Thalamic Dysfunction in Schizophrenia Suggested by Whole-Night Deficits in Slow and Fast Spindles

Abstract

Slow waves and sleep spindles are the two main oscillations occurring during NREM sleep. While slow oscillations are primarily generated and modulated by the cortex, sleep spindles are initiated by the thalamic reticular nucleus (TRN), and regulated by thalamo-reticular and thalamo-cortical circuits. In a recent high-density electroencephalographic (hd-EEG) study we found that 18 medicated schizophrenics had reduced sleep spindles compared to healthy and depressed subjects during the first NREM episode. Here we investigated whether spindle deficits were: a) present in a larger sample of schizophrenic patients; b) consistent across the night; c) related to antipsychotic medications; d) suggestive of impairments in specific neuronal circuits. Whole night hd-EEG recordings were performed in 49 schizophrenics, 20 non-schizophrenic patients on antipsychotics and 44 healthy subjects. In addition to sleep spindles, several parameters of slow waves were assessed. Schizophrenics had whole-night deficits in spindle power (12–16 Hz) and in slow (12–14 Hz) and fast (14–16 Hz) spindle amplitude, duration, number and integrated spindle activity (ISA) in prefrontal, centroparietal and temporal regions. ISA and spindle number had the largest effect sizes (ES≥2.21). By contrast, no slow wave deficits were found in schizophrenics. These results indicate that spindle deficits i) can be reliably established in schizophrenics, ii) are stable across the night, iii) are unlikely to be due to antipsychotic medications, and iv) point to deficits in TRN and thalamo-reticular circuits.

Coordination of Slow Waves With Sleep Spindles Predicts Sleep-Dependent Memory Consolidation in Schizophrenia

“…There was no deficit in delta power. Previous investigations of SW activity in schizophrenia have been inconsistent reporting no differences during NREM sleep in medicated patients 61,62 , reduced N3 SW count and delta power in antipsychotic-naïve and unmedicated patients 63,64 and reduced delta power in N3 but not N2 in medicated patients 65 . These inconsistencies may reflect differences in definitions of delta power, sleep stages considered and medication status of the participants.…”

Adult Neurogenesis and Mental Illness

“…Prolonged sleep deprivation has been suggested to be a risk factor for developing mood disorders like depression and anxiety disorders (Kahn-Greene et al, 2007;Taylor et al, 2005;Tkachenko et al, 2014), and patients with schizophrenia show impairments in various stages of sleep (Ferrarelli et al, 2010;Keshavan et al, 1998). Similarly, in animal studies, sleep deprivation can increase anxiety-like behavior in mice (Silva et al, 2004), and rodent models of anxiety, depression, and schizophrenia produce fragmented sleep (Grnli et al, 2004;Jakubcakova et al, 2012;Oliver et al, 2012;Phillips et al, 2012;Popa et al, 2006).…”

The calcium-binding protein parvalbumin modulates the firing 1 properties of the reticular thalamic nucleus bursting neurons

“…Changes in burst structure are likely to affect the information transfer gated by the inhibitory feedback projections exerted by RTN neurons on the thalamic relay cells. The outcome of this alteration could affect the transthalamic corticortical connectivity (Gollo et al 2010;Paz et al 2011;Sherman and Guillery 2011;Theyel et al 2010;Villa et al 1999) such to generate an impaired processing of the information associated to psychiatric disorders (Ferrarelli et al 2010;Gogolla et al 2009;Lawrence et al 2010;Pinault 2011;Reynolds et al 2001;Wills et al 2011). …”