088","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5340-8028","authenticated-orcid":true,"given":"Zhenyu","family":"Xie","sequence":"first","affiliation":[{"name":"University of South China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Ji","sequence":"additional","affiliation":[{"name":"The Second Hospital of Hebei Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3685-576X","authenticated-orcid":true,"given":"M\u00fcrsel","family":"Karadas","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Chongqing Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyao","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Chongqing Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9310-6677","authenticated-orcid":true,"given":"Yi","family":"Yuan","sequence":"additional","affiliation":[{"name":"Yanshan University"},{"name":"Yanshan University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"jneaeb075bib1","doi-asserted-by":"publisher","first-page":"2594","DOI":"10.1152\/jn.00499.2016","type":"journal-article","article-title":"Slow gamma rhythms in CA3 are entrained by slow gamma activity in the dentate gyrus","volume":"116","author":"Hsiao","year":"2016","journal-title":"J. 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