Sleep spindle alterations relate to working memory deficits in individuals at clinical high-risk for psychosis

Abstract

Abstract Study Objectives Sleep spindles are waxing and waning EEG waves exemplifying the main fast oscillatory activity occurring during NREM sleep. Several recent studies have established that sleep spindle abnormalities are present in schizophrenia spectrum disorders, including in early-course and first-episode patients, and those spindle deficits are associated with some of the cognitive impairments commonly observed in these patients. Cognitive deficits are often observed before the onset of psychosis and seem to predict poor functional outcomes in individuals at clinical high-risk for psychosis (CHR). Yet, the presence of spindle abnormalities and their relationship with cognitive dysfunction has not been investigated in CHR. Methods In this study, overnight high-density (hd)-EEG recordings were collected in 24 CHR and 24 healthy control (HC) subjects. Spindle density, duration, amplitude, and frequency were computed and compared between CHR and HC. Furthermore, WM was assessed for both HC and CHR, and its relationship with spindle parameters was examined. Results CHR had reduced spindle duration in centro-parietal and prefrontal regions, with the largest decrease in the right prefrontal area. Moderation analysis showed that the relation between spindle duration and spindle frequency was altered in CHR relative to HC. Furthermore, CHR had reduced WM performance compared to HC, which was predicted by spindle frequency, whereas in HC spindle frequency, duration, and density all predicted working memory performance. Conclusion Altogether, these findings indicate that sleep spindles are altered in CHR individuals, and spindle alterations are associated with their cognitive deficits, thus representing a sleep-specific putative neurophysiological biomarker of cognitive dysfunction in psychosis risk.