A sensory signature of unaffected biological parents predicts the risk of autism in their offspring.

AIM: Despite the emphasis on sensory dysfunction phenotypes in the revised diagnostic criteria for autism spectrum disorder (ASD), there has been limited research, particularly in the field of neurobiology, investigating the concordance in sensory features between individuals with ASD and their genetic relatives. Therefore, our objective was to examine whether neurobehavioral sensory patterns could serve as endophenotypic markers for ASD. METHODS: We combined questionnaire- and lab-based sensory evaluations with sensory fMRI measures to examine the patterns of sensory responsivity in 30 clinically diagnosed with ASD, 26 matched controls (CON), and 48 biological parents for both groups (27 parents of individuals with ASD [P-ASD] and 21 for individuals with CON [P-CON]). RESULTS: The ASD and P-ASD groups had higher sensory responsivity and rated sensory stimuli as more unpleasant than the CON and P-CON groups, respectively. They also exhibited greater hemodynamic responses within the sensory cortices. Overlapping activations were observed within these sensory cortices in the ASD and P-ASD groups. Using a machine learning approach with robust prediction models across cohorts, we demonstrated that the sensory profile of biological parents accurately predicted the likelihood of their offspring having ASD, achieving a prediction accuracy of 71.4%. CONCLUSIONS: These findings provide support for the hereditary basis of sensory alterations in ASD and suggest a potential avenue to improve ASD diagnosis by utilizing the sensory signature of biological parents, especially in families with a high risk of ASD. This approach holds promising prospects for early detection, even before the birth of the offspring.

Combination therapy with human amniotic epithelial cells and hyaluronic acid promotes immune balance recovery in type 1 diabetic rats through local engraftment.

Stem cell engraftment is currently a promising approach for type 1 diabetes mellitus (T1DM) treatment. In our previous study, engraftment of a combination of human amniotic epithelial cells (hAECs) and hyaluronic acid (HA) showed potent anti-diabetic effect in streptozotocin (STZ)-induced T1DM mice via tail vein injection. Here, we adopted a different route of stem cell delivery, that is via pancreatic subcapsular transplantation. This combined local engraftment of hAECs and HA in STZ-induced T1DM rats showed potent anti-diabetic activity, leading to stronger hypoglycaemia, more intact islet structure and increased number of insulin-positive cells compared with those with hAECs or insulin treatments. Engraftment of hAECs alone increased the proportion of Th1 and T-reg cells and decreased the proportion of Th2 and Th17 cells to protect islet ß cells in STZ-induced T1DM rats, whereas the combined engraftment of hAECs and HA showed more potent regulatory capacity, considerably decreased the level of TNF-α and IL-17 and increased the level of TGF-ß1 compared with those by other treatments. The potent synergistic effect of HA contributed to the recovery of immune balance in the diabetic rat model, thereby suggesting a new strategy for effective treatment of T1DM.

Autoantibody profiling of monoamine oxidase A knockout mice, an autism spectrum disorder model.

Monoamine oxidase A (MAO A) is the critical enzyme to degrade serotonin in the brain and the knockout mouse exhibits hyperserotonemia and abnormalities that are observed in autism spectrum disorder (ASD). Thus, the MAO A knockout mouse is a valuable model for studying neurological and behavioral impairments in ASD. Based on the immune dysfunction hypothesis, dysregulated humoral immunity may cause neurological impairments. To address this hypothesis, we use high-density proteome microarray to profile the serum antibodies in both wild-type and MAO A knockout mice. The distingue autoantibody signatures were observed in the MAO A knockout and wild-type controls and showed 165 up-regulated and 232 down-regulated autoantibodies. The up-regulated autoantibodies were prone to target brain tissues while down-regulated ones were enriched in sex organs. The identified autoantibodies help bridge the gap between ASD mouse models and humoral immunity, not only yielding insights into the pathological mechanisms but also providing potential biomarkers for translational research in ASD.

A network analysis of disordered eating symptoms, big-five personality traits, and psychological distress in Chinese adults.

OBJECTIVE: Previous studies have revealed associations between disordered eating symptoms, big-five personality traits, and psychological distress. However, limited research has explored these relationships as a network, including their interconnections, and even less has done so in non-Western populations. We employed network analysis to investigate the co-occurrence of disordered eating symptoms, big-five personality traits, and psychological distress in Chinese adults. METHOD: A sample of 500 Chinese adults (256 men) completed measures assessing big-five personality traits, psychological distress, and disordered eating symptoms. The network of personality traits, psychological distress, and disordered eating symptoms was estimated, including its central and bridge nodes. RESULTS: The central nodes in the network were the facets of openness (like adventure), extraversion (like going to social and recreational parties), and disordered eating symptoms (dissatisfaction with body weight or shape). Moreover, certain facets of neuroticism (always worrying something bad will happen), psychological distress (feeling worthless), and an inverse facet of extraversion (bored by parties with lots of people) were identified as essential bridge nodes in maintaining the structure of the network. CONCLUSION: Our findings suggest that personality traits (e.g., openness and extraversion) and body dissatisfaction are important in maintaining the network in a community sample of Chinese adults. While future replication is needed, findings from this study suggest that individuals with negative self-thinking, predisposed neuroticism, and extraversion may be at risk of developing disordered eating symptoms. PUBLIC SIGNIFICANCE: The present study contributes to existing knowledge by employing a network perspective to examine the associations between disordered eating symptoms, big-five personality traits, and psychological distress in a Chinese adult community sample. The identified facets of neuroticism and extraversion and symptoms of psychological distress may be worthy of targeting in the prevention and treatment of disordered eating in the Chinese context.

Neuromodulation of the right temporoparietal junction alters amygdala functional connectivity to authority pressure.

Past historical events and experimental research have shown that complying with orders from an authority has a strong impact on harming/destructive behavior, but no one has ever looked into the potential intervention and its neural underpinning to reveal the toll of coercion. We used a paradigm of virtual obedience to authority, in which an experimenter ordered a volunteer to press a handheld button to initiate actions that carried different consequences, including harming or helping others. In this study, we scanned the brain with functional neuroimaging and applied transcranial direct current stimulation (tDCS) to modulate the activation of the right temporoparietal junction (rTPJ) in healthy volunteers in a single-blinded, sham-controlled, crossover trial with anodal, cathodal, and sham stimulation. We observed that cathodal stimulation, compared to anodal and sham stimulation, significantly reduced reaction times (RTs) to initiating harming actions. The effect of tDCS on the rTPJ, orbitofrontal cortex, and anterior cingulate cortex had opposite directions depending on coercive harming or helping actions. Cathodal tDCS-induced changes in the strength of the functional connectivity between the rTPJ and amygdala predicted the effect of cathodal tDCS on harming RTs. The findings provide evidence supporting the rTPJ having a role in coercion-induced changes in the sense of agency. Neuromodulation with tDCS might help in unveiling the power of authority and assisting in the emergence of prosocial behavior, thus shedding light on coping strategies against coercion beyond merely examining its effects.

Exploring the bidirectional relationships between night eating, loss of control eating, and sleep quality in Chinese adolescents: A four-wave cross-lagged study.

OBJECTIVE: This study examined the bidirectional relationships between sleep quality, loss of control (LOC) eating, and night eating in Chinese adolescents using longitudinal data over an 18-month study period. METHOD: Four-waves of data measurement (Waves 1-4), at 6-month intervals, were conducted with 2566 adolescents aged 11-17 years at baseline. A set of questionnaires were used to assess night eating, LOC eating, and sleep quality at each wave of data collection. Cross-lagged models were applied to analyze the bidirectional relationships between night eating, LOC eating, and sleep quality. RESULTS: Results indicated that higher night eating scores consistently predicted poorer sleep quality and higher LOC eating scores at Waves 1, 2, and 3. Furthermore, poorer sleep quality predicted higher night eating scores at Wave 1 and Wave 3, and higher LOC eating scores predicted higher night eating scores at Wave 1 and Wave 2. DISCUSSION: These findings highlight that night eating, LOC eating, and sleep quality were interrelated across time in Chinese adolescents. Improving sleep quality and reducing LOC eating might be promising in the prevention of night eating in adolescents. Similarly, reducing night eating might be promising in improving sleep quality and reducing LOC eating in adolescents. PUBLIC SIGNIFICANCE: This study explored the bidirectional relationship between night eating, LOC eating, and sleep quality in Chinese adolescents using cross-lagged models. Findings indicate bidirectional relationships between these variables and highlight the potential utility in incorporating sleep, LOC eating, and night eating interventions in eating pathology prevention designs for adolescents.

The key to group fitness: The presence of another synchronizes moral attitudes and neural responses during moral decision-making.

Morality encompasses a set of norms that originate from the group's consensus and cultural evolution. Accordingly, the mere presence of another person is very well capable of shaping moral judgment and decision-making in a way that benefits group coherence. Here, we measured justice sensitivity (JSI), implicit moral attitudes (mIAT), and neural activity during mental simulation of interpersonal morally-laden behaviors (helping and harming) when participants were either alone or when they thought a confederate was present. Both JSI and mIAT, as well as various brain networks, were modulated and, further, synchronized by the presence of a confederate. Participants with lower scores on the mIAT and JSI enhanced their moral attitudes when they were in the presence of a confederate. This change was driven by increased signal in the amygdala and anterior insula when the low mIAT participants mentally simulated harming another person, but was effected by decreased activity in the dorsomedial- and dorsolateral-prefrontal cortex in the high JSI participants. The presence of another significantly impacts moral attitudes as well as neural correlates underlying moral behavior. Together, the results support the view that both individual dispositions and social influence shape and synchronize people's moral computations, and fits with the theoretical perspective that morality has evolved to promote group fitness.

Effects of hyaluronic acid on differentiation of human amniotic epithelial cells and cell-replacement therapy in type 1 diabetic mice.

Our hypothesis is that hyaluronic acid may regulate the differentiation of human amniotic epithelial cells (hAECs) into insulin-producing cells and help the treatment of type 1 diabetes. Herein, a protocol for the stepwise in vitro differentiation of hAECs into functional insulin-producing cells was developed by mimicking the process of pancreas development. Treatment of hAECs with hyaluronic acid enhanced their differentiation of definitive endoderm and pancreatic progenitors. Endodermal markers Sox17 and Foxa2 and pancreatic progenitor markers Pax6, Nkx6.1, and Ngn3 were upregulated an enhanced gene expression in hAECs, but hAECs did not express the ß cell-specific transcription factor Pdx1. Interestingly, hyaluronic acid promoted the expression of major pancreatic development-related genes and proteins after combining with commonly used inducers of stem cells differentiation into insulin-producing cells. This indicated the potent synergistic effects of the combination on hAECs differentiation in vitro. By establishing a multiple injection transplantation strategy via tail vein injections, hAECs transplantation significantly reduced hyperglycemia symptoms, increased the plasma insulin content, and partially repaired the islet structure in type 1 diabetic mice. In particular, the combination of hAECs with hyaluronic acid exhibited a remarkable therapeutic effect compared to both the insulin group and the hAECs alone group. The hAECs' paracrine action and hyaluronic acid co-regulated the local immune response, improved the inflammatory microenvironment in the damaged pancreas of type 1 diabetic mice, and promoted the trans-differentiation of pancreatic α cells into ß cells. These findings suggest that hyaluronic acid is an efficient co-inducer of the differentiation of hAECs into functional insulin-producing cells, and hAECs treatment with hyaluronic acid may be a promising cell-replacement therapeutic approach for the treatment of type 1 diabetes.

The development of social comparisons and sharing behavior across 12 countries.

Humans are social beings, and acts of prosocial behavior may be influenced by social comparisons. To study the development of prosociality and the impact of social comparisons on sharing, we conducted experiments with nearly 2500 children aged 3-12 years across 12 countries across five continents. Children participated in a dictator game where they had the opportunity to share up to 10 of their stickers with another anonymous child. Then, children were randomized to one of two treatments. In the "shared a little" treatment children were told that another child from their school had shared 1 sticker, whereas in the "shared a lot" treatment children were told that another child from their school had shared 6 stickers in the same game. There was a strong increase in baseline sharing with age in all countries and in both treatments. The "shared a lot" treatment had a positive treatment effect in increasing sharing overall, which varied across countries. However, cross-cultural comparisons did not yield expected significant differences between collectivist and individualist countries. Our results provide interesting evidence for the development of sharing behavior by age across the world and show that social information about the sharing of peers is important for children's decision making.

microRNA-146a downregulates IL-17 and IL-35 and inhibits proliferation of human periodontal ligament stem cells.

Periodontitis is characterized by increased levels of proinflammatory factors, such as interleukin-17 (IL-17) and IL-35. In this study, the expression of microRNA-146a (miRNA-146a), IL-17, and IL-35 in the plasma of patients with periodontitis and healthy controls were detected by quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. miRNA-146a mimic was transfected into periodontal ligament stem cells (PDLSCs) isolated from periodontitis-affected teeth and healthy teeth. Cell proliferation and expression of IL-17 and IL-35 were detected by cell counting kit-8 assay and Western blot analysis, respectively. It was observed that miRNA-146a was downregulated but IL-17 and IL-35 were upregulated in the plasma of patients with periodontitis than in healthy controls. miRNA-146a was inversely correlated with IL-17 and IL-35 in patients with periodontitis. miRNA-146a overexpression inhibited proliferation of PDLSCs derived from both periodontitis-affected teeth and healthy teeth. miRNA-146a overexpression led to downregulated IL-17 and IL-35 expression in PDLSCs isolated from periodontitis-affected teeth. We, therefore, conclude that miRNA-146a may improve periodontitis by downregulating IL-17 and IL-35 expression and inhibiting proliferation of human PDLSCs.

The development of children's preferences for equality and equity across 13 individualistic and collectivist cultures.

A concern for fairness is a fundamental and universal element of morality. To examine the extent to which cultural norms are integrated into fairness cognitions and influence social preferences regarding equality and equity, a large sample of children (N 2,163) aged 4-11 were tested in 13 diverse countries. Children participated in three versions of a third-party, contextualized distributive justice game between two hypothetical recipients differing in terms of wealth, merit, and empathy. Social decision-making in these games revealed universal age-related shifts from equality-based to equity-based distribution motivations across cultures. However, differences in levels of individualism and collectivism between the 13 countries predicted the age and extent to which children favor equity in each condition. Children from the most individualistic cultures endorsed equitable distributions to a greater degree than children from more collectivist cultures when recipients differed in regards to wealth and merit. However, in an empathy context where recipients differed in injury, children from the most collectivist cultures exhibited greater preferences to distribute resource equitably compared to children from more individualistic cultures. Children from the more individualistic cultures also favored equitable distributions at an earlier age than children from more collectivist cultures overall. These results demonstrate aspects of both cross-cultural similarity and divergence in the development of fairness preferences.

Mismatch negativity (MMN) stands at the crossroads between explicit and implicit emotional processing.

The amygdala is known as a key brain region involved in the explicit and implicit processing of emotional faces, and plays a crucial role in salience detection. Not until recently was the mismatch negativity (MMN), a component of the event-related potentials to an odd stimulus in a sequence of stimuli, utilized as an index of preattentive salience detection of emotional voice processing. However, their relationship remains to be delineated. This study combined the fMRI scanning and event-related potential recording by examining amygdala reactivity in response to explicit and implicit (backward masked) perception of fearful and angry faces, along with recording MMN in response to the fearfully and angrily spoken syllables dada in healthy subjects who varied in trait anxiety (STAI-T). Results indicated that the amplitudes of fearful MMN were positively correlated with left amygdala reactivity to explicit perception of fear, but negatively correlated with right amygdala reactivity to implicit perception of fear. The fearful MMN predicted STAI-T along with left amygdala reactivity to explicit fear, whereas the association between fearful MMN and STAI-T was mediated by right amygdala reactivity to implicit fear. These findings suggest that amygdala reactivity in response to explicit and implicit threatening faces exhibits opposite associations with emotional MMN. In terms of emotional processing, MMN not only reflects preattentive saliency detection but also stands at the crossroads of explicit and implicit perception. Hum Brain Mapp 38:140-150, 2017. © 2016 Wiley Periodicals, Inc.

Testosterone administration in females modulates moral judgment and patterns of brain activation and functional connectivity.

Morality is defined as prescriptive norms regarding how people should treat one another, and includes concepts of fairness, justice, and rights. One recent study with moral dilemmas suggested that testosterone administration increases utilitarian judgments, which depends on second-to-fourth (2D: 4D) digit ratio, as a proxy of prenatal priming. However, the neural mechanism by which acute testosterone modulates moral reasoning remains to be determined. Using a placebo-controlled within-subject design, the current study examined the neuromodulatory effect of testosterone in young females by combining moral dilemmas, 2D: 4D, functional magnetic resonance imaging (fMRI), and subjective ratings of morally laden scenarios. Results showed that testosterone administration elicited more utilitarian responses to evitable dilemmas. The high 2D: 4D group scored more punishments for moral evaluation, whereas the low 2D: 4D group did the opposite. The activity in the amygdala, anterior insular cortex, and dorsolateral prefrontal cortex (dlPFC) was increased when participants evaluated morally unorthodox actions (intentional harm). The activity in the posterior superior temporal sulcus/temporoparietal junction (pSTS/TPJ) to accidental harm was decreased, specific to the high 2D: 4D group. The functional connectivity between the amygdala and dlPFC was reduced. The activity in the pSTS/TPJ to perceived agency predicted utilitarian responses to evitable dilemmas. The findings demonstrate the acute effect of testosterone on neural responses associated with moral judgment, and provide evidence to support that prenatal sex-hormones priming could be important for early neurodevelopment, which plays a crucial role in the neural and behavioral manifestations of testosterone on adult moral reasoning. Hum Brain Mapp 37:3417-3430, 2016. © 2016 Wiley Periodicals, Inc.

Testosterone modulates preattentive sensory processing and involuntary attention switches to emotional voices.

Testosterone is capable of altering facial threat processing. Voices, similar to faces, convey social information. We hypothesized that administering a single dose of testosterone would change voice perception in humans. In a placebo-controlled, randomly assigned, double-blind crossover design, we administered a single dose of testosterone or placebo to 18 healthy female volunteers and used a passive auditory oddball paradigm. The mismatch negativity (MMN) and P3a in responses to fearfully, happily, and neutrally spoken syllables dada and acoustically matched nonvocal sounds were analyzed, indicating preattentive sensory processing and involuntary attention switches. Results showed that testosterone administration had a trend to shorten the peak latencies of happy MMN and significantly enhanced the amplitudes of happy and fearful P3a, whereas the happy- and fearful-derived nonvocal MMN and P3a remained unaffected. These findings demonstrated acute effect of testosterone on the neural dynamics of voice perception. Administering a single dose of testosterone modulates preattentive sensory processing and involuntary attention switches in response to emotional voices.

Atypical mismatch negativity to distressful voices associated with conduct disorder symptoms.

BACKGROUND: Although a general consensus holds that emotional reactivity in youth with conduct disorder (CD) symptoms arises as one of the main causes of successive aggression, it remains to be determined whether automatic emotional processing is altered in this population. METHODS: We measured auditory event-related potentials (ERP) in 20 young offenders and 20 controls, screened for DSM-IV criteria of CD and evaluated using the youth version of Hare Psychopathy Checklist (PCL:YV), State-Trait Anxiety Inventory (STAI) and Barrett Impulsiveness Scale (BIS-11). In an oddball design, sadly or fearfully spoken 'deviant' syllables were randomly presented within a train of emotionally neutral 'standard' syllables. RESULTS: In young offenders meeting with CD criteria, the ERP component mismatch negativity (MMN), presumed to reflect preattentive auditory change detection, was significantly stronger for fearful than sad syllables. No MMN differences for fearful versus sad syllables were observed in controls. Analyses of nonvocal deviants, matched spectrally with the fearful and sad sounds, supported our interpretation that the MMN abnormalities in juvenile offenders were related to the emotional content of sounds, instead of purely acoustic factors. Further, in the young offenders with CD symptoms, strong MMN amplitudes to fearful syllables were associated with high impulsive tendencies (PCL:YV, Factor 2). Higher trait and state anxiety, assessed by STAI, were positively correlated with P3a amplitudes to fearful and sad syllables, respectively. The differences in group-interaction MMN/P3a patterns to emotional syllables and nonvocal sounds could be speculated to suggest that there is a distinct processing route for preattentive processing of species-specific emotional information in human auditory cortices. CONCLUSIONS: Our results suggest that youths with CD symptoms may process distressful voices in an atypical fashion already at the preattentive level. This auditory processing abnormality correlated with increased impulsivity and anxiety. Our results may help to shed light on the neural mechanisms of aggression.

Affective mirror and anti-mirror neurons relate to prosocial help in rats.

Although empathic emotion is closely related to prosocial behavior, neuronal substrate that accounts for empathy-associated prosocial action remains poorly understood. We recorded neurons in the anterior cingulate cortex (ACC) and insular cortex (InC) in rats when they observed another rat in pain. We discovered neurons with anti-mirror properties in the ACC and InC, in addition to those with mirror properties. ACC neurons show higher coupling between activation of self-in-pain and others-in-pain, whereas the InC has a higher ratio of neurons with anti-mirror properties. During others-in-pain, ACC neurons activated more when actively nose-poking toward others and InC neurons activated more when freezing. To further illustrate prosocial function, we examined neuronal activities in the helping behavior test. Both ACC and InC neurons showed specific activation to rat rescuing which is contributed by mirror, but not anti-mirror neurons. Our work indicates the functional involvement of mirror neuron system in prosocial behaviors.

Appetitive traits and body mass index in Chinese adolescents: An 18-month longitudinal study with latent growth curve analyses.

A longitudinal approach with Latent Growth Curve Modeling (LGCM) was adopted to explore the trajectories of appetitive traits corresponding to BMI in Chinese adolescents. Within a large sample of adolescents (N = 2566, 45.9% boys) aged from 11 to 17 years (M = 13.80, SD = 1.56) at the baseline survey, our results indicated that appetitive traits of emotional overeating, food fussiness, and hunger increased significantly over time while enjoyment of food decreased over time. Slowness in eating and satiety responsiveness significantly increased in girls, while emotional undereating significantly decreased in boys. Moreover, the growth parameters of emotional undereating and satiety responsiveness were significantly and negatively related to BMI in girls. Our findings evidence that certain appetitive traits could change over time in adolescence and these changes relate to weight status. Gender differences are suggested in the design of future intervention and treatment of overweight/obesity in Chinese adolescents.

The neural correlates of emotional conflict monitoring as an early manifestation of affective and cognitive declines in persons with Type 2 diabetes.

Patients with Type 2 diabetes are known to be more susceptible to experience dementia and depression/anxiety. The neural circuits of emotional conflict monitoring, as indicated by a Stroop task, might become altered in terms of cognitive and affective impairments in diabetes. This study investigated alterations in the emotional conflict monitoring and associations of corresponding brain activities with metabolic parameters in persons with Type 2 diabetes. Participants with normal cognitive and affective functioning, including 40 persons with Type 2 diabetes and 30 non-diabetes control subjects, underwent a functional MRI paradigm with the face-word emotional Stroop task and detailed cognitive and affective assessments, including the Montreal Cognitive Assessment and Beck Anxiety Inventory. Compared with the controls, people with diabetes exhibited stronger emotional interference, as indicated by differential reaction times between congruent and incongruent trials (Δcon). Δcon was correlated with Montreal Cognitive Assessment test scores and fasting glucose levels. People with diabetes demonstrated altered brain activation and functional connectivity in the neural network for emotional conflict monitoring. The neural network for emotional conflict monitoring mediated the association of pancreatic function with anxiety scores as well as the relationship between Δcon and Montreal Cognitive Assessment scores. Results suggested that alterations in the neural network underlying emotional conflict monitoring might present before clinically measurable cognitive and affective decrements were apparent, thereby bridging the gap between dementia and anxiety/depression in persons with diabetes.

Voice and emotion processing in the human neonatal brain.

Although the voice-sensitive neural system emerges very early in development, it has yet to be demonstrated whether the neonatal brain is sensitive to voice perception. We measured the EEG mismatch response (MMR) elicited by emotionally spoken syllables "dada" along with correspondingly synthesized nonvocal sounds, whose fundamental frequency contours were matched, in 98 full-term newborns aged 1-5 days. In Experiment 1, happy syllables relative to nonvocal sounds elicited an MMR lateralized to the right hemisphere. In Experiment 2, fearful syllables elicited stronger amplitudes than happy or neutral syllables, and this response had no sex differences. In Experiment 3, angry versus happy syllables elicited an MMR, although their corresponding nonvocal sounds did not. Here, we show that affective discrimination is selectively driven by voice processing per se rather than low-level acoustical features and that the cerebral specialization for human voice and emotion processing emerges over the right hemisphere during the first days of life.