(A) Spindle activity (grey) is nested in the slow oscillation (SO, black), preferably in the up-state (close to the SO peak or as shown in the inset close to 0°) (B) Coupling between SOs and spindles can be quantified by their coupling strength (length of the vector in red) as well as their coupling direction (where the vector is pointing). Several studies suggested that there is a narrow (< 90°, in green) optimal window to successfully initiate the hippocampal-neocortical dialogue in support of memory formation. Critically, SOs and spindle first grow into synchrony during maturation, wile a temporal dispersion can be observed later in life as a function of age- or disease-related cognitive decline. Examples include age-related prefrontal atrophy [43,44], mild cognitive impairment (MCI, [53]), hippocampal damage after autoimmune encephalitis [51] as well as precursors of neurodegenerative disease [52,55]. (C-E) SO-spindle coupling has been found to track both task-specific behavioral performance (panel C), as well as task-independent metrics, such as neuropsychological test scores (panel D) or the burden of precursors of imminent cognitive decline (panel E). Jointly, these findings suggest that SO-spindle coupling indexes the integrity of memory pathways, which constitute the foundation for information transfer in the PFC-MTL network. The graphs in C-E are adapted from data reported in [43,45,52] with permission.