Brain Structure and Function

, Volume 223, Issue 7, pp 3327–3345 | Cite as

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
Original Article


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.


SSRI Serotonin Virtual violence Medial prefrontal cortex Pharmaco-fMRI 



The authors would like to thank Cordula Kemper for assistance with measurements, the study participants for their participation, and the Brain Imaging Facility of the Interdisciplinary Centre for Clinical Research (ICCR) Aachen for technical support.


This study was funded by the German Research Foundation [DFG IRTG 2150, MA 2631/6-1]; the German Ministry for Education and Research [BMBF; APIC: 01EE1405A, 01EE1405B, 02EE1405C] and the Interdisciplinary Centre for Clinical Research (ICCR) Aachen (N4-2). This project has received funding from the European Union’s Horizon 2020 Framework Programme for Research and Innovation under Grant Agreement No 720270 (Human Brain Project SGA1).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

The experiment was designed and conducted according to the Code of Ethics of the World Medical Association (Declaration of Helsinki) and the study protocol was approved by the local Ethics Committee.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

429_2018_1693_MOESM1_ESM.tif (265 kb)
Supplementary material 1 (TIF 265 KB)
429_2018_1693_MOESM2_ESM.docx (24 kb)
Supplementary material 2 (DOCX 23 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Dhana Wolf
    • 1
  • Martin Klasen
    • 1
  • Patrick Eisner
    • 1
  • Florian D. Zepf
    • 2
    • 3
  • Mikhail Zvyagintsev
    • 1
  • Nicola Palomero-Gallagher
    • 1
    • 4
  • René Weber
    • 5
  • Albrecht Eisert
    • 6
    • 7
  • Klaus Mathiak
    • 1
    • 8
  1. 1.Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical FacultyRWTH AachenAachenGermany
  2. 2.Centre and Discipline of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Division of Psychiatry and Clinical Neurosciences and Division of Paediatrics and Child Health, School of MedicineThe University of Western AustraliaPerthAustralia
  3. 3.Specialised Child and Adolescent Mental Health ServicesDepartment of Health in Western AustraliaPerthAustralia
  4. 4.Institute of Neuroscience and Medicine (INM-1)Research Centre JülichJülichGermany
  5. 5.Media Neuroscience Lab, Department of CommunicationUniversity of California Santa BarbaraSanta BarbaraUSA
  6. 6.Department of PharmacyRWTH AachenAachenGermany
  7. 7.Department of Pharmacology and ToxicologyRWTH AachenAachenGermany
  8. 8.JARA-Translational Brain MedicineAachenGermany

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