Toward a Neural Basis for Social Behavior

Nearly 25 years ago, the shared interests of psychologists and biologists in understanding the neural basis of social behavior led to the inception of social neuroscience. In the past decade, this field has exploded, in large part due to the infusion of studies that use fMRI. At the same time, tensions have arisen about how to prioritize a diverse range of questions and about the authority of neurobiological data in answering them. The field is now poised to tackle some of the most interesting and important questions about human and animal behavior but at the same time faces uncertainty about how to achieve focus in its research and cohesion among the scientists who tackle it. The next 25 years offer the opportunity to alleviate some of these growing pains, as well as the challenge of answering large questions that encompass the nature and bounds of diverse social interactions (in humans, including interactions through the internet); how to characterize, and treat, social dysfunction in psychiatric illness; and how to compare social cognition in humans with that in other animals

Deconstructing Theory-of-Mind Impairment in High-Functioning Adults with Autism

Inferring the beliefs, desires, and intentions of other people (“theory of mind,” ToM) requires specialized psychological processes that represent the minds of others as distinct from our own. ToM is engaged ubiquitously in our everyday social behavior and features a specific developmental trajectory that is notably delayed in children with autism spectrum disorder (ASD). In healthy individuals, model-based analyses of social learning and decision-making have successfully elucidated specific computational components of ToM processing. However, the use of this approach to study ToM impairment in ASD has been extremely limited. To better characterize specific ToM impairment in ASD, we developed a novel learning task and applied model-based analyses in high-functioning adults with ASD and matched healthy controls. After completing a charitable donation task, participants performed a “mentalizer” task in which they observed another person (the agent) complete the same charity task. The mentalizer task probed the participants’ ability to acquire and use ToM representations. To accurately predict agent behavior, participants needed to dynamically track the agent’s beliefs (true or false) about an experimental context that varied over time and use that information to infer the agent’s intentions from their actions. ASD participants were specifically impaired at using their estimates of agent belief to learn agent intentions, though their ability to track agent belief was intact and their reasoning about belief and intentions was rational. Furthermore, model parameters correlated with aspects of social functioning, e.g., ADOS severity scores. Together, these results identify novel, and more specific, targets for future research

Reply to Krueger: Good point, wrong paper

Psycholog

Do Emotion Regulation Intentions and Strategies Differ Between Situations?

Abstract -The present study examined relationships between actual and desired emotional states, meta-beliefs concerning the utility of distinct emotions, and emotion regulation strategies used by individuals in a sport situation as well as an emotion-eliciting situation from a different aspect of their lives. Participants (N = 924) reported their emotions, metabeliefs for optimal emotional states, and their use of emotion regulation strategies across two broad categories of situations: Before sports competition, and a situation from daily life. Results indicated that prior to competition, high activation emotions such as anger, anxiety and excitement were preferred. In terms of strategy use, analyses revealed greater intention to use of strategies intended to increase pleasant and unpleasant emotions were associated with daily life. In conclusion, results indicated that meta-beliefs for optimal emotional states, and strategies used to regulate emotions vary between situations. We suggest that the ability to regulate emotions in a flexible manner to suit the specific dynamics of various situations is proposed to be helpful in the pursuit of personally meaningful goals and that training of a variety of emotion regulation skills could be beneficial

COVID-Dynamic: A Large-Scale Longitudinal Study of Socioemotional and Behavioral Change Across the Pandemic

The COVID-19 pandemic has caused enormous societal upheaval globally. In the US, beyond the devastating toll on life and health, it triggered an economic shock unseen since the great depression and laid bare preexisting societal inequities. The full impacts of these personal, social, economic, and public-health challenges will not be known for years. To minimize societal costs and ensure future preparedness, it is critical to record the psychological and social experiences of individuals during such periods of high societal volatility. Here, we introduce, describe, and assess the COVID-Dynamic dataset, a within-participant longitudinal study conducted from April 2020 through January 2021, that captures the COVID-19 pandemic experiences of \u3e1000 US residents. Each of 16 timepoints combines standard psychological assessments with novel surveys of emotion, social/political/moral attitudes, COVID-19-related behaviors, tasks assessing implicit attitudes and social decision-making, and external data to contextualize participants’ responses. This dataset is a resource for researchers interested in COVID-19-specific questions and basic psychological phenomena, as well as clinicians and policy-makers looking to mitigate the effects of future calamities

Race and reputation: perceived racial group trustworthiness influences the neural correlates of trust decisions

Decisions to trust people with whom we have no personal history can be based on their social reputation-a product of what we can observe about them (their appearance, social group membership, etc.)-and our own beliefs. The striatum and amygdala have been identified as regions of the brain involved in trust decisions and trustworthiness estimation, respectively. However, it is unknown whether social reputation based on group membership modulates the involvement of these regions during trust decisions. To investigate this, we examined blood-oxygenation-level-dependent (BOLD) activity while participants completed a series of single-shot trust game interactions with real partners of varying races. At the time of choice, baseline BOLD responses in the striatum correlated with individuals' trust bias-that is, the overall disparity in decisions to trust Black versus White partners. BOLD signal in the striatum was higher when deciding to trust partners from the race group that the individual participant considered less trustworthy overall. In contrast, activation of the amygdala showed greater BOLD responses to Black versus White partners that scaled with the amount invested. These results suggest that the amygdala may represent emotionally relevant social group information as a subset of the general detection function it serves, whereas the striatum is involved in representing race-based reputations that shape trust decisions

Measuring intracellular pH in the heart using hyperpolarized carbon dioxide and bicarbonate: a 13C and 31P magnetic resonance spectroscopy study

AIMS: Technological limitations have restricted in vivo assessment of intracellular pH (pH(i)) in the myocardium. The aim of this study was to evaluate the potential of hyperpolarized [1-(13)C]pyruvate, coupled with (13)C magnetic resonance spectroscopy (MRS), to measure pH(i) in the healthy and diseased heart. METHODS AND RESULTS: Hyperpolarized [1-(13)C]pyruvate was infused into isolated rat hearts before and immediately after ischaemia, and the formation of (13)CO(2) and H(13)CO(3)(-) was monitored using (13)C MRS. The HCO(3)(-)/CO(2) ratio was used in the Henderson-Hasselbalch equation to estimate pH(i). We tested the validity of this approach by comparing (13)C-based pH(i) measurements with (31)P MRS measurements of pH(i). There was good agreement between the pH(i) measured using (13)C and (31)P MRS in control hearts, being 7.12 +/- 0.10 and 7.07 +/- 0.02, respectively. In reperfused hearts, (13)C and (31)P measurements of pH(i) also agreed, although (13)C equilibration limited observation of myocardial recovery from acidosis. In hearts pre-treated with the carbonic anhydrase (CA) inhibitor, 6-ethoxyzolamide, the (13)C measurement underestimated the (31)P-measured pH(i) by 0.80 pH units. Mathematical modelling predicted that the validity of measuring pH(i) from the H(13)CO(3)(-)/(13)CO(2) ratio depended on CA activity, and may give an incorrect measure of pH(i) under conditions in which CA was inhibited, such as in acidosis. Hyperpolarized [1-(13)C]pyruvate was also infused into healthy living rats, where in vivo pH(i) from the H(13)CO(3)(-)/(13)CO(2) ratio was measured to be 7.20 +/- 0.03. CONCLUSION: Metabolically generated (13)CO(2) and H(13)CO(3)(-) can be used as a marker of cardiac pH(i) in vivo, provided that CA activity is at normal levels

A natural product compound inhibits coronaviral replication in vitro by binding to the conserved Nsp9 SARS-CoV-2 protein

The Nsp9 replicase is a conserved coronaviral protein that acts as an essential accessory component of the multi-subunit viral replication/transcription complex. Nsp9 is the predominant substrate for the essential nucleotidylation activity of Nsp12. Compounds specifically interfering with this viral activity would facilitate its study. Using a native mass-spectrometry-based approach to screen a natural product library for Nsp9 binders, we identified an ent-kaurane natural product, oridonin, capable of binding to purified SARS-CoV-2 Nsp9 with micromolar affinities. By determining the crystal structure of the Nsp9-oridonin complex, we showed that oridonin binds through a conserved site near Nsp9’s C-terminal GxxxG-helix. In enzymatic assays, oridonin’s binding to Nsp9 reduces its potential to act as substrate for Nsp12’s Nidovirus RdRp-Associated Nucleotidyl transferase (NiRAN) domain. We also showed using in vitro cellular assays oridonin, while cytotoxic at higher doses has broad antiviral activity, reducing viral titer following infection with either SARS-CoV-2 or, to a lesser extent, MERS-CoV. Accordingly, these preliminary findings suggest that the oridonin molecular scaffold may have the potential to be developed into an antiviral compound to inhibit the function of Nsp9 during coronaviral replication

Increased oxidative metabolism following hypoxia in the type 2 diabetic heart, despite normal hypoxia signalling and metabolic adaptation

Hypoxia activates the hypoxia-inducible factor (HIF), promoting glycolysis and suppressing mitochondrial respiration. In the type 2 diabetic heart, glycolysis is suppressed whereas fatty acid metabolism is promoted. The diabetic heart experiences chronic hypoxia as a consequence of increased obstructive sleep apnoea and cardiovascular disease. Given the opposing metabolic effects of hypoxia and diabetes, we questioned whether diabetes affects cardiac metabolic adaptation to hypoxia. Control and type 2 diabetic rats were housed for 3 weeks in normoxia or 11% oxygen. Metabolism and function were measured in the isolated perfused heart using radiolabelled substrates. Following chronic hypoxia, both control and diabetic hearts upregulated glycolysis, lactate efflux and glycogen content and decreased fatty acid oxidation rates, with similar activation of HIF signalling pathways. However, hypoxia-induced changes were superimposed on diabetic hearts that were metabolically abnormal in normoxia, resulting in glycolytic rates 30% lower, and fatty acid oxidation 36% higher, in hypoxic diabetic hearts than hypoxic controls. Peroxisome proliferator-activated receptor α target proteins were suppressed by hypoxia, but activated by diabetes. Mitochondrial respiration in diabetic hearts was divergently activated following hypoxia compared with controls. These differences in metabolism were associated with decreased contractile recovery of the hypoxic diabetic heart following an acute hypoxic insult. In conclusion, type 2 diabetic hearts retain metabolic flexibility to adapt to hypoxia, with normal HIF signalling pathways. However, they are more dependent on oxidative metabolism following hypoxia due to abnormal normoxic metabolism, which was associated with a functional deficit in response to stress