How Stress Alters Neural Systems of Reinforcement: A Model of Depressive Etiology

Abstract

The primary goal of the proposed research is to identify how stress is internalized to affect cognitive functioning and increase the risk for Major Depressive Disorder (MDD). Dysfunctional stress reactivity has been proposed to be a risk factor for ongoing affective distress, yet mechanisms underlying this process remain unexplained. The medial prefrontal cortex (mPFC) has been implicated in the etiology of MDD, in the reactivity to stress, as well as in the adaptation of behavior to reinforcement. The combined activities of this particular neural system identify it as a focal node by which stress may be internalized to affect cognitive, emotional, and behavioral functioning. The experiments detailed here examined electroencephalographic (EEG) features that reflect cognitive control functions in the mPFC. Participants underwent EEG assessment as they completed a reinforcement (reward and punishment) learning task sensitive to mPFC-basal ganglia functioning, both with and without a laboratory stress manipulation. This experiment assessed how stress reactivity altered neural systems of reinforcement, and it contrasted these same factors with currently depressed individuals. In this series of investigations, we have identified a measure of how, and a possible mechanism by which, punishment information is internalized in stress reactivity and in the expression of MDD: error and punishment signals are increasingly coupled with the salience of "bad" outcomes. Stress-related alteration of reward and punishment learning systems - particularly in the mPFC - is a viable candidate for how dysfunctional stress reactive responses are translated into ongoing cognitive and affective distress in depression.