Oxytocin effects on amygdala reactivity to angry faces in males and females with antisocial personality disorder.

The amygdala is a key region in current neurocircuitry models of reactive aggression as it is crucially involved in detecting social threat and provocation. An increased amygdala reactivity to angry faces has been reported in aggression-prone individuals and the neuropeptide oxytocin (OT) could dampen anger-related amygdala reactivity in a number of mental disorders. One example is the antisocial personality disorder (ASPD) which has so far only been studied in limited numbers. To address the question whether OT can normalize amygdala hyperreactivity to emotional faces, we conducted a functional magnetic resonance imaging experiment with 20 men and 18 women with ASPD and 20 male and 20 female healthy control (HC) participants in a double-blind, randomized, placebo (PLC)-controlled within-subject design. Participants were exposed to an emotion classification task (fearful, angry, and happy faces) after receiving an intranasal dose (24 IU) of synthetic OT or PLC. We found OT to attenuate right amygdala hyperactivity to angry faces in participants with ASPD to such an extent that the intensity of amygdala activity in the ASPD group in the OT condition decreased to the level of amygdala activity in the PLC condition in the HC group. There was also a trend that OT effects were generally larger in women than in men. These findings suggest that OT differentially modulates the amygdala following social threatening or provoking cues in dependence of psychopathology (ASPD vs. HC) and sex (male vs. female). Particularly female ASPD patients could benefit from OT in the treatment of reactive aggression.

Evaluation of different acute-phase proteins for herd health diagnostics in early postpartum Holstein Friesian dairy cows.

This research communication describes (1) the comparison of acute-phase protein (APP) concentrations in transition dairy cows on different farms using both pooled and individual blood samples, and (2) the association among different APP and clinical health parameters. The first hypothesis was that early postpartum dairy cows from different farms differ in the level of inflammation, which might be determined using APP assays in both pooled and individual blood samples. The second hypothesis was that the APP haptoglobin (Hp) might be the most sensitive parameter to detect cows at risk of excessive postpartum inflammation concomitant with systemic disease. Serum concentrations of Hp, serum amyloid-A (SAA), total protein (TP), albumin (Alb), coeruloplasmin (Cp) and C-reactive protein (CRP) in 100 fresh lactating cows (within 0-8 d postpartum) from 10 farms were compared and associated to clinical health parameters (rectal body temperature, vaginal discharge (Metricheck™ score), rumen fill, vulvovaginal laceration) using both pooled and individual blood samples. Mean serum concentrations of Hp, SAA and TP revealed significant differences among farms. Pooled serum samples of farms showed high correlations with the mean of individual samples. Only Hp was significantly positively correlated to both body temperature and Metricheck™ score. In conclusion, Hp differentiates dairy farms regarding the inflammatory state of transition cows using individual and pooled serum samples within the first week postpartum. It also mirrors the individual degree of inflammation, thus proving to be a diagnostic parameter of high interest during the periparturient period.

Force-feedback assisted and virtual fixtures based K-wire drilling simulation.

One common method to fix fractures of the human hand after an accident is an osteosynthesis with Kirschner wires (K-wires) to stabilize the bone fragments. The insertion of K-wires is a delicate minimally invasive surgery, because surgeons operate almost without a sight. Since realistic training methods are time consuming, costly and insufficient, a virtual-reality (VR) based training system for the placement of K-wires was developed. As part of this, the current work deals with the real-time bone drilling simulation using a haptic force-feedback device. To simulate the drilling, we introduce a virtual fixture based force-feedback drilling approach. By decomposition of the drilling task into individual phases, each phase can be handled individually to perfectly control the drilling procedure. We report about the related finite state machine (FSM), describe the haptic feedback of each state and explain, how to avoid jerking of the haptic force-feedback during state transition. The usage of the virtual fixture approach results in a good haptic performance and a stable drilling behavior. This was confirmed by 26 expert surgeons, who evaluated the virtual drilling on the simulator and rated it as very realistic. To make the system even more convincing, we determined real drilling feed rates through experimental pig bone drilling and transferred them to our system. Due to a constant simulation thread we can guarantee a precise drilling motion. Virtual fixtures based force-feedback calculation is able to simulate force-feedback assisted bone drilling with high quality and, thus, will have a great potential in developing medical applications.

Individualized treatment response prediction of dialectical behavior therapy for borderline personality disorder using multimodal magnetic resonance imaging.

INTRODUCTION: Individualized treatment prediction is crucial for the development and selection of personalized psychiatric interventions. Here, we use random forest classification via pretreatment clinical and demographical (CD), functional, and structural magnetic resonance imaging (MRI) data from patients with borderline personality disorder (BPD) to predict individual treatment response. METHODS: Before dialectical behavior therapy (DBT), 31 female patients underwent functional (three different emotion regulation tasks) and structural MRI. DBT response was predicted using CD and MRI data in previously identified anatomical regions, which have been reported to be multimodally affected in BPD. RESULTS: Amygdala and parahippocampus activation during a cognitive reappraisal task (in contrasts displaying neural activation for emotional challenge and for regulation), along with severity measures of BPD psychopathology and gray matter volume of the amygdala, provided best predictive power with neuronal hyperractivities in nonresponders. All models, except one model using CD data solely, achieved significantly better accuracy (>70.25%) than a simple all-respond model, with sensitivity and specificity of >0.7 and >0.7, as well as positive and negative likelihood ratios of >2.74 and <0.36 each. Surprisingly, a model combining all data modalities only reached rank five of seven. Among the functional tasks, only the activation elicited by a cognitive reappraisal paradigm yielded sufficient predictive power to enter the final models. CONCLUSION: This proof of principle study shows that it is possible to achieve good predictions of psychotherapy outcome to find the most valid predictors among numerous variables via using a random forest classification approach.

Change in Emotional and Theory of Mind Processing in Borderline Personality Disorder: A Pilot Study.

Changes in emotional processing (EP) and in theory of mind (TOM) are central across treatment approaches for patients with borderline personality disorder (BPD). Although the assessment of EP relies on the observation of a patient's self-criticism in a two-chair dialogue, an individual's TOM assessments is made based on responses to humorous stimuli based on false beliefs. For this pilot study, we assessed eight patients with BPD before and after a 3-month-long psychiatric treatment, using functional magnetic resonance imaging and behavioral tasks. We observed arousal increase within the session of the two-chair dialogue (d = 0.36), paralleled by arousal decrease between sessions (d = 0.80). We found treatment-associated trends for neural activity reduction in brain areas central for EP and TOM. Our exploratory findings using an integrative assessment procedure of changes in EP and TOM point toward evidence for treatment effects at the brain systems level related to behavioral modulation.

Assessing the marks of change: how psychotherapy alters the brain structure in women with borderline personality disorder.

BACKGROUND: There is increasing evidence that psychotherapy can alter the function of the brain of patients with borderline personality disorder (BPD). However, it is not known whether psychotherapy can also modify the brain structure of patients with BPD. METHODS: We used structural MRI data of female patients with BPD before and after participation in 12 weeks of residential dialectical behavioural therapy (DBT) and compared them to data from female patients with BPD who received treatment as usual (TAU). We applied voxel-based morphometry to study voxel-wise changes in grey matter volume over time. RESULTS: We included 31 patients in the DBT group and 17 in the TAU group. Patients receiving DBT showed an increase of grey matter volume in the anterior cingulate cortex, inferior frontal gyrus and superior temporal gyrus together with an alteration of grey matter volume in the angular gyrus and supramarginal gyrus compared with patients receiving TAU. Furthermore, therapy response correlated with increase of grey matter volume in the angular gyrus. LIMITATIONS: Only women were investigated, and groups differed in size, medication (controlled for) and intensity of the treatment condition. CONCLUSION: We found that DBT increased grey matter volume of brain regions that are critically implicated in emotion regulation and higher-order functions, such as mentalizing. The role of the angular gyrus for treatment response may reside in its cross-modal integrative function. These findings enhance our understanding of psychotherapy mechanisms of change and may foster the development of neurobiologically informed therapeutic interventions.

Assessing the marks of change: how psychotherapy alters the brain structure in women with borderline personality disorder.

BACKGROUND: There is increasing evidence that psychotherapy can alter the function of the brain of patients with borderline personality disorder (BPD). However, it is not known whether psychotherapy can also modify the brain structure of patients with BPD. METHODS: We used structural MRI data of female patients with BPD before and after participation in 12 weeks of residential dialectical behavioural therapy (DBT) and compared them to data from female patients with BPD who received treatment as usual (TAU). We applied voxel-based morphometry to study voxel-wise changes in grey matter volume over time. RESULTS: We included 31 patients in the DBT group and 17 in the TAU group. Patients receiving DBT showed an increase of grey matter volume in the anterior cingulate cortex, inferior frontal gyrus and superior temporal gyrus together with an alteration of grey matter volume in the angular gyrus and supramarginal gyrus compared with patients receiving TAU. Furthermore, therapy response correlated with increase of grey matter volume in the angular gyrus. LIMITATIONS: Only women were investigated, and groups differed in size, medication (controlled for) and intensity of the treatment condition. CONCLUSION: We found that DBT increased grey matter volume of brain regions that are critically implicated in emotion regulation and higher-order functions, such as mentalizing. The role of the angular gyrus for treatment response may reside in its cross-modal integrative function. These findings enhance our understanding of psychotherapy mechanisms of change and may foster the development of neurobiologically informed therapeutic interventions.

Oxytocin improves facial emotion recognition in young adults with antisocial personality disorder.

Deficient facial emotion recognition has been suggested to underlie aggression in individuals with antisocial personality disorder (ASPD). As the neuropeptide oxytocin (OT) has been shown to improve facial emotion recognition, it might also exert beneficial effects in individuals providing so much harm to the society. In a double-blind, randomized, placebo-controlled crossover trial, 22 individuals with ASPD and 29 healthy control (HC) subjects (matched for age, sex, intelligence, and education) were intranasally administered either OT (24 IU) or a placebo 45min before participating in an emotion classification paradigm with fearful, angry, and happy faces. We assessed the number of correct classifications and reaction times as indicators of emotion recognition ability. Significant group×substance×emotion interactions were found in correct classifications and reaction times. Compared to HC, individuals with ASPD showed deficits in recognizing fearful and happy faces; these group differences were no longer observable under OT. Additionally, reaction times for angry faces differed significantly between the ASPD and HC group in the placebo condition. This effect was mainly driven by longer reaction times in HC subjects after placebo administration compared to OT administration while individuals with ASPD revealed descriptively the contrary response pattern. Our data indicate an improvement of the recognition of fearful and happy facial expressions by OT in young adults with ASPD. Particularly the increased recognition of facial fear is of high importance since the correct perception of distress signals in others is thought to inhibit aggression. Beneficial effects of OT might be further mediated by improved recognition of facial happiness probably reflecting increased social reward responsiveness.

New Service Excellence Model for eHealth and AAL Solutions - A Framework for Continuous New Service Development.

The development of eHealth and AAL (Ambient Assisted Living) services with the aim to reduce the complexity of living environments for the elderly often does not lead to the desired results on the market. The design of an eHealth/AAL specific framework for continuous New Service Development is presented in this paper. Our research addresses this challenge with a new Service Excellence Model (SEM) and outlines the benefits of this specific approach. The research is based on the data of the DALIA project (Assistant for DAily LIfe Activities at Home) and the PenAAL project (Performance Measurement Index for AAL solutions), parts of which the projects were the classification of relevant business dimensions and the development of a related scoring tool for continuous benchmarking and improvement.

Brain Mechanisms Underlying Reactive Aggression in Borderline Personality Disorder-Sex Matters.

BACKGROUND: Aggression in borderline personality disorder (BPD) is thought to be mediated through emotion dysregulation via high trait anger. Until now, data comparing anger and aggression in female and male patients with BPD have been widely missing on the behavioral and particularly the brain levels. METHODS: Thirty-three female and 23 male patients with BPD and 30 healthy women and 26 healthy men participated in this functional magnetic resonance imaging study. We used a script-driven imagery task consisting of narratives of both interpersonal rejection and directing physical aggression toward others. RESULTS: While imagining both interpersonal rejection and acting out aggressively, a sex × group interaction was found in which male BPD patients revealed higher activity in the left amygdala than female patients. In the aggression phase, men with BPD exhibited higher activity in the lateral orbitofrontal and dorsolateral prefrontal cortices compared with healthy men and female patients. Positive connectivity between amygdala and posterior middle cingulate cortex was found in female patients but negative connectivity was found in male patients with BPD. Negative modulatory effects of trait anger on amygdala-dorsolateral prefrontal cortex and amygdala-lateral orbitofrontal cortex coupling were shown in male BPD patients, while in female patients trait anger positively modulated dorsolateral prefrontal cortex-amygdala coupling. Trait aggression was found to positively modulate connectivity of the left amygdala to the posterior thalamus in male but not female patients. CONCLUSIONS: Data suggest poor top-down adjustment of behavior in male patients with BPD despite their efforts at control. Female patients appear to be less aroused through rejection and to successfully dampen aggressive tension during the imagination of aggressive behavior.

Pain-mediated affect regulation is reduced after dialectical behavior therapy in borderline personality disorder: a longitudinal fMRI study.

Borderline Personality Disorder (BPD) is characterized by affective instability, but self-injurious behavior appears to have an emotion-regulating effect. We investigated whether pain-mediated affect regulation can be altered at the neural level by residential Dialectical Behavior Therapy (DBT), providing adaptive emotion regulation techniques. Likewise, we investigated whether pain thresholds or the appraisal of pain change after psychotherapy. We investigated 28 patients with BPD undergoing DBT (self-referral), 15 patients with treatment as usual and 23 healthy control subjects at two time points 12 weeks apart. We conducted an fMRI experiment eliciting negative emotions with picture stimuli and induced heat pain to investigate the role of pain in emotion regulation. Additionally, we assessed heat and cold pain thresholds.At first measurement, patients with BPD showed amygdala deactivation in response to painful stimulation, as well as altered connectivity between left amygdala and dorsal anterior cingulate cortex. These effects were reduced after DBT, as compared with patients with treatment as usual. Pain thresholds did not differ between the patient groups. We replicated the role of pain as a means of affect regulation in BPD, indicated by increased amygdala coupling. For the first time, we could demonstrate that pain-mediated affect regulation can be changed by DBT.

Neural correlates of distraction in borderline personality disorder before and after dialectical behavior therapy.

Neural underpinnings of emotion dysregulation in borderline personality disorder (BPD) are characterized by limbic hyperactivity and disturbed prefrontal activity. It is unknown whether neural correlates of emotion regulation change after a psychotherapy which has the goal to improve emotion dysregulation in BPD, such as dialectical behavioral therapy (DBT). We investigated distraction as a main emotion regulation strategy before and after DBT in female patients with BPD. Thirty-one BPD patients were instructed to either passively view or memorize letters before being confronted with negative or neutral pictures in a distraction task during functional magnetic resonance imaging. This paradigm was applied before and after a 12-week residential DBT-based treatment program. We compared the DBT group to 15 BPD control patients, who continued their usual, non-DBT-based treatment or did not have any treatment, and 22 healthy participants. Behaviorally, BPD groups and healthy participants did not differ significantly with respect to alterations over time. On the neural level, BPD patients who received DBT-based treatment showed an activity decrease in the right inferior parietal lobe/supramarginal gyrus during distraction from negative rather than neutral stimuli when compared to both control groups. This decrease was correlated with improvement in self-reported borderline symptom severity. DBT responders exhibited decreased right perigenual anterior cingulate activity when viewing negative (rather than neutral) pictures. In conclusion, our findings reveal changes in neural activity associated with distraction during emotion processing after DBT in patients with BPD. These changes point to lower emotional susceptibility during distraction after BPD symptom improvement.

AAL Service Performance Measurement Cube - Key Criteria for AAL New Service Development.

UNLABELLED: The living environments of senior citizens are gaining in complexity with regard to health, mobility, information, support and behaviour. The development of Ambient Assisted Living (AAL) services in order to reduce this complexity is becoming increasingly important. The question is: What relevant criteria support the development, measurement and evaluation of business models of hybrid AAL services which have to be considered in an appropriate Performance Measurement Set? Within the EU funded research project DALIA (Assistant for Daily Life Activities at Home) a Service Performance Measurement Criteria (SPMC) Set has been developed and described. With the help of literature review and expert interviews relevant performance criteria were identified and described in the context of Analytic Hierarchy Process (AHP). In conjunction with an AAL business models scanning, a set of performance measurement criteria could be created. DISCUSSION: The development and application of a specific AAL SPMC Set offers the possibility in a targeted and conceptual way advance the development of marketable AAL services. Here it will be important to integrate with software support the SPMC Set in the service development process of future marketable AAL applications. With the application of an adjusted AAL Service Performance Measurement Cube, the conceptual development of marketable AAL services can be maintained and relevant decisions can be supported.

Effects of Psychotherapy on Neuronal Correlates of Reappraisal in Female Patients With Borderline Personality Disorder.

BACKGROUND: Emotion dysregulation is a fundamental aspect of borderline personality disorder (BPD). Accordingly, one major focus of dialectical behavior therapy (DBT) is to teach strategies to regulate emotional reactions. To date, little is known about the neural mechanisms linked to the amelioration of BPD symptoms after therapy. In the present study, we used functional magnetic resonance imaging to investigate neural correlates of explicit emotion regulation before and after DBT. METHODS: Female BPD patients (n = 32) performed a reappraisal task before and after a 12-week inpatient DBT program and were compared with 24 healthy control participants. Based on the change in symptom severity, the BPD group was separated into responders and nonresponders and compared with a clinical control group of 16 BPD patients. Both control groups were scanned twice within 12 weeks. RESULTS: After DBT, BPD patients showed decreased insula and anterior cingulate cortex activity during reappraisal. Anterior cingulate connectivity to medial and superior frontal gyrus, superior temporal gyrus, and inferior parietal cortices increased after DBT. Responders exhibited reduced activation in amygdala, anterior cingulate cortex, orbitofrontal, and dorsolateral prefrontal cortex together with increased connectivity within a limbic-prefrontal network during the reappraisal of negative stimuli after psychotherapy. CONCLUSIONS: This study revealed reduced activity and increased connectivity in neural networks related to salience processing and emotion regulation after therapy. Attenuated limbic hyperarousal together with an elevated coupling between limbic and prefrontal and inferior parietal control regions in BPD patients after successful therapy may indicate more efficient emotion regulation during reappraisal of negative pictures.

Investigating action understanding: inferential processes versus action simulation.

In our daily life, we continuously monitor others' behaviors and interpret them in terms of goals, intentions, and reasons. Despite their central importance for predicting and interpreting each other's actions, the functional mechanisms and neural circuits involved in action understanding remain highly controversial. Two alternative accounts have been advanced. Simulation theory assumes that we understand actions by simulating the observed behavior through a direct matching process that activates the mirror-neuron circuit. The alternative interpretive account assumes that action understanding is based on specialized inferential processes activating brain areas with no mirror properties. Although both approaches recognize the central role of contextual information in specifying action intentions, their respective accounts of this process differ in significant respects. Here, we investigated the role of context in action understanding by using functional brain imaging while participants observed an unusual action in implausible versus plausible contexts. We show that brain areas that are part of a network involved in inferential interpretive processes of rationalization and mentalization but that lack mirror properties are more active when the action occurs in an implausible context. However, no differential activation was found in the mirror network. Our findings support the assumption that action understanding in novel situations is primarily mediated by an inferential interpretive system rather than the mirror system.

Calcium tetraboride-does it exist? Synthesis and properties of a carbon-doped calcium tetraboride that is isotypic with the known rare earth tetraborides.

Crystalline samples of carbon-doped CaB4 were synthesized by solid-state reactions in sealed niobium ampules from the elements Ca, B, and C. The structure was determined by single-crystal X-ray diffraction (P4/mbm, Z = 4, a = 7.0989(7) A, c = 4.1353(5) A, R1 = 0.026, and wR2 = 0.058) revealing an atom arrangement containing a three-dimensional boron network built up from B6 octahedra and B2 dumbbells which is well-known from the structures of rare earth tetraborides. Crystals of CaB(4-x)Cx are black with a metallic luster and behave stable against mineral acids. Band structure calculations indicate that CaB4 is a stable semiconducting compound with a narrow band gap and that carbon should not necessarily be required for the stability of this compound. The presence of carbon in the crystalline samples of CaB(4-x)Cx was indicated by electron energy loss spectroscopy, but the carbon content in the samples was estimated to be less than 5% according to inductively coupled plasma-atomic emission spectrometry measurements. The distribution of boron and carbon atoms in the structure was investigated by means of 11B and 13C solid-state magic angle spinning NMR. Measurements of the magnetic susceptibility indicate a temperature-independent paramagnetism down to 20 K.

On the efficacy of piracetam in geriatric patients with acute cerebral ischemia: a clinically controlled double-blind study.

Using a randomized, double blind group comparison, the efficacy and tolerance of piracetam as an additional therapy of hydroxyethyl starch, venous infusion and low dose heparin treatment, which are the basis of therapy in our hospital, has been studied in patients displaying acute cerebral ischemia. A total of 56 patients were enrolled, of whom 27 were given piracetam and 29 served as a control during a 28-day period. Using single photon emission computer tomography (SPECT) analysis, we observed that in 23 piracetam-treated patients (85.2%) a reduction in the area of brain regions displaying an impaired flow rate occurred (P < 0.001; Fisher's exact two-sided test). Only six of placebo-treated patients (20.7%) showed an improved flow rate. Analysis of the recorded computer tomography map gave an improvement coefficient >2 (flow rate marginally or better improved) for 23 piracetam patients as compared with 5 placebo patients (P < 0.001, Uleman test).

ABO blood group system, age, sex, risk factors and cardiac infarction.

In a retrospective study in 3100 patients of different ages the relationship between blood group and cardiac infarction was investigated in 450 patients. The patients were divided in two age groups: those who were 65 yr old and older and younger patients (age less than 65 yr). The predominance of blood group A in patients with cardiac infarction was highly significant in both age groups (P less than 0.005, two-tailed Chi-square test). Step-wise excluding all patients with at least one of the risk factors, hypertension, hyperuricemia, diabetes mellitus, smoking, and hyperlipemia similar results were found: the predominance of blood group A in the elderly patients with cardiac infarction was even higher than before excluding the risk factors (P less than 0.001). The predominance of blood group A was also demonstrated at a lower level in younger patients with cardiac infarction (P less than 0.05). Our investigation strongly suggests the existence of a genetic factor associated with blood group A and independent of the other risk factors which is also responsible for a greater incidence of cardiac infarction.

[Pharmacokinetics of naftidrofuryl in multimorbidity in geriatric patients]. / Pharmakokinetik von Naftidrofuryl bei multimorbiden geriatrischen patienten.

The present pharmacokinetic study of a drug used in geriatric patients with multiple diseases reveals that the half-life in the elderly was extended for about three times as long as in the corresponding control group. There are significant positive as well as negative correlations between the kinetic data and routine parameters of the metabolism. These statistical correlations should be controlled by experimental studies.

The influence of age and multimorbidity on the pharmacokinetics and metabolism of spironolactone.

The pharmacokinetics of the metabolites of spironolactone (canrenone and fluorigenic metabolites) were investigated in 10 geriatric female patients with multimorbidity after a multiple daily oral administration of 100 mg spironolactone under steady state conditions. The concentration determinations were carried out simultaneously with a specific HPLC method and a less specific fluorimetric method. On comparison of the pharmacokinetic parameters with the respective values of a control group of younger healthy female subjects, the serum concentrations in the elderly patients were found to be twice as high. In addition, a statistically significant positive correlation with age was found in the patients for the kinetic parameters investigated. A positive correlation existed between erythrocyte count and the pharmacokinetic parameters of canrenone, especially with the area under the concentration/time curve. No such association was detectable, however, for the total fraction of fluorigenic metabolites (including canrenone). The results of our investigation indicate that, in addition to the known high binding of canrenone to plasma proteins, there is also possibly a (restrictive) binding to erythrocytes.