Cross-Band Coupling of EEG Infraslow Oscillations during NREM Sleep in Mice

The infraslow oscillation (ISO) is a ~ 0.02 Hz rhythmic fluctuation in electroencephalographic (EEG) power during NREM sleep. Prior studies were limited to sigma-band ISO, linked to rhythmic norepinephrine release in mice. Whether ISOs exist in other bands, and how ISOs across bands are coupled, remain unknown. We analyzed cross-band ISO coupling across six frequency bands during NREM using a wild-type (WT) discovery dataset of 122 recordings from 72 mice and WT validation of 7 mice. A transgenic (TG) validation of 6 mice was added to test ISO coupling's robustness to Cre knock-in on the LepR gene (LepR-Cre). Band power time series were filtered to the ISO range of 0.01-0.03 Hz. Cross-band coupling was assessed using Spearman's correlation and phase-locking value (PLV) across all 15 band pairs. ISOs were strongest in alpha, sigma, beta, and theta bands, weak in gamma, and absent in delta. Alpha, sigma, beta, and theta ISOs formed a highly correlated motif with replication in WT and TG (r = 0.61-0.77), while gamma had moderate correlation (r = 0.30-0.42), and delta was uncorrelated (p > 0.05). All band pairs showed significant phase locking with replication (FDR-corrected q < 0.01), with stronger consistency in alpha, sigma, theta, and beta (PLV 0.54-0.71), and weaker consistency involving delta and gamma (PLV 0.12-0.37). EEG ISOs extend beyond the sigma band to alpha, beta, and theta bands, forming a strongly coupled motif that may reflect a fundamental organization principle of sleep microstructures at a minute scale.