The ventrolateral prefrontal cortices (VLPFC) are crucial regions involved in voluntary emotion regulation. However, the lateralization of the VLPFC in downregulating negative emotions remains unclear; and whether the causal role of the VLPFC is generalizable to upregulating positive emotions is unexplored. This study used transcranial magnetic stimulation (TMS) to examine the causal relationship between the left/right VLPFC and social emotion reappraisal. One hundred and twenty participants were randomly assigned to either active (left and right VLPFC groups, n = 40/40) or sham (vertex, n = 40) TMS groups. Participants were instructed to passively receive social feedback or use reappraisal strategies to positively regulate their emotions. While the subjective emotional rating showed that the bilateral VLPFC facilitated the reappraisal success, the electrophysiological measure of the late positive potential (LPP) demonstrated a more critical role of the right VLPFC on social pain relief (decreased LPP amplitudes) and social reward magnification (enhanced LPP amplitudes). In addition, the influence of emotion regulation on social evaluation was found to be mediated by the memory of social feedback, indicating the importance of memory in social behavioral shaping. These findings suggest clinical protocols for the rehabilitation of emotionregulatory function in patients with affective and social disorders.

Human beings have a fundamental need to belong. Evaluating and dealing with social exclusion and social inclusion events, which represent negative and positive social interactions, respectively, are closely linked to our physical and mental health. In addition to traditional paradigms that simulate scenarios of social interaction, images are utilized as effective visual stimuli for research on socio-emotional processing and regulation. Since the current mainstream emotional image database lacks social stimuli based on a specific social context, we introduced an open-access image database of social inclusion/exclusion in young Asian adults (ISIEA). This database contains a set of 164 images depicting social interaction scenarios under three categories of social contexts (social exclusion, social neutral, and social inclusion). All images were normatively rated on valence, arousal, inclusion score, and vicarious feeling by 150 participants in Study 1. We additionally examined the relationships between image ratings and the potential factors influencing ratings. The importance of facial expression and social context in the image rating of ISIEA was examined in Study 2. We believe that this database allows researchers to select appropriate materials for socially related studies and to flexibly conduct experimental control.

A clear understanding of the neural circuit underlying emotion regulation (ER) is important for both basic and translational research. However, a lack of evidence based on combined neuroimaging and neuromodulation techniques calls into question 1) whether the change of prefrontal-subcortical activity intrinsically and causally contributes to the ER effect and 2) whether the prefrontal control system directly modulates the subcortical affective system. Accordingly, we combined fMRI recordings with transcranial magnetic stimulation (TMS) to map the causal connections between the prefrontal cortex (PFC) and subcortical affective structures (amygdala and insula). A total of 117 human adult participants (57 males and 60 females) were included in the study. The results revealed that TMS-induced ventrolateral PFC (VLPFC) facilitation led to enhanced activity in the VLPFC and ventromedial PFC (VMPFC) as well as attenuated activity in the amygdala and insula during reappraisal but not during non-reappraisal (i.e., baseline). Moreover, the activated VLPFC intensified the prefrontal-subcortical couplings via the VMPFC during reappraisal only. This study provides combined TMS-fMRI evidence that down-regulating negative emotion involves the prefrontal control system suppressing the subcortical affective system, with the VMPFC serving as a crucial hub within the VLPFC-subcortical network, suggesting an indirect pathway model of the ER circuit. Our findings outline potential protocols for improving ER ability by intensifying the VLPFC-VMPFC coupling in patients with mood and anxiety disorders.Significance StatementUsing fMRI to examine the TMS effect, we uncovered that the opposite neural changes in prefrontal (enhanced) and subcortical (attenuated) regions are not a by-product of emotion regulation (ER), instead, this prefrontal-subcortical activityper secausally contributes to the ER effect. Furthermore, using TMS to amplify the neural changes within the ER circuit, the “bridge” role of the VMPFC is highlighted under the reappraisal versus non-reappraisal contrast. This “perturb-and-measure” approach overcomes the correlational nature of fMRI data, helping us to identify brain regions that causally support reappraisal (the VLPFC and VMPFC) and those that are modulated by reappraisal (the amygdala and insula). The uncovered ER circuit is important for understanding the neural systems underlying reappraisal and valuable for translational research.

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