Posted November 18, 2019

When we are deeply engaged in a cognitive task like decision making, there is research to suggest that this triggers the neurons in the brain to fire in specific patterns called gamma oscillations. It has been observed that the brains of people with Alzheimer’s disease have a decrease in the number of these neural fluctuations. What if there was a way to non-invasively stimulate the brain to create more gamma oscillations?

A team led by Li-Huei Tsai, PH.D., of MIT has explored this question and the research was presented at a recent meeting of the Society for Neuroscience.

The team used a mouse model for Alzheimer’s that expresses human genes linked to Alzheimer’s disease and aggressively develops amyloid plaques and microglia abnormalities.  The research team then exposed these mice to a combination of auditory stimulation and light to induce gamma oscillations in areas of the brain crucial for memory performance – the CA1 region of the hippocampus.

Alzheimer’s disease includes the presentation of amyloid-beta protein bundles and tau tangles in the brain. Another feature that can arise in Alzheimer’s disease is the abnormal neuronal activity that can disrupt the neural circuits involved in higher cognitive functions. On the flip side, neural activity can be modulated to reduce cognitive impairments associated with Alzheimer’s disease, at least according to this latest research paper.

How did Dr. Tsai improve cognitive performance in mice with Alzheimer’s like symptoms? The key insight with a technology called GENUS. GENUS stands for gamma entrainment using sensory stimulus which is the name behind Dr. Tsai’s new approach to improve cognitive function and decrease the accumulation of amyloid plaques in the Alzheimer’s mouse model. Our modern understanding of Alzheimer’s disease goes beyond tau tangles and amyloid plaques to incorporate neural activity. Abnormal neural activity can exacerbate the progression of Alzheimer’s disease by disrupting the neural circuits involved in higher cognitive function. Neural activity can be modulated which begs the question, can modulation of neural activity by used to improve cognitive function in Alzheimer’s disease?

The modulation of neural activity at 40 Hz led to glia and vasculature changes in addition to improved cognition in mice. Mice exposed to auditory stimulus plus visual GENUS induces microglia clustering around plaques and exhibited reduced amyloid pathology throughout the neocortex. Microglia are present in all regions of the brain throughout life. They play an important role in immunological surveillance in the central nervous system and when healthy are poised to react to foreign invaders. The biggest finding from the paper was that combining auditory and visual GENUS induced a microglia-clustering response in the hippocampus and medial prefrontal cortex. Surprisingly, amyloid plaques weren’t just reduced in these specific brain regions but throughout the neocortex. This paper reveals a non-invasive approach to elicit system-wide effects on AD-related pathology and improvements in cognition in an AD mouse model.

This research was presented at the Society for Neuroscience Meeting in Chicago that gathered thousands of neuroscientists from around the world to discuss and debut cutting-edge research on the brain. Dr. Li-Huei Tsai, a member of the Cure Alzheimer’s Fund Research Leadership Group, delivered a Presidential Lecture at the meeting.

To hear an interview with Dr. Li-Huei Tsai about this research, check out her interview on Radiolab, “Bringing Gamma Back”