Altered Neural Oscillatory Coupling Reveals Cognitive Control Deficits with Hierarchical Characteristics and Emotional Specificity in Major Depressive Disorder

Cognitive control deficits are a prevalent feature of major depressive disorder (MDD) and are influenced by emotional contexts. However, it remains unclear whether these deficits specifically exist at particular hierarchical levels of cognitive control and whether they are selectively exacerbated under distinct emotional contexts. Furthermore, the neural mechanisms underlying such deficits and their association with depressive symptoms remain to be further elucidated.

To fill these gaps, two experiments were conducted. In Experiment 1, 54 MDDs and 41 healthy controls (HCs) performed emotional and non-emotional hierarchical cognitive control tasks. Hierarchical demands were manipulated using low- and high-abstraction rules. Based on hierarchy- and emotion-specific deficits identified in Experiment 1, Experiment 2 (34 MDDs; 28 HCs) introduced rule memory set-size manipulation to test whether the deficit generalized to other hierarchical cognitive control subprocesses. Electroencephalography and eye-tracking were simultaneously recorded. Phase-amplitude coupling (PAC) quantified cross-frequency interactions subserving cognitive control.

Delta-beta PAC was selectively reduced in MDDs compared with HCs during high-abstraction conditions under negative emotional contexts, but not in low-abstraction conditions or other contexts. Under the same conditions, MDDs also failed to show the typical memory-related increase in theta-gamma PAC. Moreover, emotion regulation scores significantly mediated the pathway from PAC abnormalities to depressive severity.

Our findings indicate that altered neural oscillatory coupling reveals cognitive control deficits in MDD that exhibit both hierarchical characteristics and emotional specificity. These neural abnormalities may contribute to depressive severity through maladaptive emotion regulation strategies, providing a novel biological account of the pathophysiological mechanisms underlying MDD.