Sex-dependent multimodal response profiles to psychosocial stress.

INTRODUCTION: Sex differences in stress reactions are often reported in the literature. However, the sex-dependent interplay of different facets of stress is still not fully understood. Particularly in neuroimaging research, studies on large samples combining different indicators of stress remain scarce. MATERIALS AND METHODS: In a functional magnetic resonance imaging study, a sample of 140 healthy participants (67 females using oral contraceptives) underwent a standardized stress induction protocol, the ScanSTRESS. During the experiment, salivary cortisol and subjective ratings were obtained at multiple time points and heart rate was recorded. RESULTS: Sex differences emerged in different facets of the stress response:Women reacted with enhanced subjective feelings of stress and increases in heart rate, while men showed more pronounced neural activation in stress-related brain regions such as the inferior frontal gyrus and insula. Subjective feelings of stress and (para) hippocampal activity were negatively related in women,whereas a slightly positive association was observed in men. DISCUSSION: These results provide further insight in the sex-specific stress response patterns. Moreover, they emphasize the role of the hippocampus in the regulation of the stress response. This paves the way for the identification of sex-dependent vulnerability factors that can, in the future, be implemented in the prevention and treatment of stress-related disorders.

A Systematic Review on Common and Distinct Neural Correlates of Risk-taking in Substance-related and Non-substance Related Addictions.

Both substance-related as well as non-substance-related addictions may include recurrent engagement in risky actions despite adverse outcomes. We here apply a unified approach and review task-based neuroimaging studies on substance-related (SRAs) and non-substance related addictions (NSRAs) to examine commonalities and differences in neural correlates of risk-taking in these two addiction types. To this end, we conducted a systematic review adhering to the PRISMA guidelines. Two databases were searched with predefined search terms to identify neuroimaging studies on risk-taking tasks in individuals with addiction disorders. In total, 19 studies on SRAs (comprising a total of 648 individuals with SRAs) and 10 studies on NSRAs (comprising a total of 187 individuals with NSRAs) were included. Risk-related brain activation in SRAs and NSRAs was summarized individually and subsequently compared to each other. Results suggest convergent altered risk-related neural processes, including hyperactivity in the OFC and the striatum. As characteristic for both addiction types, these brain regions may represent an underlying mechanism of suboptimal decision-making. In contrast, decreased DLPFC activity may be specific to SRAs and decreased IFG activity could only be identified for NSRAs. The precuneus and posterior cingulate show elevated activity in SRAs, while findings regarding these areas were mixed in NSRAs. Additional scarce evidence suggests decreased ventral ACC activity and increased dorsal ACC activity in both addiction types. Associations between identified activation patterns with drug use severity underpin the clinical relevance of these findings. However, this exploratory evidence should be interpreted with caution and should be regarded as preliminary. Future research is needed to evaluate the findings gathered by this review.

Identifying the duration of emotional stimulus presentation for conscious versus subconscious perception via hierarchical drift diffusion models.

To investigate subliminal priming effects, different durations for stimulus presentation are applied ranging from 8 to 30 ms. This study aims to select an optimal presentation span whichleads to a subconscious processing. 40 healthy participants rated emotional faces (sad, neutral or happy expression) presented for 8.3 ms, 16.7 ms and 25 ms. Alongside subjective and objectivestimulus awareness, task performance was estimated via hierarchical drift diffusion models. Participants reported stimulus awareness in 65 % of the 25 ms trials,in 36 % of 16.7 ms trials, and in 2.5 % of 8.3 ms trials.Emotion-dependent responses were reflected in decreased performance (drift rates, accuracy)during sad trials. The detection rate (probability of making a correct response) during 8.3 ms was 12.2 % and slightly above chance level (33.333 % for three response options) during 16.7 ms trials (36.8 %). The experiments suggest a presentation time of 16.7 ms as optimal for subconscious priming. An emotion-specific response was detected during 16.7 ms while the performanceindicates a subconscious processing.

Anxiety in women referred for colposcopy: a prospective observational study.

PURPOSE: To evaluate the occurrence of anxiety in women attending a colposcopic examination within the new cervical cancer screening in Germany. METHODS: One hundred and fifty-six patients were asked to fill out Spielbergers STAI inventory form prior to their colposcopic examination. For the statistical analysis, a two by two between-group design was applied including the following group factors: the repeat factors included patients, who presented to our centre of dysplasia for the first time (new) and patients who have had an examination in our centre before (repeat). Further, the factor diagnosis included two groups: first, patients with cervical dysplasia and second, patients with vulva diseases. RESULTS: The analysis of the STAI results showed that patients presenting with cervical dysplasia for the first time had the highest levels of anxiety, directly followed by new patients in the vulva group. The ANOVA revealed a main effect of the repeat factor, F(1,140) = 7.53, p = 0.007. There was no significant effect of diagnosis. CONCLUSION: Regardless of the diagnosis, patients being transferred for a colposcopy within the cervical cancer screening program for the first time have very high anxiety levels. The prospect of a potentially painful examination seems to be a key factor. Only a scientific evaluation of the new cervical cancer screening will be able to show if the rising numbers of colposcopic examinations is really worth the risk of exposing so many more women to the emotional distress of a colposcopy.

A meta-analysis on shared and distinct neural correlates of the decision-making underlying altruistic and retaliatory punishment.

Individuals who violate social norms will most likely face social punishment sanctions. Those sanctions are based on different motivation aspects, depending on the context. Altruistic punishment occurs if punishment aims to re-establish the social norms even at cost for the punisher. Retaliatory punishment is driven by anger or spite and aims to harm the other. While neuroimaging research highlighted the neural networks supporting decision-making in both types of punishment in isolation, it remains unclear whether they rely on the same or distinct neural systems. We ran an activation likelihood estimation meta-analysis on functional magnetic resonance imaging data on 24 altruistic and 19 retaliatory punishment studies to investigate the neural correlates of decision-making underlying social punishment and whether altruistic and retaliatory punishments share similar brain networks. Social punishment reliably activated the bilateral insula, inferior frontal gyrus, midcingulate cortex (MCC), and superior and medial frontal gyri. This network largely overlapped with activation clusters found for altruistic punishment. However, retaliatory punishment revealed only one cluster in a posterior part of the MCC, which was not recruited in altruistic punishment. Our results support previous models on social punishment and highlight differential involvement of the MCC in altruistic and retaliatory punishments, reflecting the underlying different motivations.

The association of the 5-HTTLPR polymorphism and the response to different stressors in healthy males.

The experience of stress is related to individual wellbeing and vulnerability to psychopathology. Therefore, understanding the determinants of individual differences in stress reactivity is of great concern from a clinical perspective. The functional promotor polymorphism of the serotonin transporter gene (5-HTTLPR/rs25531) is such a factor, which has been linked to the acute stress response as well as the adverse effect of life stressors. In the present study, we compared the impact of two different stress induction protocols (Maastricht Acute Stress Test and ScanSTRESS) and the respective control conditions on affective ratings, salivary cortisol levels and cognitive performance. To this end, 156 healthy young males were tested and genotyped for the 5-HTTLPR/rs25531 polymorphism. While combined physiological and psychological stress in the MAST led to a greater cortisol increase compared to control conditions as well as the psychosocial ScanSTRESS, subjective stress ratings were highest in the ScanSTRESS condition. Stress induction in general affected working memory capacity but not response inhibition. Subjective stress was also influenced by 5-HTTLPR/rs25531 genotype with the high expression group showing lower stress ratings than lower expression groups. In line with previous research, we identified the low expression variant of the serotonin transporter gene as a risk factor for increased stress reactivity. While some dimensions of the human stress response may be stressor specific, cognitive outcomes such as working memory performance are influenced by stress in general. Different pathways of stress processing and possible underlying mechanisms are discussed.

The Cross-Modal Effects of Sensory Deprivation on Spatial and Temporal Processes in Vision and Audition: A Systematic Review on Behavioral and Neuroimaging Research since 2000.

One of the most significant effects of neural plasticity manifests in the case of sensory deprivation when cortical areas that were originally specialized for the functions of the deprived sense take over the processing of another modality. Vision and audition represent two important senses needed to navigate through space and time. Therefore, the current systematic review discusses the cross-modal behavioral and neural consequences of deafness and blindness by focusing on spatial and temporal processing abilities, respectively. In addition, movement processing is evaluated as compiling both spatial and temporal information. We examine whether the sense that is not primarily affected changes in its own properties or in the properties of the deprived modality (i.e., temporal processing as the main specialization of audition and spatial processing as the main specialization of vision). References to the metamodal organization, supramodal functioning, and the revised neural recycling theory are made to address global brain organization and plasticity principles. Generally, according to the reviewed studies, behavioral performance is enhanced in those aspects for which both the deprived and the overtaking senses provide adequate processing resources. Furthermore, the behavioral enhancements observed in the overtaking sense (i.e., vision in the case of deafness and audition in the case of blindness) are clearly limited by the processing resources of the overtaking modality. Thus, the brain regions that were previously recruited during the behavioral performance of the deprived sense now support a similar behavioral performance for the overtaking sense. This finding suggests a more input-unspecific and processing principle-based organization of the brain. Finally, we highlight the importance of controlling for and stating factors that might impact neural plasticity and the need for further research into visual temporal processing in deaf subjects.

Blunted insula activation reflects increased risk and reward seeking as an interaction of testosterone administration and the MAOA polymorphism.

Testosterone, a male sex hormone, has been suggested to partly explain mixed findings in males and females when investigating behavioral tendencies associated with the MAOA polymorphism. Prior studies indicated that the MAOA polymorphism represents a vulnerability factor for financial risk-taking and harm avoidance and that testosterone increases human risk-taking. We therefore assumed an interactive influence of the MAOA polymorphism and testosterone application on decision making and corresponding neural correlates in a risk and reward context. Stratified for the MAOA polymorphism (S =short, L =long), 103 healthy males were assigned to a placebo or testosterone group (double blind, randomized) receiving a topical gel containing 50 mg testosterone. During a functional MRI scan, the participants performed a sequential decision making task. Our results indicate that testosterone and the MAOA polymorphism jointly influence sequential decision making. The MAOA-S variant was associated with less automatic harm avoidance as reflected in response times on safe decisions. Moreover, after testosterone administration, MAOA-S carriers were more risk-taking. Overall activity in the anterior cingulate cortex, anterior insula and inferior frontal gyrus increased with growing risk for losses. In the anterior insula, testosterone administration mitigated this effect solely in MAOA-S carriers. This might be a reflection of an improved coping during risk-reward conflicts subsequently modulating risky decision making. While the molecular basis is not well defined so far, our results support the assumption of testosterone as a modulatory factor for previously reported sex differences of behavioral associations with the MAOA-S variant. Hum Brain Mapp 38:4574-4593, 2017. © 2017 Wiley Periodicals, Inc.

Exogenous testosterone decreases men's personal distance in a social threat context.

BACKGROUND: Testosterone can motivate human approach and avoidance behavior. Specifically, the conscious recognition of and implicit reaction to angry facial expressions is influenced by testosterone. The study tested whether exogenous testosterone modulates the personal distance (PD) humans prefer in a social threat context. METHODS: 82 healthy male participants underwent either transdermal testosterone (testosterone group) or placebo application (placebo group). Each participant performed a computerized stop-distance task before (T1) and 3.5h after (T2) treatment, during which they indicated how closely they would approach a human, animal or virtual character with varying emotional expression. RESULTS: Men's PD towards humans and animals varied as a function of their emotional expression. In the testosterone group, a pre-post comparison indicated that the administration of 50mg testosterone was associated with a small but significant reduction of men's PD towards aggressive individuals. Men in the placebo group did not change the initially chosen PD after placebo application independent of the condition. However comparing the testosterone and placebo group after testosterone administration did not reveal significant differences. While the behavioral effect was small and only observed as within-group effect it was repeatedly and selectively shown for men's PD choices towards an angry woman, angry man and angry dog in the testosterone group. In line with the literature, our findings in young men support the influential role of exogenous testosterone on male's approach behavior during social confrontations.

[Violence and health. Symptoms, consequences and treatment of victimized patients]. / Gewalt und Gesundheit. Symptome, Folgen und Behandlung betroffener Patientinnen und Patienten.

BACKGROUND: Violence has many faces and often results in a variety of consequences. Some studies indicated different types of violence and health consequences in men and women. However, it is still unclear whether this is reflected in clinical context, for example in a patient sample of a German university hospital. OBJECTIVES: The primary goal of the present study was to analyze associations of violence with health, gender and social, economic, job-related, psychological and physical consequences. In addition, the effects of psychological treatment were examined. MATERIALS AND METHODS: One line of research refers to the survey of more than 5000 patients of the university hospital Aachen, evaluating violence experience and several health complaints anonymously. Another line of research deals with detailed interviews with victims of violence and their experienced consequences. A final data source stems from the evaluation of psychological counseling of patients with prior experience of violence. Changes in subjectively perceived depressive symptoms and acceptance of the treatment are evaluated. RESULTS AND CONCLUSIONS: Experience of violence increases the risk for several health problems, especially the experience of multiple types of violence. The interviews showed that more than 60% of the victims had a clinical diagnosis--independent of sex. The risk for a clinical diagnosis increased with multiple violence experiences during childhood. Patients with a clinical diagnosis indicated more subjective consequences of violence, and consequences of violence were more pronounced in patients that experienced multiple types of violence. The good acceptance as well as the effects on symptomatology and other relevant therapeutic variables provides a first indication for a successful treatment of victims of violence in a clinical context.

Prefrontal tDCS modulates risk-taking in male violent offenders.

Detrimental decision-making is a major problem among violent offenders. Non-invasive brain stimulation offers a promising method to directly influence decision-making and has already been shown to modulate risk-taking in non-violent controls. We hypothesize that anodal transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex beneficially modulates the neural and behavioral correlates of risk-taking in a sample of violent offenders. We expect offenders to show more risky decision-making than non-violent controls and that prefrontal tDCS will induce stronger changes in the offender group. In the current study, 22 male violent offenders and 24 male non-violent controls took part in a randomized double-blind sham-controlled cross-over study applying tDCS over the right dorsolateral prefrontal cortex. Subsequently, participants performed the Balloon Analogue Risk Task (BART) during functional magnetic resonance imaging (fMRI). Violent offenders showed significantly less optimal decision-making compared to non-violent controls. Active tDCS increased prefrontal activity and improved decision-making only in violent offenders but not in the control group. Also, in offenders only, prefrontal tDCS influenced functional connectivity between the stimulated area and other brain regions such as the thalamus. These results suggest baseline dependent effects of tDCS and pave the way for treatment options of disadvantageous decision-making behavior in this population.

A quasi-experimental study in sibling dyads: differential provocation-aggression patterns in the interactive taylor aggression paradigm.

Introduction: The Taylor Aggression Paradigm (TAP) is a well-established tool for assessing provocation-induced reactive aggression. We introduce an interactive version, the iTAP, with real-time opponents across 60 trials, including five simulated provocation trials in the middle. In this quasi-experimental study, we evaluate the effectiveness of the paradigm to investigate reactive aggression in interacting participants. The design allows us to employ the TAP in settings of high familiarity dyads, addressing an existing gap. Method: Twenty-eight healthy same-sex adult sibling pairs (N = 56) competed against each other in the iTAP, exemplifying high familiarity through their social and emotional co-development, and mutual knowledge. Additionally, we explore naturally arising aggression types in terms of sibling pairs' reciprocal aggression trajectories across trials. Lastly, we investigate situational and personal variables influencing reactive aggression on the iTAP within high familiarity dyads. Results: In line with non-interactive TAP versions, siblings employed a global "tit-for-tat" strategy in response to heightened provocation: Aggression increased during manipulated trials of increasing provocation, persisted during real interaction and declined in the final block, suggesting sibling co-regulation which was underscored by the convergence in within-pair aggression level. We found no gender differences in these dynamics but a trend for higher initial aggression levels within brother pairs and higher responsiveness to increased provocation in sister pairs. Overall aggression levels were related to situational variables including trial outcome (lost, won, and tie), Further, siblings' state anger correlated positively with aggression scores on the iTAP. Aggression was not reliably related to personal variables predicting aggression. We identified subgroups of sibling pairs with distinct provocation-aggression patterns related to differences in reported behavioral motivations and emotional states. The results highlight situational over personal variables in determining aggressive behavior on the task in this sample of healthy adults. While no direct link between sibling relationship quality and aggression was found, the overall behavior was likely influenced by the familiarity between siblings and the specific context of their relationship. Conclusion: The iTAP demonstrates promise as a tool for studying reciprocal aggressive behavior. The emergence of different interaction patterns underscores the ecological validity introduced by the interactive context, which complements the standard versions of the TAP.

Increased anger and stress and heightened connectivity between IFG and vmPFC in victims during social interaction.

Self-identification as a victim of violence may lead to increased negative emotions and stress and thus, may change both structure and function of the underlying neural network(s). In a trans-diagnostic sample of individuals who identified themselves as victims of violence and a matched control group with no prior exposure to violence, we employed a social exclusion paradigm, the Cyberball task, to stimulate the re-experience of stress. Participants were partially excluded in the ball-tossing game without prior knowledge. We analyzed group differences in brain activity and functional connectivity during exclusion versus inclusion in exclusion-related regions. The victim group showed increased anger and stress levels during all conditions. Activation patterns during the task did not differ between groups but an enhanced functional connectivity between the IFG and the right vmPFC distinguished victims from controls during exclusion. This effect was driven by aberrant connectivity in victims during inclusion rather than exclusion, indicating that victimization affects emotional responses and inclusion-related brain connectivity rather than exclusion-related brain activity or connectivity. Victims may respond differently to the social context itself. Enhanced negative emotions and connectivity deviations during social inclusion may depict altered social processing and may thus affect social interactions.

Empathy in schizophrenia: neural alterations during emotion recognition and affective sharing.

Introduction: Deficits in emotion recognition and processing are characteristic for patients with schizophrenia [SCZ]. Methods: We targeted both emotion recognition and affective sharing, one in static and one in dynamic facial stimuli, during functional magnetic resonance imaging [fMRI] in 22 SCZ patients and 22 matched healthy controls [HC]. Current symptomatology and cognitive deficits were assessed as potential influencing factors. Results: Behaviorally, patients only showed a prolonged response time in age-discrimination trials. For emotion-processing trials, patients showed a difference in neural response, without an observable behavioral correlate. During emotion and age recognition in static stimuli, a reduced activation of the bilateral anterior cingulate cortex [ACC] and the right anterior insula [AI] emerged. In the affective sharing task, patients showed a reduced activation in the left and right caudate nucleus, right AI and inferior frontal gyrus [IFG], right cerebellum, and left thalamus, key areas of empathy. Discussion: We conclude that patients have deficits in complex visual information processing regardless of emotional content on a behavioral level and that these deficits coincide with aberrant neural activation patterns in emotion processing networks. The right AI as an integrator of these networks plays a key role in these aberrant neural activation patterns and, thus, is a promising candidate area for neurofeedback approaches.

Brain network changes in adult victims of violence.

Introduction: Stressful experiences such as violence can affect mental health severely. The effects are associated with changes in structural and functional brain networks. The current study aimed to investigate brain network changes in four large-scale brain networks, the default mode network, the salience network, the fronto-parietal network, and the dorsal attention network in self-identified victims of violence and controls who did not identify themselves as victims. Materials and methods: The control group (n = 32) was matched to the victim group (n = 32) by age, gender, and primary psychiatric disorder. Sparse inverse covariance maps were derived from functional resting-state measurements and from T1 weighted structural data for both groups. Results: Our data underlined that mostly the salience network was affected in the sample of self-identified victims. In self-identified victims with a current psychiatric diagnosis, the dorsal attention network was mostly affected underlining the potential role of psychopathological alterations on attention-related processes. Conclusion: The results showed that individuals who identify themselves as victim demonstrated significant differences in all considered networks, both within- and between-network.

Context effects, skin conductance responses and personality traits - Influencing variables on risk-taking within a modified version of the balloon analog risk task.

When individuals take risks, they must weigh potential costs and benefits associated with a decision. Differences in risk-taking appear to be influenced by contextual, and inter-individual factors. However, it is still ambiguous to what extent these characteristics jointly influence risk-taking. We investigated how risk-taking varies as function of context effects, incentives, skin conductance responses (SCR), and personality traits such as impulsivity and sensitivity to reward and punishment. Sixty-eight healthy participants conducted a modified version of the Balloon Analogue Risk Task (BART) composed of a gain-framed (G-BART) and loss-framed (L-BART) context with each a low and a high outcome magnitude condition. While the goal in G-BART was to maximize gains, the goal in L-BART was to minimize losses. In both versions, participants can potentially accumulate the same amounts. We conducted trial-by-trial mixed model analyses to account for within- and between-participant effects. Participants showed greater risk-taking when playing L-BART than G-BART; more risk-taking was observed in the high compared to the low outcome magnitude condition. Furthermore, higher SCR were associated with less risk-taking. Lower impulsivity was related to a greater difference in risk-taking in both contexts, with greater risk-taking in L-BART. Likewise, sensitivity to reward was associated with a greater difference in risk-taking in both contexts, with greater risk-taking in G-BART. Finally, greater sensitivity to punishment was related to risk-taking among participants describing themselves as sensitive to rewards. Results support a multidimensional state-trait model of risk-taking suggesting that risk-taking is favored by loss-aversion along with incentives, psychophysiological arousal, and personality traits.

The role of dominance in sibling relationships: differences in interactive cooperative and competitive behavior.

Siblings strongly influence each other in their social development and are a major source of support and conflict. Yet, studies are mostly observational, and little is known about how adult sibling relationships influence social behavior. Previous tasks exploring dynamically adjusting social interactions have limitations in the level of interactivity and naturalism of the interaction. To address these limitations, we created a cooperative tetris puzzle-solving task and an interactive version of the chicken game task. We validated these two tasks to study cooperative and competitive behavior in real-time interactions (N = 56). Based on a dominance questionnaire (DoPL), sibling pairs were clustered into pairs that were both low in dominance (n = 7), both high in dominance (n = 8), or one low and one high in dominance (n = 13). Consistent with our hypothesis, there were significantly more mutual defections, less use of turn-taking strategies, and a non-significant trend for reduced success in solving tetris puzzles together among high dominance pairs compared to both other pair types. High dominant pairs also had higher Machiavellian and hypercompetitiveness traits and more apathetic sibling relationships. Both tasks constitute powerful and reliable tools to study personality and relationship influences on real and natural social interactions by demonstrating the different cooperative and competitive dynamics between siblings.

Ensemble graph neural network model for classification of major depressive disorder using whole-brain functional connectivity.

Major depressive disorder (MDD) is characterized by impairments in mood and cognitive functioning, and it is a prominent source of global disability and stress. A functional magnetic resonance imaging (fMRI) can aid clinicians in their assessments of individuals for the identification of MDD. Herein, we employ a deep learning approach to the issue of MDD classification. Resting-state fMRI data from 821 individuals with MDD and 765 healthy controls (HCs) is employed for investigation. An ensemble model based on graph neural network (GNN) has been created with the goal of identifying patients with MDD among HCs as well as differentiation between first-episode and recurrent MDDs. The graph convolutional network (GCN), graph attention network (GAT), and GraphSAGE models serve as a base models for the ensemble model that was developed with individual whole-brain functional networks. The ensemble's performance is evaluated using upsampling and downsampling, along with 10-fold cross-validation. The ensemble model achieved an upsampling accuracy of 71.18% and a downsampling accuracy of 70.24% for MDD and HC classification. While comparing first-episode patients with recurrent patients, the upsampling accuracy is 77.78% and the downsampling accuracy is 71.96%. According to the findings of this study, the proposed GNN-based ensemble model achieves a higher level of accuracy and suggests that our model produces can assist healthcare professionals in identifying MDD.

Structural imaging studies of patients with chronic pain: an anatomical likelihood estimate meta-analysis.

ABSTRACT: Neuroimaging is a powerful tool to investigate potential associations between chronic pain and brain structure. However, the proliferation of studies across diverse chronic pain syndromes and heterogeneous results challenges data integration and interpretation. We conducted a preregistered anatomical likelihood estimate meta-analysis on structural magnetic imaging studies comparing patients with chronic pain and healthy controls. Specifically, we investigated a broad range of measures of brain structure as well as specific alterations in gray matter and cortical thickness. A total of 7849 abstracts of experiments published between January 1, 1990, and April 26, 2021, were identified from 8 databases and evaluated by 2 independent reviewers. Overall, 103 experiments with a total of 5075 participants met the preregistered inclusion criteria. After correction for multiple comparisons using the gold-standard family-wise error correction ( P < 0.05), no significant differences associated with chronic pain were found. However, exploratory analyses using threshold-free cluster enhancement revealed several spatially distributed clusters showing structural alterations in chronic pain. Most of the clusters coincided with regions implicated in nociceptive processing including the amygdala, thalamus, hippocampus, insula, anterior cingulate cortex, and inferior frontal gyrus. Taken together, these results suggest that chronic pain is associated with subtle, spatially distributed alterations of brain structure.

Dimensions of Pathological Aggression: From Neurobiology to Therapy.

This Special Issue brings together recent research on aggression on different scales, starting from animal models in low-aggression, healthy populations to patients with aggression problems [...].