Central serotonin modulates neural responses to virtual violent actions in emotion regulation networks

Dhana Wolf, Martin Klasen, Patrick Eisner, Florian D. Zepf, Mikhail Zvyagintsev, Nicola Palomero-Gallagher, René Weber, Albrecht Eisert, Klaus Mathiak

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Disruptions in the cortico-limbic emotion regulation networks have been linked to depression, anxiety, impulsivity, and aggression. Altered transmission of the central nervous serotonin (5-HT) contributes to dysfunctions in the cognitive control of emotions. To date, studies relating to pharmaco-fMRI challenging of the 5-HT system have focused on emotion processing for facial expressions. We investigated effects of a single-dose selective 5-HT reuptake inhibitor (escitalopram) on emotion regulation during virtual violence. For this purpose, 38 male participants played a violent video game during fMRI scanning. The SSRI reduced neural responses to violent actions in right-hemispheric inferior frontal gyrus and medial prefrontal cortex encompassing the anterior cingulate cortex (ACC), but not to non-violent actions. Within the ACC, the drug effect differentiated areas with high inhibitory 5-HT1A receptor density (subgenual s25) from those with a lower density (pregenual p32, p24). This finding links functional responses during virtual violent actions with 5-HT neurotransmission in emotion regulation networks, underpinning the ecological validity of the 5-HT model in aggressive behavior. Available 5-HT receptor density data suggest that this SSRI effect is only observable when inhibitory and excitatory 5-HT receptors are balanced. The observed early functional changes may impact patient groups receiving SSRI treatment.

Original languageEnglish
Pages (from-to)3327-3345
Number of pages19
JournalBrain Structure and Function
Issue number7
StatePublished - 1 Sep 2018

Bibliographical note

Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature.


  • Medial prefrontal cortex
  • Pharmaco-fMRI
  • SSRI
  • Serotonin
  • Virtual violence


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