Gamma Oscillations, Sensory Stimulation, and Glymphatic Function: Toward User-Friendly Auditory Interventions for...

The glymphatic system is a brain-wide clearance pathway that facilitates the removal of interstitial solutes, including amyloid-β, and plays a critical role in maintaining brain homeostasis. Impairments in glymphatic transport have been implicated in aging and neurodegenerative diseases, including Alzheimer's disease. While glymphatic activity is most pronounced during sleep, emerging evidence suggests that specific patterns of neural activity, including gamma-frequency oscillations entrained by sensory stimulation, can modulate glymphatic transport even during wakefulness. Preclinical studies further indicate that 40 Hz sensory stimulation, delivered via light, sound, or multisensory paradigms, can induce gamma oscillations, reduce pathological protein accumulation, and enhance cognitive performance in animal models of Alzheimer's disease. Early clinical investigations similarly suggest that gamma-frequency sensory stimulation may improve blood-based biomarkers, neuroimaging measures, and cognitive outcomes in patients with Alzheimer's disease. To translate gamma-frequency stimulation into broadly applicable preventive or therapeutic strategies, approaches must be both effective and tolerable for long-term use. Conventional auditory gamma stimulation can be perceived as acoustically rough or monotonous, reducing listener comfort and limiting acceptability for prolonged use in broader populations. User-friendly auditory formats, such as "gamma music" and the more recently introduced "immersive gamma music", have been proposed as potentially useful approaches for delivering gamma-frequency stimulation while improving listening comfort and facilitating sustained use. Collectively, gamma-frequency sensory stimulation represents a promising approach to support healthy brain aging and mitigate neurodegenerative processes, particularly when implemented via user-friendly auditory formats that facilitate repeated and long-term use. While these findings are encouraging, further research is needed to validate these approaches and determine their clinical relevance.