Darwin's Duchenne: Eye constriction during infant joy and distress

Darwin proposed that smiles with eye constriction (Duchenne smiles) index strong positive emotion in infants, while cry-faces with eye constriction index strong negative emotion. Research has supported Darwin's proposal with respect to smiling, but there has been little parallel research on cry-faces (open-mouth expressions with lateral lip stretching). To investigate the possibility that eye constriction indexes the affective intensity of positive and negative emotions, we first conducted the Face-to-Face/Still-Face (FFSF) procedure at 6 months. In the FFSF, three minutes of naturalistic infant-parent play interaction (which elicits more smiles than cry-faces) are followed by two minutes in which the parent holds an unresponsive still-face (which elicits more cry-faces than smiles). Consistent with Darwin's proposal, eye constriction was associated with stronger smiling and with stronger cry-faces. In addition, the proportion of smiles with eye constriction was higher during the positive-emotion eliciting play episode than during the still-face. In parallel, the proportion of cry-faces with eye constriction was higher during the negative-emotion eliciting still-face than during play. These results are consonant with the hypothesis that eye constriction indexes the affective intensity of both positive and negative facial configurations. A preponderance of eye constriction during cry-faces was observed in a second elicitor of intense negative emotion, vaccination injections, at both 6 and 12 months of age. The results support the existence of a Duchenne distress expression that parallels the more well-known Duchenne smile. This suggests that eye constriction-the Duchenne marker-has a systematic association with early facial expressions of intense negative and positive emotion. © 2013 Mattson et al

Kappa Opioid receptor-induced aversion requires p38 MAPK activation in VTA dopamine neurons

The endogenous dynorphin-κ opioid receptor (KOR) system encodes the dysphoric component of the stress response and controls the risk of depression-like and addiction behaviors; however, the molecular and neural circuit mechanisms are not understood. In this study, we report that KOR activation of p38α MAPK in ventral tegmental (VTA) dopaminergic neurons was required for conditioned place aversion (CPA) in mice. Conditional genetic deletion of floxed KOR or floxed p38α MAPK by Cre recombinase expression in dopaminergic neurons blocked place aversion to the KOR agonist U50,488. Selective viral rescue by wild-type KOR expression in dopaminergic neurons of KOR(−/−) mice restored U50,488-CPA, whereas expression of a mutated form of KOR that could not initiate p38α MAPK activation did not. Surprisingly, while p38α MAPK inactivation blocked U50,488-CPA, p38α MAPK was not required for KOR inhibition of evoked dopamine release measured by fast scan cyclic voltammetry in the nucleus accumbens. In contrast, KOR activation acutely inhibited VTA dopaminergic neuron firing, and repeated exposure attenuated the opioid response. This adaptation to repeated exposure was blocked by conditional deletion of p38α MAPK, which also blocked KOR-induced tyrosine phosphorylation of the inwardly rectifying potassium channel (GIRK) subunit Kir3.1 in VTA dopaminergic neurons. Consistent with the reduced response, GIRK phosphorylation at this amino terminal tyrosine residue (Y12) enhances channel deactivation. Thus, contrary to prevailing expectations, these results suggest that κ opioid-induced aversion requires regulation of VTA dopaminergic neuron somatic excitability through a p38α MAPK effect on GIRK deactivation kinetics rather than by presynaptically inhibiting dopamine release. SIGNIFICANCE STATEMENT Kappa opioid receptor (KOR) agonists have the potential to be effective, nonaddictive analgesics, but their therapeutic utility is greatly limited by adverse effects on mood. Understanding how KOR activation produces dysphoria is key to the development of better analgesics and to defining how the endogenous dynorphin opioids produce their depression-like effects. Results in this study show that the aversive effects of κ receptor activation required arrestin-dependent p38α MAPK activation in dopamine neurons but did not require inhibition of dopamine release in the nucleus accumbens. Thus, contrary to the prevailing view, inhibition of mesolimbic dopamine release does not mediate the aversive effects of KOR activation and functionally selective κ opioids that do not activate arrestin signaling may be effective analgesics lacking dysphoric effects

Midgut epithelial endocrine cells are a rich source of the neuropeptides APSGFLGMRamide (Cancer borealis tachykinin-related peptide Ia) and GYRKPPFNGSIFamide (Gly\u3csup\u3e1\u3c/sup\u3e-SIFamide) in the crabs Cancer borealis, Cancer magister and Cancer productus

Over a quarter of a century ago, Mykles described the presence of putative endocrine cells in the midgut epithelium of the crab Cancer magister (Mykles, 1979). In the years that have followed, these cells have been largely ignored and nothing is known about their hormone content or the functions they play in this species. Here, we used a combination of immunohistochemistry and mass spectrometric techniques to investigate these questions. Using immunohistochemistry, we identified both SIFamide-and tachykinin-related peptide (TRP)-like immunopositive cells in the midgut epithelium of C. magister, as well as in that of Cancer borealis and Cancer productus. In each species, the SIFamide-like labeling was restricted to the anterior portion of the midgut, including the paired anterior midgut caeca, whereas the TRP-like immunoreactivity predominated in the posterior midgut and the posterior midgut caecum. Regardless of location, label or species, the morphology of the immunopositive cells matched that of the putative endocrine cells characterized ultrastructurally by Mykles (Mykles, 1979). Matrix-assisted laser desorption/ ionization-Fourier transform mass spectrometry identified the peptides responsible for the immunoreactivities as GYRKPPFNGSIFamide (Gly 1-SIFamide) and APSGFLGMRamide [Cancer boreatis tachykinin-related peptide Ia (CabTRP Ia)], respectively, both of which are known neuropeptides of Cancer species. Although the function of these midgut-derived peptides remains unknown, we found that both Gly1-SIFamide and CabTRP Ia were released when the midgut was exposed to high-potassium saline. In addition, CabTRP Ia was detectable in the hemolymph of crabs that had been held without food for several days, but not in that of fed animals, paralleling results that were attributed to TRP release from midgut endocrine cells in insects. Thus, one function that midgut-derived CabTRP Ia may play in Cancer species is paracrine/hormonal control of feeding-related behavior, as has been postulated for TRPs released from homologous cells in insects

In Support of a Patient-Driven Initiative and Petition to Lower the High Price of Cancer Drugs

Comment in Lowering the High Cost of Cancer Drugs--III. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--I. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--IV. [Mayo Clin Proc. 2016] In Reply--Lowering the High Cost of Cancer Drugs. [Mayo Clin Proc. 2016] US oncologists call for government regulation to curb drug price rises. [BMJ. 2015

An Open Resource for Non-human Primate Imaging.

Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design, and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 25 independent data collections aggregated across 22 sites (total = 217 non-human primates). We also outline the unique pitfalls and challenges that should be considered in the analysis of non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets

Representing Trends and Moment-to-Moment Variability in Dyadic and Family Processes Using State-Space Modeling Techniques

State–space modeling techniques provide a convenient modeling platform for representing systematic trends as well as patterns of intraindividual variability around these trends. Their flexibility in accommodating multivariate processes renders them particularly suited to studying dyadic and family processes that show complex ebbs and flows over time. Using dyadic data collected during the Face-to-Face/Still-Face (FFSF) procedure, examples are provided to explicate the use of state–space models to capture two kinds of changes: systematic trends that are relatively smooth and slow-varying, and transient patterns of intraindividual variability that are manifested on a moment-to-moment basis

Analysis of eye gaze pattern of infants at risk of autism spectrum disorder using Markov models

This paper presents the possibility of using pattern recognition algorithms of infant gaze patterns at six months of age among children at high risk for an autism spectrum disorder (ASD). ASDs, which must be diagnosed by 3 years of age, are characterized by communication and interaction impairments which frequently involve disturbances of visual attention and gaze patterning. We used video cameras to record the face-to-face interactions of 32 infant subjects with their parents. The video was manually coded to determine the eye gaze pattern of infants by marking where the infant was looking in each frame (either at their parent's face or away from their parent's face). In order to identify infants ASD diagnosis at three years, we analyzed infant eye gaze patterns at six months. Variable-order Markov Models (VMM) were used to create models for typically developing comparison children as well as children with an ASD. The models correctly classified infants who did and did not develop an ASD diagnosis with an accuracy rate of 93.75 percent. Employing an assessment tool at a very young age offers the hope of early intervention, potentially mitigating the effects of the disorder throughout the rest of the child's life

A break in parental interaction does not affect the temporal dependency of infant social engagement, but disrupts non-social engagement

Abstract Infant looking patterns during interaction offer an early window into social and nonsocial engagement. Recent evidence indicates that infant looks exhibit temporal dependency—one look duration predicts the next look duration. It is unknown, however, whether temporal dependency emerges as infants structure their own looking or whether it is influenced by interaction. We examined whether a perturbation of social interaction affected temporal dependency. Using the Face-to-Face/Still-Face procedure, we compared temporal dependency during parental interaction (the Face-to-Face & Reunion episodes) to parental non-responsiveness (the Still-Face episode). Overall, the durations of successive infant looks were predictable; past behavior constrained current behavior. The duration of one look at the parent (Face Look) predicted the duration of the next Face Look. Likewise, the duration of a look at any place that was not the parent’s face (Away Look) predicted the duration of the next Away Look. The temporal dependency of Face Looks (social engagement) was unaffected by the Still-Face perturbation, but the temporal dependency of Away Looks (nonsocial engagement) declined during the Still-Face. Infant temporal structuring of engagement during social looking is not dependent on parental interaction while the disruption of interaction affects infants’ structuring of their own non-social engagement

The eyes have it: Making positive expressions more positive and negative expressions more negative.

Facial expressions frequently involve multiple individual facial actions. How do facial actions combine to create emotionally meaningful expressions? Infants produce positive and negative facial expressions at a range of intensities. It may be that a given facial action can index the intensity of both positive (smiles) and negative (cry-face) expressions. Objective, automated measurements of facial action intensity were paired with continuous ratings of emotional valence to investigate this possibility. Degree of eye constriction (the Duchenne marker) and mouth opening were each uniquely associated with smile intensity and, independently, with cry-face intensity. Additionally, degree of eye constriction and mouth opening were each unique predictors of emotion valence ratings. Eye constriction and mouth opening index the intensity of both positive and negative infant facial expressions, suggesting parsimony in the early communication of emotion

The eyes have it: making positive expressions more positive and negative expressions more negative

Facial expressions frequently involve multiple individual facial actions. How do facial actions combine to create emotionally meaningful expressions? Infants produce positive and negative facial expressions at a range of intensities. It may be that a given facial action can index the intensity of both positive (smiles) and negative (cry-face) expressions. Objective, automated measurements of facial action intensity were paired with continuous ratings of emotional valence to investigate this possibility. Degree of eye constriction (the Duchenne marker) and mouth opening were each uniquely associated with smile intensity and, independently, with cry-face intensity. In addition, degree of eye constriction and mouth opening were each unique predictors of emotion valence ratings. Eye constriction and mouth opening index the intensity of both positive and negative infant facial expressions, suggesting parsimony in the early communication of emotion