Unconscious discrimination of social cues from eye whites in infants

Human eyes serve two key functions in face-to-face social interactions: they provide cues about a person’s emotional state and attentional focus (gaze direction). Both functions critically rely on the morphologically unique human sclera and have been shown to operate even in the absence of conscious awareness in adults. However, it is not known whether the ability to respond to social cues from scleral information without conscious awareness exists early in human ontogeny and can therefore be considered a foundational feature of human social functioning. In the current study, we used event-related brain potentials (ERPs) to show that 7-mo-old infants discriminate between fearful and nonfearful eyes (experiment 1) and between direct and averted gaze (experiment 2), even when presented below the perceptual threshold. These effects were specific to the human sclera and not seen in response to polarity-inverted eyes. Our results suggest that early in ontogeny the human brain detects social cues from scleral information even in the absence of conscious awareness. The current findings support the view that the human eye with its prominent sclera serves critical communicative functions during human social interactions.Eyes play a key role in human social encounters, as they are critically involved in perceiving others as having minds (1), in attributing mental states to others (2), and in social coordination during face-to-face interactions (3). The presence of eyes has also been shown to increase cooperative behavior in laboratory and in real-world contexts (2, 4–7). The human eye is unique in that it is characterized by a prominent white sclera several times larger than that of other primates (8, 9), which allows for the efficient communication and detection of social information. It is thought that the human sclera is adapted to facilitate interpersonal communication and cooperative interactions among humans (10). When humans observe others’ faces, eyes are typically the first features that are scanned for information (11), and, compared with other primates, humans show a stronger focus on the eye region than on other parts of the face when scanning faces (12, 13). Conversely, failure to devote special attention to the eye region during face perception has been linked to severe social deficits that can, for instance, be observed in autism spectrum disorder (14).One reason why human eyes have such prime importance is that emotion perception, as a vital part of any social interaction, heavily relies on information from the eye region (14). This is especially important for the detection of fear in others, as one of the most basic forms of identifying threatening situations. Fear detection has been observed in response to eyes alone (15, 16). This mechanism operates exceptionally fast (17) and occurs irrespective of conscious awareness (15). On a neural level, the processing of fearful eyes critically depends on the amygdala. Depending on the context (18, 19), fearful eyes can elicit an enhanced activation of the amygdala (20), even if not perceived consciously (15). Patients with bilateral amygdala lesions show deficits in recognizing fear, which disappear when they are instructed to focus on the eye region (21). Furthermore, there is recent evidence to show that the amygdala is involved in reflexively directing attention to the eyes and in predicting gaze to fearful eyes (22, 23).Another important social cue conveyed by the eye is the direction of gaze. Eye gaze can inform us about another person’s attentional focus, thereby providing clues about future behavior (24). Critically, eye gaze and emotion perception have been shown to powerfully interact. For example, fearful eyes elicit stronger behavioral and neural responses when averted from than when directed at an observer (25, 26). This presumably relates to the fact that averted fearful eyes inform an observer about a potential danger in the environment (clear threat), whereas directed fearful eyes signal fear of the observer (ambiguous threat). At the brain level, this also relies on the amygdala, as reflected in a differential activation for direct compared with averted gaze (25, 27). Furthermore, behavioral studies suggest that similar to emotion processing, eye gaze discrimination operates even in the absence of conscious awareness (28).Attending and responding to eyes is thought to play a vital role in the early development of social skills (29). From birth, infants respond sensitively to human eyes: Newborns prefer direct gaze faces over averted gaze faces (30) and even show a rudimentary form of gaze following (31). Newborns’ sensitivity to eyes has been shown to be specific to the human sclera, as behavioral preferences disappear when the contrast polarity of the eye is reversed (32). Nevertheless, the ability to attend to the eyes and follow gaze improves considerably over the course of the first year of life and is viewed as an important marker of healthy social development (33, 34). Indeed, orienting to the eyes is present early in infancy but declines between 2 and 6 mo in infants later diagnosed with autism (29). With respect to responding to emotional information, newborns also show a basic sensitivity to (familiar) emotional facial expressions for which they may also use eye cues (30, 35, 36). However, it is not until the age of 7 mo that they show a robust attentional bias to fear, as reflected in their neural and behavioral responses (37–41). The developmental emergence of this fear bias has been linked to the maturation of frontolimbic circuits (42–45) and occurs at a point in development when infants begin to first experience fear themselves (46, 47). Despite our growing understanding of the developmental origins of emotion and gaze processing in humans, some fundamental questions concerning the exact nature of this ability remain unanswered.In the present study we therefore addressed two key questions, which are essential to understanding the mechanisms that underpin sensitive responding to human eyes in infants. First, we asked whether infants’ detection of social cues such as fear and gaze from eyes occurs in the absence of conscious awareness. Second, we examined whether the detection of these social cues can be seen in response to scleral information alone. To address these questions, we conducted two experiments, based on an established paradigm from adult literature (15), which investigated whether the infant brain can discriminate between fearful and nonfearful eyes (experiment 1) and between direct and averted fearful eyes (experiment 2), even if the stimuli are not perceived consciously. We hypothesized that if the eyes indeed serve a critical function in human social communication, then the unconscious detection of social cues from scleral information should be evident early in ontogeny. Specifically, according to our hypothesis, using event-related brain potentials (ERPs), we expected infants to show evidence for neural discrimination between fearful and nonfearful human eyes (experiment 1) and direct and averted gaze (experiment 2).     

Impact of point-of-care testing for CYP2C19 on platelet inhibition in patients with acute coronary syndrome and early dual antiplatelet therapy in the emergency setting

Aims

Only limited data exist about the role of point of care CYP2C19 testing in the acute setting in the early phase of acute coronary syndromes (ACS). Therefore, the present study was designed to investigate the impact of CYP2C19 loss-of–function point-of-care (POC) genotyping in patients presenting with acute coronary syndromes (ACS) and treated with dual antiplatelet therapy in the emergency setting.

Methods and Results

137 subjects with ACS scheduled for percutaneous coronary intervention were consecutively enrolled. Pre- and on-treatment platelet aggregation was assessed by multiple electrode aggregometry (MEA) after stimulation with adenosine diphosphate (ADP). Patients were loaded according to current guideline adherent indications and contraindications for use of P2Y₁₂ inhibitors in ACS. POC genotyping for CYP2C19*2 was performed in the emergency room after obtaining a buccal swab using the Spartan RX CYP2C19 system and obtaining patient’s informed consent. Prasugrel and ticagrelor treated patients had significantly lower PR compared to clopidogrel-treated patients. The benefits of prasugrel and ticagrelor compared to clopidogrel treated patients in terms of platelet inhibition were more pronounced in CYP2C19*2 carriers. Non-carriers showed similar inhibition regardless of particular P2Y₁₂ inhibitor treatment. Statistical analyses adjusting for factors associated with response (e.g. smoking) revealed that CYP2C19*2 allele carrier status and loading with different type of P2Y12 receptor blockers were significant predictors of on-treatment platelet reactivity in the early phase of ACS.

Conclusion

The results of this pilot study of treatment of patients in the early phase of ACS indicate that CYP2C19*2 POC genotyping might help to identify patients at risk with poor response to clopidogrel treatment, thereby benefiting from reloading and switching to alternative P2Y₁₂ receptor inhibition.     

Energetics of stalk intermediates in membrane fusion are controlled by lipid composition

We have used X-ray diffraction on the rhombohedral phospholipid phase to reconstruct stalk structures in different pure lipids and lipid mixtures with unprecedented resolution, enabling a quantitative analysis of geometry, as well as curvature and hydration energies. Electron density isosurfaces are used to study shape and curvature properties of the bent lipid monolayers. We observe that the stalk structure is highly universal in different lipid systems. The associated curvatures change in a subtle, but systematic fashion upon changes in lipid composition. In addition, we have studied the hydration interaction prior to the transition from the lamellar to the stalk phase. The results indicate that facilitating dehydration is the key to promote stalk formation, which becomes favorable at an approximately constant interbilayer separation of 9.0 ± 0.5 Å for the investigated lipid compositions.