Neural activity and fundamental learning, motivated by monetary loss and reward, are intact in mild to moderate major depressive disorder

<div><p>Introduction</p><p>Reduced motivation is an important symptom of major depression, thought to impair recovery by reducing opportunities for rewarding experiences. We characterized motivation for monetary outcomes in depressed outpatients (N = 39, 22 female) and controls (N = 22, 11 female) in terms of their effectiveness in seeking rewards and avoiding losses. We assessed motivational function during learning of associations between stimuli and actions, as well as when learning was complete. We compared the activity within neural circuits underpinning these behaviors between depressed patients and controls.</p><p>Methods</p><p>We used a Go/No-Go task that assessed subjects’ abilities in learning to emit or withhold actions to obtain monetary rewards or avoid losses. We derived motivation-relevant parameters of behavior (learning rate, Pavlovian bias, and motivational influence of gains and losses). After learning, participants performed the task during functional magnetic resonance imaging (fMRI). We compared neural activation during anticipation of action emission vs. action inhibition, and for actions performed to obtain rewards compared to actions that avoid losses.</p><p>Results</p><p>Depressed patients showed a similar Pavlovian bias to controls and were equivalent in terms of withholding action to gain rewards and emitting action to avoid losses, behaviors that conflict with well-described Pavlovian tendencies to approach rewards and avoid losses. Patients were not impaired in overall performance or learning and showed no abnormal neural responses, for example in bilateral midbrain or striatum. We conclude that basic mechanisms subserving motivated learning are thus intact in moderate depression.</p><p>Implications</p><p>Therapeutically, the intact mechanisms identified here suggest that learning-based interventions may be particularly effective in encouraging recovery. Etiologically, our results suggest that the severe motivational deficits clinically observed in depression are likely to have complex origins, possibly related to an impairment in the representation of future states necessary for long-term planning.</p>