Does fragmented sleep mediate the relationship between deficits in sleep spindles and memory consolidation in schizophrenia?

Abstract

Abstract Study Objectives Sleep spindles, defining EEG oscillations of non-rapid eye movement (NREM) stage 2 sleep (N2), mediate sleep-dependent memory consolidation (SDMC). Spindles are also thought to protect sleep continuity by suppressing thalamocortical sensory relay. Schizophrenia is characterized by spindle deficits and a correlated reduction of SDMC. We investigated whether this relationship is mediated by sleep fragmentation. Methods In overnight polysomnography records from 56 participants with chronic schizophrenia and 59 healthy controls, we detected spindles (12-15 Hz) during N2 at central electrodes using a validated algorithm. Our primary measures of sleep continuity were the sleep fragmentation index and, in a subset of the data, visually scored arousals. SDMC was measured as overnight improvement on the finger tapping motor sequence task (MST). Results Participants with schizophrenia showed reductions of both spindle density (#/min) and SDMC in the context of normal sleep continuity and architecture. Spindle density predicted SDMC in both groups. In contrast, neither increased sleep fragmentation nor arousals predicted lower spindle density or worse SDMC in either group. Conclusions Our findings fail to support the hypothesis that sleep fragmentation accounts for spindle deficits, impaired SDMC, or their relationship in individuals with chronic schizophrenia. Instead, our findings are consistent with the hypothesis that spindle deficits directly impair memory consolidation in schizophrenia. Since sleep continuity and architecture are intact, research aimed at developing interventions should instead focus on understanding dysfunction within the thalamocortical-hippocampal circuitry that both generates spindles and synchronizes them with other NREM oscillations to mediate sleep-dependent memory consolidation.