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

Abstract

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.

Serotonergic Contributions to Human Brain Aggression Networks

“…Each participant was measured in an ATD and a placebo condition, taking place on separate days. Findings from a third condition (escitalopram) have previously been reported in Wolf et al (2018). The measurements were separated by at least 1 week allowing for a sufficient washout.…”

“…Transfer effects between playing realistic and salient violent video games and real-life aggression have been demonstrated in both experimental and longitudinal behavioral studies (Prescott et al, 2018). Thus, a violent video game task can serve as a valid aggression model and has been employed in various neuroimaging studies on aggression (e.g., Klasen et al, 2013; Zvyagintsev et al, 2016; Wolf et al, 2018). Serotonin levels were manipulated via ATD challenge in a double-bind, randomized, and placebo-controlled design.…”

Interpretation of Social Interactions: Functional Imaging of Cognitive-Semiotic Categories During Naturalistic Viewing

“…The sign-interpretant relation of the UCs has scarcely been used as a construct for neuroimaging studies. We investigated conventionality in co-speech gestures with the sign-interpretant relation of thirdness (UC3, Wolf et al, 2018 ). Perceiving a gesture as conventional increased intersubject covariance (ISC) in left inferior frontal gyrus (IFG) and posterior STG.…”

Predicting Antidepressant Citalopram Treatment Response via Changes in Brain Functional Connectivity After Acute Intravenous Challenge

“…These regions also display high individual prediction weights for all factors and might represent the influence of MDD on emotion processing (Loeffler et al, 2018 ). Furthermore, activation of these regions was shown to be indicative for future recurrence of depression (Langenecker et al, 2018b ) and can be modulated using SSRIs (Wolf et al, 2018 ). Leaver et al ( 2018 ) predicted electroconvulsive therapy outcomes with BACs of 58–68%: Across CV splits, FP, motor and superior temporal regions were most often selected as important nodes.…”