Clinical Studies
Gamma-Music Based Intervention for Mild Alzheimer's Disease
An NIH-funded clinical trial exploring non-invasive music-based brain stimulation for cognitive health.
The Challenge
Understanding Alzheimer's Disease
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.
The Approach
Music as a Therapeutic Intervention
Despite their recent successes, it is a major challenge to translate gamma-frequency neurostimulation from a laboratory study to a behavioral intervention. The 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 Protocol
A Novel Brain Stimulation Protocol
Our clinical trial is testing a novel protocol for music-based brain stimulation. Harnessing the fact that music listening is an intrinsically rewarding activity, the study uses music to stimulate theta and gamma brain rhythms. Musical rhythms contain theta-band acoustic energy, and activates theta-gamma phase amplitude coupling. Thus music listening is itself a form of noninvasive rhythmic brain stimulation.
We couple the music with theta-gamma light stimulation that automatically adapts to music. The visual rhythm synchronizes to the theta frequencies in the musical rhythm, producing theta-modulated burst pulses of gamma that simulate the healthy brain's response to musical rhythm to enhance phase-amplitude coupling in the brain. This novel brain-stimulation approach is being tested in individuals with mild cognitive impairment and early stage AD. They listen to self-selected music and watch synchronized lights.
Results
Early Trial Findings
Oscillo's gamma-enhanced music-based intervention (gMBI) is administered in the patient's home 30 minutes/day for 8-weeks; the control intervention includes listening to a health education podcast (the health-education intervention, HEI). Before and after the therapy patients undergo a battery of tests, including electroencephalography (EEG), structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), functional MRI (fMRI), blood draws, and tests of cognition and memory. Patient usage data in both conditions is monitored.
We find that patients comply better with the Treatment protocol (gMBI) than with the Control protocol (HEI). After 8 weeks, neural oscillations are strengthened, hippocampal activation increases, memory improves, and cognitive function is preserved in the treatment group relative to the controls.
JOIN OUR CLINICAL TRIAL
Enroll in our NIH-funded Clinical Trial
Oscillo, in partnership with the Music, Imaging and Neural Dynamics (MIND) lab at Northeastern University, is currently conducting a Phase I Clinical Trial (NCT05984524) in individuals with Mild Cognitive Impairment (MCI) and early stage Alzheimer's Disease (AD).