Reduced sleep spindles and spindle coherence in schizophrenia: mechanisms of impaired memory consolidation?

Abstract

Background: Sleep spindles are thought to induce synaptic changes and thereby contribute to memory consolidation during sleep. Patients with schizophrenia show dramatic reductions of both spindles and sleep-dependent memory consolidation, which may be causally related.

Methods: To examine the relations of sleep spindle activity to sleep-dependent consolidation of motor procedural memory, 21 chronic, medicated schizophrenia outpatients and 17 healthy volunteers underwent polysomnography on two consecutive nights. On the second night, participants were trained on the finger-tapping motor sequence task (MST) at bedtime and tested the following morning. The number, density, frequency, duration, amplitude, spectral content, and coherence of stage 2 sleep spindles were compared between groups and examined in relation to overnight changes in MST performance.

Results: Patients failed to show overnight improvement on the MST and differed significantly from control participants who did improve. Patients also exhibited marked reductions in the density (reduced 38% relative to control participants), number (reduced 36%), and coherence (reduced 19%) of sleep spindles but showed no abnormalities in the morphology of individual spindles or of sleep architecture. In patients, reduced spindle number and density predicted less overnight improvement on the MST. In addition, reduced amplitude and sigma power of individual spindles correlated with greater severity of positive symptoms.

Conclusions: The observed sleep spindle abnormalities implicate thalamocortical network dysfunction in schizophrenia. In addition, the findings suggest that abnormal spindle generation impairs sleep-dependent memory consolidation in schizophrenia, contributes to positive symptoms, and is a promising novel target for the treatment of cognitive deficits in schizophrenia.

Figure 1

Frequency and time-frequency decomposition of individual spindle events used to define amplitude, frequency, and duration variables. A) EEG trace of a sleep spindle waveform filtered at 12–15Hz, B) FFT transform of the same sleep spindle C) Wavelet decomposition of the spindle, representing spectral power across time. Spindle duration defined as half-height width of wavelet energy.

Figure 2

Spindle activity. A) Bar graph of sleep spindle density during stage 2 sleep averaged across electrode sites with standard error bars. B) Left: Bar graph of sigma-band coherence during spindles averaged across electrode sites with standard error bars. Right: Topographical map of reduced sigma coherence of spindles in schizophrenia across electrodes. Solid lines indicate electrode pairs showing a significant reduction in schizophrenia following correction for multiple comparisons (p<.0006); dashed lines indicate significance at the uncorrected p<.05 level. C) Spectral power in controls (heavy line) and patients (light line) at the Cz electrode, where sigma power was maximal. The sigma band baseline (12–15Hz; dashed line) is a best fit to the 11–12Hz and 15–16Hz data. D) Logarithm of spectral power across the broader 0–25Hz range. There were no group differences in the delta (1–4Hz), theta (4–7Hz), alpha (8–12Hz), or beta (13–25Hz) frequency bands. Spectral profiles were similar across all recording sites.

Figure 3

Overnight improvement on the Motor Sequence Task (MST) in patients and controls. A) Bar graphs of overnight improvement with standard error bars. B) Motor skill learning across training and the first three test trials for controls (triangles) and schizophrenia patients (circles). The y-axis is scaled separately for controls (left) and patients (right) to highlight the qualitative similarity of learning curves on Day 1 and the failure of overnight improvement in the schizophrenia group only. The dashed line is the regression line fit to data from the last 6 training trials. The discontinuity in the x-axis represents a night of sleep. Patients and controls did not differ in the amount of learning during training (63% vs 58%, p=.77), but only controls showed significant overnight improvement.

Figure 4

Overnight improvement as a function of spindle density and number in patients and controls. Regression includes one outlier (gray triangle), with outlier excluded, r = −0.23, p = 0.40.

Figure 5

Overnight improvement as a function of spindle density and number in all participants combined, with the best fit non-linear saturating function lines.