From mechanisms to clinical applications: Advances in 40 Hz gamma oscillation modulation for the treatment of neurological disorders.

This review systematically summarizes the mechanisms of 40 Hz gamma rhythm neuromodulation and its research advances in neurological disorders. As a key rhythm for brain information integration, 40 Hz gamma oscillations are generated by the interaction between excitatory and inhibitory neurons, and play a central role in cognitive functions such as attention and memory. They are commonly characterized by decreased power or loss of synchrony in various diseases including Alzheimer's disease, Parkinson's disease, and schizophrenia, serving as a shared electrophysiological hallmark. Extrinsic 40 Hz stimulation (e.g., transcranial alternating current stimulation, light flickering, acoustic stimulation) can restore endogenous gamma rhythms through the entrainment effect, improve excitation-inhibition balance, enhance synaptic plasticity, and promote the clearance of pathological proteins by activating microglia and other mechanisms. Clinical studies have shown that this technology improves cognitive, emotional, and motor functions, with advantages of non-invasiveness and high safety. Despite challenges such as individual variability, marked methodological heterogeneity (e.g., inconsistent stimulation parameters, small sample sizes, and lack of multicenter randomized controlled trials), and unclear long-term effects, 40 Hz neuromodulation still demonstrates broad therapeutic potential and provides a novel rhythmic intervention strategy for neurological disorders.