Gamma-Music Based Intervention for Mild Alzheimer's Disease - Project Summary / Abstract
Alzheimer’s Disease (AD) is characterized by cognitive deficits such as memory loss, as well as deficits in the
motivation that drives daily activities. These cognitive and motivational deficits are linked to widespread neuronal
and synaptic atrophy, coupled with aggregated extracellular Aβ-plaque and tau deposits, and atypical neural
activity across multiple frequencies. Recent work in mouse models of AD have shown that inducing gamma
oscillations with a non-invasive gamma-frequency (40 Hz) light-flickering and auditory tone-stimulation regimes
reduced Aβ plaques and improved spatial and recognition memory. In humans, restoring gamma-frequency
activity while preserving its phase-amplitude coupling with theta-band activity are shown to recover human
memory performance in older adults, and in patients with mild AD, thus offering a promising route towards a
novel therapy that can prevent brain atrophy while improving cognition. Despite their recent successes, it is a
major challenge to translate gamma-frequency neurostimulation from a laboratory study to a behavioral
intervention. Our goal is to promote healthy neurocognitive aging using lifestyle interventions; in particular,
interventions that sustainably elevate mood and reward motivated behavior while encouraging social bonding
may be most promising in slowing the progression of AD. Music listening engages multiple brain networks
involved in sensory processing, movement, language, attention, learning and memory, emotion and reward, and
social connectedness. Music-Based Interventions (MBIs) have the potential to manage symptoms, slow disease
progression, and improve quality of life. Our lab has recently shown that an eight-week MBI can increase auditory
functional connectivity to the reward system. Here we propose to test a novel protocol for music-based brain
stimulation, gamma-MBI: gamma-light stimulation that automatically adapts to music-based intervention.
Harnessing the fact that music listening is an intrinsically rewarding activity, we propose to use music as a carrier
for gamma sensory stimulation. As music contains theta-band acoustic energy, music listening is a form of theta-
band noninvasive brain stimulation. We will test and refine a novel brain-stimulation tool using gamma-frequency
lights coupled with self-selected music for a gamma-music-based intervention for participants with mild
Alzheimer’s Disease. Results will yield a gamma-stimulation protocol that reliably influences brain activity (Aim
1), is adaptive, motivating and rewarding to use (Aim 2), and will generate predictions as to who might benefit
the most from gamma-MBI (Aim 3). By bridging the gap between neurostimulation and behavioral intervention
by combining music therapy with gamma-band neurostimulation, the present project aims to find a sustainable
intervention that delays the progression of AD. Our team is uniquely qualified to address all aspects of this
innovative and ambitious project.
