Abstract Body

Rhythmic neural activity in the gamma range (30-80 Hz) is modulated during various aspects of cognitive function and has been shown to be disrupted in several neurological conditions including Alzheimer's disease (AD). It is well established that local network oscillations at specific frequencies can be induced in cortical areas using sensory stimuli. We have applied this approach, which we term Gamma ENtrainment Using Sensory stimuli (GENUS), using patterned light and sound stimulation at 40 Hz in AD model mice. Remarkably, GENUS augmented gamma oscillatory power in multiple brain regions. Moreover, chronic application led to marked reduction of amyloid and tau pathology, attenuated neurodegeneration, and improved cognitive function in multiple AD mouse models. These beneficial effects elicited by GENUS are likely facilitated by microglia activation and increased capillary-mediated clearance. Recently, we found that GENUS also increases glymphatic clearance of interstitial solutes. In humans, combined light and sound stimulation increases gamma oscillatory power in extended brain regions including deep brain areas such as the amygdala, hippocampus and posterior insula. We found that GENUS is safe even after prolonged exposure. Preliminary data suggests that AD individuals undergoing GENUS regimen exhibit reduction in sleep fragmentation and repair enhancement of structural and functional connectivity in the brain. We are continuing the treatment and evaluation of GENUS in human subjects, including whether GENUS treatment can delay or prevent the onset of dementia.