Performing a Motor Action Enhances Social Reward Processing and Modulates the Neural Processing of Predictive Cues.

Associative learning affects many areas of human behavior. Recently, we showed that the neural response to monetary reward is enhanced by performing an action, suggesting interactions between neural systems controlling motor behavior and reward processing. Given many psychiatric disorders are associated with social anhedonia, a key open question is whether such effects generalize to social rewards, and in how far they affect associative learning. We developed a novel task in which participants (n = 66) received social reward feedback and social punishment either by pressing a button or waiting. Predictive cues were linked to feedback valence with 80% accuracy. Using EEG, we measured the neural response to both predictive cues and social feedback. We found enhanced reward positivity for social reward preceded by an action, and an enhanced N2 for cues predicting negative feedback. Cue-locked P3 amplitude was reduced for cues associated with negative feedback in passive trials only, showing a modulation of outcome anticipation by performing a motor action. This was supported by connectivity analyses showing stronger directed theta synchronization, in line with increased top-down modulation of attention, in active compared with passive trials. These findings suggest that actively obtaining social feedback enhances reward sensitivity and modulates outcome anticipation.

Vibrational Circular Dichroism of a Chiral Triplet Nitrene Investigated Under Matrix-Isolation Conditions in Parahydrogen.

Vibrational circular dichroism (VCD) spectra of chiral high-spin organic radicals are expected to show a strong intensity enhancement and are thought to be difficult to predict using state-of-the-art theoretical methods. Herein we show that the chiral triplet nitrene obtained from photochemical cleavage of N2 from enantiopure 2-azido-9H-fluorenol does not feature extraordinarily strong intensities and that the experimental spectra match nicely with calculated ones. Thereby, this study demonstrates the general feasibility of studies on chiral high-spin organics by matrix-isolation VCD.

Enantioselective, Intermolecular [π2+σ2] Photocycloaddition Reactions of 2(1H)-Quinolones and Bicyclo[1.1.0]butanes.

1-Substituted bicyclo[1.1.0]butanes add enantioselectively to 2(1H)-quinolones upon irradiation (λ = 366 nm) in the presence of a chiral complexing agent. A two-point hydrogen bond between the quinolone and the template is responsible for stereocontrol in the photocycloaddition reaction. The reaction leads to the formation of products with a chiral bicyclo[2.1.1]hexane skeleton in high enantiomeric excess (91-99% ee). The chiral template can be almost quantitatively (97%) recovered and used in another reaction. A triplet reaction pathway is likely, and sensitization is a suitable tool if the reaction is to be performed with visible light (λ = 420 nm).

Enantioselective Synthesis of Arylglycines via Pd-Catalyzed Coupling of Schöllkopf Bis-Lactim Ethers with Aryl Chlorides.

Arylglycines are important pharmacophores present in several top-selling drugs. This compound class has now been made accessible from abundant aryl chlorides by a Pd-catalyzed Schöllkopf-type amino acid synthesis. In the presence of the catalyst methylnaphthyl(XPhos)-palladium bromide, the base lithium 2,2,6,6-tetramethylpyrrolidide and the additive ZnCl2 , tert-leucine-derived bis-lactim ethers were efficiently arylated at room temperature, reaching yields of 95 % and diastereoselectivities of 98 : 2. Hydrolysis gave the corresponding arylglycines in high enantiomeric excess.

Isomer-Specific Heavy-Atom Tunneling in the Ring Expansion of Fluorenylazirines.

The photolysis of 2-azidofluorene in solid argon at 3 K results in the formation of 2-fluorenylnitrene. The nitrene undergoes subsequent rearrangements to two isomeric didehydroazepines (ketenimines) which differ in the position of the N atom in the seven-membered ring. The rearrangement of the nitrene to the didehydroazepines proceeds in a two-step process. The first step is a photochemical rearrangement to form the corresponding isomeric benzazirines A and B. The second step is the opening of the three-membered rings of A and B to form the isomeric didehydroazepines. While benzazirine A could easily be detected, isomer B was not observed, despite the corresponding didehydroazepine being formed in the matrix. Further experiments revealed that A rearranges to the didehydroazepine via heavy-atom tunneling. Semiquantitative estimations based on DFT calculations confirm that A should undergo a tunneling rearrangement with tunneling rates on the order of the experimentally observed rates. In contrast, estimations for B suggest that for this isomer the tunneling rates should be much larger, resulting in lifetimes too short to be observable under the conditions of matrix isolation. These experiments demonstrate the influence of position isomerism on quantum tunneling rates.

The value of an action: Impact of motor behaviour on outcome processing and stimulus preference.

While influences of Pavlovian associations on instrumental behaviour are well established, we still do not know how motor actions affect the formation of Pavlovian associations. To address this question, we designed a task in which participants were presented with neutral stimuli, half of which were paired with an active response, half with a passive waiting period. Stimuli had an 80% chance of predicting either a monetary gain or loss. We compared the feedback-related negativity (FRN) in response to predictive stimuli and outcomes, as well as directed phase synchronization before and after outcome presentation between trials with versus without a motor response. We found a larger FRN amplitude in response to outcomes presented after a motor response (active trials). This effect was driven by a positive deflection in active reward trials, which was absent in passive reward trials. Connectivity analysis revealed that the motor action reversed the direction of the phase synchronization at the time of the feedback presentation: Top-down information flow during the outcome anticipation phase in active trials, but bottom-up information flow in passive trials. This main effect of action was mirrored in behavioural data showing that participants preferred stimuli associated with an active response. Our findings suggest an influence of neural systems that initiate motor actions on neural systems involved in reward processing. We suggest that motor actions might modulate the brain responses to feedback by affecting the dynamics of brain activity towards optimizing the processing of the resulting action outcome.

Structural covariance of amygdala subregions is associated with trait aggression and endogenous testosterone in healthy individuals.

Many studies point toward volume reductions in the amygdala as a potential neurostructural marker for trait aggression. However, most of these findings stem from clinical samples, rendering unclear whether the findings generalize to non-clinical populations. Furthermore, the notion of neural networks suggests that interregional correlations in gray matter volume (i.e., structural covariance) can explain individual differences in aggressive behavior beyond local univariate associations. Here, we tested whether structural covariance between amygdala subregions and the rest of the brain is associated with self-reported aggression in a large sample of healthy young students (n = 263; 49% women). Salivary testosterone concentrations were measured for a subset of n = 40 male and n = 36 female subjects, allowing us to investigate the influence of endogenous testosterone on structural covariance. Aggressive individuals showed enhanced covariance between left superficial amygdala (SFA) and left dorsal anterior insula (dAI), but lower covariance between right laterobasal amygdala (LBA) and right dorsolateral prefrontal cortex (dlPFC). These structural patterns overlap with functional networks involved in the genesis and regulation of aggressive behavior, respectively. With increasing endogenous testosterone, we observed stronger structural covariance between right centromedial amygdala (CMA) and right medial prefrontal cortex in men and between left CMA and bilateral orbitofrontal cortex in women. These results speak for structural covariance of amygdala subregions as a robust correlate of trait aggression in healthy individuals. Moreover, regions that showed structural covariance with the amygdala modulated by either testosterone or aggression did not overlap, suggesting a complex role of testosterone in human social behavior beyond facilitating aggressiveness.

The obedient mind and the volitional brain: A neural basis for preserved sense of agency and sense of responsibility under coercion.

Milgram's classical studies famously suggested a widespread willingness to obey authority, even to the point of inflicting harm. Important situational factors supporting obedience, such as proximity with the victim, have been established. Relatively little work has focused on how coercion affects individual cognition, or on identifying the cognitive factors that underlie inter-individual differences in the tendency to yield to coercion. Here, we used fMRI to investigate the neural systems associated with changes in volitional processes associated with sense of agency and sense of responsibility under coercion. Participants either freely chose, or were instructed by the experimenter, to give mildly painful electric shocks to another participant, or to refrain from doing so. We have previously shown that coercion reduces temporal binding, which has been proposed as an implicit proxy measure of sense of agency. We tested how reduced agency under coercion related to differences in neural activity between free choice and coercion. In contrast to previous studies and to participants performing the task outside the MRI scanner, on average there was no effect of coercion on agency for participants in the scanner. However, greater activity in the medial frontal gyrus was reliably associated with greater agency under coercion. A similar association was found using explicit responsibility ratings. Our findings suggest that medial frontal processes, perhaps related to volition during action planning and execution, may help to preserve a sense of accountability under coercion. Further, participants who administered more shocks under free choice showed reduced activity during free choice trials in brain areas associated with social cognition. Possibly, this might reflect participants cognitively distancing themselves from the recipient of the shocks under free choice, whereas this was not observed under coercion.

Regulating interpersonal stress: the link between heart-rate variability, physical exercise and social perspective taking under stress.

Social interactions can be stressful, especially if they involve provocation or ambiguity. At the same time, such interactions necessitate social cognition. The question thus arises how stress affects social cognition and how personality attributes modulate this effect. The aim of the current study was to investigate the link between emotional reactivity, physical exercise, and social cognition under stress. As a measure of social cognition, we used spontaneous perspective taking, i.e., the degree to which participants represented the mental state of another agent. Studying young female participants, we investigated how physiological regulation, measured through resting heart-rate variability, is related to spontaneous social perspective taking under stress, and to predicted anger in an ambiguous social scenario. When controlling for resting heart rate, vagally mediated heart-rate variability was negatively correlated with the effect of stress on perspective taking, indicating that good physiological regulation supports social cognition under stress. Further, participants who reported to exercise at least once a week showed higher perspective taking under stress than less active participants. Finally, we found tentative evidence for participants who exercised regularly to show reduced predicted anger in response to an ambiguous provocation. Our findings suggest that good physiological regulation and regular physical exercise support social cognition under stress.

Heavy-Atom Tunneling in Semibullvalenes: How Driving Force, Substituents, and Environment Influence the Tunneling Rates.

Invited for the cover of this issue are the groups of Elsa Sanchez-Garcia and Wolfram Sander at the Universität Duisburg-Essen and the Ruhr-Universität Bochum. The image depicts the ideas skillfully visualized by Markus Henkel on the shift in equilibrium induced by isotopic labelling. Read the full text of the article at 10.1002/chem.202001202.

Neural basis of shame and guilt experience in women with borderline personality disorder.

Borderline personality disorder (BPD) is characterized by instability of affect, emotion dysregulation, and interpersonal dysfunction. Especially shame and guilt, so-called self-conscious emotions, are of central clinical relevance to BPD. However, only few experimental studies have focused on shame or guilt in BPD and none investigated their neurobiological underpinnings. In the present functional magnetic resonance imaging study, we took a scenario-based approach to experimentally induce feelings of shame, guilt, and disgust with neutral scenarios as control condition. We included 19 women with BPD (age 26.4 ± 5.8 years; DSM-IV diagnosed; medicated) and 22 healthy female control subjects (age 26.4 ± 4.6 years; matched for age and verbal IQ). Compared to controls, women with BPD reported more intense feelings when being confronted with affective scenarios, especially higher levels of shame, guilt, and fear. We found increased amygdala reactivity in BPD compared to controls for shame and guilt, but not for disgust scenarios (p = 0.05 FWE corrected at the cluster level; p < 0.0001 cluster defining threshold). Exploratory analyses showed that this was caused by a diminished habituation in women with BPD relative to control participants. This effect was specific to guilt and shame scenarios as both groups showed amygdala habituation to disgust scenarios. Our work suggests that heightened shame and guilt experience in BPD is not related to increased amygdala activity per se, but rather to decreased habituation to self-conscious emotions. This provides an explanation for the inconsistencies in previous imaging work on amygdala involvement in BPD as well as the typically slow progress in the psychotherapy of dysfunctional self-conscious emotions in this patient group.

Heavy-Atom Tunneling in Semibullvalenes: How Driving Force, Substituents, and Environment Influence the Tunneling Rates.

The Cope rearrangement of selectively deuterated isotopomers of 1,5-dimethylsemibullvalene 2 a and 3,7-dicyano-1,5-dimethylsemibullvalene 2 b were studied in cryogenic matrices. In both semibullvalenes the Cope rearrangement is governed by heavy-atom tunneling. The driving force for the rearrangements is the small difference in the zero-point vibrational energies of the isotopomers. To evaluate the effect of the driving force on the tunneling probability in 2 a and 2 b, two different pairs of isotopomers were studied for each of the semibullvalenes. The reaction rates for the rearrangement of 2 b in cryogenic matrices were found to be smaller than the ones of 2 a under similar conditions, whereas differences in the driving force do not influence the rates. Small curvature tunneling (SCT) calculations suggest that the reduced tunneling rate of 2 b compared to that of 2 a results from a change in the shape of the potential energy barrier. The tunneling probability of the semibullvalenes strongly depends on the matrix environment; however, for 2 a in a qualitatively different way than for 2 b.

Attribution of intentional agency towards robots reduces one's own sense of agency.

In the presence of others, sense of agency (SoA), i.e. the perceived relationship between our own actions and external events, is reduced. The present study aimed at investigating whether the phenomenon of reduced SoA is observed in human-robot interaction, similarly to human-human interaction. To this end, we tested SoA when people interacted with a robot (Experiment 1), with a passive, non-agentic air pump (Experiment 2), or when they interacted with both a robot and a human being (Experiment 3). Participants were asked to rate the perceived control they felt on the outcome of their action while performing a diffusion of responsibility task. Results showed that the intentional agency attributed to the artificial entity differently affect the performance and the perceived SoA on the outcome of the task. Experiment 1 showed that, when participants successfully performed an action, they rated SoA over the outcome as lower in trials in which the robot was also able to act (but did not), compared to when they were performing the task alone. However, this did not occur in Experiment 2, where the artificial entity was an air pump, which had the same influence on the task as the robot, but in a passive manner and thus lacked intentional agency. Results of Experiment 3 showed that SoA was reduced similarly for the human and robot agents, threby indicating that attribution of intentional agency plays a crucial role in reduction of SoA. Together, our results suggest that interacting with robotic agents affects SoA, similarly to interacting with other humans, but differently from interacting with non-agentic mechanical devices. This has important implications for the applied of social robotics, where a subjective decrease in SoA could have negative consequences, such as in robot-assisted care in hospitals.

Losing Control in Social Situations: How the Presence of Others Affects Neural Processes Related to Sense of Agency.

Social contexts substantially influence individual behavior, but little is known about how they affect cognitive processes related to voluntary action. Previously, it has been shown that social context reduces participants' sense of agency over the outcomes of their actions and outcome monitoring. In this fMRI study on human volunteers, we investigated the neural mechanisms by which social context alters sense of agency. Participants made costly actions to stop inflating a balloon before it burst. On "social" trials, another player could act in their stead, but we analyzed only trials in which the other player remained passive. We hypothesized that mentalizing processes during social trials would affect decision-making fluency and lead to a decreased sense of agency. In line with this hypothesis, we found increased activity in the bilateral temporo-parietal junction (TPJ), precuneus, and middle frontal gyrus during social trials compared with nonsocial trials. Activity in the precuneus was, in turn, negatively related to sense of agency at a single-trial level. We further found a double dissociation between TPJ and angular gyrus (AG): activity in the left AG was not sensitive to social context but was negatively related to sense of agency. In contrast, activity in the TPJ was modulated by social context but was not sensitive to sense of agency.

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 (RT) 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 (FP) 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.

Anger-sensitive networks: characterizing neural systems recruited during aggressive social interactions using data-driven analysis.

Social neuroscience uses increasingly complex paradigms to improve ecological validity, as investigating aggressive interactions with functional magnetic resonance imaging (fMRI). Standard analyses for fMRI data typically use general linear models (GLM), which require a priori models of task effects on neural processes. These may inadequately model non-stimulus-locked or temporally overlapping cognitive processes, as mentalizing about other agents. We used the data-driven approach of independent component analysis (ICA) to investigate neural processes involved in a competitive interaction. Participants were confronted with an angry-looking opponent while having to anticipate the trial outcome and the opponent's behaviour. We show that several spatially distinctive neural networks with associated temporal dynamics were modulated by the opponent's facial expression. These results dovetail and extend the main effects observed in the GLM analysis of the same data. Additionally, the ICA approach identified effects of the experimental condition on neural systems during inter-trial intervals. We demonstrate that cognitive processes during aggressive interactions are poorly modelled by simple stimulus onset/duration variables and instead have more complex temporal dynamics. This highlights the utility of using data-driven analyses to elucidate the distinct cognitive processes recruited during complex social paradigms.

Avoidant Responses to Interpersonal Provocation Are Associated with Increased Amygdala and Decreased Mentalizing Network Activity.

When intentionally pushed or insulted, one can either flee from the provoker or retaliate. The implementation of such fight-or-flight decisions is a central aspect in the genesis and evolution of aggression episodes, yet it is usually investigated only indirectly or in nonsocial situations. In the present fMRI study, we aimed to distinguish brain regions associated with aggressive and avoidant responses to interpersonal provocation in humans. Participants (thirty-six healthy young women) could either avoid or face a highly (HP) and a lowly (LP) provoking opponent in a competitive reaction time task: the fight-or-escape (FOE) paradigm. Subjects avoided the HP more often, but retaliated when facing her. Moreover, they chose to fight the HP more quickly, and showed increased heart rate (HR) right before confronting her. Orbitofrontal cortex (OFC) and sensorimotor cortex were more active when participants decided to fight, whereas the mentalizing network was engaged when deciding to avoid. Importantly, avoiding the HP relative to the LP was associated with both higher activation in the right basolateral amygdala and lower relative activity in several mentalizing regions [e.g., medial and inferior frontal gyrus (IFG), temporal-parietal junction (TPJ)]. These results suggest that avoidant responses to provocation might result from heightened threat anticipation and are associated with reduced perspective taking. Furthermore, our study helps to reconcile conflicting findings on the role of the mentalizing network, the amygdala, and the OFC in aggression.

Human subthalamic nucleus - Automatic auditory change detection as a basis for action selection.

The subthalamic nucleus (STN) shapes motor behavior and is important for the initiation and termination of movements. Here we ask whether the STN takes aggregated sensory information into account, in order to exert this function. To this end, local field potentials (LFP) were recorded in eight patients suffering from Parkinson's disease and receiving deep-brain stimulation of the STN bilaterally. Bipolar recordings were obtained postoperatively from the externalized electrode leads. Patients were passively exposed to trains of auditory stimuli containing global deviants, local deviants or combined global/local deviants. The surface event-related potentials of the Parkinson's patients as well as those of 19 age-matched healthy controls were characterized by a mismatch negativity (MMN) that was most pronounced for the global/local double deviants and less prominent for the other deviant conditions. The left and right STN LFPs similarly were modulated by stimulus deviance starting at about 100ms post-stimulus onset. The MMN has been viewed as an index of an automatic auditory change detection system, more recently phrased in terms of predictive coding theory, which prepares the organism for attention shifts and for action. The LFP-data from the STN clearly demonstrate that the STN receives information on stimulus deviance, possibly as a means to bias the system to interrupt ongoing and to allow alternative actions.

Beyond self-serving bias: diffusion of responsibility reduces sense of agency and outcome monitoring.

Diffusion of responsibility across agents has been proposed to underlie decreased helping and increased aggression in group behaviour. However, few studies have directly investigated effects of the presence of other people on how we experience the consequences of our actions. This EEG study investigated whether diffusion of responsibility simply reflects a post-hoc self-serving bias, or rather has direct effects on how we process the outcomes of our actions, and our experience of agency over them. Participants made voluntary actions whose outcomes were more or less negative. Presence of another potential agent reduced participants' sense of agency over those outcomes, even though it was always obvious who caused each outcome. Further, presence of another agent reduced the amplitude of feedback-related negativity evoked by outcome stimuli, suggesting reduced outcome monitoring. The presence of other agents may lead to diffusion of responsibility by weakening the neural linkage between one's actions and their outcomes.

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.