40 Hz visual stimulation increases gamma-band functional connectivity beyond the visual cortex

Visual stimulation at 40 Hz is being investigated as a non-invasive intervention for Alzheimer’s disease, but its network-level mechanisms in the human brain remain unclear. EEG functional connectivity measures interactions between brain regions and can be used to examine how sensory stimulation and cognitive engagement affect activity across regions. We recorded EEG from 29 healthy young adults during Regular 40 Hz flicker and Irregular 30–50 Hz flicker, each with and without a target-counting task (2 × 2 within-participant). Source-space connectivity between visual, parietal, and frontal regions was estimated with the debiased squared weighted phase-lag index (dWPLI). Regular stimulation increased 38–42 Hz connectivity for all three region pairs, with the largest increase between visual and parietal regions. The increase was specific to the stimulation frequency and was observed with two source reconstruction methods and in sensor space. The visual–parietal increase remained significant after correction for source leakage (spatial mixing between reconstructed sources) and after removal of the estimated stimulus-locked component, whereas the increases in visual–frontal and parietal–frontal connectivity did not. The concurrent task did not significantly modulate the stimulation effect for any region pair. These results show that 40 Hz visual stimulation increases gamma-band connectivity beyond the visual cortex. However, this increase may be mainly driven by the same external input affecting different regions. In addition, a simple cognitive task did not significantly affect the connectivity, suggesting that the connectivity change is to some extent robust to cognitive states.