Sleeping in cycles within cycles: A nonlinear framework for NREM sleep microstructure

Non-rapid eye movement (NREM) sleep is not a static state but a dynamically regulated process in which cortical, autonomic, and neuromodulatory activity fluctuates across nested temporal scales. This review proposes that the cyclic alternating pattern (CAP), a scored marker of NREM sleep instability with a dominant periodicity near 25 s, and the approximately 50-s infraslow oscillation (ISO) of sigma/spindle activity may represent different expressions of a shared nonlinear regulatory architecture. Rather than interpreting CAP as a simple second harmonic of sigma-ISO, we propose that CAP phase A reflects a thresholded, state-dependent, subtype-specific event output of a putative broader thalamocortical-autonomic and neuromodulatory NREM sleep infraslow process, provisionally termed the NREM sleep infraslow cycle. CAP-favorable windows may arise twice within each 50-s cycle at transition phases, maximal-slope points, turning points, or other instability phases of a demeaned sigma-ISO component, producing an apparent 2:1 relationship. This coupling is likely modulated by ultradian position, CAP subtype, slow oscillation-spindle coupling, autonomic and noradrenergic state, small-world network reconfiguration, and aperiodic 1/f background activity. Phase-resolved multimodal studies could test this framework and reposition CAP as a mechanistic index of nonlinear NREM sleep-state regulation.