Pre-treatment EEG signal variability is associated with treatment success in depression

Background: Previous work suggests that major depressive disorder (MDD) is associated with disturbances in global connectivity among brain regions, as well as local connectivity within regions. However, the relative importance of these global versus local changes for successful antidepressant treatment is unknown. We used multiscale entropy (MSE), a measure of brain signal variability, to examine how the propensity for local (fine scale MSE) versus global (coarse scale MSE) neural processing measured prior to antidepressant treatment is related to subsequent treatment response. Methods: We collected resting-state EEG activity during eyes-open and closed conditions from unmedicated individuals with MDD prior to antidepressant pharmacotherapy (N=36) as well as from non-depressed controls (N=36). Treatment response was assessed after 12weeks of treatment using the Montgomery-Åsberg Depression Rating Scale (MADRS), at which time participants with MDD were characterized as either responders (≥50% MADRS decrease) or non-responders. MSE was calculated from baseline EEG, and compared between controls, future treatment responders and non-responders. Putative interactions with the well-documented age effect on signal variability (increased reliance on local neural communication with increasing age, indexed by greater finer-scale variability) were assessed. Results: Only in responders, we found that reduced MSE at fine temporal scales (especially fronto-centrally) and increased MSE diffusely at coarser temporal scales was related to the magnitude of the antidepressant response. In controls and MDD non-responders, but not MDD responders, there was an increase in MSE with age at fine temporal scales and a decrease in MSE with age at coarse temporal scales. Conclusion: Our results suggest that an increased propensity toward global processing, indexed by greater MSE at coarser timescales, at baseline appears to facilitate eventual antidepressant treatment response. Keywords: Depression, Treatment, Response, Multi-scale entropy (MSE), Electroencephalography (EEG), Signal variability, Spectral power density (SPD