Investigating Gamma Frequency Band PSD in Alzheimer's Disease Using qEEG from Eyes-Open and Eyes-Closed Resting States

Background/Objectives: Gamma oscillations (30-100 Hz), which are essential for memory, attention, and cortical synchronization, remain underexplored in Alzheimer's disease (AD) research. While resting-state EEG studies have predominantly examined lower frequency bands (delta to beta), gamma activity may more accurately reflect early synaptic dysfunction and other mechanisms relevant to AD pathophysiology. AD is a common age-related neurodegenerative disorder frequently associated with altered resting-state EEG (rEEG) patterns. This study analyzed gamma power spectral density (PSD) during eyes-open (EOR) and eyes-closed (ECR) resting-state EEG in AD patients compared to cognitively normal (CN) individuals. Methods: rEEG data from 534 participants (269 CN, 265 AD) aged 40-90 were analyzed. Quantitative EEG (qEEG) analysis focused on the gamma band (30-100 Hz) using PSD estimation with the Welch method, coherence matrices, and coherence-based functional connectivity. Data preprocessing and analysis were performed using EEGLAB and Brainstorm in MATLAB R2024b. Group comparisons were conducted using ANOVA for unadjusted models and linear regression with age adjustment using log₁₀-transformed PSD values in Python (version 3.13.2, 2025). Results: AD patients exhibited significantly elevated gamma PSD in frontal and temporal regions during EOR and ECR states compared to CN. During ECR, gamma PSD was markedly higher in the AD group (Mean = 0.0860 ± 0.0590) than CN (Mean = 0.0042 ± 0.0010), with a large effect size (Cohen's d = 1.960, p < 0.001). Conversely, after adjusting for age, the group difference was no longer statistically significant (β = -0.0047, SE = 0.0054, p = 0.391), while age remained a significant predictor of gamma power (β = -0.0008, p = 0.019). Pairwise coherence matrix and coherence-based functional connectivity were increased in AD during ECR but decreased in EOR relative to CN. Conclusions: Gamma oscillatory activity in the 30-100 Hz range differed significantly between AD and CN individuals during resting-state EEG, particularly under ECR conditions. However, age-adjusted analyses revealed that these differences are not AD-specific, suggesting that gamma band changes may reflect aging-related processes more than disease effects. These findings contribute to the evolving understanding of gamma dynamics in dementia and support further investigation of gamma PSD as a potential, age-sensitive biomarker.