Clinical, genetic, and functional characterization of adrenocorticotropin receptor mutations using a novel receptor assay.

The ACTH receptor (MC2R) is expressed predominantly in the adrenal cortex, but is one of five G protein-coupled, seven-transmembrane melanocortin receptors (MCRs), all of which bind ACTH to some degree. Testing of MC2R activity is difficult because most cells express endogenous MCRs; hence, ACTH will elicit background activation of assayable reporter systems. Inactivating mutations of MC2R lead to hereditary unresponsiveness to ACTH, also known as familial glucocorticoid deficiency (FGD). These patients are usually seen in early childhood with very low cortisol concentrations, normal mineralocorticoids, hyperpigmentation, and increased bodily growth. Several MC2R mutations have been reported in FGD, but assays of the activities of these mutants are cumbersome. We saw two patients with typical clinical findings of FGD. Genetic analysis showed that patient 1 was homozygous for the mutation R137W, and patient 2 was a compound heterozygote for S74I and Y254C. We tested the activity of these mutations in OS-3 cells, which are unresponsive to ACTH but have intact downstream cAMP signal transduction. OS-3 cells transfected with a cAMP-responsive luciferase reporter plasmid (pCREluc) were unresponsive to ACTH, but cotransfection with a vector expressing human MC2R increased luciferase activity more than 40-fold. Addition of ACTH to cells cotransfected with the pCREluc reporter and wild-type MC2R activated luciferase expression with a 50% effective concentration of 5.5 x 10(-9) M ACTH, which is similar to previously reported values. By contrast, the MC2R mutant R137W had low activity, and the S74I or Y254C mutants elicited no measurable response. This assay provides excellent sensitivity in an easily assayed transient transfection system, providing a more rapid and efficient measurement of ACTH receptor activity.

Listening to your heart and feeling yourself: effects of exposure to interoceptive signals during the ultimatum game

The ultimatum game (UG) is commonly used to study the tension between financial self-interest and social equity motives. Here, we investigated whether experimental exposure to interoceptive signals influences participants' behavior in the UG. Participants were presented with various bodily sounds--i.e., their own heart, another person's heart, or the sound of footsteps--while acting both in the role of responder and proposer. We found that listening to one's own heart sound, compared to the other bodily sounds: (1) increased subjective feelings of unfairness, but not rejection behavior, in response to unfair offers and (2) increased the unfair offers while playing in the proposer role. These findings suggest that heightened feedback of one's own visceral processes may increase a self-centered perspective and drive socioeconomic exchanges accordingly. In addition, this study introduces a valuable procedure to manipulate online the access to interoceptive signals and for exploring the interplay between viscero-sensory information and cognition.

Restoring tactile awareness through the rubber hand illusion in cervical spinal cord injury

BACKGROUND Bodily sensations are an important component of corporeal awareness. Spinal cord injury can leave affected body parts insentient and unmoving, leading to specific disturbances in the mental representation of one's own body and the sense of self. OBJECTIVE Here, we explored how illusions induced by multisensory stimulation influence immediate sensory signals and tactile awareness in patients with spinal cord injuries. METHODS The rubber hand illusion paradigm was applied to 2 patients with chronic and complete spinal cord injury of the sixth cervical spine, with severe somatosensory impairments in 2 of 5 fingers. RESULTS Both patients experienced a strong illusion of ownership of the rubber hand during synchronous, but not asynchronous, stroking. They also, spontaneously reported basic tactile sensations in their previously numb fingers. Tactile awareness from seeing the rubber hand was enhanced by progressively increasing the stimulation duration. CONCLUSIONS Multisensory illusions directly and specifically modulate the reemergence of sensory memories and enhance tactile sensation, despite (or as a result of) prior deafferentation. When sensory inputs are lost, and are later illusorily regained, the brain updates a coherent body image even several years after the body has become permanently unable to feel. This particular example of neural plasticity represents a significant opportunity to strengthen the sense of the self and the feelings of embodiment in patients with spinal cord injury.

Double-blind comparison of rectally administered diazepam to placebo for pediatric sedation: the cardiovascular response.

The sedative and cardiovascular effects of rectally administered diazepam (0.6 mg/kg) were compared to placebo in uncooperative children who required sedation during dental treatment. Twelve healthy preschool children, who required amalgam restorations, were treated during two standardized restorative appointments in a double-blind, crossover study. Blood pressure and pulse were obtained during four specified intervals during the appointment. The behavior of the children during the treatment visits was videotaped and later statistically analyzed using a kinesics/vocalization instrument. Behavioral ratings of cooperation were significantly improved during the treatment visit following diazepam. All interfering bodily movements, patient vocalizations and operator commands for the diazepam group were reduced significantly (p≤0.0001). No significant differences were observed for noninterfering behavioral response. Rectally administered diazepam did not alter blood pressure or pulse significantly in these sedated children when compared to the placebo. These findings indicate that rectal diazepam is an effective sedative agent with minimal effect on the cardiovascular system for the management of the young pediatric dental patient.

In What Sense Are Emotions Evaluations?

Abstract: In this chapter, we first introduce the idea that emotions are evaluations. Next, we explore two approaches attempting to account for this idea in terms of attitudes that are alleged to become emotional when taking evaluative contents. According to the first approach, emotions are evaluative judgments. According to the second, emotions are perceptual experiences of evaluative properties. We explain why this theory remains unsatisfactory insofar as it shares with the evaluative judgement theory the idea that emotions are evaluations in virtue of their contents. We then outline an alternative – the attitudinal theory of emotions. It parts with current theorizing about the emotions in elucidating the fact that emotions are evaluations not in terms of what they represent, but in terms of the attitude subjects take towards what they represent. We explore what sorts of attitudes emotions are and claim that they are felt bodily attitudes.

Well-being and learning in school

Although there are various definitions for the term “well-being,” it is agreed that well-being in school represents a set of subjective feelings and attitudes toward school. Moreover, enjoyment (some use the term “happiness”) is recognized as a core element of well-being in general as well as at school. Well-being in school is defined as an indicator of the quality of scholastic life, and contributes to students’ physical and psychological health and development. As such it is strongly connected to learning. Well-being in school consists of cognitive, emotional, and physical components, i.e., a learner’s thoughts, feelings, and bodily sensations. Consequently, it differs significantly from an individual’s cognitive appraisals like satisfaction, or from discrete positive emotions like enjoyment. Well-being in school can be described through the relationship of positive and negative aspects of school life

Mental Causation versus Physical Causation: No Contest

Common sense supposes thoughts can cause bodily movements and thereby cause changes in where the agent is or how his surroundings are. Many philosophers suppose that any such outcome is realized in a complex state of affairs involving only microparticles; that previous microphysical developments were sufficient to cause that state of affairs; hence that, barring overdetermination, causation by the mental is excluded. This paper argues that the microphysical swarm that realizes the outcome is an accident (Aristotle) or a coincidence (David Owens) and has no cause, though each component movement in it has one. Mental causation faces no competition "from below".

Being Moved by the Self and Others: Influence of Empathy on Self-Motion Perception

BACKGROUND: The observation of conspecifics influences our bodily perceptions and actions: Contagious yawning, contagious itching, or empathy for pain, are all examples of mechanisms based on resonance between our own body and others. While there is evidence for the involvement of the mirror neuron system in the processing of motor, auditory and tactile information, it has not yet been associated with the perception of self-motion. METHODOLOGY/PRINCIPAL FINDINGS: We investigated whether viewing our own body, the body of another, and an object in motion influences self-motion perception. We found a visual-vestibular congruency effect for self-motion perception when observing self and object motion, and a reduction in this effect when observing someone else's body motion. The congruency effect was correlated with empathy scores, revealing the importance of empathy in mirroring mechanisms. CONCLUSIONS/SIGNIFICANCE: The data show that vestibular perception is modulated by agent-specific mirroring mechanisms. The observation of conspecifics in motion is an essential component of social life, and self-motion perception is crucial for the distinction between the self and the other. Finally, our results hint at the presence of a "vestibular mirror neuron system".

Balancing the mind: vestibular induced facilitation of egocentric mental transformations

The body schema is a key component in accomplishing egocentric mental transformations, which rely on bodily reference frames. These reference frames are based on a plurality of different cognitive and sensory cues among which the vestibular system plays a prominent role. We investigated whether a bottom-up influence of vestibular stimulation modulates the ability to perform egocentric mental transformations. Participants were significantly faster to make correct spatial judgments during vestibular stimulation as compared to sham stimulation. Interestingly, no such effects were found for mental transformation of hand stimuli or during mental transformations of letters, thus showing a selective influence of vestibular stimulation on the rotation of whole-body reference frames. Furthermore, we found an interaction with the angle of rotation and vestibular stimulation demonstrating an increase in facilitation during mental body rotations in a direction congruent with rightward vestibular afferents. We propose that facilitation reflects a convergence in shared brain areas that process bottom-up vestibular signals and top-down imagined whole-body rotations, including the precuneus and tempero-parietal junction. Ultimately, our results show that vestibular information can influence higher-order cognitive processes, such as the body schema and mental imagery.

Who is honest and why: Baseline activation in anterior insula predicts inter-individual differences in deceptive behavior

Humans engage in deceptive behavior that negatively affects others. The propensity to deceive is,however, characterized by vast inter-individual heterogeneity that is poorly understood. Attempts to investigate the origins of this heterogeneity have so far mainly relied on subjective measures and have shown little predictive power. Here, we used resting electroencephalography to measure objective and stable individual differences in neural baseline activation in combination with an ecologically valid deception paradigm. Results showed that task-independent baseline activation in the anterior insula, a brain area implicated in mapping internal bodily states and in representing emotional arousal and consciousfeelings, predicts individuals’ propensity for deceptive behavior. The higher the neural baseline activation in this area is, the lower individuals’ propensity to deceive. Moreover, results provide evidence that high baseline activation in the anterior insula is associated with negative affect and dispositional tendencies to avoid aversive emotional situations. These results provide converging neural and psychological evidence that individuals might avoid a deceptive act due to a highly active negative emotional system which would make a deceptive act too stressful and bothersome.

How best to preserve and reveal the structural intricacies of cartilaginous tissue.

No single processing technique is capable of optimally preserving each and all of the structural entities of cartilaginous tissue. Hence, the choice of methodology must necessarily be governed by the nature of the component that is targeted for analysis, for example, fibrillar collagens or proteoglycans within the extracellular matrix, or the chondrocytes themselves. This article affords an insight into the pitfalls that are to be encountered when implementing the available techniques and how best to circumvent them. Adult articular cartilage is taken as a representative pars pro toto of the different bodily types. In mammals, this layer of tissue is a component of the synovial joints, wherein it fulfills crucial and diverse biomechanical functions. The biomechanical functions of articular cartilage have their structural and molecular correlates. During the natural course of postnatal development and after the onset of pathological disease processes, such as osteoarthritis, the tissue undergoes structural changes which are intimately reflected in biomechanical modulations. The fine structural intricacies that subserve the changes in tissue function can be accurately assessed only if they are faithfully preserved at the molecular level. For this reason, a careful consideration of the tissue-processing technique is indispensable. Since, as aforementioned, no single methodological tool is capable of optimally preserving all constituents, the approach must be pre-selected with a targeted structure in view. Guidance in this choice is offered.

Cenesthopathy in adolescence: An appraisal of diagnostic overlaps along the anxiety–hypochondriasis–psychosis spectrum

Objective To discuss the diagnostic validity of unusual bodily perceptions along the spectrum from age-specific, often transitory and normal, to pathological phenomena in adolescence to hypochondriasis and finally to psychosis. Methods Critical literature review of the cornerstone diagnostic groups along the spectrum embracing anxiety and cenesthopathy in adolescence, hypochondriasis, and cenesthopathy and psychosis, followed by a discussion of the diagnostic overlaps along this spectrum. Results The review highlights significant overlaps between the diagnostic cornerstones. It is apparent that adolescents with unusual bodily perceptions may conceptually qualify for more than one diagnostic group along the spectrum. To determine whether cenesthopathies in adolescence mirror emerging psychosis, a number of issues need to be considered, i.e. age and mode of onset, gender, level of functioning and drug use. The role of overvalued ideas at the border between hypochondriasis and psychosis must be considered. Conclusion As unusual bodily symptoms may in some instances meet formal psychosis risk criteria, a narrow understanding of these symptoms may lead to both inappropriate application of the new DSM-5 attenuated psychosis syndrome and of treatment selection. On the other hand, the possibility of a psychotic dimension of unusual bodily symptoms in adolescents must always be considered as most severe expression of the cenesthopathy spectrum.

Declining transition rates to psychosis: The role of diagnostic spectra and symptom overlaps in individuals with attenuated psychosis syndrome

Transition to psychosis in at-risk individuals has markedly declined in recent years. So far it has never been discussed in detail that with the growing awareness and increasing availability of early psychosis services, a much broader diagnostic spectrum is now being seen in these services. Subsequently, subjects present with symptoms that meet psychosis risk on a purely psychometric basis but may be the phenotypical expression of another underlying mental disorder. Here we critically review four groups of symptoms and clinical features that are frequently reported by individuals with suspected psychosis risk states, yet share strong commonalities with other mental disorders and conditions: isolated hallucinations; unusual bodily perceptions, hypochondriatic fears and cenesthetic psychotic symptoms; depersonalization; obsessive–compulsive, overvalued and delusional ideas. Of the 616 individuals so far assessed in the Bruderholz Early Psychosis Outpatient Service for Adolescents and Young Adults, 218 (30.5%) met ultra-high risk (UHR) criteria, 188 (86.2%) of whom suffered from one of the four above-mentioned symptom groups. The appraisal of the diagnostic spectra and their overlapping symptoms constitute a tremendous challenge in the clinical assessment of each referred individual. The final conclusion of a clinical assessment should not end with the mere assignment – or non-assignment – to a presumed psychosis risk group, but needs to take into account the ‘Gestalt’ of these particular symptoms and clinical features and thus be based on many more facets than solely a psychometric or nosological approach. Such an approach may break down the heterogeneous psychosis risk group and enable appropriate treatment regimes.

Interactions between dorsolateral and ventromedial prefrontal cortex underlie context-dependent stimulus valuation in goal-directed choice.

External circumstances and internal bodily states often change and require organisms to flexibly adapt valuation processes to select the optimal action in a given context. Here, we investigate the neurobiology of context-dependent valuation in 22 human subjects using functional magnetic resonance imaging. Subjects made binary choices between visual stimuli with three attributes (shape, color, and pattern) that were associated with monetary values. Context changes required subjects to deviate from the default shape valuation and to integrate a second attribute in order to comply with the goal to maximize rewards. Critically, this binary choice task did not involve any conflict between opposing monetary, temporal, or social preferences. We tested the hypothesis that interactions between regions of dorsolateral and ventromedial prefrontal cortex (dlPFC; vmPFC) implicated in self-control choices would also underlie the more general function of context-dependent valuation. Consistent with this idea, we found that the degree to which stimulus attributes were reflected in vmPFC activity varied as a function of context. In addition, activity in dlPFC increased when context changes required a reweighting of stimulus attribute values. Moreover, the strength of the functional connectivity between dlPFC and vmPFC was associated with the degree of context-specific attribute valuation in vmPFC at the time of choice. Our findings suggest that functional interactions between dlPFC and vmPFC are a key aspect of context-dependent valuation and that the role of this network during choices that require self-control to adjudicate between competing outcome preferences is a specific application of this more general neural mechanism.

Ego depletion after social interference

The present study examines whether social interference (i.e., interference with one’s goal attainment by the bodily presence of others) depletes the limited resource of self-control strength. In an experimental laboratory study (N = 34), half the participants experienced social interference whereas the other half did not experience social interference by two confederates during a dexterity task. Afterwards, we measured participants’ momentary self-control strength applying a Stroop colour-naming task. In line with our prediction, participants’ performance in the Stroop task indicated that social interference reduced self-control strength. We discuss implications for crowding research and crowding in natural settings.