LAUSR

Patients with major depressive disorder (MDD) exhibit abnormal rumination, including both adaptive and maladaptive forms. However, the neural substrates of rumination in depression remain poorly understood. We hypothesize that divergent spatiotemporal complexity of brain oscillations would be associated with the levels of rumination in MDD. We employed the multi-scale entropy (MSE), power and phase-amplitude coupling (PAC) to estimate the complexity of rhythmic dynamics from the eye-closed high-density electroencephalographic (EEG) data in treatment-naive patients with MDD (n = 24) and healthy controls (n = 22). The depressive, brooding, and reflective subscales of the Ruminative Response Scale were assessed. MDD patients showed higher MSE in timescales finer than 5 (cluster P = 0.038) and gamma power (cluster P = 0.034), as well as lower PAC values between alpha/low beta and gamma bands (cluster P = 0.002- 0.021). Higher reflective rumination in MDD was region-specifically associated with the more localized EEG dynamics, including the greater MSE in scales finer than 8 (cluster P = 0.008), power in gamma (cluster P = 0.018) and PAC in low beta-gamma (cluster P = 0.042), as well as weaker alpha-gamma PAC (cluster P = 0.016- 0.029). Besides, the depressive and brooding rumination in MDD showed the lack of correlations with global long-range EEG variables. Our findings support the disturbed neural communications and point to the spatial reorganization of brain networks in a timescale-dependent migration toward local during adaptive and maladaptive rumination in MDD. These findings may provide potential implications on probing and modulating dynamic neuronal fluctuations during the rumination in depression.