Increased aperiodic neural activity during sleep in major depressive disorder

Abstract BackgroundIn major depressive disorder (MDD), patients often express subjective sleep complaints while polysomnographic studies report only subtle alterations in neural oscillations. We hypothesize that the study of aperiodic electroencephalographic (EEG) dynamics, a marker of excitation-to-inhibition balance, may bring new insights into our understanding of sleep abnormalities in MDD. Specifically, we investigate aperiodic neural activity during sleep and its relationships with the time of sleep, depression severity, and responsivity to antidepressant treatment. MethodsPolysomnography was recorded in 38 MDD patients (in unmedicated and 7d medicated states) and 38 age-matched healthy controls (N1=76). Aperiodic EEG activity was evaluated using the Irregularly Resampled Auto-Spectral Analysis with slopes’ means and intra-individual variability as outcome measures. Depression severity was assessed with the Hamilton Depression Rating Scale. We replicated the analysis using two independently collected datasets of medicated patients and controls (N2=60, N3=80). ResultsUnmedicated patients showed flatter aperiodic slopes compared to controls during N2 (p-value=0.002) and steeper slopes compared to their later medicated state (p-values<0.02) during all sleep stages. Within unmedicated patients, slopes were flatter during late compared to early N2 sleep (p-value=0.006). Late N2 slopes further correlated with depression severity after 7d of antidepressant treatment (r=-0.34, p-value=0.04). Variability of slopes was increased in both unmedicated (p-values<0.03) and medicated states (p-values <0.006) of patients’ N2, N3, and REM sleep compared to controls. ConclusionFlatter slopes of aperiodic EEG power with increased variability may reflect unstable, noisy neural activity due to increased excitation-to-inhibition balance, representing a new disease-relevant feature of sleep in MDD.