Somatic symptom distress is not related to cardioceptive accuracy.

OBJECTIVE: (Cardiac) interoception was long considered a key mechanism behind symptom perception in persistent somatic symptoms (PSS). In this study, we aimed to extend earlier findings to clarify this potential interoceptive mechanisms of PSS. METHODS: A cross-sectional sample of 251 participants (23.1% with self-reported functional somatic syndrome) completed a laboratory study with two cardioceptive accuracy tasks (Schandry task and a new cardiac signal detection task) and multiple questionnaires. Somatic symptom distress and associated constructs were assessed with the PHQ-15, as well as with a novel multidimensional questionnaire measure (HiTOP-SF1) derived from the somatoform spectrum of the Hierarchical Taxonomy of Psychopathology (HiTOP). Correlations (frequentist and Bayesian) and structural equation modelling (SEM) helped further investigate the interplay between these variables. RESULTS: There were no significant correlations between measures of interoception and somatic symptom distress. Self-report and behavioral cardioceptive accuracy measures did not correlate significantly. No significant covariances emerged between diagnostic tools and cardioceptive accuracy; Bayesian analyses supported the lack of association between interoception and symptom perception. CONCLUSIONS: Cardiac interoception (specifically cardioceptive accuracy) unlikely represents a key mechanism in PSS etiology. We recommend investigating other factors in PSS.

Respiratory Interoception and Pathological Illness Anxiety: Disentangling Bias.

OBJECTIVE: Biased interoception decoupled from physiology might be relevant in the etiology of pathological illness anxiety (PIA). Empirical evidence for interoceptive deviations in illness anxiety is scarce but potentially informative to optimize treatments. We hypothesized that persons with PIA differ fundamentally in the classification of bodily sensations from those without PIA. METHODS: In a respiratory categorization task, participants breathed into a pulmonary training device. Inspiration effort was varied by eight resistive loads. The lower/higher four loads were introduced as belonging to arbitrary categories "A"/"B," respectively. Participants memorized respiratory sensations in a first experimental block and were asked to label the resistances in a second block. We calculated the sensitivity of resistance classification according to category and response bias in terms of categorical misclassification. Data of 39 participants with PIA and 35 controls were compared with regard to sensitivity and response bias by group, resistive load, and their interaction in a multiple regression. RESULTS: With similar sensitivity, patients more often labeled loads above the categorical border erroneously as belonging to category A, thus underestimating their resistance ( ß = -0.06, p = .001; η2 = 0.02). CONCLUSIONS: Individuals with PIA showed a systematic "wait and see" approach. Altered respiroception in PIA might stem from biased perception during training phase, the recognition phase, biased memory, or a combination of these. Its exact characteristics remain unknown, and future research must address the challenge of developing reliable and valid paradigms accounting for the variability of interoceptive biases. REGISTRATION: This work was preregistered on OSF ( https://osf.io/9shcw ).

Serum Biomarkers of a Pro-Neuroinflammatory State May Define the Pre-Operative Risk for Postoperative Delirium in Spine Surgery.

Advances in spine surgery enable technically safe interventions in older patients with disabling spine disease, yet postoperative delirium (POD) poses a serious risk for postoperative recovery. This study investigates biomarkers of pro-neuroinflammatory states that may help objectively define the pre-operative risk for POD. This study enrolled patients aged ≥60 scheduled for elective spine surgery under general anesthesia. Biomarkers for a pro-neuroinflammatory state included S100 calcium-binding protein ß (S100ß), brain-derived neurotrophic factor (BDNF), Gasdermin D, and the soluble ectodomain of the triggering receptor expressed on myeloid cells 2 (sTREM2). Postoperative changes of Interleukin-6 (IL-6), Interleukin-1ß (IL-1ß), and C-reactive protein (CRP) were assessed as markers of systemic inflammation preoperatively, intraoperatively, and early postoperatively (up to 48 h). Patients with POD (n = 19, 75.7 ± 5.8 years) had higher pre-operative levels of sTREM2 (128.2 ± 69.4 pg/mL vs. 97.2 ± 52.0 pg/mL, p = 0.049) and Gasdermin D (2.9 ± 1.6 pg/mL vs. 2.1 ± 1.4 pg/mL, p = 0.29) than those without POD (n = 25, 75.6 ± 5.1 years). STREM2 was additionally a predictor for POD (OR = 1.01/(pg/mL) [1.00-1.03], p = 0.05), moderated by IL-6 (Wald-χ2 = 4.06, p = 0.04). Patients with POD additionally showed a significant increase in IL-6, IL-1ß, and S100ß levels on the first postoperative day. This study identified higher levels of sTREM2 and Gasdermin D as potential markers of a pro-neuroinflammatory state that predisposes to the development of POD. Future studies should confirm these results in a larger cohort and determine their potential as an objective biomarker to inform delirium prevention strategies.

Symptom Perception in Pathological Illness Anxiety: Tactile Sensitivity and Bias.

OBJECTIVE: Symptom perception in pathological illness anxiety (PIA) might be biased so that somatic signals are overreported. In the somatic signal detection task (SSDT), performance in detecting weak tactile stimuli gives information on overreporting or underreporting of stimuli. This task has not yet been applied in PIA. METHODS: Participants with PIA (n = 44) and healthy controls (n = 40) underwent two versions of the SSDT in randomized order. In the original version, tactile and auxiliary light-emitting diode (LED) stimuli were each presented in half of the trials. In the adapted version, illness or neutral words were presented alongside tactile stimuli. Participants also conducted a heartbeat mental tracking task. RESULTS: We found significantly higher sensitivity and a more liberal response bias in LED versus no-LED trials, but no significant differences between word types. An interaction effect showed a more pronounced increase of sensitivity from no LED to LED trials in participants with PIA when compared with the adapted SSDT and control group (F(1,76) = 5.34, p = .024, η2 = 0.066). Heartbeat perception scores did not differ between groups (BF01 of 3.63). CONCLUSIONS: The increase in sensitivity from no LED to LED trials in participants with PIA suggests stronger multisensory integration. Low sensitivity in the adapted SSDT indicates that attentional resources were exhausted by processing word stimuli. Word effects on response bias might have carried over to the original SSDT when the word version was presented first, compromising group effects regarding bias. TRIAL REGISTRATION: The study was preregistered on OSF (https://osf.io/sna5v/).

Interoceptive accuracy and bias in somatic symptom disorder, illness anxiety disorder, and functional syndromes: A systematic review and meta-analysis.

Somatic symptom disorder, illness anxiety disorder, and functional syndromes are characterized by burdensome preoccupation with somatic symptoms. Etiological models propose either increased interoceptive accuracy through hypervigilance to the body, or decreased and biased interoception through top-down predictions about sensory events. This systematic review and meta-analysis summarizes findings of 68 studies examining interoceptive accuracy and 8 studies examining response biases in clinical or non-clinical groups. Analyses yielded a medium population effect size for decreased interoceptive accuracy in functional syndromes, but no observable effect in somatic symptom disorder and illness anxiety disorder. The overall effect size was highly heterogeneous. Regarding response bias, there was a small significant effect in somatic symptom disorder and illness anxiety disorder. Our findings strengthen the notion of top-down factors that result in biased rather than accurate perception of body signals in somatic symptom disorder and illness anxiety disorder.

Embodied feelings-A meta-analysis on the relation of emotion intensity perception and interoceptive accuracy.

Emotion theories emphasize the relevance of (predicted) bodily changes for the construction of one's own emotions and an extensive overlap of brain regions involved during emotion intensity perception and somatosensory processing. The ability to accurately perceive bodily changes and its impact on the perception of emotion intensity has been studied for at least 40 years. The results of previous studies were summarized in a meta-analysis to examine how closely interoceptive accuracy and emotion intensity are related. After a systematic literature search, 4036 studies were screened for eligibility. Only studies assessing adults from general population samples were considered. Samples recruited to examine mental disorders or neurological conditions were excluded. Thirty studies with a quantifiable measure for the relation of interoceptive accuracy and emotion intensity perception were included in the meta-analysis. Interoceptive accuracy was significantly related with emotion intensity perception, when emotions were experimentally induced (k= 22, r= 0.15). However, the relationship was only found when IAPS images (k= 9, r= 0.33) or facial expressions (k= 3, r= 0.24) were used for emotion induction. No significant relation was found in studies without emotion induction (k= 19, r = -0.007). There was considerable bias, varying dependent on bias assessment method, study protocol and examined risk of bias dimension. We discuss the impact of differences in study protocols, review the operationalization of interoceptive accuracy critically and derive directions for future research.

The Influence of Alcohol on Rumination and Metacognitions in Major Depressive Disorder.

Background and Objectives: Comorbidity between major depressive disorder (MDD) and alcohol use disorder (AUD) is highly prevalent but reasons for this association are unclear. Rumination may activate metacognitive beliefs that contribute to the development and maintenance of rumination and depression. Negative metacognitions can further lead to other dysfunctional coping strategies (i.e., consumption of alcohol). We examined whether alcohol reduces (state) metacognitions, rumination and other disorder-specific processes in a group of individuals suffering from MDD. Method: In an experiment with three randomized conditions we investigated whether the consumption of alcohol, placebo or no alcohol (orange juice) affects (meta-)cognitions, depressive symptoms and / or psychophysiological variables while participants ruminate. Results: Voluntary rumination increased self-reported sadness, tension and rumination, tensed facial muscles and increased heart rate, but did not affect (state) metacognitions and heart rate variability. The consumption of alcohol did not influence rumination, metacognitions, depressive or psychophysiological measures. Limitations: We recruited a depressed population but excluded pathological alcohol use due to ethical considerations. Conclusions: We found no evidence that alcohol consumption affects rumination, metacognitions and other disorder-specific processes in MDD. However, rumination had a negative effect on various depression-specific processes, although it did not activate (negative state) metacognitions.

Magnetite-binding proteins from the magnetotactic bacterium Desulfamplus magnetovallimortis BW-1.

Magnetite-binding proteins are in high demand for the functionalization of magnetic nanoparticles. Binding analysis of six previously uncharacterized proteins from the magnetotactic Deltaproteobacterium Desulfamplus magnetovallimortis BW-1 identified two new magnetite-binding proteins (Mad10, Mad11). These proteins can be utilized as affinity tags for the immobilization of recombinant fusion proteins to magnetite.

Interoception in preschoolers: New insights into its assessment and relations to emotion regulation and stress.

Interoception may play an important role for emotion regulation and stress, thereby affecting mental health in children and adults. Yet, little is known on interoception in preschool children. Therefore, we investigated interoceptive accuracy using the adapted Jumping Jack Paradigm (JJP) and its relationship with emotion regulation and stress. In Study I, 40 preschoolers completed the JJP and an emotion regulation task, demonstrating a positive relationship between interoceptive accuracy and emotion regulation at trend level (R² = 0.231, p = .023; ß = .278, p = .073). In Study II, 31 preschoolers completed the adapted JJP before and after an acute laboratory stress test. Higher total cortisol output following acute stress induction was associated with reduced interoceptive accuracy (r = -0.670, p = .017). Extending earlier findings in adults and school-children, the relationship of interoceptive accuracy with emotion regulation and stress highlights the importance to investigate interoception in early childhood.

Interoceptive Sensibility, Alexithymia, and Emotion Regulation in Individuals Suffering from Fibromyalgia.

INTRODUCTION: People suffering from fibromyalgia syndrome report various difficulties in emotional processing, possibly resulting from changes in bodily perception (interoception). In our study, we investigated the relationships between interoceptive sensibility (IS) and two disease-relevant emotional components (alexithymia and emotion regulation) in fibromyalgia sufferers compared to healthy individuals. METHODS: Fifty-five fibromyalgia sufferers and 55 healthy individuals, matched with regard to age and gender, participated in our cross-sectional study. All participants completed the following self-report measures: the Multidimensional Assessment of Interoceptive Awareness, the Toronto Alexithymia Scale, and the Emotion Regulation Skills Questionnaire. Depression and anxiety scores served as confounding variables. RESULTS: Fibromyalgia sufferers reported a stronger tendency to note as well as to avoid (unpleasant) body sensations. IS and psychopathology each explained about thirty percent of the variance in emotion regulation in fibromyalgia sufferers. Alexithymia was related to IS and emotion regulation in controls but not in fibromyalgia sufferers. CONCLUSION: Disturbances in interoception could be seen as the starting point of emotional difficulties in people with fibromyalgia. Following the fear-avoidance-model, experiential avoidance may restrict patients' ability to adaptively regulate emotional states, possibly initiating a vicious cycle of psychological distress and pain.

Cardiac interoception: A novel signal detection approach and relations to somatic symptom distress.

Interoception is essential for the maintenance of physical and mental health. Paradigms assessing cardioceptive accuracy do not separate sensitivity from bias or are very demanding. We present the piloting (study 1; N = 60) and psychometric evaluation and validation (study 2; N = 84) of a novel task for the assessment of cardiac interoceptive perception following the principles of signal detection theory. By disentangling sensitivity and response bias, we demonstrate that the previously used interoceptive accuracy score of the heartbeat mental tracking task represents an amalgam of sensitivity and response bias. The new task demonstrated adequate test-retest reliabilities for sensitivity (d') and response bias (c). Sensitivity was inversely related (ß = -.36) to somatic symptom distress after statistically controlling for response bias. The novel cardiovascular signal detection task is easy to implement, feasible, and promising in terms of unraveling the role of (cardiac) interoceptive perception in psychopathology. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Somatosensory Illusions Elicited by Sham Electromagnetic Field Exposure: Experimental Evidence for a Predictive Processing Account of Somatic Symptom Perception.

OBJECTIVE: According to the predictive processing theory of somatic symptom generation, body sensations are determined by somatosensory input and central nervous predictions about this input. We examined how expectations shape predictions and consequently bodily perceptions in a task eliciting illusory sensations as laboratory analogue of medically unexplained symptoms. METHODS: Using the framework of signal detection theory, the influence of sham Wi-Fi on response bias (c) and somatosensory sensitivity (d') for tactile stimuli was examined using the somatic signal detection task (SSDT). A healthy student sample (n = 83) completed the SSDT twice (sham Wi-Fi on/off) in a randomized order after watching a film that promoted adverse health effects of electromagnetic fields. RESULTS: When expecting a Wi-Fi signal to be present, participants showed a significantly more liberal response bias c (p = .010, ηp2 = 0.08) for tactile stimuli in the SSDT as evidence of a higher propensity to experience somatosensory illusions. No significant alteration of somatosensory sensitivity d' (p = .76, ηp2 < 0.002) was observed. CONCLUSIONS: Negative expectations about the harmfulness of electromagnetic fields may foster the occurrence of illusory symptom perceptions via alterations in the somatosensory decision criterion. The findings are in line with central tenets of the predictive processing account of somatic symptom generation. This account proposes a decoupling of percept and somatosensory input so that perception becomes increasingly dependent on predictions. This biased perception is regarded as a risk factor for somatic symptom disorders.

Radular stylus of Cryptochiton stelleri: A multifunctional lightweight and flexible fiber-reinforced composite.

Chitons are herbivorous invertebrates that use rows of ultrahard magnetite-based teeth connected to a flexible belt (radula) to rasp away algal deposits growing on and within rocky outcrops along coastlines around the world. Each tooth is attached to the radula by an organic structure (stylus) that provides mechanical support during feeding. However, the underlying structures within the stylus, and their subsequent function within the chiton have yet to be investigated. Here, we investigate the macrostructural architecture, the regional material and elemental distribution and subsequent nano-mechanical properties of the stylus from the Northern Pacific dwelling Cryptochiton stelleri. Using a combination of µ-CT imaging, optical and electron microscopy, as well as elemental analysis, we reveal that the stylus is a highly contoured tube, mainly composed of alpha-chitin fibers, with a complex density distribution. Nanoindentation reveals regiospecific and graded mechanical properties that can be correlated with both the elemental composition and material distribution. Finite element modeling shows that the unique macroscale architecture, material distribution and elemental gradients have been optimized to preserve the structural stability of this flexible, yet robust functionally-graded fiber-reinforced composite tube, providing effective function during rasping. Understanding these complex fiber-based structures offers promising blueprints for lightweight, multifunctional and integrated materials.

Decoding Biomineralization: Interaction of a Mad10-Derived Peptide with Magnetite Thin Films.

Protein-surface interactions play a pivotal role in processes as diverse as biomineralization, biofouling, and the cellular response to medical implants. In biomineralization processes, biomacromolecules control mineral deposition and architecture via complex and often unknown mechanisms. For studying these mechanisms, the formation of magnetite nanoparticles in magnetotactic bacteria has become an excellent model system. Most interestingly, nanoparticle morphologies have been discovered that defy crystallographic rules (e.g., in the species Desulfamplus magnetovallimortis strain BW-1). In certain conditions, this strain mineralizes bullet-shaped magnetite nanoparticles, which exhibit defined (111) crystal faces and are elongated along the [100] direction. We hypothesize that surface-specific protein interactions break the nanoparticle symmetry, inhibiting the growth of certain crystal faces and thereby favoring the growth of others. Screening the genome of BW-1, we identified Mad10 (Magnetosome-associated deep-branching) as a potential magnetite-binding protein. Using atomic force microscope (AFM)-based single-molecule force spectroscopy, we show that a Mad10-derived peptide, which represents the most conserved region of Mad10, binds strongly to (100)- and (111)-oriented single-crystalline magnetite thin films. The peptide-magnetite interaction is thus material- but not crystal-face-specific. It is characterized by broad rupture force distributions that do not depend on the retraction speed of the AFM cantilever. To account for these experimental findings, we introduce a three-state model that incorporates fast rebinding. The model suggests that the peptide-surface interaction is strong in the absence of load, which is a direct result of this fast rebinding process. Overall, our study sheds light on the kinetic nature of peptide-surface interactions and introduces a new magnetite-binding peptide with potential use as a functional coating for magnetite nanoparticles in biotechnological and biomedical applications.

Contingent biofeedback outperforms other methods to enhance the accuracy of cardiac interoception: A comparison of short interventions.

BACKGROUND AND OBJECTIVES: Deviations in interoception might contribute to the development and maintenance of mental disorders. The improvement of interoceptive accuracy (IA) is desirable but assessment and training methods remain controversial. For instance, it was assumed that performance increases in heartbeat counting paradigms after cardiac feedback were due to an improvement of knowledge with regard to heart rate rather than due to an actual improvement in IA. METHODS: Here, we examined effects of contingent cardiac feedback training, non-contingent cardiac feedback, mindfulness practice, and a waiting period with external attentional focus on IA. 100 healthy participants underwent a mental tracking paradigm before and after 20 min of training or waiting. RESULTS: Results revealed a significant increase of IA in the contingent feedback condition (d = 1.21, p ≤ .001) and no significant changes after non-contingent feedback, mindfulness practice or waiting (d ≤ 0.37; p ≥ .06). Furthermore, IA increase was significantly higher after the contingent feedback training compared to all other conditions, including non-contingent feedback. LIMITATIONS: Future studies need to replicate these findings in clinical samples and examine time dependent effects. CONCLUSIONS: The results provide evidence for the trainability of heartbeat perception. IA improvements may reduce the symptom burden in people suffering from mental disorders and psychophysiological conditions that have been linked to lower interoceptive accuracy such as depression, somatic symptom disorder, chronic pain, and functional somatic syndromes. Consequently, exploration of biofeedback training procedures shall be continued with the aim of identifying relevant mediators of beneficial effects and future implementation in clinical practice.

eHealth literacy research-Quo vadis?

The concept of electronic health (eHealth) literacy evolved from the social and information sciences and describes competencies necessary to use electronic health services. As it is a rather new topic, and as there is no current overview of the state of the art in research, it is not possible to identify research gaps. Therefore, the objective of this viewpoint article is to increase knowledge on the current state of the art of research in eHealth literacy and to identify gaps in scientific research which should be focused on by the research community in the future. The article provides a current viewpoint of the concept of eHealth literacy and related research. Gaps can be found in terms of a missing "gold standard" regarding both the definition and the measurement of eHealth literacy. Furthermore, there is a need for identifying the implications on eHealth developers, which evolve from the measurement of eHealth literacy in eHealth users. Finally, a stronger inclusion of health professionals, both in the evolving concept and in the measurement of eHealth literacy, is needed in the future.

Don't worry, be happy - Neural correlates of the influence of musically induced mood on self-evaluation.

Self-evaluation affects one's own mental state, social interactions and everyday life. Mood, in turn, has an impact on self-evaluation. However, the influence of mood on self-evaluation at the neural level has barely been examined. In this fMRI study, the interaction of mood and self-perception was investigated in 20 healthy participants. Happy, sad and neutral music was presented while participants were instructed to immerse themselves in the mood of the music and to rate how well presented traits characterized themselves. In a lexical control condition, subjects had to count a specific letter in the word. Behavioral data reflected successful mood induction. While self-ascription of positive traits was unaffected by mood, self-ascription of negative characteristics was decreased by negative affect. A positive correlation was found between self-worth scores and the difference in the amount of self-ascribed positive versus negative traits during negative mood induction. At the neural level, amygdalo-hippocampal, superior and middle temporal structures were differently involved in self-evaluation (vs. lexical processing) depending on the mood. While activation of the amygdalo-hippocampal complex was found during sad in comparison to both happy and neutral mood, superior/middle temporal gyrus (STG/MTG) activation was only found when contrasting sad vs. neutral mood. Further, a correlation analysis with self-worth ratings revealed a positive relation to STG activation during self-ascription of trait adjectives in sad compared to neutral mood. Our results underscore the importance of the current emotional state for self-evaluation and identify some neural correlates of this effect. Our findings in healthy research participants suggest a compensatory mechanism during sad mood induction to maintain a positive self-image, which is supported by activation of limbic and fronto-temporal cortex. Studies in clinically depressed populations could reveal whether this compensatory mechanism is aberrant.

Impaired Emotional Mirroring in Parkinson's Disease-A Study on Brain Activation during Processing of Facial Expressions.

BACKGROUND: Affective dysfunctions are common in patients with Parkinson's disease, but the underlying neurobiological deviations have rarely been examined. Parkinson's disease is characterized by a loss of dopamine neurons in the substantia nigra resulting in impairment of motor and non-motor basal ganglia-cortical loops. Concerning emotional deficits, some studies provide evidence for altered brain processing in limbic- and lateral-orbitofrontal gating loops. In a second line of evidence, human premotor and inferior parietal homologs of mirror neuron areas were involved in processing and understanding of emotional facial expressions. We examined deviations in brain activation during processing of facial expressions in patients and related these to emotion recognition accuracy. METHODS: 13 patients and 13 healthy controls underwent an emotion recognition task and a functional magnetic resonance imaging (fMRI) measurement. In the Emotion Hexagon test, participants were presented with blends of two emotions and had to indicate which emotion best described the presented picture. Blended pictures with three levels of difficulty were included. During fMRI scanning, participants observed video clips depicting emotional, non-emotional, and neutral facial expressions or were asked to produce these facial expressions themselves. RESULTS: Patients performed slightly worse in the emotion recognition task, but only when judging the most ambiguous facial expressions. Both groups activated inferior frontal and anterior inferior parietal homologs of mirror neuron areas during observation and execution of the emotional facial expressions. During observation, responses in the pars opercularis of the right inferior frontal gyrus, in the bilateral inferior parietal lobule and in the bilateral supplementary motor cortex were decreased in patients. Furthermore, in patients, activation of the right anterior inferior parietal lobule was positively related to accuracy in the emotion recognition task. CONCLUSION: Our data provide evidence for a contribution of human homologs of monkey mirror areas to the emotion recognition deficit in Parkinson's disease.

Real-time monitoring of calcium carbonate and cationic peptide deposition on carboxylate-SAM using a microfluidic SAW biosensor.

A microfluidic biosensor with surface acoustic wave technology was used in this study to monitor the interaction of calcium carbonate with standard carboxylate self-assembled monolayer sensor chips. Different fluids, with and without biomolecular components, were investigated. The pH-dependent surface interactions of two bio-inspired cationic peptides, AS8 and ES9, which are similar to an extracellular domain of the chitin synthase involved in mollusc shell formation, were also investigated in a biological buffer system. A range of experimental conditions are described that are suitable to study non-covalent molecular interactions in the presence of ionic substances, such as, mineral precursors below the solubility equilibrium. The peptide ES9, equal to the mollusc chitin synthase epitope, is less sensitive to changes in pH than its counterpart AS8 with a penta-lysine core, which lacks the flanking acidic residues. This study demonstrates the extraordinary potential of microfluidic surface acoustic wave biosensors to significantly expand our experimental capabilities for studying the principles underlying biomineralization in vitro.

Neural correlates of impaired emotion processing in manifest Huntington's disease.

The complex phenotype of Huntington's disease (HD) encompasses motor, psychiatric and cognitive dysfunctions, including early impairments in emotion recognition. In this first functional magnetic resonance imaging study, we investigated emotion-processing deficits in 14 manifest HD patients and matched controls. An emotion recognition task comprised short video clips displaying one of six basic facial expressions (sadness, happiness, disgust, fear, anger and neutral). Structural changes between patients and controls were assessed by means of voxel-based morphometry. Along with deficient recognition of negative emotions, patients exhibited predominantly lower neural response to stimuli of negative valences in the amygdala, hippocampus, striatum, insula, cingulate and prefrontal cortices, as well as in sensorimotor, temporal and visual areas. Most of the observed reduced activity patterns could not be explained merely by regional volume loss. Reduced activity in the thalamus during fear correlated with lower thalamic volumes. During the processing of sadness, patients exhibited enhanced amygdala and hippocampal activity along with reduced recruitment of the medial prefrontal cortex. Higher amygdala activity was related to more pronounced amygdala atrophy and disease burden. Overall, the observed emotion-related dysfunctions in the context of structural neurodegeneration suggest both disruptions of striatal-thalamo-cortical loops and potential compensation mechanism with greater disease severity in manifest HD.