Gamma entrainment as a neuro–glial–vascular intervention technique: A narrative review for neural network remodeling

With increasing lifespans, the rising prevalence of neurological disorders, such as Alzheimer’s and Parkinson’s diseases, has resulted in an urgent need to develop novel techniques for the prevention and treatment of neurodegenerative disorders. Although invasive neurosurgical techniques, such as stereotactic surgery and deep brain stimulation for Parkinson’s disease or anti-amyloid infusion therapy for Alzheimer’s disease, have demonstrated promising outcomes, the impracticality of such interventions for the general aging population has sparked the inception of non-invasive techniques, such as gamma entrainment using sensory stimuli. Using a combination of sensory stimuli to induce gamma oscillations across multiple brain regions, this approach synchronizes neuronal firing, which in turn influences cerebrospinal fluid dynamics, myelin plasticity, and vascular remodeling, and ultimately may help to rewire aberrant circuitry. Such techniques can be applied for primary and secondary prevention efforts, targeting at-risk populations or the early stages of disease, respectively. Research on this approach has made the most significant progress in Alzheimer’s disease, but there are some mixed findings. This review aims to develop a framework for understanding the brain-wide effects of gamma entrainment as a neuromodulatory tool for neuromodulation. Overall, existing literature suggests that non-invasive sensory stimulation exerts its influence by altering the neuro–glial–vascular landscape, thereby exerting positive effects on cognitive function, and thus, has important implications for central nervous system disorders accompanied by cognitive impairment.