Reward pursuit during a translational reward task predicts anhedonia reductions following rTMS in patients with major depressive disorder

Background: People with major depressive disorder (MDD) often struggle to pursue previously rewarding activities, which may relate to deficits experiencing pleasure, termed anhedonia. Anhedonia remains a challenge to target and treat. Repetitive transcranial magnetic stimulation (rTMS) alleviates anhedonia in some patients with MDD, though rTMS is logistically burdensome. Identifying novel, translational phenotypes of reward pursuit may help identify who is most likely to respond to treatment. We used a translational reward task (Web-Surf) to test if reward pursuit strategies in patients with MDD predicts anhedonia reductions following rTMS. Methods: Patients with treatment-resistant MDD (N=32) underwent daily, rTMS treatment and completed Web-Surf weekly. Depression and anhedonia symptoms were measured with the Patient Health Questionnaire. We examined if the number of rewards earned, at baseline, correlated with self-reported hedonic experience and anhedonia reductions following rTMS. We also tested if changes in reward earnings, over the rTMS course, were specific to patients with reduced anhedonia. Results: Patients with MDD who earned more desired rewards at baseline reported a more pleasurable experience during Web-Surf (baseline) and exhibited greater anhedonia reductions (late treatment – baseline). Patients increasingly earned more desired rewards over the therapy course, specifically those who showed a decline in anhedonia with rTMS. Reward earning trajectories did not change among patients who showed no improvement in anhedonia. Conclusions: We present a novel translational reward-pursuit metric that corresponds with anhedonia reductions following rTMS therapy. Anhedonia reductions related to both baseline reward pursuit and reward- pursuit trajectories. This translational phenotype shows promise as a biomarker for clinical treatment response in depression.