[Strategies for Shared Decision-making in Therapy for Patients with Oncological Disease - Quo vadis?] / Strategien zur gemeinsamen Entscheidungsfindung in der Therapie bei Patient_innen mit onkologischen Erkrankungen.

Strategies for Shared Decision-making in Therapy for Patients with Oncological Disease - Quo vadis? Abstract. Shared decision-making (SDM) for therapeutic interventions in oncology is a complex process in which numerous person-, treatment-, and context-related factors can influence the choice of suitable treatment options and final treatment decisions. SDM plays a crucial role in this process by supporting the inclusion of the patient in the doctor-patient encounter and in treatment decision-making. Preference-sensitive decisions can render SDM a particular burden for the patient. Both physicians and patients see the lack of patient preparation as limiting the effectiveness of SDM. Electronic or web-based patient decision aids could help prepare patients with an oncologic diagnosis for the SDM process in advance of the physician-patient encounter. The aim of this review is to provide an up-to-date overview of the role of SDM and its future development in oncology. In doing so, the use of patient decision aids within a phase model of SDM for oncology will be highlighted with particular emphasis on the potential use of Chatbot technology to prepare patients for participation in SDM and to optimize physician-patient communication. The paper also highlights some major research gaps for the future development of Chatbots as patient decision aids in oncology.

[Patient Decision Aids for Values Clarification and Preference Elicitation - Challenges and Developments]. / Patienten-Entscheidungshilfen zur Werteklärung und Präferenzerhebung.

Patient Decision Aids for Values Clarification and Preference Elicitation - Challenges and Developments Abstract. Shared decision-making is especially appropriate when the available evidence does not indicate which medical intervention is the better option, so that the final decision depends on the patient's personal values and preferences. The process of value clarification and preference elicitation can be time-consuming and cognitively and emotionally demanding for patients. Increasingly, decision aids provide tasks (e.g., on benefit-harm trade-offs) to help patients work through this process, better prepare for medical consultations, and make values-congruent medical decisions with their physicians. Most clinically validated decision aids are paper-based flyers and educational brochures. There are also computer-, audio-, video-, or web-based decision aids. The web-based aids make little use of the potential of interactive technologies, despite the known benefits of these technologies. The aims of this paper are to provide an overview of decision aids for and challenges of values clarification and preference elicitation and to highlight some developments in interactive web-based technologies that might facilitate values clarification and preference elicitation.

Perspective and agency during video gaming influences spatial presence experience and brain activation patterns.

BACKGROUND: The experience of spatial presence (SP), i.e., the sense of being present in a virtual environment, emerges if an individual perceives himself as 1) if he were actually located (self-location) and 2) able to act in the virtual environment (possible actions). In this study, two main media factors (perspective and agency) were investigated while participants played a commercially available video game. METHODS: The differences in SP experience and associated brain activation were compared between the conditions of game play in first person perspective (1PP) and third person perspective (3PP) as well as between agency, i.e., active navigation of the video game character (active), and non-agency, i.e., mere passive observation (passive). SP was assessed using standard questionnaires, and brain activation was measured using electroencephalography (EEG) and sLORETA source localisation (standard low-resolution brain electromagnetic tomography). RESULTS: Higher SP ratings were obtained in the 1PP compared with the 3PP condition and in the active compared with the passive condition. On a neural level, we observed in the 1PP compared with the 3PP condition significantly less alpha band power in the parietal, the occipital and the limbic cortex. In the active compared with the passive condition, we uncovered significantly more theta band power in frontal brain regions. CONCLUSION: We propose that manipulating the factors perspective and agency influences SP formation by either directly or indirectly modulating the ego-centric visual processing in a fronto-parietal network. The neuroscientific results are discussed in terms of the theoretical concepts of SP.

Knowledge extraction from pointer movements and its application to detect uncertainty.

Pointer-tracking methods can capture a real-time trace at high spatio-temporal resolution of users' pointer interactions with a graphical user interface. This trace is potentially valuable for research on human-computer interaction (HCI) and for investigating perceptual, cognitive and affective processes during HCI. However, little research has reported spatio-temporal pointer features for the purpose of tracking pointer movements in on-line surveys. In two studies, we identified a set of pointer features and movement patterns and showed that these can be easily distinguished. In a third study, we explored the feasibility of using patterns of interactive pointer movements, or micro-behaviours, to detect response uncertainty. Using logistic regression and k-fold cross-validation in model training and testing, the uncertainty model achieved an estimated performance accuracy of 81%. These findings suggest that micro-behaviours provide a promising approach toward developing a better understanding of the relationship between the dynamics of pointer movements and underlying perceptual, cognitive and affective psychological mechanisms.

Impact of single and combined rare diseases on adult inpatient outcomes: a retrospective, cross-sectional study of a large inpatient population.

BACKGROUND: Little is known about the impact of rare diseases on inpatient outcomes. OBJECTIVE: To compare outcomes of inpatients with 0, 1, or > 1 rare disease. A catalogue of 628 ICD-10 coded rare diseases was applied to count rare diseases. DESIGN: Retrospective, cross-sectional study. SUBJECTS: 165,908 inpatients, Swiss teaching hospital. MAIN MEASURES: Primary outcome: in-hospital mortality. SECONDARY OUTCOMES: length of stay (LOS), intensive care unit (ICU) admissions, ICU LOS, and 30-day readmissions. Associations with single and combined rare diseases were analyzed by multivariable regression. KEY RESULTS: Patients with 1 rare disease were at increased risk of in-hospital death (odds ratio [OR]: 1.80; 95% confidence interval [CI]: 1.67, 1.95), combinations of rare diseases showed stronger associations (OR 2.78; 95% CI 2.39, 3.23). Females with 1 rare disease had an OR of 1.69 (95% CI 1.50, 1.91) for in-hospital death, an OR of 2.99 (95% CI 2.36, 3.79) if they had a combination of rare diseases. Males had an OR of 1.85 (95% CI 1.68, 2.04) and 2.61 (95% CI 2.15, 3.16), respectively. Rare diseases were associated with longer LOS (for 1 and > 1 rare diseases: increase by 28 and 49%), ICU admissions (for 1 and > 1: OR 1.64 [95% CI 1.57, 1.71] and 2.23 [95% CI 2.01, 2.48]), longer ICU LOS (for 1 and > 1 rare diseases: increase by 14 and 40%), and 30-day readmissions (for 1 and > 1: OR 1.57 [95% CI 1.47, 1.68] and 1.64 [95% CI 1.37, 1.96]). CONCLUSIONS: Rare diseases are independently associated with worse inpatient outcomes. This might be the first study suggesting even stronger associations of combined rare diseases with in-hospital deaths, increased LOS, ICU admissions, increased ICU LOS, and 30-day readmissions.

Clinical Relevance of Anti-TNF Antibody Trough Levels and Anti-Drug Antibodies in Treating Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: The majority of patients treated with anti-tumor necrosis factor (TNF) therapy develop anti-drug antibodies (ADAs), which might result in loss of treatment efficacy. Strict guidelines on measuring trough levels (TLs) and ADA in clinical routine do not exist. To provide real-world data, we took advantage of our tertiary inflammatory bowel disease (IBD) center patient cohort and determined indicators for therapeutic drug monitoring (TDM) and actual consequences in patient care. METHODS: We retrospectively collected clinical data of 104 IBD patients treated with infliximab or adalimumab in our IBD clinic. Patients with TL and ADA measurements between June 2015 and February 2018 were included. RESULTS: The main reason for determining TL was increased clinical disease. Subtherapeutic TLs were found in 33 patients, therapeutic TLs in 33 patients, and supratherapeutic TLs in 38 patients. Adjustments in anti-TNF therapy occurred more frequently (p = 0.01) in patients with subtherapeutic TL (24 of 33 patients; 73%) as compared to patients with therapeutic and supratherapeutic TLs (26 of 71 patients; 37%). No correlation could be found between TL and disease activity (p = 0.16). Presence of ADA was found in 16 patients, correlated with the development of infusion reactions (OR: 10.6, RR: 5.4, CI: 2.9-38.6), and was associated with subtherapeutic TL in 15 patients (93.8%). Treatment adaptations were based on TL and/or ADA presence in 36 of 63 patients. CONCLUSIONS: TDM showed significant treatment adaptations in patients with subtherapeutic TL. Conversely, in patients with therapeutic and supratherapeutic TLs, reasons for adaptations were based on considerations other than TL, such as clinical disease activity. Further studies should focus on decision-making in patients presenting with supratherapeutic TL in remission.

Comparing Multimorbidity Patterns Among Discharged Middle-Aged and Older Inpatients Between Hong Kong and Zurich: A Hierarchical Agglomerative Clustering Analysis of Routine Hospital Records.

Background: Multimorbidity, defined as the co-occurrence of ≥2 chronic conditions, is clinically diverse. Such complexity hinders the development of integrated/collaborative care for multimorbid patients. In addition, the universality of multimorbidity patterns is unclear given scarce research comparing multimorbidity profiles across populations. This study aims to derive and compare multimorbidity profiles in Hong Kong (HK, PRC) and Zurich (ZH, Switzerland). Methods: Stratified by sites, hierarchical agglomerative clustering analysis (dissimilarity measured by Jaccard index) was conducted with the objective of grouping inpatients into clinically meaningful clusters based on age, sex, and 30 chronic conditions among 20,000 randomly selected discharged multimorbid inpatients (10,000 from each site) aged ≥ 45 years. The elbow point method based on average within-cluster dissimilarity, complemented with a qualitative clinical examination of disease prevalence, was used to determine the number of clusters. Results: Nine clusters were derived for each site. Both similarities and dissimilarities of multimorbidity patterns were observed. There was one stroke-oriented cluster (3.9% in HK; 6.5% in ZH) and one chronic kidney disease-oriented cluster (13.1% in HK; 11.5% ZH) in each site. Examples of site-specific multimorbidity patterns, on the other hand, included a myocardial infarction-oriented cluster in ZH (2.3%) and several clusters in HK with high prevalence of heart failure (>65%) and chronic pain (>20%). Conclusion: This is the first study using hierarchical agglomerative clustering analysis to profile multimorbid inpatients from two different populations to identify universalities and differences of multimorbidity patterns. Our findings may inform the coordination of integrated/collaborative healthcare services.

Multimorbidity and cardiovascular disease: a perspective on low- and middle-income countries.

New and changing patterns of multimorbidity (MM), i.e., multiple concurrent acute or chronic diseases in a person, are emerging in low- and middle-income countries (LMICs). The interplay of underlying population-specific factors and lifestyle habits combined with the colliding epidemics of communicable and non-communicable diseases presents new disease combinations, complexities and risks that are not common in high-income countries (HICs). The complexities and risks include those arising from potentially harmful drug-drug and drug-disease interactions (DDIs), the management of which may be considered as MM in the true sense. A major concern in LMICs is the increasing burden of leading cardiovascular diseases, prevalence of associated risk factors and co-occurrence with other morbidities. New models of MM management and integrated care can respond to the needs of specific multimorbid populations, with some LMICs making substantial progress (e.g., integration of tuberculosis and HIV services in South Africa). But there is a dearth of relevant data on the changing patterns and underlying factors and determinants of MM, the associated complexities and risks of DDIs in MM management, and the barriers to integrated care in LMICs. This requires careful attention.

Unmet challenges in treating hypertension in patients with borderline personality disorder: A systematic review.

BACKGROUND: Caregivers encounter serious and substantial challenges in managing hypertension in patients with subclinical or clinical borderline personality disorder (BPD). These challenges include therapeutic conflicts resulting from harmful drug-drug, and drug-disease interactions. Current guidelines provide no recommendations for concurrent psychotropic and antihypertensive treatment of hypertensive BPD patients who are at even greater cardiovascular risk. METHODS: We conducted a systematic literature review to assess the extent of available evidence on prevalence rates, cardiovascular risk factors, therapeutic conflicts, and evidence-based treatment recommendations for patients with co-occurring hypertension and BPD. Search terms were combined for hypertension and BPD in PubMed, MEDLINE, EMBASE, Cochrane, and PsycINFO databases. RESULTS: We included 11 articles for full-text evaluation and found a very high prevalence of hypertension and substantial cardiovascular risk in studies on co-occurring BPD and hypertension. However, we identified neither studies on harmful drug-drug and drug-disease interactions nor studies with treatment recommendations for co-occurring hypertension and BPD. CONCLUSIONS: Increased prevalence of hypertension in BPD patients, and therapeutic conflicts of psychotropic agents strongly suggest careful evaluation of treatment strategies in this patient group. However, no studies or guidelines recommend specific therapies or strategies to resolve therapeutic conflicts in patients with hypertension and BPD. This evidence gap needs attention in this population at high risk for cardiovascular disease.

Management of hyperglycaemia in persons with non-insulin-dependent type 2 diabetes mellitus who are started on systemic glucocorticoid therapy: a systematic review.

OBJECTIVES: What is the most effective pharmacological intervention for glycaemic control in known type 2 diabetes mellitus (DM) without prior insulin treatment and newly started on systemic glucocorticoid therapy? DESIGN: We conducted a systematic literature review. DATA SOURCES: We searched MEDLINE, Embase and Cochrane Library databases and Google for articles from 2002 to July 2018. ELIGIBILITY CRITERIA: We combined search terms relating to DM (patients, >16 years of age), systemic glucocorticoids, glycaemic control, randomised controlled trials (RCTs) and observational studies. DATA EXTRACTION AND SYNTHESIS: We screened and evaluated articles, extracted data and assessed risk of bias and quality of evidence according to Grading of Recommendations Assessment, Development and Evaluation guidelines. RESULTS: Eight of 2365 articles met full eligibility criteria. Basal-bolus insulin (BBI) strategy for patients under systemic glucocorticoid therapy was comparatively effective but provided insufficient glucose control, depending on time of day. BBI strategy with long-acting insulin and neutral protamin Hagedorn as basal insulin provided similar overall glycaemic control. Addition of various insulin strategies to standard BBI delivered mixed results. Intermediate-acting insulin (IMI) as additional insulin conferred no clear benefits, and glycaemic control with sliding scale insulin was inferior to BBI or IMI. No studies addressed whether anticipatory or compensatory insulin adjustments are better for glycaemic control. CONCLUSION: The lack of suitably designed RCTs and observational studies, heterogeneity of interventions, target glucose levels and glucose monitoring, poor control of DM subgroups and low to moderate quality of evidence render identification of optimal pharmacological interventions for glycaemic control and insulin management difficult. Even findings on the widely recommended BBI regimen as intensive insulin therapy for patients with DM on glucocorticoids are inconclusive. High-quality evidence from studies with well-defined DM phenotypes, settings and treatment approaches is needed to determine optimal pharmacological intervention for glycaemic control. PROSPERO REGISTRATION NUMBER: CRD42015024739.

Long-term Outcomes of Kidney Transplantation in Fabry Disease.

BACKGROUND: Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene that obliterate or markedly reduce α-galactosidase A activity. This results in the systemic accumulation of its glycosphingolipid substrates in body fluids and organs, including the kidney. Fabry nephropathy can lead to end-stage renal disease requiring kidney transplantation. Little is known about its long-term outcomes and the overall patient survival after kidney transplantation. METHODS: Here, we report 17 Fabry patients (15 male and 2 female subjects) who received kidney transplants and their long-term treatment and follow-up at 4 specialized Fabry centers. RESULTS: The posttransplant follow-up ranged to 25 years, with a median of 11.5 (range, 0.8-25.5] years. Graft survival was similar, and death-censored graft survival was superior to matched controls. Fabry patients died with functioning kidneys, mostly from cardiac causes. In 2 male subjects 14 and 23 years posttransplant, the grafts had a few typical FD lamellar inclusions, presumably originating from invading host macrophages and vascular endothelial cells. CONCLUSIONS: We conclude that kidney transplantation has an excellent long-term outcome in FD.

Choosing Wisely - An international and multimorbid perspective.

Some medical diagnostic and therapeutic interventions are non-beneficial or even harmful. The Choosing Wisely campaign has encouraged the generation of "top five" lists of unnecessary low-value services in different specialist areas. In the USA alone, where the campaign was launched, these lists include a total of 450 evidence-based recommendations. Medical scientific societies in further countries such as Canada, Australia, New Zealand, England, Switzerland and Germany have since initiated Choosing Wisely campaigns. Besides implementing top five lists, these aim to change attitudes, expectations and practices in the culture of medicine. The field of internal medicine has initiated change in Switzerland (Swiss Society of General Internal Medicine: Smarter Medicine) and Germany (German Society of Internal Medicine: Klug entscheiden). Formulating Choosing Wisely principles in managing complex patients with multiple concurrent acute or chronic diseases, i. e., multimorbidity (MM), will present a particular challenge. Research is needed to determine the primary sources of overuse in specific combinations of diseases (i. e., MM clusters) and spearhead corresponding recommendations. National Choosing Widely campaigns may serve as a forerunner to a more global initiative.

The frequent and underrecognised co-occurrence of acute exacerbated COPD and depression warrants screening: a systematic review.

Patients with acute exacerbated chronic obstructive pulmonary disease (AECOPD) and concurrent depression suffer significant psychological stress and decreased quality of life. The aim of this study was to collate data, guidelines and recommendations from publications on the screening and management of depressive mood disorders in patients hospitalised with AECOPD.We systematically searched four databases for publications reporting screening or management of depression in patients hospitalised for AECOPD. The identification of articles was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.Out of 1494 original articles screened, 35 met all inclusion criteria. These report a prevalence of depression in AECOPD ranging between 9.5% and 85.6%. Some studies report high postadmission mortality rates for depressive AECOPD patients, and higher readmission rates in depressive versus nondepressive AECOPD patients. Importantly, none of the 35 publications included suggestions on the screening and management of depression in AECOPD.Depression and AECOPD frequently co-occur, and this worsens outcomes. Yet we did not find recommendations on management, and few interventional studies. Patients hospitalised with AECOPD should be systematically screened for depression and treatment recommendations should be developed for these patients. Randomised studies on how to screen and treat depression in hospitalised AECOPD are necessary.

The multimorbidity interaction severity index (MISI): A proof of concept study.

Therapeutic decision-making for patients with multimorbidity (MM) is challenging. Clinical practice guidelines inadequately address harmful interactions and resulting therapeutic conflicts within and among diseases. A patient-specific measure of MM severity that takes account of this conflict is needed.As a proof of concept, we evaluated whether the new Multimorbidity Interaction Severity Index (MISI) could be used to reliably differentiate patients in terms of lower versus higher potential for harmful interactions.Two hypothetical patient cases were generated, each with 6 concurrent morbidities. One case had a low (i.e., low conflict case) and the other a high (i.e., high conflict case) potential for harmful interactions. All possible interactions between conditions and treatments were extracted from each case's record into a multimorbidity interaction matrix. Experienced general internists (N = 18) judged each interaction in the matrix in terms of likely resource utilization needed to manage the interaction. Based on these judgements, a composite index of MM interaction severity, that is, the MISI, was generated for each physician and case.The difference between each physician's MISI score for the 2 cases (MISIdiff) was computed. Based on MISIdiff, the high conflict case was judged to be of significantly greater MM severity than was the low conflict case. The positive values of the inter-quartile range, a measure of variation (or disagreement) between the 2 cases, indicated general consistency of individual physicians in judging MM severity.The data indicate that the MISI can be used to reliably differentiate hypothetical multimorbid patients in terms of lesser versus greater severity of potentially harmful interactive effects. On this basis, the MISI will be further developed for use in patient-specific assessment and management of MM. The clinical relevance of the MISI as an alternative approach to defining MM severity is discussed.

Arousal, valence, and the uncanny valley: psychophysiological and self-report findings.

The main prediction of the Uncanny Valley Hypothesis (UVH) is that observation of humanlike characters that are difficult to distinguish from the human counterpart will evoke a state of negative affect. Well-established electrophysiological [late positive potential (LPP) and facial electromyography (EMG)] and self-report [Self-Assessment Manikin (SAM)] indices of valence and arousal, i.e., the primary orthogonal dimensions of affective experience, were used to test this prediction by examining affective experience in response to categorically ambiguous compared with unambiguous avatar and human faces (N = 30). LPP and EMG provided direct psychophysiological indices of affective state during passive observation and the SAM provided self-reported indices of affective state during explicit cognitive evaluation of static facial stimuli. The faces were drawn from well-controlled morph continua representing the UVH' dimension of human likeness (DHL). The results provide no support for the notion that category ambiguity along the DHL is specifically associated with enhanced experience of negative affect. On the contrary, the LPP and SAM-based measures of arousal and valence indicated a general increase in negative affective state (i.e., enhanced arousal and negative valence) with greater morph distance from the human end of the DHL. A second sample (N = 30) produced the same finding, using an ad hoc self-rating scale of feelings of familiarity, i.e., an oft-used measure of affective experience along the UVH' familiarity dimension. In conclusion, this multi-method approach using well-validated psychophysiological and self-rating indices of arousal and valence rejects - for passive observation and for explicit affective evaluation of static faces - the main prediction of the UVH.

Identifying with fictive characters: structural brain correlates of the personality trait 'fantasy'.

The perception of oneself as absorbed in the thoughts, feelings and happenings of a fictive character (e.g. in a novel or film) as if the character's experiences were one's own is referred to as identification. We investigated whether individual variation in the personality trait of identification is associated with individual variation in the structure of specific brain regions, using surface and volume-based morphometry. The hypothesized regions of interest were selected on the basis of their functional role in subserving the cognitive processing domains considered important for identification (i.e. mental imagery, empathy, theory of mind and merging) and for the immersive experience called 'presence'. Controlling for age, sex, whole-brain volume and other traits, identification covaried significantly with the left hippocampal volume, cortical thickness in the right anterior insula and the left dorsal medial prefrontal cortex, and with gray matter volume in the dorsolateral prefrontal cortex. These findings show that trait identification is associated with structural variation in specific brain regions. The findings are discussed in relation to the potential functional contribution of these regions to identification.

Perceptual discrimination difficulty and familiarity in the Uncanny Valley: more like a "Happy Valley".

The Uncanny Valley Hypothesis (UVH) predicts that greater difficulty perceptually discriminating between categorically ambiguous human and humanlike characters (e.g., highly realistic robot) evokes negatively valenced (i.e., uncanny) affect. An ABX perceptual discrimination task and signal detection analysis was used to examine the profile of perceptual discrimination (PD) difficulty along the UVH' dimension of human likeness (DHL). This was represented using avatar-to-human morph continua. Rejecting the implicitly assumed profile of PD difficulty underlying the UVH' prediction, Experiment 1 showed that PD difficulty was reduced for categorically ambiguous faces but, notably, enhanced for human faces. Rejecting the UVH' predicted relationship between PD difficulty and negative affect (assessed in terms of the UVH' familiarity dimension), Experiment 2 demonstrated that greater PD difficulty correlates with more positively valenced affect. Critically, this effect was strongest for the ambiguous faces, suggesting a correlative relationship between PD difficulty and feelings of familiarity more consistent with the metaphor happy valley. This relationship is also consistent with a fluency amplification instead of the hitherto proposed hedonic fluency account of affect along the DHL. Experiment 3 found no evidence that the asymmetry in the profile of PD along the DHL is attributable to a differential processing bias (cf. other-race effect), i.e., processing avatars at a category level but human faces at an individual level. In conclusion, the present data for static faces show clear effects that, however, strongly challenge the UVH' implicitly assumed profile of PD difficulty along the DHL and the predicted relationship between this and feelings of familiarity.

Equal pain-Unequal fear response: enhanced susceptibility of tooth pain to fear conditioning.

Experimental fear conditioning in humans is widely used as a model to investigate the neural basis of fear learning and to unravel the pathogenesis of anxiety disorders. It has been observed that fear conditioning depends on stimulus salience and subject vulnerability to fear. It is further known that the prevalence of dental-related fear and phobia is exceedingly high in the population. Dental phobia is unique as no other body part is associated with a specific phobia. Therefore, we hypothesized that painful dental stimuli exhibit an enhanced susceptibility to fear conditioning when comparing to equal perceived stimuli applied to other body sites. Differential susceptibility to pain-related fear was investigated by analyzing responses to an unconditioned stimulus (UCS) applied to the right maxillary canine (UCS-c) vs. the right tibia (UCS-t). For fear conditioning, UCS-c and USC-t consisted of painful electric stimuli, carefully matched at both application sites for equal intensity and quality perception. UCSs were paired to simple geometrical forms which served as conditioned stimuli (CS+). Unpaired CS+ were presented for eliciting and analyzing conditioned fear responses. Outcome parameter were (1) skin conductance changes and (2) time-dependent brain activity (BOLD responses) in fear-related brain regions such as the amygdala, anterior cingulate cortex, insula, thalamus, orbitofrontal cortex, and medial prefrontal cortex. A preferential susceptibility of dental pain to fear conditioning was observed, reflected by heightened skin conductance responses and enhanced time-dependent brain activity (BOLD responses) in the fear network. For the first time, this study demonstrates fear-related neurobiological mechanisms that point toward a superior conditionability of tooth pain. Beside traumatic dental experiences our results offer novel evidence that might explain the high prevalence of dental-related fears in the population.

Perceptual and category processing of the Uncanny Valley hypothesis' dimension of human likeness: some methodological issues.

Mori's Uncanny Valley Hypothesis(1,2) proposes that the perception of humanlike characters such as robots and, by extension, avatars (computer-generated characters) can evoke negative or positive affect (valence) depending on the object's degree of visual and behavioral realism along a dimension of human likeness (DHL) (Figure 1). But studies of affective valence of subjective responses to variously realistic non-human characters have produced inconsistent findings (3, 4, 5, 6). One of a number of reasons for this is that human likeness is not perceived as the hypothesis assumes. While the DHL can be defined following Mori's description as a smooth linear change in the degree of physical humanlike similarity, subjective perception of objects along the DHL can be understood in terms of the psychological effects of categorical perception (CP) (7). Further behavioral and neuroimaging investigations of category processing and CP along the DHL and of the potential influence of the dimension's underlying category structure on affective experience are needed. This protocol therefore focuses on the DHL and allows examination of CP. Based on the protocol presented in the video as an example, issues surrounding the methodology in the protocol and the use in "uncanny" research of stimuli drawn from morph continua to represent the DHL are discussed in the article that accompanies the video. The use of neuroimaging and morph stimuli to represent the DHL in order to disentangle brain regions neurally responsive to physical human-like similarity from those responsive to category change and category processing is briefly illustrated.

Category Processing and the human likeness dimension of the Uncanny Valley Hypothesis: Eye-Tracking Data.

The Uncanny Valley Hypothesis (Mori, 1970) predicts that perceptual difficulty distinguishing between a humanlike object (e.g., lifelike prosthetic hand, mannequin) and its human counterpart evokes negative affect. Research has focused on affect, with inconsistent results, but little is known about how objects along the hypothesis' dimension of human likeness (DHL) are actually perceived. This study used morph continua based on human and highly realistic computer-generated (avatar) faces to represent the DHL. Total number and dwell time of fixations to facial features were recorded while participants (N = 60) judged avatar versus human category membership of the faces in a forced choice categorization task. Fixation and dwell data confirmed the face feature hierarchy (eyes, nose, and mouth in this order of importance) across the DHL. There were no further findings for fixation. A change in the relative importance of these features was found for dwell time, with greater preferential processing of eyes and mouth of categorically ambiguous faces compared with unambiguous avatar faces. There were no significant differences between ambiguous and human faces. These findings applied for men and women, though women generally dwelled more on the eyes to the disadvantage of the nose. The mouth was unaffected by gender. In summary, the relative importance of facial features changed on the DHL's non-human side as a function of categorization ambiguity. This change was indicated by dwell time only, suggesting greater depth of perceptual processing of the eyes and mouth of ambiguous faces compared with these features in unambiguous avatar faces.