Evidence that non-invasive sensory stimulation of the brain’s 40 Hz gamma frequency rhythms can reduce Alzheimer’s pathology and symptoms, already manifested by light and sound by multiple research groups in mice and humans, now extends to tactile stimulation. A new study by scientists from the Massachusetts Institute of Technology shows that Alzheimer’s disease model mice that were exposed to vibration at 40 Hz per hour daily for several weeks showed improved brain health and motor function compared to untreated controls.
The MIT group isn’t the first to show that tactile stimulation of gamma frequency can affect brain activity and improve motor function, but they are the first to show that stimulation can also reduce levels of phospholipid Alzheimer’s protein, preventing neurons from dying or losing their synapse circuit connections, and reduce neuronal DNA damage.
This work demonstrates a third sensory method that we can use to increase gamma power in the brain. We are very excited to see that 40 Hz touch stimulation benefits motor abilities, which has not been shown with other methods. It will be interesting to see if tactile stimulation can benefit people with impairments in motor function.”
Li-Huei Tsai, corresponding study author, director of the Picower Institute for Learning, Memory, and Brain Aging Initiative at MIT, and the Picower Professor in the Department of Brain and Cognitive Sciences (BCS)
Ho-Jun Suk, Nicole Buie, Guojie Xu, and Arit Banerjee are the lead authors of the study in Frontiers in aging neuroscienceand Ed Boyden, Y. Eva Tan Professor of Neurotechnology at MIT, co-senior author of the paper. Boyden, an affiliate member of the Picwoer Institute, is also appointed to BCS as well as the Departments of Bioengineering, Media Arts and Sciences, McGovern Institute for Brain Research, and K. Lisa Yang Cener for Bionics.
In a series of research papers that began in 2016, a collaboration led by Tsai’s lab showed that flashing light and/or acoustic clicking at 40 Hz (a technique called GENUS for Gamma Entrainment using sensory stimuli), reduces levels of the proteins amyloid-beta and tau. , prevents neuronal death, preserves synapses, and even preserves learning and memory in a variety of Alzheimer’s mouse models. The team recently showed in pilot clinical studies that 40 Hz light and sound stimulation was safe, succeeded in increasing brain activity and connectivity and appeared to produce significant clinical benefits in a small group of human volunteers with early-stage Alzheimer’s disease. Other groups have replicated and confirmed the health benefits of 40Hz sensory stimulation, and an MIT company, Cognito Therapeutics, has launched Phase III clinical trials of light and sound stimulation as a treatment for Alzheimer’s disease.
The new study tested whether 40 Hz whole-body tactile stimulation produced meaningful benefits in two common mouse models of neurodegeneration of Alzheimer’s disease, the P301S tau mouse, which recapitulates the tau pathology of the disease, and the CK-p25 mouse, which recapitulates synapse loss and damage seen. DNA in human disease. The team focused their analyzes on two regions of the brain: the primary somatosensory cortex (SSp), where tactile sensations are processed, and the primary motor cortex (MOp), where the brain orders movement to the body.
To produce the vibration stimulus, the researchers placed the cages of the rats above loudspeakers playing 40 Hz sound, which caused the cages to vibrate. Unstimulated control mice in cages were scattered in the same room such that all mice heard the same 40 Hz sound. Therefore the differences measured between stimulated and control mice were made by adding tactile stimulation.
The researchers first confirmed that 40 Hz vibration made a difference in neural activity in the brains of healthy (ie, non-Alzheimer’s) mice. As measured by expression of c-fos protein, the activity increased 2-fold in SSp and more than 3-fold in MOp, a statistically significant increase in the latter case.
Once the researchers knew that 40 Hz tactile stimulation could increase neural activity, they evaluated the effect on disease in two mouse models. To ensure that both sexes are represented, the team used male P301S mice and female CK-p25 mice.
P301S mice stimulated for three weeks showed significant neuronal preservation compared to unstimulated controls in both brain regions. Stimulated mice also showed a significant decrease in tau in SSp by two measures, and showed similar trends in MOp.
CK-p25 mice received six weeks of vibration stimulation. These mice showed higher levels of synaptic protein markers in both brain regions than non-shaking control mice. They also showed low levels of DNA damage.
Finally, the team evaluated the motor abilities of rats exposed to vibration versus no exposure. They found that both mouse models were able to stay on a rotating rod for much longer. P301S mice were also suspended on a wire grid for significantly longer than control mice while CK-p25 mice showed a positive, albeit nonsignificant, trend.
The authors conclude, “The present study, together with our previous studies using visual or auditory GENUS, demonstrates the potential for using non-invasive sensory stimulation as a novel therapeutic strategy to improve pathology and improve behavioral functioning in neurodegenerative diseases.”
Support for the study came from the JPB Foundation, Picower Institute for Learning and Memory, Eduardo Eurnekian, DeGroof-VM Foundation, Halis Family Foundation, Melissa and Doug Ko Hahn, Lester Gimpelson, Eleanor Schwartz Charitable Foundation, Dolby Family, and Kathleen and Miguel Octavio, Jay and Carol Miller, Ann Gao, Alex Ho, and Charles Hiken.
Suk, AH, et al. (2023) Vibrational stimulation at gamma frequency alleviates diseases related to neurodegeneration and improves motor function. Frontiers in aging neuroscience. doi.org/10.3389/fnagi.2023.1129510.