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An obvious problem presented in these studies is lack of sensitive measures to detect and quantify network hyperexcitability in human subjects. In this study we examined whether altered neuronal synchrony can be a surrogate marker to quantify network hyperexcitability in patients with Alzheimer\u2019s disease. Using magnetoencephalography (MEG) at rest, we studied 30 Alzheimer\u2019s disease patients without subclinical epileptiform activity, 20 Alzheimer\u2019s disease patients with subclinical epileptiform activity and 35 age-matched controls. Presence of subclinical epileptiform activity was assessed in patients with Alzheimer\u2019s disease by long-term video-EEG and a 1-h resting MEG with simultaneous EEG. Using the resting-state source-space reconstructed MEG signal, in patients and controls we computed the global imaginary coherence in alpha (8\u201312\u2005Hz) and delta\u2013theta (2\u20138\u2005Hz) oscillatory frequencies. We found that Alzheimer\u2019s disease patients with subclinical epileptiform activity have greater reductions in alpha imaginary coherence and greater enhancements in delta\u2013theta imaginary coherence than Alzheimer\u2019s disease patients without subclinical epileptiform activity, and that these changes can distinguish between Alzheimer\u2019s disease patients with subclinical epileptiform activity and Alzheimer\u2019s disease patients without subclinical epileptiform activity with high accuracy. Finally, a principal component regression analysis showed that the variance of frequency-specific neuronal synchrony predicts longitudinal changes in Mini-Mental State Examination in patients and controls. Our results demonstrate that quantitative neurophysiological measures are sensitive biomarkers of network hyperexcitability and can be used to improve diagnosis and to select appropriate patients for the right therapy in the next-generation clinical trials. The current results provide an integrative framework for investigating network hyperexcitability and network dysfunction together with cognitive and clinical correlates in patients with Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.1093\/brain\/awab442","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T20:16:42Z","timestamp":1639426602000},"page":"744-753","source":"Crossref","is-referenced-by-count":75,"title":["Neuronal synchrony abnormalities associated with subclinical epileptiform activity in early-onset Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4217-8785","authenticated-orcid":false,"given":"Kamalini G","family":"Ranasinghe","sequence":"first","affiliation":[{"name":"University of California San Francisco Memory and Aging Center, Department of Neurology, , San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiwamu","family":"Kudo","sequence":"additional","affiliation":[{"name":"University of California San Francisco Department of Radiology and Biomedical Imaging, , San Francisco, CA , USA"},{"name":"Ricoh Company, Ltd Medical Imaging Business Center, , Kanazawa 920-0177 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leighton","family":"Hinkley","sequence":"additional","affiliation":[{"name":"University of California San Francisco Department of Radiology and Biomedical Imaging, , San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Beagle","sequence":"additional","affiliation":[{"name":"University of California San Francisco Memory and Aging Center, Department of Neurology, , San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Lerner","sequence":"additional","affiliation":[{"name":"University of California San Francisco Memory and Aging Center, Department of Neurology, , San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Mizuiri","sequence":"additional","affiliation":[{"name":"University of California San Francisco Department of Radiology and Biomedical Imaging, , San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Findlay","sequence":"additional","affiliation":[{"name":"University of California San Francisco Department of Radiology and Biomedical Imaging, , San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce L","family":"Miller","sequence":"additional","affiliation":[{"name":"University of California San Francisco Memory and Aging Center, Department of Neurology, , San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel H","family":"Kramer","sequence":"additional","affiliation":[{"name":"University of California San Francisco Memory and Aging Center, Department of Neurology, , San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luisa","family":"Gorno-Tempini","sequence":"additional","affiliation":[{"name":"University of California San Francisco Memory and Aging Center, Department of Neurology, , San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil D","family":"Rabinovici","sequence":"additional","affiliation":[{"name":"University of California San Francisco Memory and Aging Center, Department of Neurology, , San Francisco, CA , USA"},{"name":"University of California San Francisco Epilepsy Center, Department of Neurology, , San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine P","family":"Rankin","sequence":"additional","affiliation":[{"name":"University of California San Francisco Memory and Aging Center, Department of Neurology, , San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A","family":"Garcia","sequence":"additional","affiliation":[{"name":"University of California San Francisco Epilepsy Center, Department of Neurology, , San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi E","family":"Kirsch","sequence":"additional","affiliation":[{"name":"University of California San Francisco Department of Radiology and Biomedical Imaging, , San Francisco, CA , USA"},{"name":"University of California San Francisco Epilepsy Center, Department of Neurology, , San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Vossel","sequence":"additional","affiliation":[{"name":"University of California San Francisco Memory and Aging Center, Department of Neurology, , San Francisco, CA , USA"},{"name":"University of California Los Angeles Mary S. 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