Abstract:
Under the influence of the novel coronavirus epidemic, some negative social events, such as separation of
family or friends and home isolation have increased. These events can cause negative emotion experiences
similar to physical pain, thus they are called social pain. Placebo effect refers to the positive response to the inert
treatment with no specific therapeutic properties, which has been shown to be one of the effective ways to
alleviate social pain. Studies have shown that the dorsolateral prefrontal cortex (DLPFC) plays a key role in
placebo effect. Therefore, this study aimed to explore whether activating DLPFC by using transcranial magnetic
stimulation (TMS) could improve the ability of placebo effects to regulate social pain. Besides, we also
combined neuroimaging and neuromodulation techniques to provide bidirectional evidence for the role of the
DLPFC on placebo effects.
We recruited a total of 100 participants to finish the task of negative emotional rating of the social
exclusion images. Among them, 50 participants were stimulated by TMS at the right DLPFC (rDLPFC), while
the others were assigned to the sham group. This study contained two independent variables. The between-
subject variable was TMS group (rDLPFC-activated group or sham group) and the within-subject variable was
placebo type (no-placebo and placebo). All participants received nasal spray in two blocks. In the no-placebo
condition, participants were instructed that they would receive a saline nasal spray which helped to improve
physiological readings; in placebo block, participants were told to administrate an intranasal fluoxetine spray
(saline nasal spray in fact) that could reduce unpleasantness within 10 minutes. To strengthen the expectation of
intranasal fluoxetine, participants viewed a professional introduction to fluoxetine’s clinical and academic usage
including downregulating negative emotion, such as fear, anxiety, and disgust. Participants who received the
placebo block first would be reminded that fluoxetine’s effect was over before the next block to reduce the
carry-over for the following block. Self-reported negative emotional and electroencephalogram data were
recorded.
There was a significant two-way interaction of TMS group and placebo type. Results showed that compared
with the sham group, participants in the rDLPFC-activated group reported less negative emotional feeling and
had a lower amplitude of the late positive potential (LPP) in placebo condition, a component that reflects the
emotional intensity, suggesting that activating rDLPFC can improve the ability of placebo effect to regulate
social pain.
The above finding suggested that activating DLPFC can improve the placebo effect of regulating negative
emotion. Moreover, this study is the first attempt to investigate the enhancement of placebo effects by using
TMS on emotion regulation. The findings not only support the critical role of DLPFC on placebo effect using
neuroimaging and neuromodulation techniques, but also provide a potential brain target for treating emotional
regulation deficits in patients with psychiatric disorders.