Relationship between Borderline Personality Disorder, Emotional Availability, and Cortisol Output in Mother-Child Dyads.

BACKGROUND: Mothers with borderline personality disorder (BPD) often show altered emotional availability toward their own child and heightened stress vulnerability. The aims of the present study were (1) to examine total cortisol output in saliva during mother-child interaction in mothers with BPD and their children and (2) to test whether maternal nonhostility as a subscale of emotional availability mediates the relationship between maternal BPD and child total cortisol output. METHODS: We investigated 16 mothers with BPD and 30 healthy control mothers (HC) and 29 children of mothers with BPD and 33 children of HC mothers. Children were between 5 and 12 years old. Salivary cortisol was collected prior to and twice after an episode of a 21-min standardized play situation between mother and child. Nonhostility was rated using the emotional availability scales. Analyses of covariance were computed to test for group differences in total cortisol output (measured with area under the curve with respect to ground). Pearson's correlation was calculated to test the association between maternal and child total cortisol output. To test the second question, a mediation analysis according to Preacher and Hayes was conducted. RESULTS: Mothers with BPD and their children had lower total cortisol output. Maternal and child total cortisol output was significantly correlated. Contrary to our hypothesis, maternal nonhostility did not mediate the relationship between BPD and child total cortisol output. CONCLUSION: Results imply that the hormonal stress activity of mothers with BPD and their children is altered, which may reflect modified stress regulation and stress vulnerability in mother and child and may impact on mother-child interaction. The finding of a positive association between mother's and child total cortisol output could indicate an intergenerational transmission of these alterations.

Increased child-evoked activation in the precuneus during facial affect recognition in mothers.

Successful parenting requires constant inferring of affective states. Especially vital is the correct identification of facial affect. Previous studies have shown that infant faces are processed preferentially compared to adult faces both on the behavioural and the neural level. This study specifically investigates the child-evoked neural responses to affective faces and their modulation by motherhood and attention to affect. To do so, we used a paradigm to measure neural responses during both explicit and implicit facial affect recognition (FAR) in mothers and non-mothers using child and adult faces. Increased activation to child compared to adult faces was found for mothers and non-mothers in face processing areas (bilateral fusiform gyri) and areas associated with social understanding (bilateral insulae and medial superior frontal gyrus) when pooling implicit and explicit affect recognition. Furthermore, this child-evoked activation was modulated by motherhood with an increase in mothers compared to non-mothers in the left precuneus. Additionally, explicitly recognising the affect increased child-evoked activation in the medial superior frontal gyrus in both mothers and non-mothers. These results suggest preferential treatment of affective child over adult faces, modulated by motherhood and attention to affect.

Elevated inflammatory markers in women with remitted major depressive disorder and the role of early life maltreatment.

Major depressive disorder (MDD) has been linked to elevated inflammation markers. It remains unclear whether the elevation of C-reactive protein (CRP) and interleukin-6 (IL-6) levels are not only observable in acute MDD but also in patients after remission. MDD is a common sequela of early life maltreatment (ELM), which has also been associated with elevated inflammation markers. While the majority of studies investigated (acute) MDD and ELM as isolated predictors of inflammation, a few studies found inflammation levels to be more pronounced in patients with MDD that were exposed to ELM. This investigation included both ELM and MDD in one study and aimed at distinguishing between the effects of MDD in remission (rMDD) and ELM and investigating potential accumulative effects on the inflammatory markers CRP and IL-6 in a population of N = 126 women (n = 122 for CRP and n = 66 for IL-6). We further investigated how disorder characteristics (course and severity) and specific types of ELM affect levels of CRP and IL-6. We found that rMDD predicted levels of CRP and IL-6 and physical abuse predicted levels of CRP when considering both predictors simultaneously, while other types of ELM did not. A later onset of MDD and a shorter time interval since the last episode were associated with higher levels of IL-6. Our findings contribute to the existing literature on the association between MDD and inflammation, suggesting that elevated levels of inflammation markers may persist even after remission of MDD. Our findings on physical abuse as a specific predictor of CRP in the presence of rMDD suggest that different types of ELM could result in distinct inflammation profiles.

Alterations of empathy in mothers with a history of early life maltreatment, depression, and borderline personality disorder and their effects on child psychopathology.

BACKGROUND: Early life maltreatment (ELM), borderline personality disorder (BPD), and major depressive disorder (MDD) have been associated with empathy deficits in different domains. Lack of maternal empathy has also been related to child behavioral problems. As ELM, BPD, and MDD often co-occur, we aimed to identify dissociable effects on empathy due to these three factors. In addition, we aimed to investigate their indirect effects via empathy on child psychopathology. METHODS: We included 251 mothers with and without MDD (in remission), BPD and ELM and their children, aged 5-12. We used the Interpersonal Reactivity Index as a measure of empathy on four different dimensions (personal distress, empathic concern, perspective taking, and fantasy) and the Child Behavior Checklist as a measure of child psychopathology. RESULTS: Having included all three factors (ELM, MDD, BPD) in one analysis, we found elevated personal distress in MDD and BPD, and lower levels of perspective-taking in BPD, but no effects from ELM on any empathy subscales. Furthermore, we found indirect effects from maternal BPD and MDD on child psychopathology, via maternal personal distress. CONCLUSION: The present study demonstrated the dissociable effects of maternal ELM, MDD, and BPD on empathy. Elevated personal distress in mothers with BPD and MDD may lead to higher levels of child psychopathology.

Impact of Maternal Early Life Maltreatment and Maternal History of Depression on Child Psychopathology: Mediating Role of Maternal Sensitivity?

The study addresses the impact of maternal early life maltreatment (ELM) and maternal history of depression (HoD) on offspring's mental health. Maternal sensitivity was examined as a potential mediator explaining the relationship between maternal ELM, maternal HoD and child psychopathology. Participants were 194 mothers with and without HoD and/or ELM as well as their children between 5 and 12 years. Maternal sensitivity was assessed using the Emotional Availability Scales. Parent and teacher ratings were utilized to assess child psychopathology. Path analyses showed an indirect effect of maternal HoD on parents' ratings of child psychopathology with maternal sensitivity as mediating variable. In contrast, maternal ELM was directly linked to teachers' ratings of child psychopathology; this effect was not mediated by maternal sensitivity. Our results indicate that the impact of maternal HoD, maternal ELM, and maternal sensitivity on offspring psychopathology might vary depending on the context in which child psychopathology is assessed.

[Oxytocin and maltreatment potential : Influence of maternal depression, borderline personality disorder and experience of early childhood maltreatment]. / Oxytocin und Misshandlungspotenzial : Einfluss von mütterlicher Depression, Borderline-Persönlichkeitsstörung und frühkindlicher Misshandlungserfahrung.

BACKGROUND: The "empathy hormone" oxytocin (OXT) is associated with social interaction and parent-child interaction. Mothers with mental stress factors, e.g., history of depression, borderline personality disorder or early life maltreatment in their own childhood often show distinct maternal behavior. The objectives of the study were (1) to examine the association between these three stress factors and maternal OXT within one analysis. (2) Moreover, OXT was tested as a potential mediator for the association between maternal experience of early childhood maltreatment and abuse potential against their own child. METHODS: Plasma OXT concentrations of 52 mothers during the follicular phase were collated (healthy control mothers n = 22, history of depression n = 23, borderline personality disorder n = 7). The maternal history of psychiatric disorders and experiences of early childhood maltreatment were examined via interviews. Regression and mediation analyses were applied to answer the research questions. RESULTS: Early childhood maltreatment was associated with reduced plasma OXT; however, maternal history of depression and borderline personality disorder were not related to OXT concentrations. In particular, having experienced parental antipathy in one's own childhood was associated with reduced OXT levels but OXT did not mediate the association between maternal early childhood experiences of maltreatment and abuse potential of their own child. CONCLUSION: In the present study alterations in plasma OXT concentrations were not associated with psychiatric disorders, such as a history of depression or borderline personality disorder but more with a potential etiological factor of these disorders, i.e. experience of maltreatment in their own childhood.

Child abuse potential in mothers with early life maltreatment, borderline personality disorder and depression.

BACKGROUND: Early life maltreatment (ELM), borderline personality disorder (BPD) and major depressive disorder (MDD) have been shown to increase the potential of abuse. Emotion regulation is an identified mediator for the association of ELM and BPD with abuse potential. Until now, there has been no study to account for the co-occurrence of these risk factors in one analysis, although BPD and MDD are known as common sequelae of ELM. This is paired with a lack of studies investigating the effects of abuse potential on child well-being.AimsOur study aims at (a) disentangling the effects of maternal ELM, MDD and BPD on abuse potential; (b) exploring the role of emotion regulation as a mediator; and (c) testing for intergenerational effects of abuse potential on child psychopathology. METHOD: The research design included 114 mothers with/without ELM, BPD and MDD in remission and their children, all of which were between 5 and 12 years of age. A path analysis was conducted to investigate the multiple associations between our variables. RESULTS: ELM, MDD and BPD were all associated with abuse potential, with emotion regulation acting as a mediator for BPD and MDD. Furthermore, an elevated abuse potential was related to higher psychopathology in the child. CONCLUSIONS: History of ELM as well as the common sequelae, BPD and MDD, pose risks for child abuse. Our findings suggest improvement of emotion regulation as a potential target for intervention programs. These programs should also aim at non-substantiated cases because even an elevated abuse potential affected child mental health.Declaration of interestNone.

To drink or not to drink: Harmful drinking is associated with hyperactivation of reward areas rather than hypoactivation of control areas in men.

BACKGROUND: The maintenance of harmful alcohol use can be considered a reiterated decision in favour of alcohol in concrete drinking occasions. These decisions are often made despite an intention to quit or reduce alcohol consumption. We tested if a hyperactive reward system and/or an impaired cognitive control system contribute to such unfavourable decision-making. METHODS: In this fMRI study, men with modest to harmful drinking behaviour, which was measured using the Alcohol Use Disorders Identification Test (AUDIT), repeatedly made decisions between alcoholic and nonalcoholic drinks. Based on prior individual ratings, decision pairs were created with an alcoholic decision option considered more desirable but less beneficial by the participant. By correlating AUDIT scores with brain activation during decision-making, we determined areas explicitly related to pro-alcohol decisions in men with greater drinking severity. RESULTS: Thirty-eight men participated in our study. Behaviourally, we found a positive correlation between AUDIT scores and the number of decisions for desired alcoholic drinks compared with beneficial nonalcoholic drinks. The fMRI results show that AUDIT scores were positively associated with activation in areas associated with reward and motivation processing (i.e., ventral striatum, amygdala, medial prefrontal cortex) during decisions favouring a desired, nonbeneficial alcoholic drink. Conversely, we did not find hypoactivation in areas associated with self-control (dorsolateral prefrontal cortex). These effects were not present when participants chose a desired, nonbenefical, nonalcoholic drink. LIMITATIONS: The men participating in our study had to be abstinent and would potentially consume an alcoholic drink at the end of the experiment. Hence, we did not define manifest alcohol dependence as an inclusion criterion and instead focused on less severely affected individuals. CONCLUSION: Our results indicate that with growing drinking severity, decisions for alcoholic drinks are associated with increasing activity in reward-associated neural systems, rather than decreasing activity in self-control-associated systems.

EMOTIONAL AVAILABILITY IN MOTHER-CHILD INTERACTION: THE EFFECTS OF MATERNAL DEPRESSION IN REMISSION AND ADDITIONAL HISTORY OF CHILDHOOD ABUSE.

BACKGROUND: The association between maternal depression and adverse outcomes in children is well established. Similar links have been found for maternal childhood abuse. One proposed pathway of risk transmission is reduced maternal emotional availability. Our aim was to investigate whether sensitive parenting is impaired in mothers with depression in remission, and whether among these mothers childhood abuse has an additional impact. METHODS: The mother-child interaction of 188 dyads was assessed during a play situation using the Emotional Availability Scales, which measure the overall affective quality of the interaction: maternal sensitivity, structuring, nonhostility, and nonintrusiveness. Mothers with depression in remission were compared to healthy mothers. Children were between 5 and 12 years old. Group differences and impact of additional childhood abuse were analyzed by one-factorial analyses of covariance and planned contrasts. RESULTS: Mothers with depression in remission showed less emotional availability during mother-child interaction compared to healthy control mothers. Specifically, they were less sensitive and, at trend-level, less structuring and more hostile. Among these mothers, we found an additional effect of severe maternal childhood abuse on maternal sensitivity: Mothers with depression in remission and a history of severe childhood abuse were less sensitive than remitted mothers without childhood abuse. CONCLUSIONS: Our data suggest that depression impacts on maternal emotional availability during remission, which might represent a trait characteristic of depression. Mothers with depression in remission and additional severe childhood abuse were particularly affected. These findings may contribute to the understanding of children's vulnerability to develop a depressive disorder themselves.

Cortical and subcortical responses to high and low effective placebo treatments.

The effectiveness of placebo treatments depends on the recipient's expectations, which are at least in part shaped by previous experiences. Thus, positive past experience together with an accordant verbal instruction should enhance outcome expectations and subsequently lead to higher placebo efficacy. This should be reflected in subjective valuation reports and in activation of placebo-related brain structures. We tested this hypothesis in a functional magnetic resonance imaging study, where subjects experienced different levels of pain relief and conforming information about price levels for two placebo treatments during a manipulation phase, thereby establishing a weak and a strong placebo. As expected, both placebos led to a significant pain relief and the strong placebo induced better analgesic efficacy. Individual placebo value estimates reflected treatment efficacy, i.e. subjects were willing to pay more money for the strong placebo even though pain stimulation was completed at this time. On the neural level, placebo effects were associated with activation of the rostral anterior cingulate cortex, the anterior insula, and the ventral striatum and deactivations in the thalamus and secondary somatosensory cortex. However, only placebo-related responses in rostral anterior cingulate cortex were consistent across both the anticipation of painful stimuli and their actual administration. Most importantly, rostral anterior cingulate cortex responses were higher for the strong placebo, thus mirroring the behavioral effects. These results directly link placebo analgesia to anticipatory activity in the ventral striatum, a region involved in reward processing, and highlight the role of the rostral anterior cingulate cortex, as its activity consistently scaled with increasing analgesic efficacy.

The mediating role of attachment and anger: exploring the impact of maternal early-life maltreatment on child abuse potential.

Background: Maternal early-life maltreatment (ELM) increases the risk of subsequent child maltreatment, but the underlying mechanisms of these intergenerational effects remain largely unknown. Identifying these mechanisms is crucial for developing preventive interventions that can break the cycle of abuse. Notably, previous research has shown that ELM often results in attachment insecurity and altered anger characteristics. Therefore, this study determines whether these characteristics mediate the relationship between maternal history of ELM and child abuse potential. Methods: The study sample included 254 mothers, of whom 149 had experienced ELM to at least a moderate degree. Maternal ELM was assessed using the Childhood Experience of Care and Abuse (CECA) interview. Attachment insecurity, trait anger and anger expression, and maternal abuse potential were assessed using the Vulnerable Attachment Questionnaire (VASQ), State-Trait Anger Expression Inventory (STAXI), and Child Abuse Potential Inventory (CAPI), respectively. Results: The severity of maternal ELM predicted higher child abuse potential, with attachment insecurity and anger suppression mediating this effect. Specifically, higher levels of maternal ELM were associated with greater attachment insecurity and increased anger suppression, resulting in a higher child abuse potential. Although higher levels of trait anger were directly associated with higher child abuse potential, this parameter did not mediate the relationship with ELM. In addition, no significant associations were observed between outwardly expressed anger and ELM or child abuse potential. All analyses were adjusted for maternal mental disorders, years of education, and relationship status. Discussion: Attachment insecurity and anger suppression may serve as pathways linking the maternal history of ELM to the risk of child abuse, even when considering maternal psychopathology. Overall, our findings indicate that interventions aimed at strengthening attachment and improving anger suppression may be beneficial for all mothers with ELM history and high child abuse potential, not just those who suffer from mental illness.

Boosting the Theory of Mind Network: Specific Psychotherapy Increases Neural Correlates of Affective Theory of Mind in Euthymic Bipolar Disorder.

BACKGROUND: In bipolar disorder, impaired affective theory of mind (aToM) performance and aberrant neural activation in the ToM brain network partly explain social functioning impairments. However, it is not yet known whether psychotherapy of bipolar disorder influences neuroimaging markers of aToM. METHODS: In this study, conducted within the multicentric randomized controlled trial of the BipoLife consortium, patients with euthymic bipolar disorder underwent 2 group interventions over 6 months (mean = 28.45 weeks): 1) a specific, cognitive behavioral intervention (specific psychotherapeutic intervention [SEKT]) (n = 31) targeting impulse regulation, ToM, and social skills and 2) an emotion-focused intervention (FEST) (n = 28). To compare the effect of SEKT and FEST on neural correlates of aToM, patients performed an aToM task during functional magnetic resonance imaging before and after interventions (final functional magnetic resonance imaging sample of pre- and postcompleters, SEKT: n = 16; FEST: n = 17). Healthy control subjects (n = 32) were scanned twice with the same time interval. Because ToM was trained in SEKT, we expected an increased ToM network activation in SEKT relative to FEST postintervention. RESULTS: Both treatments effectively stabilized patients' euthymic state in terms of affective symptoms, life satisfaction, and global functioning. Confirming our expectations, SEKT patients showed increased neural activation within regions of the ToM network, bilateral temporoparietal junction, posterior cingulate cortex, and precuneus, whereas FEST patients did not. CONCLUSIONS: The stabilizing effect of SEKT on clinical outcomes went along with increased neural activation of the ToM network, while FEST possibly exerted its positive effect by other, yet unexplored routes.

Daring to Feel: Emotion-Focused Psychotherapy Increases Amygdala Activation and Connectivity in Euthymic Bipolar Disorder-A Randomized Controlled Trial.

BACKGROUND: In bipolar disorder (BD), the alternation of extreme mood states indicates deficits in emotion processing, accompanied by aberrant neural function of the emotion network. The present study investigated the effects of an emotion-centered psychotherapeutic intervention on amygdala responsivity and connectivity during emotional face processing in BD. METHODS: In a randomized controlled trial within the multicentric BipoLife project, euthymic patients with BD received one of two interventions over 6 months: an unstructured, emotion-focused intervention (FEST), where patients were guided to adequately perceive and label their emotions (n = 28), or a specific, structured, cognitive behavioral intervention (SEKT) (n = 31). Before and after interventions, functional magnetic resonance imaging was conducted while patients completed an emotional face-matching paradigm (final functional magnetic resonance imaging sample of patients completing both measurements: SEKT, n = 17; FEST, n = 17). Healthy control subjects (n = 32) were scanned twice after the same interval without receiving any intervention. Given the focus of FEST on emotion processing, we expected FEST to strengthen amygdala activation and connectivity. RESULTS: Clinically, both interventions stabilized patients' euthymic states in terms of affective symptoms. At the neural level, FEST versus SEKT increased amygdala activation and amygdala-insula connectivity at postintervention relative to preintervention time point. In FEST, the increase in amygdala activation was associated with fewer depressive symptoms (r = 0.72) 6 months after intervention. CONCLUSIONS: Enhanced activation and functional connectivity of the amygdala after FEST versus SEKT may represent a neural marker of improved emotion processing, supporting the FEST intervention as an effective tool in relapse prevention in patients with BD.

Attentional bias to briefly presented emotional distractors follows a slow time course in visual cortex.

A central controversy in the field of attention is how the brain deals with emotional distractors and to what extent they capture attentional processing resources reflexively due to their inherent significance for guidance of adaptive behavior and survival. Especially, the time course of competitive interactions in early visual areas and whether masking of briefly presented emotional stimuli can inhibit biasing of processing resources in these areas is currently unknown. We recorded frequency-tagged potentials evoked by a flickering target detection task in the foreground of briefly presented emotional or neutral pictures that were followed by a mask in human subjects. We observed greater competition for processing resources in early visual cortical areas with shortly presented emotional relative to neutral pictures ~275 ms after picture offset. This was paralleled by a reduction of target detection rates in trials with emotional pictures ~400 ms after picture offset. Our finding that briefly presented emotional distractors are able to bias attention well after their offset provides evidence for a rather slow feedback or reentrant neural competition mechanism for emotional distractors that continues after the offset of the emotional stimulus.

Motherhood and theory of mind: increased activation in the posterior cingulate cortex and insulae.

Despite growing evidence on effects of parenthood on social understanding, little is known about the influence of parenthood on theory of mind (ToM), the capacity to infer mental and affective states of others. It is also unclear whether any possible effects of parenthood on ToM would generalise to inferring states of adults or are specific to children. We investigated neural activation in mothers and women without children while they predicted action intentions from child and adult faces. Region-of-interest analyses showed stronger activation in mothers in the bilateral posterior cingulate cortex, precuneus (ToM-related areas) and insulae (emotion-related areas). Whole-brain analyses revealed that mothers compared to non-mothers more strongly activated areas including the left angular gyrus and the ventral prefrontal cortex but less strongly activated the right supramarginal gyrus and the dorsal prefrontal cortex. These differences were not specific to child stimuli but occurred in response to both adult and child stimuli and might indicate that mothers and non-mothers employ different strategies to infer action intentions from affective faces. Whether these general differences in affective ToM between mothers and non-mothers are due to biological or experience-related changes should be subject of further investigation.

Emotional processing in a salient motion context: integration of motion and emotion in both V5/hMT+ and the amygdala.

Recent studies have suggested that the extent to which primary task demands draw on attentional resources determines whether or not task-irrelevant emotional stimuli are processed. Another important factor that can bias task-relevant and task-irrelevant stimulus competition is the bottom-up factor of stimulus salience. Here, we investigated the effect of stimulus salience associated with a primary motion task on the processing of emotional face distractors. Faces of different emotional valences were presented within a context of randomly moving dots. Subjects had to detect short intervals of coherent motion while ignoring the background faces. Task salience was manipulated by the level of motion coherence of the dots with high motion coherence being associated with high salience. Using functional magnetic resonance imaging, we show that emotional faces, compared with neutral faces, more strongly interfered with the primary task, as reflected in significant signal decreases in task-related motion area V5/hMT+. In addition, these faces elicited significant signal increases in the left amygdala. Most importantly, task salience was found to further increase amygdala's activity when presented together with an emotional face. Our data support a more general role of the amygdala as a behavioral relevance detector, which flexibly integrates behavioral relevant, salient context information to decode the emotional content of a visual scene.

Increased activation in the bilateral anterior insulae in response to others in pain in mothers compared to non-mothers.

Empathy allows us to share emotions and encourages us to help others. It is especially important in the context of parenting where children's wellbeing is dependent on their parents' understanding and fulfilment of their needs. To date, little is known about differences in empathy responses of parents and non-parents. Using stimuli depicting adults and children in pain, this study focuses on the interaction of motherhood and neural responses in areas associated with empathy. Mothers showed higher activation to both adults and children in pain in the bilateral anterior insulae, key regions of empathy for pain. Additionally, mothers more strongly activated the inferior frontal, superior temporal and the medial superior frontal gyrus. Differences between adult and child stimuli were only found in occipital areas in both mothers and non-mothers. Our results suggest a stronger neural response to others in pain in mothers than non-mothers regardless of whether the person is a child or an adult. This could indicate a possible influence of motherhood on overall neural responses to others in pain rather than motherhood specifically shaping child-related responses. Alternatively, stronger responses to others in pain could increase the likelihood for women to be in a relationship and subsequently to have a child.

The German research consortium for the study of bipolar disorder (BipoLife): a magnetic resonance imaging study protocol.

BACKGROUND: Bipolar disorder is one of the most severe mental disorders. Its chronic course is associated with high rates of morbidity and mortality, a high risk of suicide and poor social and occupational outcomes. Despite the great advances over the last decades in understanding mental disorders, the mechanisms underlying bipolar disorder at the neural network level still remain elusive. This has severe consequences for clinical practice, for instance by inadequate diagnoses or delayed treatments. The German research consortium BipoLife aims to shed light on the mechanisms underlying bipolar disorders. It was established in 2015 and incorporates ten university hospitals across Germany. Its research projects focus in particular on individuals at high risk of bipolar disorder, young patients in the early stages of the disease and patients with an unstable highly relapsing course and/or with acute suicidal ideation. METHODS: Functional and structural magnetic resonance imaging (MRI) data was acquired across nine sites within three different studies. Obtaining neuroimaging data in a multicenter setting requires among others the harmonization of the acquisition protocol, the standardization of paradigms and the implementation of regular quality control procedures. The present article outlines the MRI imaging protocols, the acquisition parameters, the imaging paradigms, the neuroimaging quality assessment procedures and the number of recruited subjects. DISCUSSION: The careful implementation of a MRI study protocol as well as the adherence to well-defined quality assessment procedures is one key benchmark in the evaluation of the overall quality of large-scale multicenter imaging studies. This article contributes to the BipoLife project by outlining the rationale and the design of the MRI study protocol. It helps to set the necessary standards for follow-up analyses and provides the technical details for an in-depth understanding of follow-up publications.