Hit or Run: Exploring Aggressive and Avoidant Reactions to Interpersonal Provocation Using a Novel Fight-or-Escape Paradigm (FOE)

Interpersonal provocation presents an approach-avoidance conflict to the provoked person: responding aggressively might yield the joy of retribution, whereas withdrawal can provide safety. Experimental aggression studies typically measure only retaliation intensity, neglecting whether individuals want to confront the provocateur at all. To overcome this shortcoming of previous measures, we developed and validated the Fight-or-Escape paradigm (FOE). The FOE is a competitive reaction time task in which the winner can choose the volume of a sound blast to be directed at his/her opponent. Participants face two ostensible opponents who consistently select either high or low punishments. At the beginning of each trial, subjects are given the chance to avoid the encounter for a limited number of times. In a first experiment (n=27, all women), we found that fear potentiation of the startle response was related to lower scores in a composite measure of aggression and avoidance against the provoking opponent. In a second experiment (n=34, 13 men), we altered the paradigm such that participants faced the opponents in alternating rather than in random order. Participants completed the FOE as well as the Dot-Probe Task (DPT) and the Approach-Avoidance Task (AAT). Subjects with higher approach bias scores in the AAT avoided the provoking opponent less frequently. Hence, individuals with high threat reactivity and low approach motivation displayed more avoidant responses to provocation, whereas participants high in approach motivation were more likely to engage in aggressive interactions when provoked. The FOE is thus a promising laboratory measure of avoidance and aggression

An fMRI Study on the Role of Serotonin in Reactive Aggression

Reactive aggression after interpersonal provocation is a common behavior in humans. Little is known, however, about brain regions and neurotransmitters critical for the decision-making and affective processes involved in aggressive interactions. With the present fMRI study, we wanted to examine the role of serotonin in reactive aggression by means of an acute tryptophan depletion (ATD). Participants performed in a competitive reaction time task (Taylor Aggression Paradigm, TAP) which entitled the winner to punish the loser. The TAP seeks to elicit aggression by provocation. The study followed a double-blind between-subject design including only male participants. Behavioral data showed an aggression diminishing effect of ATD in low trait-aggressive participants, whereas no ATD effect was detected in high trait-aggressive participants. ATD also led to reduced insula activity during the decision phase, independently of the level of provocation. Whereas previous reports have suggested an inverse relationship between serotonin level and aggressive behavior with low levels of serotonin leading to higher aggression and vice versa, such a simple relationship is inconsistent with the current data

When decisions of others matter to me: an electrophysiological analysis

Background: Actions of others may have immediate consequences for oneself. We probed the neural responses associated with the observation of another person"s action using event-related potentials in a modified gambling task. In this task a"performer" bet either a higher or lower number and could win or lose this amount. Three different groups of"observers" were also studied. The first (neutral) group simply observed the performer"s action, which had no consequences for the observers. In the second (parallel) group, wins/losses of the performer were paralleled by similar wins and losses by the observer. In the third (reverse) group, wins of the performer led to a loss of the observer and vice versa. Results: ERPs of the performers showed a mediofrontal feedback related negativity (FRN) to losses. The neutral and parallel observer groups did similarly show an FRN response to the performer"s losses with a topography indistinguishable from that seen in the performers. In the reverse group, however, the FRN occurred for wins of the performer which translated to losses for the observer. Conclusions: Taking into account previous experiments, we suggest that the FRN response in observers is driven by two evaluative processes (a) related to the benefit/loss for oneself and (b) related to the benefit/loss of another perso

Aggressive and psychopathic traits are linked to the acquisition of stable but imprecise hostile expectations

Individuals with hostile expectations (HEX) anticipate harm from seemingly neutral or ambiguous stimuli. However, it is unclear how HEX are acquired, and whether specific components of HEX learning can predict antisocial thought, conduct, and personality. In an online sample of healthy young individuals (n = 256, 69% women), we administered a virtual shooting task and applied computational modelling of behaviour to investigate HEX learning and its constellation of correlates. HEX acquisition was best explained by a hierarchical reinforcement learning mechanism. Crucially, we found that individuals with relatively higher self-reported aggressiveness and psychopathy developed stronger and less accurate hostile beliefs as well as larger prediction errors. Moreover, aggressive and psychopathic traits were associated with more temporally stable hostility representations. Our study thus shows that aggressiveness and psychopathy are linked with the acquisition of robust yet imprecise hostile beliefs through reinforcement learning

Self-Assessment of Individual Differences in Language Switching

Language switching is omnipresent in bilingual individuals. In fact, the ability to switch languages (code switching) is a very fast, efficient, and flexible process that seems to be a fundamental aspect of bilingual language processing. In this study, we aimed to characterize psychometrically self-perceived individual differences in language switching and to create a reliable measure of this behavioral pattern by introducing a bilingual switching questionnaire. As a working hypothesis based on the previous literature about code switching, we decomposed language switching into four constructs: (i) L1 switching tendencies (the tendency to switch to L1; L1-switch); (ii) L2 switching tendencies (L2-switch); (iii) contextual switch, which indexes the frequency of switches usually triggered by a particular situation, topic, or environment; and (iv) unintended switch, which measures the lack of intention and awareness of the language switches. A total of 582 Spanish–Catalan bilingual university students were studied. Twelve items were selected (three for each construct). The correlation matrix was factor-analyzed using minimum rank factor analysis followed by oblique direct oblimin rotation. The overall proportion of common variance explained by the four extracted factors was 0.86. Finally, to assess the external validity of the individual differences scored with the new questionnaire, we evaluated the correlations between these measures and several psychometric (language proficiency) and behavioral measures related to cognitive and attentional control. The present study highlights the importance of evaluating individual differences in language switching using self-assessment instruments when studying the interface between cognitive control and bilingualism

The role of executive functions in the control of aggressive behavior

An extensive literature suggests a link between executive functions and aggressive behavior in humans, pointing mostly to an inverse relationship, i.e., increased tendencies toward aggression in individuals scoring low on executive function tests. This literature is limited, though, in terms of the groups studied and the measures of executive functions. In this paper, we present data from two studies addressing these issues. In a first behavioral study, we asked whether high trait aggressiveness is related to reduced executive functions. A sample of over 600 students performed in an extensive behavioral test battery including paradigms addressing executive functions such as the Eriksen Flanker task, Stroop task, n-back task, and Tower of London (TOL). High trait aggressive participants were found to have a significantly reduced latency score in the TOL, indicating more impulsive behavior compared to low trait aggressive participants. No other differences were detected. In an EEG-study, we assessed neural and behavioral correlates of error monitoring and response inhibition in participants who were characterized based on their laboratory-induced aggressive behavior in a competitive reaction time task. Participants who retaliated more in the aggression paradigm and had reduced frontal activity when being provoked did not, however, show any reduction in behavioral or neural correlates of executive control compared to the less aggressive participants. Our results question a strong relationship between aggression and executive functions at least for healthy, high-functioning people

Endogenous testosterone is associated with lower amygdala reactivity to angry faces and reduced aggressive behavior in healthy young women

Testosterone and cortisol have been proposed to influence aggressive behavior by altering the neural processing of facial threat signals. However, this has not been investigated in direct social interactions. Here, we explored the joint impact of testosterone, cortisol, and brain reactivity to anger expressions on women's reactive aggression in the Social Threat Aggression Paradigm (STAP). The STAP is a competitive reaction time task in which the purported opponent displays either an angry or a neutral facial expression at the beginning of each trial and delivers increasingly loud sound blasts to the participants, successfully provoking them. Strikingly, salivary testosterone at scan-time was negatively related to both aggression and basolateral amygdala (BLA) reactivity to angry faces, whereas cortisol had no effect. When the opponent looked angry, BLA-orbitofrontal coupling was reduced, and BLA reactivity was positively related to aggression. The latter relationship was fully mediated by bilateral superior temporal gyrus (STG) activation. Our results thus support previous neurobiological models of aggression, and extend them by demonstrating that fast amygdala responses to threat modulate STG activity in order to favor aggressive retaliation. Furthermore, our study agrees with recent evidence underscoring a fear-reducing and strategically prosocial effect of testosterone on human social behavior

Population Pharmacokinetic Modeling for Twice-Daily Intravenous Busulfan in a Large Cohort of Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation—A 10-Year Single-Center Experience

Reaching target exposure of busulfan-based conditioning prior to hematopoietic stem cell transplantation is vital for favorable therapy outcomes. Yet, a wide inter-patient and inter-occasion variability in busulfan exposure has been reported, especially in children. We aimed to identify factors associated with the variability of busulfan pharmacokinetics in 124 consecutive patients transplanted at the University Children’s Hospital Zurich between October 2010 and February 2020. Clinical data and busulfan plasma levels after twice-daily intravenous administration were analyzed retrospectively by population pharmacokinetic modeling. The volume of distribution correlated with total body water. The elimination rate constant followed an age-dependent maturation function, as previously suggested, and correlated with the levels of serum albumin. Acute lymphoblastic leukemia reduced busulfan clearance by 20%. Clearance significantly decreased by 17% on average from the start to the third day of busulfan administration, in agreement with other studies. An average reduction of 31% was found in patients with hemophagocytic lymphohistiocytosis and X-linked lymphoproliferative disease. In conclusion, we demonstrate that in addition to known factors, underlying disease and serum albumin significantly impact busulfan pharmacokinetics in pediatric patients; yet, substantial unexplained variability in some patients remained. Thus, we consider repeated pharmacokinetic assessment essential to achieve the desired target exposure in twice-daily busulfan administration

Nucleus Accumbens is Involved in Human Action Monitoring: Evidence from Invasive Electrophysiological Recordings

The Nucleus accumbens (Nacc) has been proposed to act as a limbic-motor interface. Here, using invasive intraoperative recordings in an awake patient suffering from obsessive-compulsive disease (OCD), we demonstrate that its activity is modulated by the quality of performance of the subject in a choice reaction time task designed to tap action monitoring processes. Action monitoring, that is, error detection and correction, is thought to be supported by a system involving the dopaminergic midbrain, the basal ganglia, and the medial prefrontal cortex. In surface electrophysiological recordings, action monitoring is indexed by an error-related negativity (ERN) appearing time-locked to the erroneous responses and emanating from the medial frontal cortex. In preoperative scalp recordings the patient's ERN was found to be significantly increased compared to a large (n = 83) normal sample, suggesting enhanced action monitoring processes. Intraoperatively, error-related modulations were obtained from the Nacc but not from a site 5 mm above. Importantly, cross-correlation analysis showed that error-related activity in the Nacc preceded surface activity by 40 ms. We propose that the Nacc is involved in action monitoring, possibly by using error signals from the dopaminergic midbrain to adjust the relative impact of limbic and prefrontal inputs on frontal control systems in order to optimize goal-directed behavior

The influence of anger on empathy and theory of mind

Social cognition allows humans to understand and predict other people's behavior by inferring or sharing their emotions, intentions and beliefs. Few studies have investigated the impact of one's own emotional state on understanding others. Here, we tested the effect of being in an angry state on empathy and theory of mind (ToM). In a between-groups design we manipulated anger status with different paradigms in three studies (autobiographical recall (N = 45), negative feedback (N = 49), frustration (N = 46)) and checked how this manipulation affected empathic accuracy and performance in the EmpaToM. All paradigms were successful in inducing mild anger. We did not find the expected effect of anger on empathy or ToM performance but observed small behavioral changes. Together, our results validate the use of three different anger induction paradigms and speak for rather weak behavioral effects of mild state anger on empathy and ToM