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We hypothesized that the clinical efficacy of gamma entrainment depends on individual neurophysiological receptivity, specifically the capacity for neural circuit plasticity. In this open-label pilot study, we screened 37 individuals and enrolled 16 participants with early AD (CDR 0.5\u20131.0, amyloid-positive) who completed 12\u00a0weeks of home-based flickering light stimulation at individually optimized gamma frequencies (32\u201340\u00a0Hz). Pre- and post-intervention assessments included 64-channel EEG recordings and MMSE. Participants demonstrated dichotomous neurophysiological responses: 43.8% showed center frequency (CF) increase (increased CF [ICF+]) while 56.3% showed no change\/decrease (non-increased CF [ICF\u2212]). CF restoration was significantly associated with cognitive preservation (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.52,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.039). Notably, future responders exhibited distinct baseline signatures of \u201cneural reserve,\u201d characterized by higher temporal gamma power (Cohen\u2019s\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u20090.70\u20130.92) and stronger frontotemporal connectivity (Cohen\u2019s\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u20091.11\u20131.47). Almost 30% of screened candidates failed to show baseline entrainment, highlighting a distinct \u201cnon-responsive\u201d biological subtype. CF restoration following personalized gamma entrainment identifies a neurophysiological subtype capable of meaningful plasticity. Rather than a universal remedy, gamma entrainment appears to act on specific neural substrates preserved in a subset of patients. These findings suggest that baseline electrophysiological profiling could unlock gamma entrainment\u2019s therapeutic potential by stratifying likely responders for precision neuromodulation.\n                  <\/jats:p>","DOI":"10.1007\/s11357-026-02235-6","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T01:37:58Z","timestamp":1775785078000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Restoration of gamma center frequency via personalized entrainment marks cognitive preservation in early Alzheimer\u2019s disease"],"prefix":"10.1007","author":[{"given":"Yeseung","family":"Park","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyeonwook","family":"Chae","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Euisuk","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yejung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Won","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Se Joon","family":"Woo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seunghyup","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1103-3858","authenticated-orcid":false,"given":"Ki Woong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"2235_CR1","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/nature20587","volume":"540","author":"HF Iaccarino","year":"2016","unstructured":"Iaccarino HF, Singer AC, Martorell AJ, et al. 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All participants or their legal representatives provided written informed consent before participating in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}