Overnight changes in the slope of sleep slow waves during infancy

Abstract

Study objectives: Slow wave activity (SWA, 0.5-4.5 Hz) is a well-established marker for sleep pressure in adults. Recent studies have shown that increasing sleep pressure is reflected by an increased synchronized firing pattern of cortical neurons, which can be measured by the slope of sleep slow waves. Thus we aimed at investigating whether the slope of sleep slow waves might provide an alternative marker to study the homeostatic regulation of sleep during early human development.

Design: All-night sleep electroencephalography (EEG) was recorded longitudinally at 2, 4, 6, and 9 months after birth.

Setting: Home recording.

Patients or participants: 11 healthy full-term infants (5 male, 6 female).

Interventions: None.

Measurements and results: The slope of sleep slow waves increased with age. At all ages the slope decreased from the first to the last hour of non rapid-eye-movement (NREM) sleep, even when controlling for amplitude differences (P < 0.002). The decrease of the slope was also present in the cycle-by-cycle time course across the night (P < 0.001) at the age of 6 months when the alternating pattern of low-delta activity (0.75-1.75 Hz) is most prominent. Moreover, we found distinct topographical differences exhibiting the steepest slope over the occipital cortex.

Conclusions: The results suggest an age-dependent increase in synchronization of cortical activity during infancy, which might be due to increasing synaptogenesis. Previous studies have shown that during early postnatal development synaptogenesis is most pronounced over the occipital cortex, which could explain why the steepest slope was found in the occipital derivation. Our results provide evidence that the homeostatic regulation of sleep develops early in human infants.

Keywords: Sleep; development; homeostasis; infants; slope of slow waves.

Figure 1

(A) Schematic illustration of the slow wave detection method: 5 s of raw (left) and band-pass filtered (right) EEG signal of the C3-A2 derivation during NREM sleep. Right: Stars indicate detected slow waves. The slope was defined as the amplitude (local minimum of the signal, dotted line) divided by the time interval between the local minimum and the subsequent zero crossing (circles). (B) Example of detected slow waves for the derivation F3-A2: Scatter plots of all selected waves of the first (black) and last (gray) hour of NREM sleep of one subject at 2 (left) and 9 (right) months. For the first (continuous line) and last (dotted line) hour, a regression line was fitted to the data. Based on the regression parameters (slope and intercept), the slope at a fixed amplitude was determined.

Figure 2

Characteristics (amplitude, incidence, and slope) of slow waves for the first and last hour of NREM sleep (C3-A2): Bars indicate group means ± SE. Paired t-test were used to test differences within age groups from the first to last hour of NREM sleep (*P < 0.05, **P < 0.001).

Figure 3

Slope of sleep slow waves for consecutive 10 μV amplitude bins (numbers represent the upper limit) of the first and last hour of NREM sleep (C3-A2): group mean ± SE for both time points are shown. Only amplitude bins with at least 50 detected waves per subject are considered. Circle size represents the number of detected slow waves for each amplitude bin. Numbers in the upper left corner of each plot show the maximal and minimal number of detected slow waves across all subjects (mean ± SE). ANOVA factor time (first hour vs. last hour): **P < 0.001, n ≥ 5.

Figure 4

Slope of slow waves with an amplitude of 55 μV (slope55) of the first and the last hour of NREM sleep (C3-A2): group means ± SE for both time points are presented (Paired t-test First hour vs. Last hour: *P < 0.002). Insert: Overnight decrease in slope55 (in percentage of the first hour): Bars indicate group means ± SE (Paired t-test: *P < 0.05, #P < 0.06).

Figure 5

Slope of slow waves with an amplitude of 55 μV (slope55) of the first 7 NREM sleep episodes at the age of 6 months for 6 infants: Group mean values ± SE. (^aP < 0.006 vs. 1^st NREM episode, ^bP < 0.008 vs. 2 ^nd NREM episode, ^cP < 0.008 vs. 3^rd NREM episode, and ^dP < 0.05 vs. 5 ^th NREM episode). Low-delta activity (for details of the calculation see Jenni et al.) is shown in gray (right ordinate) to illustrate the different time course.

Figure 6

Topographical differences in the slope of slow waves with an amplitude of 55 μV (slope55) of the first hour of NREM sleep: Values represent group means ± SE for the frontal, central, parietal, and occipital derivation (referenced to the right mastoid). Significant group effects were found for factor age and channel (F_age = 182.84, P < 0.001; F_chan = 69.68, P < 0.001); 2 mo: n = 10 (except for channel F3-A2 n = 9), 4 mo: n = 10, 6 mo: n = 9, 9 mo: n = 7.