Systematic review: the relationship between sleep spindle activity with cognitive functions, positive and negative symptoms in psychosis

Abstract

Background Sleep disturbances are associated with worse cognitive and psychotic symptoms in individuals with schizophrenia. Growing literature reveals sleep spindle deficits in schizophrenia may be an endophenotype reflecting a dysfunctional thalamo-thalamic reticular nucleus-cortical circuit. Since thalamic functions link to cognitive, positive and negative symptoms, it is possible that sleep spindle activity is associated with these symptoms. The primary objectives of this systematic review were to assess the associations of sleep spindle activity in psychotic patients with 1) cognitive functions; and 2) positive and negative symptom severity. A secondary objective was to examine which spindle parameter would be the most consistent parameter correlating with cognitive functions, and positive and negative symptoms. Method Observational studies reporting an association between sleep spindle activity and cognitive functions, positive and negative symptoms in patients with psychotic disorders were considered eligible. We developed a comprehensive electronic search strategy to identify peer-reviewed studies in Pubmed, Embase, PsycINFO and CINAHL covering all dates up to the search date in May 2020 with no language restriction. The references of published articles were hand-searched for additional materials. The authors of published articles were contacted for newer or unpublished data. Risk of bias was assessed by Appraisal of Cross-sectional Studies (AXIS). Results A total 11 cross-sectional studies (n = 255) with low-to-moderate quality, were selected for the systematic review. 8 of them addressed the association between sleep spindle activity and cognitive functions (n = 193), of which 6 studies reported positive correlations (r only reported in 4 studies, from 0.45 to 0.75). Out of multiple cognitive domains, we have only found attention/cognitive processing speed to have a more consistent positive association with sleep spindle activity. On the other hand, 8 studies investigated the relationship between sleep spindle and positive/negative symptom severity (n = 190), but findings were inconsistent. Spindle density is the most consistent parameter correlating with cognitive functions, while the best spindle parameter for correlating with positive and negative symptom severity cannot be identified due to mixed results. Discussion This systematic review confirms the linkage between sleep spindle activity and cognitive functions. However, included studies had small sample sizes, with high risks of sampling and response bias. Moreover, confounders were often not controlled. The heterogeneous report of spindle parameters and use of cognitive assessment tools rendered meta-analysis infeasible. It is necessary to examine the longitudinal change of sleep spindle activity with the course of illness, as well as the effect of sleep spindle enhancing agents on cognitive function.

Mathematical Model Insights into EEG Origin under Transcranial Direct Current Stimulation (tDCS) in the Context of Psychosis

“…Future work should also improve the neural model by including neural mechanisms of spindles, since these are known to represent important EEG markers in psychosis and their prodrome [ 36 , 103 , 104 ]. Incorporating spiking modes of the reticular population should allow to reproduce such dynamics, switching from bursting mode in the control/healthy condition to single-action potential/tonic mode in the psychosis/ketamine condition [ 36 ].…”

Non-rapid eye movement sleep and wake neurophysiology in schizophrenia

“…More importantly, whether and how distinct NREM sleep deficits track with waking EEG, clinical symptoms, medication, and cognition within patients is not clear ( Au and Harvey, 2020 ). For example, one recent report suggested reductions in spindle density were significantly more extensive in patients experiencing auditory hallucinations compared to hallucination-free patients ( Sun et al, 2021 ).…”

The Engram’s Dark Horse: How Interneurons Regulate State-Dependent Memory Processing and Plasticity

“…Attenuated sleep oscillations, altered sleep patterns, and dysfunctional PV+ and SST+ GABAergic interneurons have also been observed in schizophrenia (Lewis and Sweet, 2009), which is a multifaceted mental disorder characterized by cognitive deficits. NREM sleep spindle disruption and suppression is a highly consistent finding in schizophrenic patients, and has predictive value of cognitive, positive, and negative symptoms (Kaskie et al, 2019;Au and Harvey, 2020;Gerstenberg et al, 2020;Markovic et al, 2020;Zhang et al, 2020). This selective disruption of sleep spindles is linked to loss of PV+ interneurons in the thalamic reticular nucleus of schizophrenic patients (Steullet et al, 2018).…”