Thalamic dysfunction in schizophrenia suggested by whole-night deficits in slow and fast spindles

Abstract

Objective: Slow waves and sleep spindles are the two main oscillations occurring during non-REM sleep. While slow oscillations are primarily generated and modulated by the cortex, sleep spindles are initiated by the thalamic reticular nucleus and regulated by thalamo-reticular and thalamo-cortical circuits. In a recent high-density EEG study, the authors found that 18 medicated schizophrenia patients had reduced sleep spindles, compared with healthy and depressed subjects, during the first non-REM episode. In the present study, the authors investigated whether spindle deficits were present in a larger sample of schizophrenia patients, were consistent across the night, were related to antipsychotic medications, and were suggestive of impairments in specific neuronal circuits.

Method: Whole-night high-density EEG recordings were performed in 49 schizophrenia patients, 20 nonschizophrenia patients receiving antipsychotic medication, and 44 healthy subjects. In addition to sleep spindles, several parameters of slow waves were assessed.

Results: Schizophrenia patients 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 activity in the prefrontal, centroparietal, and temporal regions. Integrated spindle activity and spindle number had the largest effect sizes (effect size: ≥ 2.21). In contrast, no slow wave deficits were found in schizophrenia patients.

Conclusions: These results indicate that spindle deficits can be reliably established in schizophrenia, are stable across the night, are unlikely to be due to antipsychotic medications, and point to deficits in the thalamic reticular nucleus and thalamo-reticular circuits.

Figure 1. Schizophrenics had deficits in spindle range (12–16 Hz) power and other spindle parameters

(A) Mean EEG power spectra in 0.25 Hz resolution of whole-night NREM sleep of schizophrenics, healthy and medicated controls. One-way ANOVA revealed significant differences between the three groups, from 12 to 16 Hz (F > 3.61, df = 2, 106, p < 0.05). (B) Post-hoc t-tests showed statistically significant differences between schizophrenics and healthy controls from 12.5 to 15.75 Hz and between schizophrenics and medicated controls from 12 to 16 Hz. (black bars). (C) Color plots: Topography of several spindle parameters (amplitude, duration, number, and ISA) in schizophrenics (N= 49), healthy (N=44), and medicated (N=20) control subjects. White plots: Topographic distribution of the electrodes showing a significant reduction (gray area; Statistical non-Parametric Mapping, SnPM) in spindle parameters in schizophrenic vs, healthy, schizophrenic vs. medicated, and healthy vs. medicated subjects.

Figure 2. Topography of slow (12–14 Hz) and fast (14–16 Hz) spindle deficits in schizophrenia

(Left panel) Deficits in slow (12–14 Hz) sleep spindle duration, number and integrated spindle activity (ISA) in schizophrenics vs. both healthy and medicated psychiatric controls were established in a prefrontal region (Statistical non Parametric Mapping, SnPM, p≤0.001). No significant reduction in slow spindle amplitude across the three groups as well as between healthy and medicated psychiatric controls in the other slow spindle parameters was found. (Right panel) Deficits in fast (14–16 Hz) sleep spindle duration (prefrontal), amplitude (centroparietal), as well as number and ISA (both prefrontal and centroparietal) were assessed in schizophrenics vs. both healthy and medicated psychiatric controls (SnPM, p≤0.001). Additionally, for fast spindle number and ISA a significant reduction in the left temporal cortex was established (SnPM, p≤0.001). No significant reduction in any fast spindle parameter between healthy and medicated psychiatric controls was found.

Figure 3. Slow wave parameters are not defective in schizophrenia

(A) Slow waves occurring during whole night NREM sleep were detected using an automated algorithm, and several slow wave parameters, including incidence, amplitude, down- and up-slope were measured. (B) No significant difference in the topography of each of these slow wave parameters was found across the three groups.