Schematic of the main topics of each framework. Framework 1 focuses on the definition of MAs and their diagnostic use in clinical sleep settings. Framework 2 presents novel mechanistic insights on the origins of MAs, focusing on noradrenergic locus coeruleus (LC) activity fluctuations during NREM sleep as drivers for MAs and coordinators of spectral and autonomic fluctuations. The latest findings on noradrenergic fluctuations as drivers for blood volume and cerebrospinal fluid (CSF) variations are also presented. Framework 3 discusses how the merging of the clinical sleep- and neurobiology-oriented views on MAs can be summarized in an inverted U-shaped model showing the relationship between MA frequency, noradrenergic activity fluctuations, and biological processes that support restorative NREM sleep.
