Mitagating Alzimer’s Disease Through

Binacural Beats

Written by: Ana Beatriz Costa Augusto Contrucci

Alzheimer’s disease (AD) is a severe neurodegenerative disorder that leads to difficulty in performing tasks, memory loss, and a decline in attention span. Studies agree that the common indicator of AD is the aggregation of amyloid-beta (Aβ) peptides in the brain (Murphy & LeVine, 2010). AB accumulation triggers constant activation of microglia, the immune cells of the central nervous system, which initiates neurotoxic events and leads to the neurodegenerative state (Iaccarino et al., 2016; Zhang et al., 2020). Reduced gamma (20-50 Hz) neural oscillations strongly correlate to AB peptide buildup, so the encouragement of gamma brain activity to mitigate AB is a target for AD therapy research (Iaccarino et al., 2016).

Current studies indicate that gamma entrainment (the inducement of neural oscillations) via 40 Hz light stimulation reduces AB buildup in the visual cortex of mouse AD models, leading to learning and memory improvements (Figure 1) (Adaikkan et al., 2019). However, current methods of visual stimulation tested on human patients have poor efficacy, indicating that humans would require a prolonged or different treatment to significantly alter AB load (Ismail et al., 2018). Although visual stimulation has limited benefits, auditory stimulation may prove to be a better form of treatment. Gamma frequency auditory stimulation reduces AB plaques in the auditory cortex of AD mice, but long-term research on auditory stimulation and its ability to induce a corresponding neuro-regenerative response is minimal (Martorell et al., 2019).

Inducing gamma neural oscillations through light stimulation in mouse models of AD (CK-p25 mice) can prevent neuronal loss. Source: https://www.pnas.org/doi/10.1073/ pnas.2013084117

This study proposes that the long-term use of a novel auditory stimulant known as binaural beats may reduce AB accumulation in mouse models of AD. When two different auditory tones are presented in each ear, the brain perceives a single tone at the difference of the two stimulant frequencies defined as the binaural beat (Figure 2). Studies implementing binaural beats have shown unique progress in promoting gamma entrainment and enhancing cognitive functions like working memory and attention in human studies (Rakhshan et al., 2022). Therefore, this proposal seeks to determine if long-term 40 Hz binaural beat or light stimulation treatment is more effective in reducing AB plaques in the brain of AD patients by entraining gamma frequency neural oscillations.

The difference in the frequencies represents the frequency of the binaural beat and the frequency of entrainment. Source: https://www.ennora.com/about-binaural-beats/

2 - Brainwave Entrainment through Binaural Beat Stimulation

Experiments to explore this proposal should stimulate mice models of AD with 40 Hz binaural beats to promote gamma oscillations in the auditory cortex, hippocampus, and medial prefrontal cortex, as these regions are most affected by AD and stimulant sites (Martorell et al., 2019). To determine whether gamma entrainment is in effect after repeated exposure to the stimulant, the mice should be implanted with a multi-electrode probe at the target sites to record long-term local field potentials. Further, AB levels before and after treatment can be evaluated using immunohistochemical techniques. The extent of AB accumulation and gamma entrainment of AD mice with this treatment would be compared to mice treated with 40 Hz light stimulation and a control group.

Design by Kirthi Chandra

It is hypothesized that long-term 40 Hz gamma binaural beat sensory stimulation will entrain gamma neural oscillations and therefore reduce AB levels throughout these target regions significantly more compared to light stimulation. It will be necessary to observe the differences in the extent of entrainment in the hippocampus and prefrontal cortex; given the heightened entrainment properties of binaural beats, auditory stimulation will likely be more effective than the visual stimulation in both regions. Theoretically, greater entrainment due to binaural beats would reduce AB plaques in all sites.

Completion of this study will provide information on the effectiveness of gamma binaural beats as a valid therapeutic method to mitigate the driving factor of AD. Binaural beat stimulation is much more comfortable, affordable, and safer than many existing treatment options (McLaughlin et al., 2010). Overall, binaural beat therapy could replace or work complementary to current AD sensory stimulation therapies, leading to more successful treatments for patients.

References

Adaikkan, C., Middleton, S., Marco, A., Pao, P., Mathys, H., Kim, D., Gao, F., Young, J., Suk, H., Boyden, E., McHugh, T., & Tsai, L. (2019). Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection. Neuron, 102(5), 929-943. doi: 10.1016/j.neuron.2019.04.011

Iaccarino, H., Singer, A., Martorell, A. Rudenko, A., Gao, F., Gillingham, T., Mathys, H., Seo, J., Kritskiy, O., Abdurrob, F., Adaikkan, C., Canter, R., Rueda, R., Brown, E., Boyden, E., & Tsai, L. (2016) Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature 540, 230–235. doi: 10.1038/nature20587

Ismail, R., Hansen, A. K., Parbo, P., Brændgaard, H., Gottrup, H., Brooks, D. J., & Borghammer, P. (2018, July 30). The effect of 40-Hz light therapy on amyloid load in patients with prodromal and clinical Alzheimer’s disease. International Journal of Alzheimer’s Disease. doi: 10.1155/2018/6852303

Martorell, A. J., Paulson, A. L., Suk, H. J., Abdurrob, F., Drummond, G., Guan, W., Young, J., Kim, D., Kritskiy, O., Barker, S., Mangena, V., Prince, S., Brown, E., Chung, K., Boyden, E., Singer, A., & Tsai, L. (2019, March 14). Multi-sensory gamma stimulation ameliorates Alzheimer’s-associated pathology and improves cognition. Cell, 177(2), 256-271. doi: 10.1016/j.cell.2019.02.014

Murphy, M. P., & LeVine, H. (2010). Alzheimer’s Disease and the B-Amyloid Peptide. Journal of Alzheimer’s Disease, 19(1), 311-323. doi: 10.3233/JAD2010-1221

Rakhshan, V., Hassani-Abharian, P., Joghataei, M., Nasehi, M., & Khosrowabadi, R. (2022).

Effects of the alpha, beta, and Gamma Binaural beat brain stimulation and short-term training on simultaneously assessed visuospatial and verbal working memories, Signal Detection Measures, response times, and Intrasubject response time variabilities: A within-subject randomized placebo-controlled clinical trial. BioMed Research International. doi: 10.1155/2022/8588272

Zhang, H., Longfei, J., & Jianping, J. (2020, July). Oxiracetam Offers Neuroprotection by Reducing Amyloid β-Induced Microglial Activation and Inflammation in Alzheimer’s Disease. Frontiers in Neurology, 11, 623. doi: 10.3389/fneur.2020.00623