[Evidence-based inpatient psychotherapy in borderline personality disorder]. / Evidenzbasierte stationäre Psychotherapie der Borderline-Persönlichkeitsstörung.

BACKGROUND: Borderline personality disorder (BPD) is frequent (prevalence in Germany between 0.7% and 4.5%) [11] and is associated with a high level of psychological stress and frequent emergency inpatient admissions. The provision of disorder-specific outpatient psychotherapy is still insufficient also in Germany. OBJECTIVE: This article provides an overview of the available data on the effectiveness of inpatient psychotherapy for BPD. MATERIAL AND METHODS: A qualitative review on the effectiveness and therapy outcome predictors was conducted based on a literature search in PubMed. RESULTS: Overall, very few randomized controlled trials are available; in contrast uncontrolled studies are predominant. Most evidence is available for dialectical behavior therapy (DBT) but other approaches, including psychodynamic procedures, have also been studied. DISCUSSION: The currently available data suggest an efficacy of inpatient psychotherapy for BPD; however, randomized trials with larger samples and sufficient representation including male patients are largely lacking. There is also no substantial direct evidence for the superiority of inpatient compared to outpatient psychotherapy.

Posterior cingulate cortex targeted real-time fMRI neurofeedback recalibrates functional connectivity with the amygdala, posterior insula, and default-mode network in PTSD.

BACKGROUND: Alterations within large-scale brain networks-namely, the default mode (DMN) and salience networks (SN)-are present among individuals with posttraumatic stress disorder (PTSD). Previous real-time functional magnetic resonance imaging (fMRI) and electroencephalography neurofeedback studies suggest that regulating posterior cingulate cortex (PCC; the primary hub of the posterior DMN) activity may reduce PTSD symptoms and recalibrate altered network dynamics. However, PCC connectivity to the DMN and SN during PCC-targeted fMRI neurofeedback remains unexamined and may help to elucidate neurophysiological mechanisms through which these symptom improvements may occur. METHODS: Using a trauma/emotion provocation paradigm, we investigated psychophysiological interactions over a single session of neurofeedback among PTSD (n = 14) and healthy control (n = 15) participants. We compared PCC functional connectivity between regulate (in which participants downregulated PCC activity) and view (in which participants did not exert regulatory control) conditions across the whole-brain as well as in a priori specified regions-of-interest. RESULTS: During regulate as compared to view conditions, only the PTSD group showed significant PCC connectivity with anterior DMN (dmPFC, vmPFC) and SN (posterior insula) regions, whereas both groups displayed PCC connectivity with other posterior DMN areas (precuneus/cuneus). Additionally, as compared with controls, the PTSD group showed significantly greater PCC connectivity with the SN (amygdala) during regulate as compared to view conditions. Moreover, linear regression analyses revealed that during regulate as compared to view conditions, PCC connectivity to DMN and SN regions was positively correlated to psychiatric symptoms across all participants. CONCLUSION: In summary, observations of PCC connectivity to the DMN and SN provide emerging evidence of neural mechanisms underlying PCC-targeted fMRI neurofeedback among individuals with PTSD. This supports the use of PCC-targeted neurofeedback as a means by which to recalibrate PTSD-associated alterations in neural connectivity within the DMN and SN, which together, may help to facilitate improved emotion regulation abilities in PTSD.

Does the Augmentation of Trauma Informed Hatha Yoga Increase the Effect of Dialectical Behavior Therapy for Substance Use Disorders on Psychopathological Strain of Patients with Borderline Personality Disorder and Comorbid Substance Use Disorder? Results of a Quasi-Experimental Study.

BACKGROUND: Borderline personality disorder (BPD) is one of the most common personality disorders among persons with substance use disorders (SUDs) and is characterized by severe clinical symptoms. The aim of this study was to investigate if the effect of dialectical behavior therapy for substance use disorders (DBT-S) inpatient treatment on psychopathological symptom load in patients suffering from both BPD and SUD can be augmented by weekly 60-min "Trauma Informed Hatha Yoga" sessions. MATERIALS AND METHODS: Thirty-nine patients suffering from comorbid BPD and SUD were consecutively in time included in this quasi-experimental pilot study (first intervention then control group). In the intervention group, weekly Trauma Informed Hatha Yoga sessions were added to standard DBT-S for 8 weeks. The participants of the control group received standard DBT-S. All participants completed several self-report questionnaires to assess symptoms of depression, anxiety, symptoms of BPD, and their subjective stress perception at three points in time during the study course. RESULTS: A repeated measures analysis of variance with patients' psychopharmacological medication as covariate revealed a significant main effect of time for each of the psychometric scales (State and Trait Anxiety Inventory subscale for state anxiety [STAI-S] p = 0.001, Beck Depression Inventory [BDI] p < 0.001; Borderline Symptom List 23 [BSL] p = 0.036) indicating that the psychopathological symptom load of the patients was significantly lower at the end of the DBT-S therapy compared to the beginning in both study groups. Moreover, there was a significant interaction effect of group*time on the psychometric scales STAI-T (subscale for trait anxiety) sum score (p = 0.010) and the sum score of the Perceived Stress Scale (PSS) (p = 0.043). This was expressed by the fact that the participants of the intervention group showed a significant reduction of the STAI-T sum score as well as the sum score of the Perceived Stress Scale (PSS), while the control group did not. Due to the exploratory nature of this study, correction for multiple testing was omitted. CONCLUSION: Although they are very preliminary, our results suggest that practicing Trauma Informed Hatha Yoga on a regular basis in addition to DBT-S inpatient treatment seems to reduce the level of trait anxiety and perceived stress significantly more than DBT-S inpatient treatment alone. Nevertheless, the effectiveness of Trauma Informed Hatha Yoga in reducing trait anxiety and perceived stress in patients suffering from SUD und BPD must be tested in large randomized controlled trials.

An Investigation of Awareness and Metacognition in Neurofeedback with the Amygdala Electrical Fingerprint.

Awareness theory posits that individuals connected to a brain-computer interface can learn to estimate and discriminate their brain states. We used the amygdala Electrical Fingerprint (amyg-EFP) - a functional Magnetic Resonance Imaging-inspired Electroencephalogram surrogate of deep brain activation - to investigate whether participants could accurately estimate their own brain activation. Ten participants completed up to 20 neurofeedback runs and estimated their amygdala-EFP activation (depicted as a thermometer) and confidence in this rating during each trial. We analysed data using multilevel models, predicting the real thermometer position with participant rated position and adjusted for activation during the previous trial. Hypotheses on learning regulation and improvement of estimation were not confirmed. However, participant ratings were significantly associated with the amyg-EFP signal. Higher rating accuracy also predicted higher subjective confidence in the rating. This proof-of-concept study introduces an approach to study awareness with fMRI-informed neurofeedback and provides initial evidence for metacognition in neurofeedback.

Differential mechanisms of posterior cingulate cortex downregulation and symptom decreases in posttraumatic stress disorder and healthy individuals using real-time fMRI neurofeedback.

BACKGROUND: Intrinsic connectivity networks, including the default mode network (DMN), are frequently disrupted in individuals with posttraumatic stress disorder (PTSD). The posterior cingulate cortex (PCC) is the main hub of the posterior DMN, where the therapeutic regulation of this region with real-time fMRI neurofeedback (NFB) has yet to be explored. METHODS: We investigated PCC downregulation while processing trauma/stressful words over 3 NFB training runs and a transfer run without NFB (total n = 29, PTSD n = 14, healthy controls n = 15). We also examined the predictive accuracy of machine learning models in classifying PTSD versus healthy controls during NFB training. RESULTS: Both the PTSD and healthy control groups demonstrated reduced reliving symptoms in response to trauma/stressful stimuli, where the PTSD group additionally showed reduced symptoms of distress. We found that both groups were able to downregulate the PCC with similar success over NFB training and in the transfer run, although downregulation was associated with unique within-group decreases in activation within the bilateral dmPFC, bilateral postcentral gyrus, right amygdala/hippocampus, cingulate cortex, and bilateral temporal pole/gyri. By contrast, downregulation was associated with increased activation in the right dlPFC among healthy controls as compared to PTSD. During PCC downregulation, right dlPFC activation was negatively correlated to PTSD symptom severity scores and difficulties in emotion regulation. Finally, machine learning algorithms were able to classify PTSD versus healthy participants based on brain activation during NFB training with 80% accuracy. CONCLUSIONS: This is the first study to investigate PCC downregulation with real-time fMRI NFB in both PTSD and healthy controls. Our results reveal acute decreases in symptoms over training and provide converging evidence for EEG-NFB targeting brain networks linked to the PCC.

Improved emotion regulation after neurofeedback: A single-arm trial in patients with borderline personality disorder.

Real-time functional magnetic resonance imaging (fMRI) neurofeedback training of amygdala hemodynamic activity directly targets a neurobiological mechanism, which contributes to emotion regulation problems in borderline personality disorder (BPD). However, it remains unknown which outcome measures can assess changes in emotion regulation and affective instability, associated with amygdala downregulation in a clinical trial. The current study directly addresses this question. Twenty-four female patients with a DSM-IV BPD diagnosis underwent four runs of amygdala neurofeedback. Before and after the training, as well as at a six-weeks follow-up assessment, participants completed measures of emotion dysregulation and affective instability at diverse levels of analysis (verbal report, clinical interview, ecological momentary assessment, emotion-modulated startle, heart rate variability, and fMRI). Participants were able to downregulate their amygdala blood oxygen-dependent (BOLD) response with neurofeedback. There was a decrease of BPD symptoms as assessed with the Zanarini rating scale for BPD (ZAN-BPD) and a decrease in emotion-modulated startle to negative pictures after training. Further explorative analyses suggest that patients indicated less affective instability, as seen by lower hour-to-hour variability in negative affect and inner tension in daily life. If replicated by an independent study, our results imply changes in emotion regulation and affective instability for several systems levels, including behavior and verbal report. Conclusions are limited due to the lack of a control group. A randomized controlled trial (RCT) will be needed to confirm effectiveness of the training.

Cost-effectiveness of a mindfulness-based mental health promotion program: economic evaluation of a nonrandomized controlled trial with propensity score matching.

BACKGROUND: Mental health promotion programs have been shown to reduce the burden associated with mental distress and prevent the onset of mental disorders, but evidence of cost-effectiveness is scarce. OBJECTIVE: To evaluate the cost-effectiveness of a mindfulness-based mental health prevention program provided by health coaches in a multi-site field setting in Germany. METHODS: The single-study based economic evaluation was conducted as part of a nonrandomized controlled trial, comparing the effects of a group-based prevention program to usual care based on propensity score matching. Participants (N = 1166) were recruited via a large statutory health insurance fund. Health outcome was assessed with the Hospital Anxiety and Depression Scale (HADS). Cost outcomes were actually incurred costs compiled from the health insurance' records. Incremental cost-effectiveness ratios (ICER) were analyzed from a societal and a health care perspective for a 12-month time horizon with sampling uncertainty being handled using nonparametric bootstrapping. A cost-effectiveness acceptability curve was graphed to determine the probability of cost-effectiveness at different willingness-to-pay ceiling ratios. RESULTS: From a societal perspective, prevention was cost-effective compared to usual-care by providing larger effects of 1.97 units on the HADS (95% CI [1.14, 2.81], p < 0.001) at lower mean incremental total costs of €-57 (95% CI [- 634, 480], p = 0.84), yielding an ICER of €-29 (savings) per unit improvement. From a health care perspective, the incremental health benefits were achieved at additional direct costs of €181 for prevention participants (95% CI [40, 318], p = 0.01) with an ICER of €91 per unit improvement on the HADS. Willingness-to-pay for the prevention program to achieve a 95% probability of being cost-effective compared to usual-care, was estimated at €225 per unit improvement on the HADS score from a societal, and €191 from a health care perspective respectively. Sensitivity analyses suggested differential cost-effect-ratios depending on the initial distress of participants. LIMITATIONS: Due to the complexity of the field trial, it was not feasible to randomize participants and offer an active control condition. This limitation was met by applying a rigorous matching procedure. CONCLUSIONS: Our results indicate that universal mental health promotion programs in community settings might be a cost-effective strategy to enhance well-being. Differences between the societal and health care perspective underline the call for joint funding in the dissemination of preventive services. TRIAL REGISTRATION: German Clinical Trials Registration ID: DRKS00006216 (2014/06/11, retrospective registration).

The orbitofrontal cortex processes neurofeedback failure signals.

Receiving feedback from neural activity, dubbed neurofeedback, can reinforce brain self-regulation. In a real-time functional magnetic resonance imaging (fMRI) experiment, healthy participants received amygdala neurofeedback via a visual brain-computer interface. The brain response to signals of reward and failure was modeled. In contrast to previous analyses, we take into account feedback that immediately preceded these signals. That means we tested whether responses were modulated while participants observed sequent reward and failure signals. The orbitofrontal cortex (OFC) showed a negative Blood Oxygenation Level Dependent (BOLD) response to failure signals, when they were preceded by more failure signals. When failure signals were preceded by reward, in contrast, the response was less pronounced. The results suggest weighted processing of neurofeedback value in the OFC. Learning to self-regulate the brain with neurofeedback may involve similar neural networks as the learning of goal-directed action.

fMRI neurofeedback in emotion regulation: A literature review.

OBJECTIVES: Emotion regulation is one of the most prevalent objectives for real-time fMRI neurofeedback (rt-fMRI-NF) studies. The existing studies differ in a number of methodological parameters. This study provides a literature review of the main parameters and results of studies using rt-fMRI-NF for emotion regulation enhancement. METHOD: A search of the Web of Science database up through November 8, 2018, identified 144 articles written in English, 89 of which were excluded as irrelevant for this study. The remaining 51 original studies and four secondary analyses of previously published original studies were included in the literature review. The selection of target brain areas, target populations, emotion regulation protocols, NF presentation, control group types, and emotion regulation instructions were examined in relation to achieved brain regulation and changes in cognitive or clinical outcomes. Study results were evaluated in terms of their statistical robustness. RESULTS: The results show that healthy people are able to regulate their brain activity in the presence of rt-fMRI-NF from various brain regions related to emotion regulation, including the amygdala, anterior insula, and anterior cingulate cortex. The regulation of brain activity using rt-fMRI-NF from prefrontal-limbic connectivity or from individually navigated brain areas is feasible as well. Most studies that used a control group show that rt-fMRI-NF actually induces some effects on brain regulation, cognitive variables, and clinical variables. Generally, the success of ROI regulation during NF training is related to the combination of target brain region, the type of emotion regulation task, and the population undergoing the training. In terms of patient groups, the strongest support for the beneficial effects of rt-fMRI-NF has been shown in increased positive emotion experiencing in patients with depression and in decreased anxiety in patients with anxiety disorders. Symptom reduction following NF training has been also reported in patients with PTSD, BPD, and schizophrenia, but direct comparisons with control groups in these studies makes it impossible to evaluate the added value of NF. Studies often do not report all the relevant analyses for evaluating NF success and many studies lack statistical robustness. CONCLUSIONS: Overall, rt-fMRI-NF seems a promising tool for emotion regulation enhancement with the potential to induce long-term symptom reduction in patients with various mental disorders. Preplanning of statistical analyses, careful interpretations of the results, and evaluations of the NF effect on symptom reduction in patient groups is recommended.

Whole-brain functional connectivity during script-driven aggression in borderline personality disorder.

OBJECTIVE: Intense anger and anger-related aggression are frequently reported by patients with borderline personality disorders (BPD). Recent results suggest that anger-related aggression and its control is associated with a complex interplay of different neural systems in BPD. To further investigate this, we complement standard activation and seed-based connectivity analyses by examining whole-brain changes in functional connectivity during anger and reactive aggression in BPD. METHODS: We reanalyzed functional MRI data from 33 women with BPD, all of them fulfilling BPD criterion 8, "anger proneness", according to DSM-IV, and 30 healthy women. Subjects performed a script-driven imagery task consisting of four phases: baseline, anger-induction by a narrative of interpersonal rejection, a narrative of directing physical aggression towards others, and relaxation. We used a data-driven, spatially constrained spectral clustering approach to parcellate the brain into 200 regions. For each script-phase and subject, we computed the full connectivity matrix using wavelet coefficient correlations in the 0.05-0.10 Hz range. We calculated the individual increase in connectivity from baseline to the anger-induction and physical aggression phases by subtracting the corresponding connectivity matrices per subject, as well as the increase and decrease from the anger-induction to the aggression phase. We then applied permutation-based sampling to determine a combined threshold on the strength of individual connections and the size of the discovered networks for these difference matrices. RESULTS: We discovered a single, large network showing a significantly stronger increase in connectivity from baseline to the aggression phase in female patients with BPD compared to healthy women. This network consisted of regions in the anterior and posterior cingulate cortex, precuneus, dorsomedial prefrontal cortex, superior and middle temporal gyrus, hippocampus, insula, ventrolateral and dorsolateral prefrontal cortex, superior parietal lobe, thalamus, precentral and postcentral gyrus, caudate, pallidum, cerebellum, middle occipital lobe, lingual gyrus, calcarine sulcus, and fusiform gyrus. Hub regions with highest node centrality were found in the right caudate and left thalamus. We found no significant differences for the increase of connectivity from baseline to anger-induction, as well as for the increase or decrease from the anger-induction to the aggression phase. CONCLUSIONS: We identified a large network showing a significantly stronger increase in connectivity from baseline to the aggression phase in female patients with BPD compared to healthy women. The regions constituting this network belong to four previously described functional networks: The frontoparietal cognitive control network, the extended default mode network, the visual system, and the motor system. This stronger increase in connectivity between regions of different functional brain systems associated with cognitive control of behavior, socio-affective and self-referential thinking, as well as salience processing and emotion regulation, visual perception, and action is mediated via hubs in the thalamus and caudate, i.e., core components of the thalamocorticostriatal motor loop essential for action selection and initiation. These findings suggest increased interaction of prefrontal cognitive control processes with thalamocorticostriatal action-selection processes in female patients with BPD during the processing of aggressive action impulses, which are facilitated by states of high emotional salience and associated processes of self-referential and social processing, and ineffective emotion regulation.

Long-term outcome of a mental health promotion program in Germany.

Mental health promotion programs (MHP) seek to reduce sub-syndromal symptoms of mental distress and enhance positive mental health. This study evaluates the long-term effects of a mindfulness-based MHP program ('Life Balance') provided by health coaches in a multi-site field setting on mental distress, satisfaction with life and resilience. Using a controlled design, propensity score matching was used to select a control group for participants of the MHP. The total study sample (N = 3624) comprised 83% women, with a mean age of 50 years. Data was collected via mailings 1 year after study entry. Results suggest participants experience reduced emotional distress at 12-month follow-up, with a medium between-group effect size (d = 0.40) for those participants who showed clinically relevant symptoms of mental distress at study entry. The effects of the program were more pronounced in participants with higher initial distress scores. New cases of psychopathological symptoms were prevented in 1 of 16 participants. Satisfaction with life and resilience were enhanced significantly. Our data suggest 'Life Balance' shows long-term effectiveness and indicate it is possible to design MHP programs that serve as both primary and indicated prevention, and that these programs can be applied on a population basis.

Intrinsic connectivity network dynamics in PTSD during amygdala downregulation using real-time fMRI neurofeedback: A preliminary analysis.

Posttraumatic stress disorder (PTSD) has been associated with a disturbance in neural intrinsic connectivity networks (ICN), including the central executive network (CEN), default mode network (DMN), and salience network (SN). Here, we conducted a preliminary investigation examining potential changes in ICN recruitment as a function of real-time fMRI neurofeedback (rt-fMRI-NFB) during symptom provocation where we targeted the downregulation of neural response within the amygdala-a key region-of-interest in PTSD neuropathophysiology. Patients with PTSD (n = 14) completed three sessions of rt-fMRI-NFB with the following conditions: (a) regulate: decrease activation in the amygdala while processing personalized trauma words; (b) view: process trauma words while not attempting to regulate the amygdala; and (c) neutral: process neutral words. We found that recruitment of the left CEN increased over neurofeedback runs during the regulate condition, a finding supported by increased dlPFC activation during the regulate as compared to the view condition. In contrast, DMN task-negative recruitment was stable during neurofeedback runs, albeit was the highest during view conditions and increased (normalized) during rest periods. Critically, SN recruitment was high for both the regulate and the view conditions, a finding potentially indicative of CEN modality switching, adaptive learning, and increasing threat/defense processing in PTSD. In conclusion, this study provides provocative, preliminary evidence that downregulation of the amygdala using rt-fMRI-NFB in PTSD is associated with dynamic changes in ICN, an effect similar to those observed using EEG modalities of neurofeedback.

Monitoring and control of amygdala neurofeedback involves distributed information processing in the human brain.

Brain-computer interfaces provide conscious access to neural activity by means of brain-derived feedback ("neurofeedback"). An individual's abilities to monitor and control feedback are two necessary processes for effective neurofeedback therapy, yet their underlying functional neuroanatomy is still being debated. In this study, healthy subjects received visual feedback from their amygdala response to negative pictures. Activation and functional connectivity were analyzed to disentangle the role of brain regions in different processes. Feedback monitoring was mapped to the thalamus, ventromedial prefrontal cortex (vmPFC), ventral striatum (VS), and rostral PFC. The VS responded to feedback corresponding to instructions while rPFC activity differentiated between conditions and predicted amygdala regulation. Control involved the lateral PFC, anterior cingulate, and insula. Monitoring and control activity overlapped in the VS and thalamus. Extending current neural models of neurofeedback, this study introduces monitoring and control of feedback as anatomically dissociated processes, and suggests their important role in voluntary neuromodulation.

Nonsuicidal Self-Injury in Adolescents.

BACKGROUND: 25-35% of adolescents in random samples drawn from German schools have been found to have manifested at least one episode of nonsuicidal self-injury (NSSI). The prevalence in samples from child and adolescent psychiatric clinics is approximately 50%. NSSI can arise as a symptom in the setting of various types of mental illness. METHODS: This review is based on a selective literature search carried out in the PubMed, PsycINFO, and Cochrane Library databases, with special consideration of regional study samples. RESULTS: NSSI is usually resorted to as a dysfunctional coping strategy for emotional regulation. The main risk factors for NSSI include bullying, accompanying mental illnesses, and a history of abuse and neglect in childhood. Neurobiological studies have shown abnormal stress processing in persons with NSSI and an elevated pain threshold in persons with repetitive NSSI. Psychotherapeutic interventions of various kinds lessen the frequency of NSSI; to date, no particular type of psychotherapy has been found to be clearly superior to the others. Randomized controlled trials have revealed small to moderate effects from dialectic-behavioral therapy and mentalization-based therapy in adolescent patients. No psychoactive drug has yet been found to possess specific efficacy against NSSI in adolescents. CONCLUSION: The first ever German-language clinical guidelines for the treatment of NSSI have now been issued. Psychotherapy is the treatment of first choice. More research is needed so that subgroups with different disease courses can be more clearly defined.

Evaluation of psychosocial and biological parameters in women seeking for a caesarean section and women who are aiming for vaginal delivery: a cross-sectional study.

PURPOSE: To investigate psychosocial and biological parameters that may influence decision-making concerning the mode of delivery in women with caesarean section on maternal request (CSMR). METHODS: Two hundred and two women were enrolled prospectively. The study sample (n = 93) consisted of women who aimed for CSMR, the control sample were women who seeked for vaginal delivery (n = 109). Parturients of both samples were enrolled during the pre-birth counselling at the delivery room at the University Medical Centre Mannheim, University Heidelberg, Germany. Women completed standardised questionnaires regarding psychosocial burden (SCL-R 90), fear of childbirth (W-DEQ) and anxiety (STAI), personality structure (HEXACO-Pi-R), and ambiguity tolerance (PFI, PNS, and NFC), social support (F-SozU) as well as one questionnaire assessing demographic parameters and further factors potentially influencing their choice of the mode of delivery. Hair cortisol concentration as a marker for chronic psychological stress and pressure pain threshold with a pressure algometer was assessed. RESULTS: Women in the CSMR sample had less social support (F-SozU: 2.99 ± 0.52 vs. 3.12 ± 0.32; p = 0.043) and were less educated (high school or university degree: 37 vs. 71%, p = 0.001) compared to parturients of the control sample. Women who underwent CSMR were less open-minded (HEXACO-Pi-R: 3.08 ± 0.57 vs. 3.26 ± 0.50; p = 0.016) and less extroverted (HEXACO-Pi-R: 3.34 ± 0.36 vs. 3.46 ± 0.41; p = 0.041). The control collective showed higher scores in negative appraisal of the birth ('W-DEQ-negative appraisal': 2.5 ± 0.8 vs. 2.2 ± 0.9; p = 0.006), whereas "lack of positive anticipation" was higher in the study collective ('W-DEQ-lack of positive anticipation': 3.2 ± 1.2 vs. 2.8 ± 0.8; p = 0.015). The study collective had higher pressure pain threshold values (5.07 ± 2.06 vs. 4.35 ± 1.38; p = 0.007), while no significant differences were observed in hair cortisol concentration comparing both groups (5.0 ± 11.4 vs. 4.9 ± 8.3; p = 0.426). The majority of the control collective (80%) had chosen the vaginal route as their mode of delivery before pregnancy, whereas only 21% of the women in the study collective decided to undergo CSMR before conception. The advice of social sources including both medical and non-medical aspects was rated less important in the study sample, with significant differences indicating a lower relevance of counsel from friends (p = 0.002) and midwives (p < 0.001). CONCLUSION: Women who inquired a CSMR had lower social support, were less educated, more anxious, and had a lower sensitivity for physical pain compared to women seeking for spontaneous delivery. This should be considered when counselling women requiring CSMR and could be leverage points to intervene to reduce the continuously increasing CSMR rate.

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.

ACC GABA levels are associated with functional activation and connectivity in the fronto-striatal network during interference inhibition in patients with borderline personality disorder.

Impulsivity often develops from disturbed inhibitory control, a function mainly regulated by γ-Aminobutyric acid (GABA) levels in the anterior cingulate cortex (ACC) and the fronto-striatal system. In this study, we combined MRS GABA measurements and fMRI to investigate neurochemical and neurofunctional correlates of interference inhibition, further emphasizing the direct relationship between those two systems, as well as their relations to impulsivity in patients with BPD. In addition to BOLD activation, task-dependent functional connectivity was assessed by a generalized psychophysiological interactions approach. Full factorial analyses were performed via SPM to examine the main effect (within-group associations) as well as the interaction term (group differences in the association slope). The UPPS scales were used to evaluate impulsivity traits. Compared to healthy controls (HCs), BPD patients exhibited significantly less ACC-caudate functional connectivity during interference inhibition. ACC GABA levels in BPD patients but not in HCs were positively related to the magnitude of activation in several fronto-striatal regions (e.g. ACC, frontal regions, putamen, caudate,) and the strength of ACC-caudate functional connectivity during interference inhibition. The strength of the correlations of GABA with connectivity significantly differs between the two groups. Moreover, among all the UPPS impulsivity subscales, UPPS sensation seeking in the BPD group was related to GABA and was also negatively related to the task-dependent BOLD activation and functional connectivity in the fronto-striatal network. Finally, mediation analyses revealed that the magnitude of activation in the caudate and the strength of ACC-caudate functional connectivity mediated the relationship between ACC GABA levels and UPPS sensation seeking in patients with BPD. Our findings suggest a disconnectivity of the fronto-striatal network in BPD patients during interference inhibition, particularly for patients with higher impulsivity. The ACC GABAergic system seems to play a crucial role in regulating regional BOLD activations and functional connectivity in this network, which are further associated with impulsive sensation seeking in BPD.

Alterations of amygdala-prefrontal connectivity with real-time fMRI neurofeedback in BPD patients.

With the use of real-time functional magnetic resonance imaging neurofeedback (NF), amygdala activitiy can be visualized in real time. In this study, continuous amygdala NF was provided to patients with borderline personality disorder (BPD) with the instruction to down-regulate. During four sessions of NF training, patients viewed aversive pictures and received feedback from a thermometer display, which showed the amygdala blood oxygenation level-dependent signal. Conditions of regulation and viewing without regulation were presented. Each session started with a resting-state scan and was followed by a transfer run without NF. Amygdala regulation, task-related and resting-state functional brain connectivity were analyzed. Self-ratings of dissociation and difficulty in emotion regulation were collected. BPD patients down-regulated right amygdala activation but there were no improvements over time. Task-related amygdala-ventromedial prefrontal cortex connectivity was altered across the four sessions, with an increased connectivity when regulating vs viewing pictures. Resting-state amygdala-lateral prefrontal cortex connectivity was altered and dissociation, as well as scores for 'lack of emotional awareness', decreased with training. Results demonstrated that amygdala NF may improve healthy brain connectivity, as well as emotion regulation. A randomized-controlled trial is needed to investigate whether amygdala NF is instrumental for improving neural regulation and emotion regulation in BPD patients.

fMRI neurofeedback of amygdala response to aversive stimuli enhances prefrontal-limbic brain connectivity.

Down-regulation of the amygdala with real-time fMRI neurofeedback (rtfMRI NF) potentially allows targeting brain circuits of emotion processing and may involve prefrontal-limbic networks underlying effective emotion regulation. Little research has been dedicated to the effect of rtfMRI NF on the functional connectivity of the amygdala and connectivity patterns in amygdala down-regulation with neurofeedback have not been addressed yet. Using psychophysiological interaction analysis of fMRI data, we present evidence that voluntary amygdala down-regulation by rtfMRI NF while viewing aversive pictures was associated with increased connectivity of the right amygdala with the ventromedial prefrontal cortex (vmPFC) in healthy subjects (N=16). In contrast, a control group (N=16) receiving sham feedback did not alter amygdala connectivity (Group×Condition t-contrast: p<.05 at cluster-level). Task-dependent increases in amygdala-vmPFC connectivity were predicted by picture arousal (ß=.59, p<.05). A dynamic causal modeling analysis with Bayesian model selection aimed at further characterizing the underlying causal structure and favored a bottom-up model assuming predominant information flow from the amygdala to the vmPFC (xp=.90). The results were complemented by the observation of task-dependent alterations in functional connectivity of the vmPFC with the visual cortex and the ventrolateral PFC in the experimental group (Condition t-contrast: p<.05 at cluster-level). Taken together, the results underscore the potential of amygdala fMRI neurofeedback to influence functional connectivity in key networks of emotion processing and regulation. This may be beneficial for patients suffering from severe emotion dysregulation by improving neural self-regulation.