Abstract
Depression is a debilitating disorder with high prevalence and socioeconomic cost, but the brain-physiological processes that are altered during depressive states are not well understood. Here, we build on recent findings in macaques that indicate a direct causal relationship between pupil dilation and anterior cingulate cortex mediated arousal during anticipation of reward. We translated these findings to human subjects with concomitant pupillometry/fMRI in a sample of unmedicated participants diagnosed with major depression and healthy controls. We could show that the upregulation and maintenance of arousal in anticipation of reward was disrupted in patients in a symptom-load dependent manner. We could further show that the failure to maintain reward anticipatory arousal showed state-marker properties, as it tracked the load and impact of depressive symptoms independent of prior diagnosis status. Further, group differences of anticipatory arousal and continuous correlations with symptom load were not traceable only at the level of pupillometric responses, but were mirrored also at the neural level within salience network hubs. The upregulation and maintenance of arousal during reward anticipation is a novel translational and well-traceable process that could prove a promising gateway to a physiologically informed patient stratification and targeted interventions.
Highlights
Major depressive disorder (MDD) is a mental disorder with a high prevalence and is estimated to be the top contributor to nonfatal health loss globally [1]
We found very strong evidence for a negative correlation between pupil dilation to the reward stimulus response timetime (RT)(RT)
We could previously translate these findings to humans by use of concurrent pupillometry/fMRI, where we found that reward anticipatory pupil dilation correlated with activity in the salience network [12]
Summary
Major depressive disorder (MDD) is a mental disorder with a high prevalence and is estimated to be the top contributor to nonfatal health loss globally [1]. Within the context of depression, much attention has been devoted to the processes of reward prediction and prediction error signaling. This followed the hypothesis that the common finding of anhedonia in. Several studies have observed group differences in the striatum during reward anticipation, when the task contained a learning component [6,7,8]. This was not the case in a nonlearning task: Rutledge et al [9] showed that individuals with depression exhibit reward prediction and prediction error signals in the ventral striatum similar to controls. It was proposed that evidence for attenuated prediction error signaling in depression could mirror downstream effects more closely related to aberrant behavior
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