Preliminary data on oxytocin modulation of neural reactivity in women to emotional stimuli of children depending on childhood emotional neglect.

Sensitivity for rewarding cues and distress signals from children is fundamental to human caregiving and modulated by the neuropeptide oxytocin. In a functional magnetic resonance imaging study, we investigated whether oxytocin regulates neural responses to reward or distress cues form children. In a placebo-controlled, within-subject design, we measured neural responses to positive, negative, and neutral cues from children in 22 healthy female subjects who received oxytocin (24 IU) versus placebo. Further, based on current literature, we hypothesized that oxytocin effects are modulated by experiences of childhood trauma. The task elicited valence-specific effects-positive images activated the ventromedial prefrontal cortex, left anterior cingulate cortex, and right putamen, and images of children in distress activated the bilateral amygdala, hippocampus, and right medial superior frontal cortex. The effects of oxytocin depended on subjective reports of childhood emotional neglect. Self-reported neglect interacted with oxytocin administration in the amygdala, hippocampus, and prefrontal areas. In individuals with higher scores of emotional neglect, oxytocin increased neural reactivity of limbic structures to positive and neutral images. Our findings need replication in larger samples and can therefore be considered preliminary but are in line with the recent literature on the modulating effect of childhood adversity on the sensitivity to oxytocin administration.

Method for analyzing HR-TEM micrographs to propose and/or describe structures and their interaction in crystalline materials.

A general and versatile method for the analysis and processing of HR-TEM data useful for several applications is presented. The first utility is to identify the structures seen in the micrographs; also can be extended to propose the interaction of structure dynamics between various phases; and also it can be hybridized with the chemical method to make a proposal of new structure and/or phase. The general method consisted of four steps: 1) micrograph pretreatment, 2) measurement of planar distances, 3) structure identification, and 4) structure corroboration. Crystallographic planes were immediately identified by comparing the interplanar distances. Next, crystallographic data were collected from the Crystal Structures Database (ICSD) and introduced into Diamond software to visualize the planes in each structure. In addition, from the zone axis point of view it must show the planes aligned, similar as is observed in the HR-TEM micrograph.•It was possible establish the growth mechanism of the different structures by identifying how is the structural interaction between the different oxides and sulfide phases.•Method was successful applied to propose a new TiCoMoS sulfide phase through HR-TEM results.•The method can also be extended to other areas where structural studies with HR-TEM are viable, such as biology, electronics, among others.

Breakdown of utilitarian moral judgement after basolateral amygdala damage.

Most of us would regard killing another person as morally wrong, but when the death of one saves multiple others, it can be morally permitted. According to a prominent computational dual-systems framework, in these life-and-death dilemmas, deontological (nonsacrificial) moral judgments stem from a model-free algorithm that emphasizes the intrinsic value of the sacrificial action, while utilitarian (sacrificial) moral judgments are derived from a model-based algorithm that emphasizes the outcome of the sacrificial action. Rodent decision-making research suggests that the model-based algorithm depends on the basolateral amygdala (BLA), but these findings have not yet been translated to human moral decision-making. Here, in five humans with selective, bilateral BLA damage, we show a breakdown of utilitarian sacrificial moral judgments, pointing at deficient model-based moral decision-making. Across an established set of moral dilemmas, healthy controls frequently sacrifice one person to save numerous others, but BLA-damaged humans withhold such sacrificial judgments even at the cost of thousands of lives. Our translational research confirms a neurocomputational hypothesis drawn from rodent decision-making research by indicating that the model-based algorithm which underlies outcome-based, utilitarian moral judgements in humans critically depends on the BLA.

Stable Anxiety and Depression Trajectories in Late Adolescence for Oral Contraceptive Users.

Background: The use of oral contraceptives (OCs) has been associated with increased incidences of anxiety and depression, for which adolescents seem to be particularly vulnerable. Rather than looking at singular outcomes, we examined whether OC use is associated with depressive and anxiety symptom trajectories from early adolescence into early adulthood. Materials and Methods: Data from 178 girls were drawn from the Research on Adolescent Development and Relationships (RADAR-Y) younger cohort study. We used assessments on 9 waves from age 13 until 24. Developmental trajectories of ratings on the Reynolds Adolescent Depression Scale (RADS-2) and the Screen for Child Anxiety Related Emotional Disorders (SCARED) were compared between never and ever users of OCs. Results: Never users showed increases in depressive and anxiety symptoms in late adolescence, whereas OC users showed a stable level of symptoms throughout adolescence. This effect remained after adjusting for baseline differences between groups in romantic relationships, sexual debut, educational level, smoking, drinking, and drug use. Age of OC use onset did not significantly predict symptom development. Conclusions: OC use in adolescence was related to an altered developmental trajectory of internalizing symptoms, in which OC users did not show an increase in depressive and anxiety symptoms in late adolescence, whereas never users did. The question remains whether this altered symptom trajectory can be considered a protective effect of OC use on psychopathology. Additional research is needed to improve our understanding of the long-term consequences of OC use on mental health.

Oxytocin system gene methylation is associated with empathic responses towards children.

Empathy is an essential component of sensitive caregiving behavior, which in turn is an important predictor of children's healthy social-emotional development. The oxytocin (OXT) system plays a key role in promoting sensitive parenting and empathy. In this study, we investigated how OXT system gene methylation was associated with empathic processes in nulliparous women (M age = 23.60, SD =0.44)-measuring both physiological facial muscle responses and ratings of compassion and positive affect to affective images depicting children. Linear mixed effects analyses demonstrated that lower methylation levels in the OXT and OXTR genes were related to enhanced empathic responses. The effect of OXT system gene methylation on empathic processes was partly qualified by an interaction with individual variations in women's care motivation. Our findings provide experimental evidence for an association between the methylation of OXT system genes and empathy.

Preliminary data on increased reactivity towards children in distress after testosterone administration in women: A matter of protection?

Emotional reactivity to others' distress is a vital prerequisite for a caring response. Testosterone, in contrast, is mostly associated with protection of personal dominance and decreased responsiveness to others' needs. However, experimental work also indicates that rising testosterone levels in response to infant distress can potentially facilitate protection. We assessed the impact of testosterone administration on participants' emotional reactivity to infants in distress, measuring their facial responses on the corrugator supercilii forehead muscle ('frowning') and the zygomaticus major ('smiling') as an index of emotional responses towards children. Moreover, we probed whether the effect of testosterone is moderated by participants' self-reported nurturance and protective tendencies. Our preliminary results showed that testosterone not only increased emotional reactivity to empathy eliciting images of children, but that this increase was strongest in participants with strong protective tendencies. Our administration study is the first to link testosterone to infant protection.

Moral reasoning, moral decision-making, and empathy in Korsakoff's syndrome.

Korsakoff's syndrome (KS) is a neuropsychiatric disorder, caused by a vitamin B1 deficiency. Although it is known that patients with KS display diminished theory of mind functioning and frequently exhibit marked antisocial interactions little attention has so far focused on the integrity of moral decision-making abilities, moral reasoning, and empathy. In an experimental cross-sectional design, 20 patients diagnosed with KS, and twenty age-, education-, and gender-equivalent healthy participants performed tests assessing moral decision-making, moral reasoning maturity, empathy, and executive functioning. Participants were administered the Moral Behaviour Inventory (MBI) for everyday moral dilemmas, and ten cartoons of abstract moral dilemmas. Responses were scored according to the Kohlberg stages of moral reasoning. Empathy and executive functioning were assessed with the Interpersonal Reactivity Index (IRI) and the Frontal Assessment Battery (FAB). In contrast to frontal traumatic brain injury patients, KS patients did not display a utilitarian bias, suggesting preserved moral decision-making abilities. Of interest, KS patients had significantly lower levels of moral reasoning maturity on everyday moral dilemmas, and abstract moral dilemmas. In patients, empathy was moderately related to the level of moral maturity on both tasks, while executive functioning was not. In conclusion, KS patients have preserved moral decision-making abilities, but their moral reasoning abilities are poorer in everyday and abstract situations. Lower moral reasoning abilities and lower levels of empathy together may be responsible for adverse social functioning in KS.

Methylation of oxytocin related genes and early life trauma together shape the N170 response to human faces.

Childhood trauma fundamentally shapes social cognition and basic processing of social cues, which frequently cascade into adverse behavioral outcomes. Recent studies indicate that epigenetic changes in oxytocin functioning might contribute to these long-term effects, although a deeper understanding of the underlying mechanisms is still lacking. The electroencephalographic N170 response to faces might capture a neural response at the core of these interactive effects of oxytocin gene methylation and childhood adversity, given that this response is considered to reflect fundamental face processing, to be susceptible to oxytocin administration and also to be a biomarker of various psychiatric disorders. We assessed the N170 response to neutral faces in relation to participant's (81, women) recalled childhood trauma, methylation of their oxytocin structural (OXTg) and oxytocin receptor (OXTRg) genes, and endogenous levels of cortisol and testosterone. Additionally, we investigated the interactive effect of OXTg methylation and CTQ across three face sets of varying maturity. Methylation of OXTg relates to a weakened N170 response towards adults, children and infants. Moreover, methylation of both OXTRg and OXTg shaped the directionality of adversity effects, predicting a weakened N170 response in those with high methylation and hyper-vigilance with participants with low methylation. Our results are the first to relate OXT(R)g methylation to the N170 response. They shed light on biological processes linking childhood adversity and epigenetic marks to altered behavior and potentially psychopathologies.

Geographical variations in arsenic contents in rice plants from Latin America and the Iberian Peninsula in relation to soil conditions.

Arsenic is a ubiquitous, toxic element that is efficiently accumulated by rice plants. This study assessed the spatial variability in the total As (tAs) contents and organic and inorganic forms in different types of rice, plant parts (husk, stem, leaves and phytoliths) and residues. Samples were collected in different countries in Latin America (Ecuador, Brazil and Peru) and the Iberian Peninsula (Spain and Portugal). The tAs content in commercial polished rice from the Latin American countries was similar (0.130-0.166 mg kg-1) and significantly lower than in the rice from the Iberian countries (0.191 ± 0.066 mg kg-1), and together, the tAs concentration in brown rice (236 ± 0.093 mg kg-1) was significantly higher than in polished and parboiled rice. The inorganic As (iAs) content in rice was similar in both geographical regions, and the aforementioned difference was attributed to dimethylarsinic acid (DMA). The relative abundance of organic species increased as the tAs content in rice grain increased. A meta-analysis of our and previously reported data confirmed the negative correlation between iAs/tAs and tAs. At low tAs concentrations, inorganic forms are dominant, while at higher values (tAs > 0.300 mg kg-1) the concentration of organic As increases substantially and DMA becomes the dominant form in rice grain. On the contrary, inorganic arsenic was always the dominant form, mainly as arsenate [As(V)], in leaves and stems. The presence in soils of high concentrations of amorphous Fe and Al oxides and hydroxides, which are capable of strongly adsorbing oxyanions (i.e. arsenate), was associated with low concentrations of As in rice plants. In addition, the presence of high concentrations of As(V) in stems and leaves, low concentration of As in phytoliths, and the As associated with organic matter in stems and husk, together suggest that rice plants take up more As(V) than As(III).

Functional analysis of the Chloroplast GrpE (CGE) proteins from Arabidopsis thaliana.

The function of proteins depends on specific partners that regulate protein folding, degradation and protein-protein interactions, such partners are the chaperones and cochaperones. In chloroplasts, proteins belonging to several families of chaperones have been identified: chaperonins (Cpn60s), Hsp90s (Hsp90-5/Hsp90C), Hsp100s (Hsp93/ClpC) and Hsp70s (cpHsc70s). Several lines of evidence have demonstrated that cpHsc70 chaperones are involved in molecular processes like protein import, protein folding and oligomer formation that impact important physiological aspects in plants such as thermotolerance and thylakoid biogenesis. Despite the vast amount of data existing around the function of cpHcp70s chaperones, very little attention has been paid to the roles of DnaJ and GrpE cochaperones in the chloroplast. In this study, we performed a phylogenetic analysis of the chloroplastic GrpE (CGE) proteins from 71 species. Based on their phylogenetic relationships and on a motif enrichment analysis, we propose a classification system for land plants' CGEs, which include two independent groups with specific primary structure traits. Furthermore, using in vivo assays we determined that the two CGEs from A. thaliana (AtCGEs) complement the mutant phenotype displayed by a knockout E. coli strain defective in the bacterial grpE gene. Moreover, we determined in planta that the two AtCGEs are bona fide chloroplastic proteins, which form the essential homodimers needed to establish direct physical interactions with the cpHsc70-1 chaperone. Finally, we found evidence suggesting that AtCGE1 is involved in specific physiological phenomena in A. thaliana, such as the chloroplastic response to heat stress, and the correct oligomerization of the photosynthesis-related LHCII complex.

The Basolateral Amygdala Is Essential for Rapid Escape: A Human and Rodent Study.

Rodent research delineates how the basolateral amygdala (BLA) and central amygdala (CeA) control defensive behaviors, but translation of these findings to humans is needed. Here, we compare humans with natural-selective bilateral BLA lesions to rats with a chemogenetically silenced BLA. We find, across species, an essential role for the BLA in the selection of active escape over passive freezing during exposure to imminent yet escapable threat (Timm). In response to Timm, BLA-damaged humans showed increased startle potentiation and BLA-silenced rats demonstrated increased startle potentiation, freezing, and reduced escape behavior as compared to controls. Neuroimaging in humans suggested that the BLA reduces passive defensive responses by inhibiting the brainstem via the CeA. Indeed, Timm conditioning potentiated BLA projections onto an inhibitory CeA pathway, and pharmacological activation of this pathway rescued deficient Timm responses in BLA-silenced rats. Our data reveal how the BLA, via the CeA, adaptively regulates escape behavior from imminent threat and that this mechanism is evolutionary conserved across rodents and humans.

Oxytocin reduces neural activation in response to infant faces in nulliparous young women.

Infant faces have distinctive features that together are described as baby schema, a configuration that facilitates caregiving motivation and behavior, and increases the perception of cuteness. In the current functional magnetic resonance imaging (fMRI) study, we investigated the effect of a within-subjects intranasal oxytocin administration (24 IU) and caregiving motivation on neural responses to infant faces of varying baby schema in 23 healthy nulliparous women. Overall, infant faces elicited activation in several brain regions involved in reward and salience processing, including the ventral tegmental area (VTA), putamen, amygdala, anterior cingulate cortex (ACC), and insula, and this activation was related to self-reported caregiving motivation. Critically, whereas we hypothesized enhanced neural caregiving-related responses after oxytocin administration, we observed reduced activation in the VTA, putamen and amygdala after oxytocin compared to placebo. In nulliparous women, oxytocin has been shown to reduce neural responses in the same regions in response to social stimuli using other paradigms. Oxytocin might affect neural activation toward social stimuli depending on elicited arousal and personal characteristics. The current study is the first to demonstrate this effect in response to infant faces and thereby adds to specify the role of oxytocin in human social information processing.

Ethnic effects when facing children: An ERP study.

Abundant research has highlighted a disadvantage experienced by children of ethnic minority groups in, for example, educational and health care settings. In order to understand implicit attitudes that contribute to ethnic disparities, underlying neural correlates have been widely studied. However, this has been limited to the context of adults. Using a sample of nulliparous Caucasian females (N = 46), the current study is the first to examine how early attentional and facial perceptual processing stages, assessed with event-related brain potentials (ERPs), differentiate for stimuli of young ingroup (of the same ethnicity) or outgroup (of a different ethnicity) children. Additionally, we assessed how a differentiation in ERPs may relate to subsequent adult responsiveness to children by measuring both cuteness ratings and motivation to view child faces. Similar to previous findings for adult facial stimuli, we found significant differences in attentional (N200) and facial perceptual (N170) processing when adults were faced with children of different ethnicities. Furthermore, increased differentiation in attentional processing (N200) for ingroup and outgroup children was associated with reduced cuteness ratings of outgroup children. Importantly however, participants showed no overall preference for ingroup child faces, as motivation to view child faces was even greater towards outgroup child faces. In addition, increased self-reported motivation for parental care was related to enhanced cuteness appraisals of outgroup child faces. Taken together, these findings reveal how early social categorization processes may lead to biased behavior when interacting with children of ethnic minorities.

How Oral Contraceptives Impact Social-Emotional Behavior and Brain Function.

Millions of women worldwide use oral contraceptives ('the pill'; OCs), often starting at a pubertal age when their brains are in a crucial developmental stage. Research into the social-emotional effects of OCs is of utmost importance. In this review, we provide an overview of studies that have emerged over the past decade investigating how OCs, and their main ingredients estradiol (E) and progesterone (P), influence social-emotional behaviors and underlying brain functions. Based on this overview, we present a heuristic model that postulates that OCs modulate core social-emotional behaviors and brain systems. Research domains and challenges for the future, as well as implications, are discussed.

Testosterone Administration Moderates Effect of Social Environment on Trust in Women Depending on Second-to-Fourth Digit Ratio.

Animal research has established that effects of hormones on social behaviour depend on characteristics of both individual and environment. Insight from research on humans into this interdependence is limited, though. Specifically, hardly any prior testosterone experiments in humans scrutinized the interdependency of testosterone with the social environment. Nonetheless, recent testosterone administration studies in humans repeatedly show that a proxy for individuals' prenatal testosterone-to-estradiol ratio, second-to-fourth digit-ratio (2D:4D ratio), influences effects of testosterone administration on human social behaviour. Here, we systematically vary the characteristics of the social environment and show that, depending on prenatal sex hormone priming, testosterone administration in women moderates the effect of the social environment on trust. We use the economic trust game and compare one-shot games modelling trust problems in relations between strangers with repeated games modelling trust problems in ongoing relations between partners. As expected, subjects are more trustful in repeated than in one-shot games. In subjects prenatally relatively highly primed by testosterone, however, this effect disappears after testosterone administration. We argue that impairments in cognitive empathy may reduce the repeated game effect on trust after testosterone administration in subjects with relatively high prenatal testosterone exposure and propose a neurobiological explanation for this effect.

Testosterone reduces functional connectivity during the 'Reading the Mind in the Eyes' Test.

Women on average outperform men in cognitive-empathic abilities, such as the capacity to infer motives from the bodily cues of others, which is vital for effective social interaction. The steroid hormone testosterone is thought to play a role in this sexual dimorphism. Strikingly, a previous study shows that a single administration of testosterone in women impairs performance on the 'Reading the Mind in Eyes' Test (RMET), a task in which emotions have to be inferred from the eye-region of a face. This effect was mediated by the 2D:4D ratio, the ratio between the length of the index and ring finger, a proxy for fetal testosterone. Research in typical individuals, in individuals with autism spectrum conditions (ASC), and in individuals with brain lesions has established that performance on the RMET depends on the left inferior frontal gyrus (IFG). Using functional magnetic resonance imaging (fMRI), we found that a single administration of testosterone in 16 young women significantly altered connectivity of the left IFG with the anterior cingulate cortex (ACC) and the supplementary motor area (SMA) during RMET performance, independent of 2D:4D ratio. This IFG-ACC-SMA network underlies the integration and selection of sensory information, and for action preparation during cognitive empathic behavior. Our findings thus reveal a neural mechanism by which testosterone can impair emotion-recognition ability, and may link to the symptomatology of ASC, in which the same neural network is implicated.

Dissociated neural effects of cortisol depending on threat escapability.

Evolution has provided us with a highly flexible neuroendocrine threat system which, depending on threat imminence, switches between active escape and passive freezing. Cortisol, the "stress-hormone", is thought to play an important role in both fear behaviors, but the exact mechanisms are not understood. Using pharmacological functional magnetic resonance imaging we investigated how cortisol modulates the brain's fear systems when humans are under virtual-predator attack. We show dissociated neural effects of cortisol depending on whether escape from threat is possible. During inescapable threat cortisol reduces fear-related midbrain activity, whereas in anticipation of active escape cortisol boosts activity in the frontal salience network (insula and anterior cingulate cortex), which is involved in autonomic control, visceral perception and motivated action. Our findings suggest that cortisol adjusts the human neural threat system from passive fear to active escape, which illuminates the hormone's crucial role in the adaptive flexibility of fear behaviors.

Simultaneous removal of C and N from fish effluents in filter reactors: Effect of recirculation ratio on the axial distribution of microbial communities.

We simultaneously removed carbon (C) and nitrogen (N) from fish effluents in compact filter reactors operating at different recirculation ratios (RRs) (2, 10 and without recirculation) to demonstrate microbial coexistence and determine the effect of the RR on the axial bacterial stratification. We also examined the global performance of anoxic, anaerobic and aerobic processes. Microbial communities (bacteria and archaea) were analyzed using 16s rRNA amplification followed by DGGE analyses. Their banding profiles were analyzed using ecological parameters and the most representative bands were sequenced. TOC removal was larger than 98% in the three reactors. The total N removal was 48% for the RR-2 reactor, whereas in the RR-10 reactor, there was no N removal due to the absence of nitrification in the final aerobic step. Coexistence and stratification of microorganisms were observed. The microbial communities were correlated with distinct biochemical processes in each reactor fraction. The RR had a large effect on the distribution of the microbial communities. When the RR increased from 2 to 10, the stratification decreased from 60 to 30%, suggesting a close relationship between reactor performance and the presence of nitrifiers. In the RR-10 reactor, the nitrifier concentration was only 4%. Thus, in combined processes, filter reactors should operate with a moderate RR to favor bacterial stratification and improve performance.

Oxytocin reduces neural activity in the pain circuitry when seeing pain in others.

Our empathetic abilities allow us to feel the pain of others. This phenomenon of vicarious feeling arises because the neural circuitry of feeling pain and seeing pain in others is shared. The neuropeptide oxytocin (OXT) is considered a robust facilitator of empathy, as intranasal OXT studies have repeatedly been shown to improve cognitive empathy (e.g. mind reading and emotion recognition). However, OXT has not yet been shown to increase neural empathic responses to pain in others, a core aspect of affective empathy. Effects of OXT on empathy for pain are difficult to predict, because OXT evidently has pain-reducing properties. Accordingly, OXT might paradoxically decrease empathy for pain. Here, using functional neuroimaging we show robust activation in the neural circuitry of pain (insula and sensorimotor regions) when subjects observe pain in others. Crucially, this empathy-related activation in the neural circuitry of pain is strongly reduced after intranasal OXT, specifically in the left insula. OXT on the basis of our neuroimaging data thus remarkably decreases empathy for pain, but further research including behavioral measures is necessary to draw definite conclusions.

Improved memory for reward cues following acute buprenorphine administration in humans.

In rodents, there is abundant evidence for the involvement of the opioid system in the processing of reward cues, but this system has remained understudied in humans. In humans, the happy facial expression is a pivotal reward cue. Happy facial expressions activate the brain's reward system and are disregarded by subjects scoring high on depressive mood who are low in reward drive. We investigated whether a single 0.2mg administration of the mixed mu-opioid agonist/kappa-antagonist, buprenorphine, would influence short-term memory for happy, angry or fearful expressions relative to neutral faces. Healthy human subjects (n38) participated in a randomized placebo-controlled within-subject design, and performed an emotional face relocation task after administration of buprenorphine and placebo. We show that, compared to placebo, buprenorphine administration results in a significant improvement of memory for happy faces. Our data demonstrate that acute manipulation of the opioid system by buprenorphine increases short-term memory for social reward cues.