Increased Aperiodic Neural Activity During Sleep in Major Depressive Disorder

Abstract

Background: In major depressive disorder (MDD), patients often express subjective sleep complaints, while polysomnographic studies report only subtle alterations of the electroencephalographic signal. We hypothesize that differentiating the signal into its oscillatory and aperiodic components may bring new insights into our understanding of sleep abnormalities in MDD. Specifically, we investigated aperiodic neural activity during sleep and its relationships with sleep architecture, depression severity, and responsivity to antidepressant treatment.

Methods: Polysomnography was recorded in 38 patients with MDD (in unmedicated and 7-day-medicated states) and 38 age-matched healthy control subjects (N= 76). The aperiodic power component was calculated using irregularly resampled auto-spectral analysis. Depression severity was assessed with the Hamilton Depression Rating Scale. We replicated the analysis using 2 independently collected datasets of medicated patients and control subjects (N = 60 and N = 80, respectively).

Results: Unmedicated patients showed flatter aperiodic slopes compared with control subjects during non-rapid eye movement (non-REM) stage 2 sleep (p = .009). Medicated patients showed flatter aperiodic slopes compared with their earlier unmedicated state (p values < .001) and control subjects during all sleep stages (p values < .03). In medicated patients, flatter aperiodic slopes during non-REM sleep were linked to the higher proportion of N1, lower proportion of REM, delayed onset of N3 and REM, and shorter total sleep time.

Conclusions: Flatter slopes of aperiodic electroencephalographic power may reflect noisier neural activity due to increased excitation-to-inhibition balance, representing a new disease-relevant feature of sleep in MDD.

Keywords: Antidepressants; Aperiodic power; Excitation-to-inhibition ratio; Impaired sleep; Major depressive disorder; Neural noise.

Figure 1

Electroencephalographic (EEG) power components. Total EEG spectral power (left) and its aperiodic (right) and oscillatory (middle) components averaged over frontal electrodes are plotted in the log-log space as a function of frequency for non–rapid eye movement (non-REM) (N2 + N3, top row) and REM (bottom row) sleep for each study group (different lines). Patients in both unmedicated (red lines) and medicated states (blue lines) show decreased oscillatory activity and steeper decay of the aperiodic component compared with control subjects (black lines). The total spectral power is comparable in all groups (coinciding lines of the left subgraphs).

Figure 2

Aperiodic slopes. Slopes of the broadband (0.2–48 Hz) aperiodic power component over each sleep stage and area for each study group. Unmedicated (unmed.) patients (n = 38, red) show flatter (more positive values) slopes during N2 compared with healthy control subjects (HC, n = 38, black). Seven-day-medicated (med.) patients (n = 38, blue) show flatter slopes compared with their own unmedicated state (red) and control subjects (black) during all sleep stages—but not the wakefulness after sleep onset. C, central electrodes; F, frontal electrodes; MDD, major depressive disorder; O, occipital electrodes; P, parietal electrodes; REM, rapid eye movement; T, temporal electrodes.

Figure 3

Effect of rapid eye movement (REM)–suppressive medications. Slopes of the aperiodic power component in the 0.2- to 48-Hz frequency band were averaged over each sleep stage over each area. Patients who took REM-suppressive antidepressants for 7 days (n = 21, red) showed flatter slopes (higher values) than patients who took REM-nonsuppressive antidepressants for 7 days (n = 17, black) during all sleep stages but not the wakefulness after sleep onset. C, central electrodes; F, frontal electrodes; N, non–rapid eye movement stage; O, occipital electrodes; P, parietal electrodes; T, temporal electrodes.