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Leila Mehdizadeh Fanid *1 
, Mansour Beyrami2 , Mahdi Jafari Asl3 , Behzad Nikzad4 , Siamak Dadashi5 , Zahra Zehtabi5 , Habibollah Rasouli6
, Mansour Beyrami2 , Mahdi Jafari Asl3 , Behzad Nikzad4 , Siamak Dadashi5 , Zahra Zehtabi5 , Habibollah Rasouli6
1- Department of Cognitive Neuroscience, Faculty of Educational Sciences and Psychology, University of Tabriz, Tabriz, Iran.
2- Department of Psychology, Faculty of Educational Sciences and Psychology, University of Tabriz, Tabriz, Iran.
3- Department of Biomedical Engineering, Faculty of Engineering, Shahed University, Tehran, Iran.
4- Department of Cognitive Neuroscience, Faculty of Educational Sciences and Psychology, University of Tabriz, Tabriz, Iran & Department of Psychology, University of Shahid Madani Azerbaijan, Tabriz, Iran.
5- Department of Cognitive Neuroscience, Faculty of Educational Sciences and Psychology, University of Tabriz, Tabriz, Iran
6- Research Centre of Bioscience & Biotechnology (RCBB), University of Tabriz, Tabriz, Iran.
2- Department of Psychology, Faculty of Educational Sciences and Psychology, University of Tabriz, Tabriz, Iran.
3- Department of Biomedical Engineering, Faculty of Engineering, Shahed University, Tehran, Iran.
4- Department of Cognitive Neuroscience, Faculty of Educational Sciences and Psychology, University of Tabriz, Tabriz, Iran & Department of Psychology, University of Shahid Madani Azerbaijan, Tabriz, Iran.
5- Department of Cognitive Neuroscience, Faculty of Educational Sciences and Psychology, University of Tabriz, Tabriz, Iran
6- Research Centre of Bioscience & Biotechnology (RCBB), University of Tabriz, Tabriz, Iran.
Abstract:
Alzheimer’s disease (AD), a progressive neurodegenerative disorder marked by deterioration in cognitive abilities, currently affects an estimated 24 to 50 million individuals worldwide and lacks effective non-invasive therapeutic options. Disruption of gamma-band neural oscillations (~40 Hz), which are known to underlie higher-order cognitive processes such as working memory and executive function, has been repeatedly documented in both human and animal models of AD. Targeted auditory stimulation at gamma frequencies has recently emerged as a potential neuromodulatory strategy for mitigating these deficits. In a controlled experimental framework, thirty individuals clinically diagnosed with early-stage AD, confirmed via MRI and exhibiting Mini-Mental State Examination (MMSE) scores between 10 and 20, were divided into two groups. Thirty participants with early-stage Alzheimer’s disease were enrolled and allocated into intervention (n = 15) and control (n = 15) groups using a quasi-experimental parallel-group pre–post design. The intervention group received 30 sessions of auditory stimulation using binaural beats centered at 40 Hz over the course of three weeks, while the control group listened to an acoustically comparable audio file lacking gamma-frequency modulation. Cognitive performance was assessed using computerized versions of the Corsi Block-Tapping Test, Wisconsin Card Sorting Test (WCST), and Digit Span Test. In addition, resting-state quantitative EEG (QEEG) was conducted to evaluate frontal lobe gamma-band activity under both eyes-open and eyes-closed conditions. Statistical analysis revealed that gamma-band auditory stimulation resulted in a significant enhancement of visuospatial working memory (p = 0.001, Cohen’s d = 1.42) and cognitive flexibility (p = 0.028, d = 0.78), alongside marked increases in both absolute and relative gamma power in the frontal cortex under eyes-closed conditions (p < 0.01). These findings suggest that auditory stimulation at 40 Hz selectively modulates neural circuits associated with executive and spatial cognitive functions and may serve as a viable non-invasive adjunctive intervention in early-stage Alzheimer’s disease.
Keywords: Gamma Band, Alzheimer's disease, Brain Auditory Stimulation, Working memory, Cognitive flexibility
Type of Study: Original |
Subject:
Cognitive Neuroscience
Received: 2025/06/30 | Accepted: 2025/12/23
Received: 2025/06/30 | Accepted: 2025/12/23
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