Is depression a global brain disorder with topographic dynamic reorganization?

Abstract Major depressive disorder (MDD) is characterized by a multitude of psychopathological symptoms including affective, cognitive, perceptual, sensorimotor, and social. The neuronal mechanisms underlying such co-occurrence of psychopathological symptoms remain yet unclear. Rather than linking and localizing single psychopathological symptoms to specific regions or networks, this perspective proposes a more global and dynamic topographic approach. We first review recent findings on global brain activity changes during both rest and task states in MDD showing topographic reorganization with a shift from unimodal to transmodal regions. Next, we single out two candidate mechanisms that may underlie and mediate such abnormal uni-/transmodal topography, namely dynamic shifts from shorter to longer timescales and abnormalities in the excitation-inhibition balance. Finally, we show how such topographic shift from unimodal to transmodal regions relates to the various psychopathological symptoms in MDD including their co-occurrence. This amounts to what we describe as ‘Topographic dynamic reorganization’ which extends our earlier ‘Resting state hypothesis of depression’ and complements other models of MDD.