EEG Gamma-Band Entrainment as a Biomarker of Cognitive Function in Alzheimer's Disease

Abstract

Auditory stimulation at 40Hz has shown potential to enhance neural synchrony and support cognitive functions in neurodegenerative disorders. This study analyzed EEG recordings from Alzheimer's disease (AD) patients exposed to 40Hz auditory entrainment to evaluate the relationship between gamma-band (∼40Hz) power and Mini-Mental State Examination (MMSE) scores. Using open-access EEG datasets from five AD patients, stimulus-locked EEG epochs were extracted and spectral power was computed in the 35-45Hz band. A positive correlation between 40Hz EEG power and MMSE scores was observed, suggesting that gamma-band activity may serve as a functional biomarker of cognitive resilience in AD. These findings support ongoing research indicating that gamma entrainment could provide a non-invasive biomarker and potentially a therapeutic tool for monitoring and enhancing cognitive function in dementia.

Introduction

Alzheimer’s disease (AD) is the most prevalent form of dementia, characterized by progressive memory loss, cognitive dysfunction, and the accumulation of amyloid-beta plaques in the brain. These pathological changes impact an individual’s daily functioning and social interactions. Previous research has indicated that AD is also associated with disruptions in neural oscillations, particularly in the gamma frequency range (approximately 30-80Hz), which are essential for cognitive processes such as working memory, attention, and perceptual binding.

Auditory stimulation at 40Hz has emerged as a promising method for inducing gamma-band neural activity, a phenomenon referred to as gamma entrainment. This approach has shown potential for enhancing cognitive functions by synchronizing neuronal activity. The present study investigates whether the strength of gamma-band EEG activity induced by 40Hz auditory stimulation correlates with cognitive performance, as measured by MMSE scores, in individuals with AD.

Plain Language Summary

In this study, brainwave data (EEG) from people with Alzheimer's disease was recorded while they listened to rapid, rhythmic 40Hz sound pulses. These sounds are known to stimulate brain activity in the gamma range—a type of brainwave important for memory and attention. The EEG data was analyzed to see how strong the brain’s response was in this gamma range, especially around 40Hz. The strength of that response was compared with each person’s MMSE score, which measures memory and thinking skills.

The results showed that people with higher MMSE scores tended to have stronger gamma activity in their brainwaves. This suggests that the brain’s ability to respond to 40Hz sounds may reflect how well a person’s brain is functioning. These findings add to research showing that 40Hz stimulation might help scientists track brain health and possibly improve it using sound-based therapy.

Methods

Participants

Data were obtained from five individuals diagnosed with Alzheimer’s disease. These datasets were sourced from an open-access repository and included relevant demographic information such as age, gender, and MMSE score. The MMSE scores ranged from low to moderate, reflecting varying levels of cognitive impairment.

EEG Setup and Procedure

Participants were exposed to alternating blocks of 40Hz auditory tones (Stimulus) and silent periods (Rest) during EEG recordings. Each session lasted approximately six minutes. EEG data were collected using a 64-channel system based on the international 10-20 electrode placement system.

The EEG recordings were processed using Python, including filtering, resampling, and artifact rejection. Recordings were segmented into 2-second epochs corresponding to the Stimulus condition.

Power Analysis

Power Spectral Density (PSD) analysis, a method used to measure how the power of a signal is distributed across different frequencies, was used. In this study, it helps determine how strong the brain's electrical activity is around 40Hz, which indicates how well the brain is responding to the auditory stimulation. was performed to quantify the strength of 40Hz brain activity during the Stimulus epochs. The analysis focused on the 35-45Hz frequency range, with a specific emphasis on power centered at 40Hz.

Statistical Comparison

After calculating average 40Hz power for each participant, a Pearson correlation (a statistical method used to measure the strength and direction of the linear relationship between two variables) was conducted to evaluate the relationship between EEG gamma-band power and MMSE scores.

Results

The analysis revealed that participants with higher MMSE scores generally exhibited greater 40Hz EEG power during the Stimulus condition. Although individual variations were observed, the overall trend demonstrated a positive correlation.

Additionally, higher gamma-band activity was primarily observed in central and frontal EEG regions, which aligns with previous studies investigating gamma entrainment effects.

***Clusters of similar patient outputs were grouped into 6 regions, outliers excluded

Discussion

These results suggest that 40Hz auditory stimulation elicits gamma-band activity in individuals with Alzheimer’s disease and that the strength of this response may reflect underlying cognitive function. In the context of AD, where synaptic disconnection and network disorganization impair memory and attention, this gamma synchronization may signal preserved or responsive neural circuits. The observed correlation between 40Hz EEG power and MMSE scores provides evidence that gamma entrainment could serve as a non-invasive functional marker of disease severity.

The findings are consistent with existing literature indicating that gamma entrainment can influence neural synchronization and possibly attenuate neuropathological markers in AD. Studies in animal models have shown that 40Hz stimulation reduces amyloid and tau pathology, two hallmarks of Alzheimer’s, and improves cognitive outcomes. In humans, recent trials report enhancements in memory and attention following repeated gamma stimulation sessions.

This study builds on those findings by offering preliminary evidence that even short-term exposure to 40Hz auditory entrainment reflects cognitive health in AD patients. Stronger EEG gamma responses were found in those with higher MMSE scores, supporting the idea that gamma entrainment may uncover functional brain capacities even in the presence of neurodegeneration.

Nonetheless, the study has limitations, including a small sample size and the lack of age-matched healthy controls. Only short-term EEG responses were analyzed, and longitudinal effects remain unexplored. Future research should focus on sustained intervention studies with larger cohorts to validate gamma power as a biomarker and assess its utility in clinical tracking and therapeutic outcomes in Alzheimer’s disease.

Conclusion

The observed correlation between EEG gamma-band power and MMSE scores supports the role of 40Hz auditory entrainment as a promising non-invasive method for assessing and potentially modulating cognitive function in Alzheimer’s disease. These findings align with the growing body of evidence suggesting that gamma entrainment could be both a diagnostic biomarker and an interventional strategy to improve brain function. As Alzheimer’s continues to affect millions globally, identifying accessible and non-invasive ways to evaluate and support cognitive health is an urgent priority, and EEG-based gamma entrainment may represent a viable step forward.

References

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