GENOTYPE-DEPENDENT PLASTIC EFFECTS OF VISUAL GAMMA ENTRAINMENT ON CORTICAL SPECTRAL DYNAMICS

Gamma-band entrainment using sensory stimulation (vGENUS) has been proposed as a non-invasive approach to modulate cortical dynamics and cognition, yet its cumulative and genotype-dependent effects remain poorly understood. Here, we investigated longitudinal effects of vGENUS on gamma oscillations, broadband spectral structure, and behavior in wild-type (WT) and double knock-in (dKI) mice, a model of early Alzheimer’s disease. Across repeated recording sessions, gamma power progressively increased following vGENUS, with the strongest effects observed over frontal electrodes. This potentiation was genotype-dependent: WT mice exhibited gamma enhancement across a broad frequency range, whereas dKI mice showed potentiation restricted to frequencies near the stimulation band, consistent with frequency-specific entrainment. Prior to vGENUS, dKI mice displayed flatter spectral slopes (PSS; 1–49 Hz) compared to WT during a associative memory task, indicative of altered baseline spectral organization, and were behaviorally impaired. Gamma potentiation was accompanied by further flattening of the PSS in both genotypes. This effect was more pronounced in WT mice, where pre–post differences were evident even at lower frequencies (1–20 Hz), whereas in dKI mice PSS changes emerged only when considering a broader frequency range (1–49 Hz). Despite this additional spectral flattening, behavioral performance in the Novel Object Recognition task was rescued in dKI mice following vGENUS. Our findings demonstrate progressive plastic effects of vGENUS on gamma dynamics, reveal genotype-specific spectral reorganization, and show that behavioral improvement can occur alongside broadband spectral flattening, highlighting distinct network responses to gamma entrainment and motivating further mechanistic studies of GENUS-induced cortical modulation.