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Negative affect is a fundamental dimension of human emotion. When extreme, it contributes to a variety of adverse outcomes—from physical and mental illness to divorce and premature death. Mechanistic work in animals and neuroimaging research in humans and monkeys has begun to reveal the broad contours of the neural circuits governing negative affect, but the relevance of these discoveries to everyday distress remains incompletely understood. Here we used a combination of approaches— including neuroimaging assays of threat anticipation and emotional face perception and >10,000 momentary assessments of emotional experience—to demonstrate that individuals showing greater activation in a cingulo-opercular circuit during an anxiety-eliciting laboratory paradigm experience lower levels of stressor-dependent distress in their daily lives (n=202-208). Extended amygdala activation was not significantly related to momentary negative affect. These observations provide a framework for understanding the neurobiology of negative affect in the laboratory and in the real world.STATEMENT OF RELEVANCEAnxiety, sadness, and other negative emotions are hallmarks of the human condition. When extreme, they contribute to a variety of adverse outcomes—from physical and mental illness to divorce and premature death—pointing to the need to develop a better understanding of the underlying brain circuitry. Recent work has begun to reveal the neural systems governing negative affect, but the relevance of these tantalizing laboratory discoveries to the real world has remained unclear. Here we used a combination of brain imaging and smartphone-based survey techniques to show that individuals marked by greater activation in a cingulo-opercular circuit during an anxiety-promoting laboratory paradigm tend to experience diminished distress in response to everyday stressors. These observations provide new insights into the brain systems most relevant to moment-by-moment fluctuations in negative mood, underscoring the importance of more recently evolved cortical association areas.

Purpose We aimed to (i) investigate differences in 1-minute sit-to-stand test (1MSTST) performance (i.e., the number of repetitions) between a standardised modality (i.e., starting from a conventional chair with 46 cm seat height) and an individualised modality (i.e., starting with a knee joint flexion angle of 90°), and to (ii) quantify the influence of tibia and femur length on 1MSTST performance. Methods Healthy participants were recruited for this randomised crossover study, performing each 1MSTST modality twice in a randomised order. The primary outcome was the number of repetitions in the 1MSTST. Secondary endpoints were the acute responses in peripheral oxygen saturation, heart rate, and leg fatigue and dyspnoea. Additionally, we investigated correlations of performance with knee extensor strength in both modalities. Results Thirty participants were recruited and completed the study. They achieved significantly less repetitions in the standardised 1MSTST compared to the individualised 1MSTST (B = − 12.1, 95% confidence interval [95% CI] = − 14.8/− 9.4, p Conclusion An individualisation of the 1MSTST starting position to 90° knee flexion angle leads to more repetitions compared to the traditional starting position. The higher repetition count is explained by controlling for differences in tibia length. We recommend individualisation of the 1MSTST, enabling more valid comparisons across populations and study samples. Trial registration number http://www.ClinicalTrials.gov, NCT04772417. Trial registration date February 26, 2021.

Neuroticism or negative emotionality (N/NE)—the propensity to experience and express more intense, frequent, or persistent negative affect—is a fundamental dimension of mammalian temperament. Elevated levels of N/NE are associated with a wide range of practically important outcomes, from marital stability and socioeconomic attainment to mental illness and premature death. Despite this, our understanding of the brain bases of N/NE remains far from complete. Converging lines of mechanistic and neuroimaging evidence suggest that N/NE reflects heightened reactivity to genuinely threatening stimuli in the extended amygdala, a circuit encompassing the dorsal amygdala in the region of the central nucleus (Ce) and the lateral division of the neighboring bed nucleus of the stria terminalis (BST), and that this association may be more evident when threat is uncertain. Here, we used a combination of approaches—including a multi-trait, multi-occasion composite of N/NE and neuroimaging assays of threat anticipation and perception—to demonstrate that individuals with a more negative disposition show heightened BST activation during uncertain-threat anticipation. A series of cross-validated, robust regression analyses revealed that N/NE is uniquely predicted by BST reactivity to uncertain-threat anticipation. In contrast, N/NE was unrelated to Ce activation during the anticipation of threat or to extended amygdala activation during the presentation of ‘threatening’ faces. Follow-up analyses revealed inconsistent evidence of between-task convergence in the BST and Ce, suggesting that threat-anticipation and emotional-face paradigms are not interchangeable probes of extended amygdala function. Collectively, these observations lay the foundation for the kinds of prospective-longitudinal and mechanistic studies that will be necessary to determine causation and, ultimately, to develop improved interventions for extreme N/NE.

Research questionThe assessment of cough frequency in clinical practice relies predominantly on the patient's history. Currently, objective evaluation of cough is feasible with bulky equipment during a brief time (i.e.hours up to 1 day). Thus, monitoring of cough has been rarely performed outside clinical studies. We developed a small wearable cough detector (SIVA-P3) that uses deep neural networks for the automatic counting of coughs. This study examined the performance of the SIVA-P3 in an outpatient setting.MethodsWe recorded cough epochs with SIVA-P3 over eight consecutive days in patients suffering from chronic cough. During the first 24 h, the detector was validated against cough events counted by trained human listeners. The wearing comfort and the device usage were assessed using a questionnaire.ResultsIn total, 27 participants (mean±sdage 50±14 years) with either chronic unexplained cough (n=12), COPD (n=4), asthma (n=5) or interstitial lung disease (n=6) were studied. During the daytime, the sensitivity of SIVA-P3 cough detection was 88.5±2.49% and the specificity was 99.97±0.01%. During the night-time, the sensitivity was 84.15±5.04% and the specificity was 99.97±0.02%. The wearing comfort and usage of the device was rated as very high by most participants.ConclusionSIVA-P3 enables automatic continuous cough monitoring in an outpatient setting for objective assessment of cough over days and weeks. It shows comparable sensitivity or higher sensitivity than other devices with fully automatic cough counting. Thanks to its wearing comfort and the high performance for cough detection, it has the potential for being used in routine clinical practice.

The startle response is a cross-species conserved defensive reflex that is considered a key tool for cross-species translational research on emotion and cognition. While the neural pathway mediating (affective) startle modulation has been extensively studied in rodents, human work has lagged in the past due to technical challenges. Recent technical advances, however, have finally enabled non-invasive simultaneous EMG-fMRI acquisition and hence opened new avenues for bridging the gap between clinical and basic science.We illustrate key paradigms and methodological tools for startle response assessment in rodents and humans and review evidence for primary and modulatory neural circuits underlying startle responses and their affective modulation in humans. Based on this, we suggest a refined and integrative model for primary and modulatory startle response pathways and conclude that there is strong evidence from human work on the neurobiological pathway underlying the primary startle response while evidence for the modulatory pathway is rather sparse. We suggest that the technical advances allowing for non-invasive simultaneous EMG-fMRI acquisition in combination with the proposed neuro-functional models set the stage for substantially advancing our understanding of the biological mechanisms underlying human emotions and psychopathological conditions - including specific as well as trans-diagnostic mechanisms and cross-species as well as clinical translation. In closing, we summarize detailed methodological considerations to guide future work and provide an outlook on new and exciting research perspectives enabled through the technical and theoretical advances outlined in this work.

Background:Exposure to adverse experiences is a well-established major risk factor for affective psychopathology. The vulnerability of deleterious sequelae is assumed in maladaptive processes of the defensive system, particularly in emotional processing. More specifically, childhood maltreatment has been suggested to be associated with the recruitment of specific and distinct defensive response profiles. To date it remains unclear whether these are specific or generalisable to recent adversity in adulthood.Method:This preregistered study aimed to investigate the impact of exposure to childhood and recent adversity on emotional processing in 685 healthy adults with the “Affective Startle Modulation” Paradigm (ASM).Results:First, we replicated higher trait anxiety and depression levels in individuals exposed to both types of adversity. Second, we observed blunted general skin conductance reactivity in individuals exposed to recent adversity. Third, individuals exposed to childhood maltreatment showed reduced, while individuals exposed to recent adversity showed increased discrimination between pictures of negative and neutral valence, compared to non-exposed individuals in SCR. No association between exposure to adversity and fear potentiated startle was observed. Furthermore, explorative analyses revealed moderate dimensional and categorical agreement between two childhood maltreatment questionnaires and provide insight into potential adversity-type specific effects.Conclusion:Our results support experience-dependent plasticity in sympathetic nervous system reactivity and suggest distinct response profiles in affective modulation in individuals exposed to early versus recent adversity. We emphasise the need to further explore distinct adversity profiles to further our understanding on specific psychophysiological profiles and their potential implication for prevention and intervention.

Background The startle eye-blink is the cross-species translational tool to study defensive behavior in affective neuroscience with relevance to a broad range of neuropsychiatric conditions. It makes use of the startle reflex, a defensive response elicited by an immediate, unexpected sensory event, which is potentiated when evoked during threat and inhibited during safety. In contrast to skin conductance responses or pupil dilation, modulation of the startle reflex is valence specific. Rodent models implicate a modulatory pathway centering on the brainstem (i.e., nucleus reticularis pontis caudalis) and the centromedial amygdala as key hubs for flexibly integrating valence information into differential startle magnitude. Technical advances now allow for the investigation of this pathway using combined facial electromyography and functional magnetic resonance imaging in humans. Methods We employed a multimethodological approach combining trial-by-trial facial eye-blink startle electromyography and brainstem- and amygdala-specific functional magnetic resonance imaging in humans. Validating the robustness and reproducibility of our findings, we provide evidence from two different paradigms (fear-potentiated startle, affect-modulated startle) in two independent studies (N = 43 and N = 55). Results We provide key evidence for a conserved neural pathway for acoustic startle modulation between humans and rodents. Furthermore, we provide the crucial direct link between electromyography startle eye-blink magnitude and neural response strength. Finally, we demonstrate a dissociation between arousal-specific amygdala responding and triggered valence-specific amygdala responding. Conclusions We provide neurobiologically based evidence for the strong translational value of startle responding and argue that startle-evoked amygdala responding and its affective modulation may hold promise as an important novel tool for affective neuroscience and its clinical translation.

Here, we follow the call to target measurement reliability as a key prerequisite for individual-level predictions in translational neuroscience by investigating (1) longitudinal reliability at the individual and (2) group level, (3) internal consistency and (4) response predictability across experimental phases. One hundred and twenty individuals performed a fear conditioning paradigm twice 6 months apart. Analyses of skin conductance responses, fear ratings and blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) with different data transformations and included numbers of trials were conducted. While longitudinal reliability was rather limited at the individual level, it was comparatively higher for acquisition but not extinction at the group level. Internal consistency was satisfactory. Higher responding in preceding phases predicted higher responding in subsequent experimental phases at a weak to moderate level depending on data specifications. In sum, the results suggest that while individual-level predictions are meaningful for (very) short time frames, they also call for more attention to measurement properties in the field.

Electrodermal signals are commonly used outcome measures in research on arousal, emotion, and habituation. Recently, we reported on heterogeneity in skin conductance response quantification approaches and its impact on replicability. Here we provide complementary work focusing on within-approach heterogeneity of specifications for skin conductance response quantification. We focus on heterogeneity within the baseline-correction approach (BLC) which appeared as particularly heterogeneous-for instance with respect to the pre-CS baseline window duration, the start, and end of the peak detection window. We systematically scrutinize the robustness of results when applying different BLC approach specifications to one representative pre-existing data set (N = 118) in a (partly) pre-registered study. We report high agreement between different BLC approaches for US and CS+ trials, but moderate to poor agreement for CS- trials. Furthermore, a specification curve of the main effect of CS discrimination during fear acquisition training from all potential and reasonable combinations of specifications (N = 150) and a prototypical trough-to-peak (TTP) approach indicates that resulting effect sizes are largely comparable. A second specification curve (N = 605 specific combinations) highlights a strong impact of different transformation types. Crucially, however, we show that BLC approaches often misclassify the peak value-particularly for CS- trials, leading to stimulus-specific biases and challenges for post-processing and replicability of CS discrimination across studies applying different approaches. Lastly, we investigate how negative skin conductance values in BLC, appearing most frequently for CS- (CS- > CS+ > US), correspond to values in TTP quantification. We discuss the results considering prospects and challenges of the multiverse approach and future directions. ispartof: PSYCHOPHYSIOLOGY vol:59 issue:12 ispartof: location:United States status: published

AIMS The aim of this study was to identify the problems and resources of women with urinary or fecal incontinence based on the International Classification of Function and Health (ICF) framework and detecting the impact on the personal environment and quality of life. This study forms part of a project with an overall goal to enable standardized planning and evaluation of interventions in multi-professional settings. METHODS To answer the study question a mixed-method sequential design with a priority to the quantitative approach was considered appropriate. Regarding methods, focus groups were chosen to collect data. Transcripts were analyzed with content analysis and identified concepts linked to the corresponding ICF categories by two different raters. Cohen's kappa was calculated for interrater reliability. RESULTS Thirteen women with a mean age of 69.9 years were recruited. Four focus groups were conducted, whereas saturation was reached after two focus groups. Overall transcripts 99 defined ICF categories at second level could be linked (body functions = 31, body structures = 5, activities and participation = 33, and environmental factors = 30) whereas 4 categories were not sufficiently covered by the ICF (3 = personal factors, 1 = not covered). CONCLUSIONS This study has determined 103 resources and problems based on the ICF model of women with urinary and/or fecal incontinence. In spite of these results, it was shown that four concepts are not fully covered by the ICF framework. The current data highlight the importance of an extension of the ICF model, especially towards the personal factors of patients.

BACKGROUND Research integrating multisensory home-monitoring in respiratory disease is scarce. Therefore, we created a novel multisensory home-monitoring device tailored for long-term respiratory disease management (named the CAir-Desk). We hypothesize that recent technological accomplishments can be integrated into a multisensory participant-driven platform. We also believe that this platform could improve chronic disease management and be accessible to large groups at an acceptable cost. OBJECTIVE This study aimed to report on user adherence and acceptance as well as system functionality of the CAir-Desk in a sample of participants with stable chronic obstructive pulmonary disease (COPD) or asthma. METHODS We conducted an observational usability study. Participants took part in 4 weeks of home-monitoring with the CAir-Desk. The CAir-Desk recorded data from all participants on symptom burden, physical activity, spirometry, and environmental air quality; data on sputum production, and nocturnal cough were only recorded for participants who experienced symptoms. After the study period, participants reported on their perceptions of the usability of the monitoring device through a purpose-designed questionnaire. We used descriptive statistics and visualizations to display results. RESULTS Ten participants, 5 with COPD and 5 with asthma took part in this study. They completed symptom burden questionnaires on a median of 96% (25th percentile 14%, 75th percentile 96%), spirometry recordings on 55% (20%, 94%), wrist-worn physical activity recordings on 100% (97%, 100%), arm-worn physical activity recordings on 45% (13%, 63%), nocturnal cough recordings on 34% (9%, 54%), sputum recordings on 5% (3%, 12%), and environmental air quality recordings on 100% (99%, 100%) of the study days. The participants indicated that the measurements consumed a median of 13 (10, 15) min daily, and that they preferred the wrist-worn physical activity monitor to the arm-worn physical activity monitor. CONCLUSIONS The CAir-Desk showed favorable technical performance and was well-accepted by our sample of participants with stable COPD and asthma. The obtained insights were used in a redesign of the CAir-Desk, which is currently applied in a randomized controlled trial including an interventional program.

Scientific work rests fundamentally upon data, their measurement, processing, analysis, illustration and interpretation. Raw data have to be processed to be ready for statistical analyses and interpretation. While these processing pipelines can be well defined and standardized, they are often characterized by substantial heterogeneity. Here, we present results from a systematic literature search on the different SCR response quantification approaches used in the literature by using fear conditioning research as a case example. Next, we applied seven of the identified approaches (trough-to-peak scoring, script-based baseline-correction, Ledalab as well as four different models implemented in the software PsPM) to two fear conditioning datasets differing in key procedural specifications (i.e., CS duration, reinforcement rate, number of trials). This can be viewed as a set of robustness analyses (i.e., same data subjected to different methods) aiming to investigate if and to what extent these methods yield comparable results. To our knowledge, no formal framework for the evaluation of robustness analyses exists to date, but we may borrow some criteria from a framework suggested for the evaluation of ‘replicability’ in general. Our results from seven different SCR response quantification approaches applied to two datasets suggest that there may be no single approach that consistently yields larger effect sizes across both datasets. Yet, at least some of the approaches employed show consistent effect sizes within each dataset indicating comparability. Finally, we highlight substantial heterogeneity also within most quantification approaches and discuss implications and potential remedies.

When extreme, anxiety—a state of distress and arousal prototypically evoked by uncertain danger—can be debilitating. Uncertain anticipation is a shared feature of situations that elicit signs and symptoms of anxiety across psychiatric disorders, species, and assays. Despite the profound significance of anxiety for human health and wellbeing, the neurobiology of uncertain-threat anticipation remains unsettled. Leveraging a paradigm adapted from animal research and optimized for functional MRI signal decomposition, we examined the neural circuits engaged during the anticipation of temporally uncertain and certain threat in 99 men and women. Results revealed that the neural systems recruited by uncertain and certain threat anticipation are anatomically co-localized in fronto-cortical regions, extended amygdala, and periaqueductal gray. Comparison of the threat conditions demonstrated that this circuitry can be fractionated, with fronto-cortical regions showing relatively stronger engagement during the anticipation of uncertain threat, and the extended amygdala showing the reverse pattern. Although there is widespread agreement that the bed nucleus of the stria terminalis and dorsal amygdala—the two major subdivisions of the extended amygdala—play a critical role in orchestrating adaptive responses to potential danger, their precise contributions to human anxiety have remained contentious. Follow-up analyses demonstrated that these regions show statistically indistinguishable responses to temporally uncertain and certain threat anticipation. These observations provide a framework for conceptualizing anxiety and fear, for understanding the functional neuroanatomy of threat anticipation in humans, and for accelerating the development of more effective intervention strategies for pathological anxiety.SIGNIFICANCE STATEMENTAnxiety—an emotion prototypically associated with the anticipation of uncertain harm—has profound significance for public health, yet the underlying neurobiology remains unclear. Leveraging a novel neuroimaging paradigm in a relatively large sample, we identify a core circuit responsive to both uncertain and certain threat anticipation, and show that this circuitry can be fractionated into subdivisions with a bias for one kind of threat or the other. The extended-amygdala occupies center-stage in neuropsychiatric models of anxiety, but its functional architecture has remained contentious. Here we demonstrate that its major subdivisions show statistically indistinguishable responses to temporally uncertain and certain threat. Collectively, these observations indicate the need to revise how we think about the neurobiology of anxiety and fear.RESOURCE SHARINGRaw data are available at the National Institute of Mental Health’s Data Archive. Key statistical maps are or will be publicly available at NeuroVault.org.

International audience; A semi-autonomous robotic system dedicated to road and train bridge inspection is presented in this paper. So far, bridge inspections have been performed manually by workers who either climb and rappel or use so-called mobile negative cherry pickers or specific mobile assemblies. This is a dangerous and tedious task which must be carried out during night time or when the traffic on the bridge is stopped, for safety reasons. The installation of mobile assemblies is costly, time consuming and they become not compliant with recent structures. Moreover, manual inspections require counting, measuring, locating and taking pictures of small cracks. The quality of these manual operations depends not only on the experience but also on the level of fatigue of the workers. The robotic inspection system proposed in this paper consists of three main components: a customized truck, a mobile robotic mechanism which takes pictures of the entire area of interest, and a software which automatically associates these pictures with the CAD model of the bridge.Afterwards at office, users browse the pictures of the surfaces of the bridge with the help of the CAD software and a dedicated plugin to detect, measure and comment the bridge defects to process later. The result is summed up into a report generated by the software. The requirements and the mechanical design of this system are described and an overview of the inspections realized so far with it is provided.

The startle reflex, a protective response elicited by an immediate, unexpected sensory event, ispotentiatedwhen evoked during threat andinhibitedduring safety. In contrast to skin conductance responses or pupil dilation, modulation of the startle reflex is valence-specific and consideredthecross-species translational tool for defensive responding.Rodent models implicate a modulatory pathway centering on the brainstem (i.e., nucleus reticularis pontis caudalis, PnC) and the centromedial amygdala (CeM) as key hubs for flexibly integrating valence information into differential startle magnitude.We employed innovative combined EMG-fMRI measurements in two independent experiments and samples and provide converging evidence for the involvement of these key regions in the modulatory acoustic startle reflex pathway in humans. Furthermore, we provide the crucial direct link between EMG startle eye-blink magnitude and neural response strength.We argue that startle-evoked amygdala responding and its affective modulation may hold promise as an important novel tool for affective neuroscience.

Reproducibility is fundamental to science and a recent matter of discussion. We report challenges for conceptual replications when employing different readout measures to target the same theoretical construct, particularly those requiring probed reactions. This was addressed in a fear conditioning paradigm, a prototype of emotional learning, in three experimental groups (Ntotal = 57). We demonstrate that the inclusion of startle probes (95 dB burst of white noise) to elicit a startle reflex delays the acquisition of fear as reflected by skin conductance responses and intermittent fear ratings. The inclusion of fear ratings in turn did not significantly affect fear acquisition. Hence, subtle differences in experimental design, such as the inclusion of a single additional outcome measure, may substantially impact on study results and interpretations. Thus, small effects, as are common in between-group comparisons, may be particularly susceptible to this, which has strong implications for the replication of findings across studies employing slightly different experimental designs.

Being a complex phenotype with substantial heritability, anxiety and related phenotypes are characterized by a complex polygenic basis. Thereby, one candidate pathway is neuronal nitric oxide (NO) signaling, and accordingly, rodent studies have identified NO synthase (NOS-I), encoded by NOS1, as a strong molecular candidate for modulating anxiety and hippocampus-dependent learning processes. Using a multi-dimensional and -methodological replication approach, we investigated the impact of a functional promoter polymorphism (NOS1-ex1f-VNTR) on human anxiety-related phenotypes in a total of 1019 healthy controls in five different studies. Homozygous carriers of the NOS1-ex1f short-allele displayed enhanced trait anxiety, worrying and depression scores. Furthermore, short-allele carriers were characterized by increased anxious apprehension during contextual fear conditioning. While autonomous measures (fear-potentiated startle) provided only suggestive evidence for a modulatory role of NOS1-ex1f-VNTR on (contextual) fear conditioning processes, neural activation at the amygdala/anterior hippocampus junction was significantly increased in short-allele carriers during context conditioning. Notably, this could not be attributed to morphological differences. In accordance with data from a plethora of rodent studies, we here provide converging evidence from behavioral, subjective, psychophysiological and neuroimaging studies in large human cohorts that NOS-I plays an important role in anxious apprehension but provide only limited evidence for a role in (contextual) fear conditioning.

Aims Current level-A recommended questionnaires that provide a valid assessment of urinary incontinence (UI) and/or faecal incontinence (FI), but do not cover all aspects of the burden of the disease in the sense of the bio-psycho-social model of the World Health Organization's International Classification of Functioning, Disability and Health (ICF). Therefore, an ICF oriented questionnaire for patients with UI and/or FI to assess treatment barriers (problems) as well as positive influencing factors (resources), the "ICF-Incontinence Assessment Form" will be developed. The aim of this preliminary study was (a) to identify problems and resources of UI and/or FI in current level-A recommended questionnaires and (b) to evaluate problems and resources of patients with UI and/or FI from the perspective of experienced physiotherapists. Methods (a) Current level-A recommended questionnaires for UI and/or FI were analyzed. Questions were linked to the ICF categories. (b) A 3-round Delphi technique survey among 262 physiotherapists from five German-speaking countries was used to evaluate patients' problems and resources relevant to physiotherapy. Results (a) A total of 27 identified questionnaires were linked to 110 ICF categories. No positive influencing factors could be identified. (b) After Delphi-round 3, 110 categories of problems and 71 resources were identified. Conclusion Since there is a lack of resource items in the present validated questionnaires, there is a need for a short, practical questionnaire to assess and monitor both, problems and resources of patients with UI and/or FI.

The aim of this study was to identify the problems and resources of women with urinary or fecal incontinence based on the International Classification of Function and Health (ICF) framework and detecting the impact on the personal environment and quality of life. This study forms part of a project with an overall goal to enable standardized planning and evaluation of interventions in multi-professional settings.To answer the study question a mixed-method sequential design with a priority to the quantitative approach was considered appropriate. Regarding methods, focus groups were chosen to collect data. Transcripts were analyzed with content analysis and identified concepts linked to the corresponding ICF categories by two different raters. Cohen's kappa was calculated for interrater reliability.Thirteen women with a mean age of 69.9 years were recruited. Four focus groups were conducted, whereas saturation was reached after two focus groups. Overall transcripts 99 defined ICF categories at second level could be linked (body functions = 31, body structures = 5, activities and participation = 33, and environmental factors = 30) whereas 4 categories were not sufficiently covered by the ICF (3 = personal factors, 1 = not covered).This study has determined 103 resources and problems based on the ICF model of women with urinary and/or fecal incontinence. In spite of these results, it was shown that four concepts are not fully covered by the ICF framework. The current data highlight the importance of an extension of the ICF model, especially towards the personal factors of patients.

Background The molecular genetics of Panic Disorder (PD) with and without agoraphobia (AG) are still largely unknown and linkage, candidate gene and Genome-Wide Association Studies (GWAS) of PD/AG were mostly negative or inconsistent due to phenotypic diversity, genetic heterogeneity and underpowered sample sizes. Methods Assuming a dimension from agoraphobic cognitions to full PD/AG, we (1) conducted a GWAS on a dimensional anxiety phenotype (ACQ) in 1,370 healthy volunteers, (2) evaluated the found Glycine Receptor Beta (GLRB) locus in an extended sample of healthy 2,547 volunteers, (3) validated it in a population based sample (N=3,845) with another measure of AG symptoms [SCL-90], (4) assessed it relevance for the categorical phenotype PD/AG in 506 case-control pairs, (5) measured mRNA expression in vitro and post mortem (N=76), (6) examined the effect of GLRB risk polymorphisms on startle habituation, potentiation, and generalization (N=101 healthy volunteers), complemented by a behavior avoidance test (N=115 PD/AG patients) and fMRI analysis (N=76 healthy volunteers; N=86 patients with PD/AG) of fear network and general sensory activation and (7) performed analyses of agoraphobic behavior in partial Glrb knock-out mice. Results (1) GWAS on the ACQ phenotype resulted in two genome-wide significant (p Discussion Present results provide translational evidence that genetic variation within the GLRB gene predisposes to agoraphobia by modulation of the intermediate phenotype startle reflex. GWAS on the ACQ phenotype provided genome-wide significance for the GLRB locus, that we hence confirmed by validation in an independent cohort and by association with PD/AG. Results from behavioral studies in Glrb knockdown mice further supported that this gene is involved in agoraphobic behavior. As GLRB mutations are causal in hyperekpleksia, we probed whether the startle reflex as an intermediate phenotype is modulated by genetic variation in GLRB and demonstrated that risk alleles go along with impaired startle habituation and increased startle potentiation and generalization. Further fMRI analysis showed that GLRB risk alleles are associated with increased fear-induced activation of the fear network, but also with a general fear-independent activation of the sensory network. Our data propose how a genetic risk factor might via an intermediate neurobiological phenotype lead to development of a mental disorder, thus opening perspectives for novel therapeutic approaches.

Gradient-elasticity and more generally gradient-enhanced continuum models have been extensively developed since the beginning of the twentieth century. These models have shown the ability to account for the effect of the underlying material heterogeneity at the macroscopic scale of the continuum. Despite of a great theoretical interest, gradient-enhanced models are usually difficult to interpret physically and even more to identify experimentally. This paper proposes an attempt to validate and identify from experimental data, a gradient-elasticity model for a material with a periodic micro-structure. A set of dedicated experimental and numerical tools are developed for this purpose: first, the design of an experiment, then two-scale displacement field measurements by digital image correlation with dedicated post-processing techniques and finally a model updating technique. This paper ends up with the full set of first and second-order elastic constants of a gradient-elastic model which macroscopic kinematic has been validated by investigating the deformation of the unit cells at the microscopic scale.

The so-called 'replicability crisis' has sparked methodological discussions in many areas of science in general, and in psychology in particular. This has led to recent endeavours to promote the transparency, rigour, and ultimately, replicability of research. Originating from this zeitgeist, the challenge to discuss critical issues on terminology, design, methods, and analysis considerations in fear conditioning research is taken up by this work, which involved representatives from fourteen of the major human fear conditioning laboratories in Europe. This compendium is intended to provide a basis for the development of a common procedural and terminology framework for the field of human fear conditioning. Whenever possible, we give general recommendations. When this is not feasible, we provide evidence-based guidance for methodological decisions on study design, outcome measures, and analyses. Importantly, this work is also intended to raise awareness and initiate discussions on crucial questions with respect to data collection, processing, statistical analyses, the impact of subtle procedural changes, and data reporting specifically tailored to the research on fear conditioning. publisher: Elsevier articletitle: Don’t fear ‘fear conditioning’: Methodological considerations for the design and analysis of studies on human fear acquisition, extinction, and return of fear journaltitle: Neuroscience & Biobehavioral Reviews articlelink: http://dx.doi.org/10.1016/j.neubiorev.2017.02.026 content_type: article copyright: © 2017 The Authors. Published by Elsevier Ltd. ispartof: Neuroscience and Biobehavioral Reviews vol:77 pages:247-285 ispartof: location:United States status: published

Representing a phylogenetically old and very basic mechanism of inhibitory neurotransmission, glycine receptors have been implicated in the modulation of behavioral components underlying defensive responding toward threat. As one of the first findings being confirmed by genome-wide association studies for the phenotype of panic disorder and agoraphobia, allelic variation in a gene coding for the glycine receptor beta subunit (GLRB) has recently been associated with increased neural fear network activation and enhanced acoustic startle reflexes. On the basis of two independent healthy control samples, we here aimed to further explore the functional significance of the GLRB genotype (rs7688285) by employing an intermediate phenotype approach. We focused on the phenotype of defensive system reactivity across the levels of brain function, structure, and physiology. Converging evidence across both samples was found for increased neurofunctional activation in the (anterior) insular cortex in GLRB risk allele carriers and altered fear conditioning as a function of genotype. The robustness of GLRB effects is demonstrated by consistent findings across different experimental fear conditioning paradigms and recording sites. Altogether, findings provide translational evidence for glycine neurotransmission as a modulator of the brain’s evolutionary old dynamic defensive system and provide further support for a strong, biologically plausible candidate intermediate phenotype of defensive reactivity. As such, glycine-dependent neurotransmission may open up new avenues for mechanistic research on the etiopathogenesis of fear and anxiety disorders.

Epidemiologische Studien weisen auf eine hohe Komorbiditat zwischen chronischen Schmerzen und einer Major Depression hin. Dies konnte fur zahlreiche Schmerzerkrankungen inklusive der somatoformen Schmerzstorung, des Fibromyalgiesyndroms, Migrane und Nackenschmerzen gezeigt werden. Eine duale Diagnose ist nach wie vor selten, da Patienten typischerweise in der arztlichen Untersuchung bevorzugt von somatischen Beschwerden berichten. Die Komorbiditat spiegelt sich auch auf Hirnebene wider, da sowohl chronische Schmerzen als auch eine depressive Symptomatik uber identische Strukturen vermittelt werden. Wahrend der letzten Jahre lies sich mithilfe moderner bildgebender Verfahren zeigen, dass sowohl psychopharmakologische als auch psychotherapeutische Verfahren, die im Rahmen der Therapie chronischer Schmerzen angewendet werden, die bestehende Dysfunktionalitat dieser Hirnregionen behandeln und dadurch zu einer klinischen Verbesserung fuhren. Insbesondere Antidepressiva, die Serotonin und Noradrenalin im synaptischen Spalt erhohen, sowie kognitive Verhaltenstherapie haben aus psychiatrischer Sicht einen besonderen Stellenwert in der Therapie chronischer Schmerzen.

Current treatments for anxiety disorders are effective but limited by the high frequency of clinical relapse. Processes underlying relapse are thought to be experimentally modeled in fear conditioning experiments with return fear (ROF) inductions. Thereby reinstatement-induced ROF might be considered a model to study mechanisms underlying adversity-induced relapse. Previous studies have reported differential ROF (i.e. specific for the danger stimulus) but also generalized ROF (i.e. for safe and danger stimuli), but reasons for these divergent findings are not clear yet. Hence, the response pattern (i.e. differential or generalized) following reinstatement may be of importance for the prediction of risk or resilience for ROF. The aim of this study was to investigate state anxiety as a potential individual difference factor contributing to differentiability or generalization of return of fear. Thirty-six participants underwent instructed fear expression, extinction and ROF induction through reinstatement while physiological (skin conductance response, fear potentiated startle) and subjective measures of fear and US expectancy were acquired. Our data show that, as expected, high state anxious individuals show deficits in SCR discrimination between dangerous and safe cues after reinstatement induced ROF (i.e. generalization) as compared to low state anxious individuals. The ability to maintain discrimination under aversive circumstances is negatively associated with pathological anxiety and predictive of resilient responding while excessive generalization is a hallmark of anxiety disorders. Therefore, we suggest that experimentally induced ROF might prove useful in predicting relapse risk in clinical settings and might have implications for possible interventions for relapse prevention.

Prior research showed that mere instructions about the contingency between a conditioned stimulus (CS) and an unconditioned stimulus (US) can generate fear reactions to the CS. Little is known, however, about the extent to which actual CS-US contingency experience adds anything beyond the effect of contingency instructions. Our results extend previous studies on this topic in that it included fear potentiated startle as an additional dependent variable and examined return of fear (ROF) following reinstatement. We observed that CS-US pairings can enhance fear reactions beyond the effect of contingency instructions. Moreover, for all measures of fear, instructions elicited immediate fear reactions that could not be completely overridden by subsequent situational safety information. Finally, ROF following reinstatement for instructed CS+s was unaffected by actual experience. In summary, our results demonstrate the power of contingency instructions and reveal the additional impact of actual experience of CS-US pairings.

A vast number of imaging studies have demonstrated the impact of serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) on emotion and memory-related networks in the context of Major Depressive Disorder (MDD). Underlying molecular mechanisms that affect the functionality of these networks have been examined in detail in animals and corroborate imaging findings. The crucial role of 5-HT and BDNF signaling in the context of MDD is reflected in the etiologic models of MDD such as the monoamine or neuroplasticity hypothesis as well as in pharmacological models of antidepressant response. While antidepressant drug treatment has been primarily linked to the modulation of emotion-related networks, cognitive behavioral therapy has been implicated in a top-down control of limbic structures. Initially, a simple lack of monoamines or BDNF has been proposed as causal factor of MDD etiology. However, recent findings suggest a much more complex neurobiology emphasizing epistatic and epigenetic mechanisms responsible for structural and functional changes observed in emotion and memory-related brain regions of healthy subjects and MDD patients. In this review, which focuses on neuroimaging studies in the context of MDD, the authors will provide a comprehensive overview of these networks as well as on the specific role of 5-HT and BDNF in their development and function.