Increasing evidence shows that the right ventrolateral prefrontal cortex (rVLPFC) plays an important role in emotion regulation, especially for social-relevant negative emotions. Negative interpersonal experiences and social events contribute largely to the occurrence of depression. Meanwhile, patients diagnosed with major depressive disorder are characterized by impaired social functions. Previous studies have revealed that depressed patients frequently show impaired emotional regulation for social pain. Recently, the work of our lab found that using transcranial magnetic stimulation (TMS) to activate the rVLPFC significantly reduced the subjects' negative emotional feelings and improved their emotional regulation ability for down-regulating social pain. In order to improve the emotional regulation ability in depressed patients when they are in front of negative social events, this study examined the changed emotional regulation ability in depression following the activation of the rVLPFC using the TMS. A total of 127 patients who were diagnosed with major depressive disorder were recruited in this study. Participants were randomly assigned to experimental (n = 64) or control group (n = 63) while their age, gender, depressive level, social anxious level, rejection sensitivity and empathy ability were counterbalanced between the two groups. During the experiment, the participants were required to view pictures containing social exclusion events or reinterpret the situation using reappraisal strategy, followed by rating their negative emotional feeling on a 9-point scale. The experiment had two conditions, i.e., a passive viewing block and a cognitive reappraisal block. The results showed that the main effect of the task was significant: the negative emotional intensity reported by participants was lower during cognitive reappraisal when compared to that during passive viewing, indicating a successful manipulation of explicit emotional regulation. Meanwhile, the main effect of the group was significant: the negative emotional intensity reported by the experimental group was significantly reduced compared to that reported by the control group, suggesting the critical role of rVLPFC in emotional regulation. More importantly, the interaction between task and group was significant: while the two groups reported comparable distressful feelings during the passive view block, the experimental group reported decreased negative feelings compared to the control group during the cognitive reappraisal block. This result indicated that enhanced activation of the rVLPFC could effectively improve the ability of explicit down-regulating social pain using the cognitive reappraisal strategy in depressed patients. The current findings provide strong evidence for the causal relationship between the VLPFC and explicit emotional regulation using the cognitive reappraisal strategy. Also this study provides a potential neural target for clinical treatments of emotional regulation impairment in patients with social dysfunctions including individuals diagnosed with major depressive disorder, social anxiety disorder, and autism spectrum disorder. Future studies are suggested to use other paradigms (e.g., Cyberball, Chat Rooms, Online Ostracism, and Island Getaway) to induce a "first-hand" social pain and exclude the potential influence of empathy. Furthermore, optimized multi-session TMS protocols are required to enhance and prolong the TMS effects observed in this study. Also, the TMS-based treatment effects in depression should be compared between the left and the right part of the ventrolateral prefrontal cortices, and across different emotional regulation strategies including cognitive reappraisal, distraction, distancing, etc.
