Preliminary Evidence for Perturbation-Based tACS-EEG Biomarkers of Gamma Activity in Alzheimer's Disease

作     者：Palmisano, Annalisa Pezanko, Luke R. Cappon, Davide Tatti, Elisa Macone, Joanna Koch, Giacomo Smeralda, Carmelo L. Romanella, Sara M. Ruffini, Giulio Rivolta, Davide Press, Daniel Z. Pascual-Leone, Alvaro El-Fakhri, Georges Santarnecchi, Emiliano 

作者机构：Harvard Med Sch Massachusetts Gen Hosp Gordon Ctr Med Imaging Precis Neurosci & Neuromodulat Program Boston MA 02115 USA Harvard Med Sch Berenson Allen Ctr Noninvas Brain Stimulat Beth Israel Deaconess Med Ctr Boston MA 02115 USA Univ Bari Aldo Moro Dept Educ Psychol & Commun Bari Italy TUD Dresden Univ Technol Chair Lifespan Dev Neurosci D-01069 Dresden Germany CUNY Sch Med New York NY USA Santa Lucia Fdn Rome Italy Univ Siena Siena Brain Invest & Neuromodulat Lab Neurol & Clin Neurophysiol Sect Dept Med Surg & Neurosci Siena Italy Neuroelect Barcelona Barcelona Spain Hebrew SeniorLife Hinda & Arthur Marcus Inst Aging Res Boston MA USA Deanna & Sidney Wolk Ctr Memory Hlth Boston MA USA Harvard Med Sch Dept Neurol Boston MA USA Yale Univ Sch Med Dept Radiol & Biomed Imaging Dept Biomed Informat & Data Sci New Haven CT USA 

出 版 物：《INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY》 (Int. J. Geriatr. Psychiatry)

年 卷 期：2025年第40卷第1期

页      面：e70025页

核心收录：

学科分类：1002[医学-临床医学] 10[医学] 

基　　金：European Research Council Alzheimer's Drug Discovery Foundation (ADDF) [GA 201902-2017902] Association for Frontotemporal Dementia (AFTD) European Research Council (ERC Synergy Galvani) under the European Union European Union [R01AG076708, R01AG059089, R03AG072233] National Institutes of Health BrightFocus Foundation 

主　　题：Alzheimer's disease biomarkers gamma activity transcranial alternating current stimulation 

摘      要：BackgroundAlzheimer s disease (AD) is characterized by impaired inhibitory circuitry and GABAergic dysfunction, which is associated with reduced fast brain oscillations in the gamma band (gamma, 30-90 Hz) in several animal models. Investigating such activity in human patients could lead to the identification of novel biomarkers of diagnostic and prognostic value. The current study aimed to test a multimodal Perturbation-based transcranial Alternating Current Stimulation-Electroencephalography (tACS)-EEG protocol to detect how responses to tACS in AD patients correlate with patients clinical phenotype. MethodsFourteen participants with mild to moderate dementia due to AD underwent a baseline assessment including cognitive status, peripheral neuroinflammation, and resting-state (rs)EEG. The tACS-EEG recordings included brief (6 ) tACS blocks of gamma (i.e., 40 Hz) stimulation administered through 4 different montages, with Pre/Post 32-Channels EEG for each block. Changes in tACS-EEG and rsEEG gamma band power with respect to baseline were adopted as a metric of induction and compared with cognitive scores and neuroinflammatory biomarkers. ResultsWe found positive correlations between 40 Hz-induced gamma activity in fronto-central-parietal areas and patient cognitive status and negative ones with neuroinflammatory markers. Participants with greater cognitive impairment exhibited less gamma induction and higher peripheral neuroinflammation. The same analysis performed with spectral power from baseline rsEEG resulted in no significant correlations, promoting the value of tACS-based perturbation for capturing individual differences in pathology-related brain features. ConclusionsOur work suggests a link between tACS-induced gamma band spectral power and clinical severity, with weaker gamma induction corresponding to more severe clinical/cognitive impairment. This study provides preliminary support for the development of novel physiological biomarkers and therapeutic t