Hypoactivation of the Ventromedial Frontal Cortex in Major Depressive Disorder: A Magnetoencephalography Study of the Reward Positivity.

Background: The reward positivity (RewP) is a sensitive and specific electrophysiological marker of reward receipt. These characteristics make it a compelling candidate marker of dysfunctional reward processing in major depressive disorder. We previously proposed that the RewP is a temporal nexus for multiple dimensions of reward value and that a diminished RewP in depression might only reflect a deficit in some of these features. Specifically, we predicted a diminished ventromedial contribution in depression in the context of maintained reward learning.

Methods: We collected magnetoencephalography recordings of reward receipt in 43 individuals with major depressive disorder (35 female) and 38 healthy control individuals (21 female). Magnetoencephalography allows effective source estimation due to the absence of volume conduction that compromises electroencephalographic recordings.

Results: The magnetoencephalography RewP analog was generated by a broad set of cortical areas, but only right ventromedial and right ventral temporal areas were diminished in major depressive disorder. These areas correlated with a principal component of anhedonia derived from multiple questionnaires. Compellingly, Brodmann area 25 was the frontal region with the largest representation in both of these effects.

Conclusions: These findings not only advance our understanding underlying the computation of the RewP, but are also consistent with findings from other types of functional source imaging in depression, as well as from deep brain stimulation treatments. Together, these discoveries suggest that the RewP may be a valuable marker for objective assessment of reward affect and its disruption in anhedonia.