0106 New Insights into the Spatiotemporal Organization of Sleep Micro-Architecture: Spindles, Slow Oscillations and Phase Precession of Spindle-SO Coupling

Abstract Introduction Spindles (11-16 Hz) and slow oscillations (0.5-1.5 Hz; SO) are fundamental elements of the NREM sleep microarchitecture, often co-occurring in a phase-dependent manner. This cross-frequency coupling is critical for the temporal coordination of neural activity in sleep and for memory consolidation. However, each of these elements occur locally at different times and in different regions across the brain. In this study, we present evidence in humans for a novel spatiotemporal relationship between spindles and SO, termed phase precession, and then compare the properties of this relationship across the lifespan. Methods We studied 101 participants free of major neurological disease, ranging in age from 20 to 85 years. Continuous overnight scalp EEG was sleep-staged, and spindles and SO were detected, using previously-published algorithms. The SO phases corresponding to spindle detections were plotted against the anterior-posterior scalp position. Circular-linear statistics were then used to determine the best fit line, and quantify the slope, strength (R value), and significance. Linear and logistic regression models were used to test the association of these phase precession parameters with demographics. Results Visual inspection of circular phase plots across the brain topography revealed a striking pattern. There was a systematic shift in phase, with spindles occurring at sequentially earlier SO phases relative to their anterior-posterior position. Phase-position plots confirmed this relationship at both an individual and group level. Examining phase precession properties across demographics, we found that older age is associated with reduced phase precession strength (F=5.15, b=-0.001, R=0.37, p=0.008), and a flattening of the slope (F=2.64, b=-0.005, R=0.23, p=0.016). In contrast, we did not find any significant differences between male and female sex (p>0.05). Conclusion We report a novel spatiotemporal organization of spindle-SO coupling, characterized by a systematic precession of the SO phase of spindles along the anterior-posterior axis of the brain. We speculate that phase precession provides a potential mechanistic explanation for how the coupling of sleep oscillations could support memory consolidation in a coordinated manner across the brain. Underscoring its relevance, we show that the integrity of phase precession strength and slope declines with advancing age. Support (if any) NINDS R25NS065743 and Mass General Neuroscience Transformative Scholars Award