Altered neural reward and loss processing and prediction error signalling in depression

Abstract

Dysfunctional processing of reward and punishment may play an important role in depression. However, functional magnetic resonance imaging (fMRI) studies have shown heterogeneous results for reward processing in fronto-striatal regions. We examined neural responsivity associated with the processing of reward and loss during anticipation and receipt of incentives and related prediction error (PE) signalling in depressed individuals. Thirty medication-free depressed persons and 28 healthy controls performed an fMRI reward paradigm. Regions of interest analyses focused on neural responses during anticipation and receipt of gains and losses and related PE-signals. Additionally, we assessed the relationship between neural responsivity during gain/loss processing and hedonic capacity. When compared with healthy controls, depressed individuals showed reduced fronto-striatal activity during anticipation of gains and losses. The groups did not significantly differ in response to reward and loss outcomes. In depressed individuals, activity increases in the orbitofrontal cortex and nucleus accumbens during reward anticipation were associated with hedonic capacity. Depressed individuals showed an absence of reward-related PEs but encoded loss-related PEs in the ventral striatum. Depression seems to be linked to blunted responsivity in fronto-striatal regions associated with limited motivational responses for rewards and losses. Alterations in PE encoding might mirror blunted reward- and enhanced loss-related associative learning in depression.

Keywords: depression; fMRI; loss; prediction error; reward.

Fig. 1

Reward paradigm. Trials began with the visual presentation of different incentive cues which predicted potential monetary outcomes (gains/losses) with either low ( ± 0.2 €) or high ( ± 2.0 €) magnitudes. Trial outcome depended on the subject’s response (button press) to a flash light that appeared after cue offset. The individual response time threshold was adaptively determined.

Fig. 2

Panels A–C show figures of axial (A), coronal (B) and sagittal (C) brain sections that correspond to the shape and location of the frontal mask (blue coloured), including the dlPFC, OFC, mPFC and ACC, and striatal mask (pink coloured), including the caudate nucleus and putamen. Regions of interest were specified by mask files supplied by the Wake Forest University PickAtlas v2.0 (Tzourio-Mazoyer et al., 2002; Maldjian et al., 2003). The masks were overlaid on a structural template image provided by MarsBaR (Matthew et al., 2002).

Fig. 3

Panels A and C depict significantly reduced activation of fronto-striatal regions in depressed individuals compared with healthy controls during high gain anticipation (A) and in the rostral part of the anterior cingulate cortex during high loss anticipation (C). The colour scale represents t-scores. Panel B depicts the partial correlation between the SHAPS (higher total SHAPS scores indicate higher levels of hedonic capacity) and the maximal peak activation (beta weights) for the orbitofrontal cortex (R²=0.184) and the nucleus accumbens (R²=0.023), adjusted for depression severity measured by the HAM-D scale.