Colloquium on the Brain and Cognition with Li-Huei Tsai, PhD, MIT
Date: Thursday, February 27, 2025 | Time: 4:00pm | Location: 46-3002, Singleton Auditorium
Frequency Matters: Harnessing 40 Hz Stimulation for Alzheimer's Disease and Neuroprotection
Rhythmic neural activity in the gamma range (30–80 Hz) plays a crucial role in cognitive function and is disrupted in several neurological conditions, including Alzheimer’s disease (AD). We developed a method called Gamma ENtrainment Using Sensory stimuli (GENUS), which uses patterned light and sound stimulation at 40 Hz in AD model mice to assess the effects of enhancing gamma oscillations. Our findings demonstrate that GENUS increases gamma power across multiple brain regions. Moreover, daily application significantly reduces amyloid and tau pathology, mitigates neuronal and synaptic degeneration, and improves cognitive function in various AD mouse models.
In addition, GENUS induces morphological and gene expression changes in glial cells and the vasculature. It also enhances cerebrospinal fluid influx and facilitates glial-mediated and lymphatic-like brain waste clearance—known as glymphatic clearance—through a vasoactive intestinal peptide interneuron-dependent mechanism. We provide evidence that enhanced glymphatic clearance is essential for the reduction of amyloid burden in the cortex following GENUS.
Our current efforts focus on deciphering the cellular, molecular, and neural circuit mechanisms underlying the therapeutic effects of gamma entrainment. I will discuss our latest findings on how gamma oscillations regulate multiple neuromodulatory systems to drive protective effects, including the modulation of visceral organs. If time permits, I will also present clinical findings using GENUS and explore the feasibility of this non-invasive sensory stimulation approach for treating neurological disorders in human patients. These results highlight the potential of GENUS as a promising therapeutic avenue for Alzheimer’s disease, offering a non-invasive approach to engage neuromodulatory systems and restore brain function.
Li-Huei Tsai received her P.h.D degree from the University of Texas Southwestern Medical Center at Dallas. She then took postdoctoral training from Ed Harlow’s laboratory at Cold Spring Harbor laboratory and Massachusetts General Hospital. She joined the faculty in the Department of Pathology at Harvard Medical School in 1994 and was named an investigator of Howard Hughes Medical Institute in 1997. In 2006, she was appointed Professor in the Department of Brain and Cognitive Sciences, and joined the Picower Institute for Learning and Memory at MIT, where she now also serves as the Director.
