❚ What Is Brainwave Entrainment?
Brainwave entrainment is a method to naturally synchronize the brain in response to periodic sensory, visual or tactile rhythmic sensory stimulation, such as pulses of sound or light. The pulses elicit the brain’s frequency-following response, encouraging the brainwaves to align to the frequency of a given beat.
❚ Capturing Brainwaves with EEG
An electroencephalograph (EEG) is a tool for measuring electrical activity in the brain by means of small discs (electrodes) placed on the scalp. The electrodes detect tiny electrical changes that result from the activity of your brain cells. Such changes in brain activity may be useful in diagnosing and tracking brain disorders.
❚ Brainwaves & Diseases Associated with BND
When the signaling pathways of neurons are disrupted, it leads to what is known as Brain Network Dysfunction (BND). BND is commonly observed in neurological and psychiatric disorders such as Alzheimer’s Disease (AD), Mild Cognitive Impairment (MCI), bipolar disorder, anxiety, depression and attention deficit disorders.
Studies have indicated that the changes in brainwave activity occurs long before neurodegeneration of the brain takes place, and even decades before symptoms appear.
❚ Research Studies
Various studies on the clinical application of audio-visual entrainment are being examined and completed in the last few years. This increased interest in research associated with light based interventions has opened the door to a greater understanding on how exogenous stimulations such as light can be utilized to impact neural and physiological functions in the body. An indicative and non-exhaustive list of studies with clinical implications is listed below:
❚ Gamma Frequency Entrainment Attenuates Amyloid Load and Modifies Microglia
Iaccarino H. F. et al. (2016)
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❚ Noninvasive 40-Hz Light Flicker to Recruit Microglia and Reduce Amyloid Beta Load
Singer A. C. et al. (2018)
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❚ Gamma Band Neural Stimulation in Humans and the Promise of a New Modality to Prevent and Treat Alzheimer’s Disease
McDermott B. et al. (2018)
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❚ Multi-sensory Gamma Stimulation Ameliorates Alzheimer’s-Associated Pathology and Improves Cognition
Martorell, A. J. et al. (2019)
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❚ Gamma Entrainment: Impact on Neurocircuits, Glia, and Therapeutic Opportunities
Adaikkan C. & Tsai L-H. (2019)
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❚ Optimal Flickering Light Stimulation for Entraining Gamma Waves in the Human Brain
Lee K., Park Y., Suh S.W. et al. (2021)
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Source: New Insights Into the Pathogenesis of Alzheimer’s Disease – Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/A-series-of-studies-from-Li-Huei-Tsai-indicating-that-gamma-stimulations-ameliorate_fig2_338505918 [accessed 12 Oct, 2021]
❚ Therapeutics Opportunities
Considering that abnormalities in brainwave patterns are often observed in brain disorders, it has been hypothesized that restoring them could have a preventative or therapeutic effect in diseases associated with BND.
To test this hypothesis, researchers (H. F. Iaccarino et al., 2016) conducted a study in which they successfully synchronized gamma waves in an Alzheimer’s mouse model by exposing mice to a 40 Hz flashing light. Mice exposed to 40 Hz flashing light had (1) increased activity of microglia (immune defense), (2) a reduction of Amyloid Beta & Tau plaques across the cortex, and (3) showed improvement in cognitive performance.
At a second stage, they conducted a trial using a similar approach, exposing Alzheimer’s Disease patients to visual and auditory stimuli at 40 Hz, one hour daily for 6-9 months. After 6 months, participants in the treatment group showed (in comparison to placebo group):
> 84% slowdown of functional decline (ADCS-ADL score)
> 83% decrease in memory and cognitive decline (MMSE score)
> 61% reduction of brain atrophy and loss of brain volume
❚ Our Clinical Study on Alzheimer’s: ALZLIGHT
OptoCeutics’ ALZLIGHT uses flickering light to induce 40 Hz gamma oscillation similar to the previously mentioned studies. However, the novelty in our technology is our way of masking the light by alternating the spectral composition of a white light, rendering the flicker invisible to the conscience perception while still entraining 40 Hz oscillations in the brain (i.e. the light appears continuous even though it is flickering at 40 Hz frequency).
In the study, subjects will be exposed to invisible spectral flickering light (active setting) or continuous non-flickering white light (sham setting) for 1 hour each day. The sham setting is a high quality sham intervention as subjects will be blinded to the setting.
The focus will be on 1) safety of the intervention 2) feasibility of the proposed intervention time and method 3) indication of efficacy.
❚ Our Partners’ Research
❚ Research Background
GAMMA BRAIN WAVES
The neuronal changes resulting from Alzheimer’s Disease are associated with the disruption of neural gamma oscillations (20-50 Hz) required for typical cognitive functioning.
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LIGHT FLICKER STIMULATION
Recent studies found that exposure to 40 Hz flickering light corrects aberrant gamma oscillations and reduces Aβ and Tau protein accumulation in multiple Alzheimer’s disease mice models.
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NEUROPROTECTION & IMPROVED COGNITION
Additionally, the exposure to 40 Hz flickering light therapy, for one hour a day, resulted in neuroprotective effects, and improved cognition and memory in mice models.
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NEUROIMMUNE SIGNALING
Mice exposed to 40 Hz light for 1 hour a day had increased expression of cytokines (proteins important for cell signaling) and indirectly impacted the activity of neuronal microglial cells (immune defence cells).
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