Objective: This study extended a classic self-referential learning paradigm by investigating the effects of intranasally-administered oxytocin in high and low socially anxious participants during social learning , as a function ofsocial anxiety levels and sex. Methods: In a randomized double-blinded design, 160 participants were either given intranasal oxytocin (24 I.U.) or placebo. Subsequently, while lying in an MR scanner, participants were shown neutral faces that were paired with positively, neutrally, or negatively valenced self-referential sentences, during which we measured self-reported arousal and sympathy of the facial stimuli, pupil dilation, and changes in the brain-oxygen-level dependent signal. Four-factor mixed analyses of variance with the between-subjects factors group (high socially anxious vs. low socially anxious), substance (oxytocin vs. placebo), and sex (male vs. female) and the within-subjects factor sentence valence (positive vs. neutral vs. negative) were conducted for each measure, respectively.Results: Administration of intranasal oxytocin yielded (1) an increase in sympathy ratings in high socially anxious compared to low socially anxious individuals and (2) decreased arousal ratings for positively-conditioned faces in low socially anxious participants. As a objective physiological measure of arousal, pupil dilation mirrored the behavioral results. Oxytocin effects on neural activation in the insula interacted with anxiety levels and sex: low socially anxious individuals yielded lower activation under oxytocin than placebo; the converse was observed in high socially anxious individuals. This interaction also differed between sexes, as men yielded higher activation levels than women. These findings were more prominent for the positively- and negatively-conditioned faces. Within the amygdala, high socially anxious men yielded higher activation than high socially anxious women in the left hemisphere, and low socially anxious men yielded higher activation than low socially anxious women from positively- and negatively-conditioned faces, though no influence of oxytocin was detected.Conclusion: These results challenge the amygdalocentric view of the role of emotions in social learning, instead contributing to the growing body of findings implicating the insula therein, revealing an interaction between oxytocin, sex, and emotional valence. Such discoveries raise an interesting set of questions regarding the computational goals of regions such as the insula in emotional learning and how neural activity can play a diagnostic or prognostic role in social anxiety, potentially leading to new treatment opportunities that may combine oxytocin and neurofeedback differentially for men and women.

Background:Early life maltreatment is a risk factor for psychiatric disorders, including post-traumatic stress disorder (PTSD). Post-traumatic stress disorder is a severe and heterogeneous disorder with fluctuating states of emotional over- and undermodulation, including hypervigilance, dissociation, and emotion regulation deficits. The perception and regulation of emotions have been linked to interoception, the cortical representation and sensing of inner bodily processes. Although first therapeutic approaches targeting bodily sensations have been found effective in patients with PTSD, and deficits in interoceptive signal representation have been reported in other trauma-related disorders, such as borderline personality disorder (BPD), the role of interoception remains largely unexplored for PTSD.Objective:The objective was to investigate the cortical representation of cardiac interoceptive signals in patients with PTSD and its associations with early life maltreatment, trait dissociation, and emotion dysregulation.Methods:Twenty-four medication-free patients with PTSD and 31 healthy controls (HC) completed a 5-min resting electrocardiogram (ECG) with parallel electroencephalogram (EEG). Heartbeat evoked potential (HEP) amplitudes as a measure for cortical representation of cardiac interoceptive signals were compared between groups and correlated with self-report questionnaires.Results:We did not find significantly different mean HEP amplitudes in patients with PTSD compared to HC, although HEPs of patients with PTSD were descriptively higher. No significant associations between mean HEP amplitudes and early life maltreatment, trait dissociation or emotion dysregulation were obtained within the groups.Conclusion:The current finding does not indicate deficits in interoceptive signal representation at rest in individuals with PTSD. Whether patients with PTSD show altered HEP modulations during emotion regulation tasks and might benefit from therapeutic approaches aiming at changing the perception of bodily signals, needs to be investigated in future studies.

Introduction: Facial expressions and vocal intonation are key signals in the communication of emotions. Individuals with posttraumatic stress disorder (PTSD) are known to show an impaired perception of facial emotions. So far, research on multimodal emotional stimuli or the priming effects on emotion processing has been absent in PTSD. Therefore, we conducted a study to investigate the influence of vocal priming on facial emotion processing and classification in PTSD using electroencephalography. Methods: Twenty-one women with PTSD compared to 28 healthy women were asked to classify emotion-morphed faces with predominantly angry, ambiguous, or predominantly happy expressions primed by either an angry or a happy voice. Responses and reaction times as well as the N170, a component reflecting configural face processing, were analyzed. Results: Patients with PTSD were slower in classifying emotional faces that were primed by either an angry or happy voice compared to the healthy controls (HCs; eta(2) = 0.14). Additionally, patients with PTSD were faster in classifying facial expressions after angry compared to happy vocal primes (eta(2) = 0.14). HCs did not show this effect. Correlation analyses revealed positive associations between emotion (dys-)regulation and reaction times in patients with PTSD but not in HCs (r = 0.64-0.76). Furthermore, patients with PTSD showed greater N170 amplitudes for predominantly angry and ambiguous faces than HCs (eta(2) = 0.07). Conclusion: Data suggest that patients with PTSD experience more difficulties when processing complex social stimuli than HCs. The altered processing of complex social-emotional signals could amplify PTSD symptoms, thus qualifying as an explicit therapy target.

Background: Emotional dysregulation, a core feature of borderline personality disorder (BPD) has recently been linked to deficits in the cortical representation of bodily signals. Oxytocin modulates the salience of external social cues. However, its role in interoception is still not fully understood. The aim of the current study was to replicate reduced heartbeat-evoked potentials (HEPs) as a marker for the cortical representation of cardiac signals in BPD and to explore potential effects of oxytocin on HEP amplitude. Methods: Fifty-three medication-free women with a DSM-IV diagnosis of BPD and sixty healthy female controls (HCs) participated in the study. In a randomized, double-blind placebo-controlled trial, participants self-administered either 24 I.U. of oxytocin or placebo and took part in a 5-minute resting-state electrocardiogram (ECG) with parallel electroencephalogram (EEG) measurement. In addition, emotional dysregulation and BPD symptomatology were assessed with self-report questionnaires. Results: Patients with BPD had significantly lower mean HEP amplitudes than HCs. Furthermore, HEP amplitudes were negatively correlated with emotional dysregulation in the whole sample. However, oxytocin had no significant effect on HEP amplitude. Limitations: Only female participants were investigated and no clinicial controls were included. Conclusions: This is the first replication from an independent sample showing a reduced cortical representation of cardiac signals in BPD patients. This, together with other body-related symptoms, suggests deficits in the processing of bodily signals, which seem to be associated with emotional dysregulation. Whether oxytocin influences HEP during emotion regulation tasks needs to be investigated in future studies.

Early life maltreatment (ELM) is the major single risk factor for impairments in social functioning and mental health in adulthood. One of the most prevalent and most rapidly increasing forms of ELM is emotional neglect. According to bio-behavioral synchrony assumptions, the oxytocin and attachment systems play an important mediating role in the interplay between emotional neglect and social dysfunctioning. Therefore, the aim of the present study was to investigate whether fear and avoidance of social functioning, two important and highly prevalent facets of social dysfunctioning in adulthood, are shaped by emotional neglect, plasma oxytocin levels and attachment representations. We assessed emotional neglect as well as other forms of ELM with the Childhood Trauma Questionnaire, current attachment representations with the Adult Attachment Projective Picture System, and fear and avoidance of social situations with the Liebowitz Social Anxiety Scale in a population-based sample of N = 121 men and women. Furthermore, 4.9 ml blood samples were drawn from each participant to assess peripheral plasma oxytocin levels. Applying a sequential mediation model, results revealed that emotional neglect was associated with lower plasma oxytocin levels which in turn were associated with insecure attachment representations which were related to elevated fear and avoidance of social situations (a1d21b2: F3,117 = 20.84, P < .001). Plasma oxytocin and current attachment representations hence fully and sequentially mediate the effects of emotional neglect on social fear and avoidance, two important facets of adult social dysfunctioning, confirming bio-behavioral synchrony assumptions.

According to longitudinal studies, most individuals with borderline personality disorder (BPD) achieve remission. Since BPD is characterized by disturbed emotion recognition, this study investigated behavioral and electrophysiological correlates of facial emotion classification and processing in remitted BPD. 32 women with remitted BPD (rBPD), 32 women with current BPD (cBPD), and 28 healthy women (HC) participated in an emotion classification paradigm comprising blends of angry and happy faces while behavioral and electroencephalographic (event-related potentials) data were recorded. rBPD demonstrated a convergence in behavior towards HC in terms of responses and reaction times. They evaluated maximally ambiguous faces more positively and exhibited faster reaction times when classifying predominantly happy faces compared to cBPD. Group × facial emotion interaction effects were found in early electrophysiological processes with post hoc tests indicating differences between rBPD and cBPD but not between rBPD and HC. However, BPD-like impairments were still found in rBPD in later processing (P300). Our results suggest a reduction in negativity bias in rBPD on the behavioral level and a normalization of earlier stages of facial processing on the neural level, while alterations in later, more cognitive processing do not remit. Early processing may be more state-like, while later impairments may be more trait-like. Further research may need to focus on these stable components.

In Part 2 of Primary Headache disorders, we discuss the fourth Primary Headache Disorder, Tension-Type Headache (TTHA). We are again using the ICHD-III (Beta) definitions of such headaches, taking into consideration episodic and chronic TTHA, as well as the presence or absence of pericranial muscle tenderness. We discuss the pathophysiology and pharmacotherapeutic treatment of TTHA, and the aspects of the Myofascial Pain Syndrome that enhance and help the development of TTHA. We then discuss Medication Overuse Headache (MOH), itself a Secondary headache disorder, but one that is extremely important as it assists with the chronification of both migraine and TTHA. Finally we discuss how to manage and treat those patients with MOH. Chronic migraine, which is TTHA, Migraine as well as, in many patients, MOH, is discussed along with the treatment of this multifaceted disorder.

CO2 capture and storage (CCS) represents an important option to mitigate climate change. However, the implementation of CCS is slow. We analysed one of the unsuccessful projects in the Netherlands that is referred to as the Barendrecht CO2 storage project, with an emphasis on the role of the national government. We performed an event analysis based on debates in the Dutch Parliament, interviews with the relevant stakeholders and published literature. We show that the opinion of the national government regarding this project changed over time. Consensus on the necessity of CCS was assumed at the start of the project. However, over time, the local opposition intensified, and both CCS as a climate mitigation strategy and its implementation, including its location, were contested. An important contributor was the lack of solid outside support, whereas the views of opponents were strongly represented. Additionally, due to multiple delays, the momentum was lost, which ended the enthusiasm of initial supporters. To ensure implementation of future CCS projects, overall national support should therefore be guaranteed prior to the start of the project.

Traumatic experiences have severe impact on the autonomous nervous system. Heart rate variability (HRV) is a reliable psychophysiological marker for the autonomous nervous system functioning. Reduced vagally mediated HRV has been found in patients with post-traumatic stress disorder (PTSD) and, in some studies, in patients with borderline personality disorder (BPD). In this study, we compared HRV parameters of patients with PTSD, current BPD, and BPD in remission with healthy volunteers in a 5 min resting-state electrocardiogram recording. 91 unmedicated female participants took part in the study (18 with PTSD, 27 with the current BPD, 23 with BPD in remission, and 23 healthy volunteers). We found significant group differences in both time-domain and frequency-domain (total power, low-frequency and high-frequency power) HRV parameters. Root mean square of the successive differences (RMSSD) was lowest in patients with PTSD (M = 48.6 ms, SD = 23.5 ms) followed by patients with BPD in remission (M = 57.7 ms, SD = 31.5 ms) and patients with the current BPD (M = 71.1 ms, SD = 44.5 ms), while the highest RMSSD was found in healthy volunteers (M = 84.1 ms, SD = 41.7 ms). Variance of HRV was higher in patients with BPD than in patients with PTSD. In addition, RMSSD was significantly negatively correlated with self-reported early life maltreatment assessed with the Childhood Trauma Questionnaire. Our findings point out a complex interaction between traumatic experiences, the functioning of the autonomic nervous system, and psychopathology. Alterations in HRV might be related to early life maltreatment or associated psychological factors rather than diagnostic entities.

IMPORTANCE The ability to perceive and regulate one's own emotions has been tightly linked to the processing of afferent bodily signals (interoception). Thus, disturbed interoception might contribute to the core feature of emotional dysregulation in borderline personality disorder (BPD), as increased levels of depersonalization, body image disturbances, and reduced sensitivity to physical pain suggest poor body awareness in BPD. OBJECTIVE To determine neural correlates of disturbed body awareness in BPD and its associations with emotional dysregulation and to explore improvements in body awareness with BPD symptom remission. DESIGN, SETTING, AND PARTICIPANTS Case-control study performed at Heidelberg University Hospital, Heidelberg, Germany. Heartbeat evoked potentials (HEPs), an indicator of the cortical representation of afferent signals from the cardiovascular system, were investigated in 34 medication-free patients with BPD, 31 healthy volunteers, and 17 medication-free patients with BPD in remission. The HEPs were assessed using 5-minute resting-state electroencephalograms and parallel electrocardiograms. Core BPD symptoms, history of childhood traumatization, and psychiatric disorders were assessed by means of self-reports and structured interviews. To measure neural correlates of disturbed body awareness, high-resolution T1-weighted structural magnetic resonance imaging scans were collected and analyzed using voxel-based morphometry and region-of-interest-based approaches. The study was performed between 2012 and 2014, and data analysis was performed in 2014. MAIN OUTCOMES AND MEASURES Mean HEP amplitudes in resting-state electroencephalograms and their correlation with self-reported emotional dysregulation, as well as with gray matter volume. RESULTS Patients with BPD had significantly reduced mean HEP amplitudes compared with healthy volunteers (F1,61 = 11.32, P = .001), whereas the mean HEP amplitudes of patients with BDP in remission lie somewhere in between these 2 groups of participants (P > .05). The HEP amplitudes were negatively correlated with emotional dysregulation (R = -0.30, P = .01) and positively associated with gray matter volume in the left anterior insula (R = 0.53, P < .05) and the bilateral dorsal anterior cingulate cortex (R = 0.47, P < .05), 2 structures that have been identified as core regions for interoception. CONCLUSIONS AND RELEVANCE The results indicate state-dependent deficits in the cortical processing of bodily signals in patients with BPD, which appear to be associated with core features of BPD. The analysis of patients with BPD in remission suggests an improvement in cortical representation of bodily signals with symptom remission. Results recommend the integration of techniques to strengthen bodily awareness in psychotherapeutic interventions of BPD.