Value-based neural representations predict social decision preferences.

Social decision-making is omnipresent in everyday life, carrying the potential for both positive and negative consequences for the decision-maker and those closest to them. While evidence suggests that decision-makers use value-based heuristics to guide choice behavior, very little is known about how decision-makers' representations of other agents influence social choice behavior. We used multivariate pattern expression analyses on fMRI data to understand how value-based processes shape neural representations of those affected by one's social decisions and whether value-based encoding is associated with social decision preferences. We found that stronger value-based encoding of a given close other (e.g. parent) relative to a second close other (e.g. friend) was associated with a greater propensity to favor the former during subsequent social decision-making. These results are the first to our knowledge to explicitly show that value-based processes affect decision behavior via representations of close others.

Corticostriatal Connectivity during Prosocial Decision-making Relates to Giving Behavior during Adolescence.

Prosocial behavior during adolescence becomes more differentiated based on the recipient of the action as well as the perceived value or benefit, relative to the cost to self, for the recipients. The current study investigated how functional connectivity of corticostriatal networks tracked the value of prosocial decisions as a function of target recipient (caregiver, friend, stranger) and age of the giver, and how they related to giving behavior. Two hundred sixty-one adolescents (9-15 and 19-20 years of age) completed a decision-making task in which they could give money to caregivers, friends, and strangers while undergoing fMRI. Results indicated that adolescents were more likely to give to others as the value of the prosocial decision (i.e., the difference between the benefit to other relative to the cost to self) increased; this effect was stronger for known (caregiver and friends) than unknown targets, and increased with age. Functional connectivity between the nucleus accumbens (NAcc) and OFC increased as the value of the prosocial decisions decreased for strangers, but not for known others, irrespective of choice. This differentiated NAcc-OFC functional connectivity during decision-making as a function of value and target also increased with age. Furthermore, regardless of age, individuals who evinced greater value-related NAcc-OFC functional connectivity when considering giving to strangers relative to known others showed smaller differentiated rates of giving between targets. These findings highlight the role of corticostriatal development in supporting the increasing complexity of prosocial development across adolescence.

Basal ganglia neurons in healthy and parkinsonian primates generate recurring sequences of spikes.

The spiking activity of basal ganglia neurons can be characterized by summary statistics such as the average firing rate, or by measures of firing patterns, such as burst discharges, or oscillatory fluctuations of firing rates. Many of these features are altered by the presence of parkinsonism. This study examined another distinct attribute of firing activity, i.e., the occurrence of repeating sequences of interspike intervals (ISIs). We studied this feature in extracellular electrophysiological recordings that were made in the basal ganglia of rhesus monkeys, before and after they had been rendered parkinsonian by treatment with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neurons in both pallidal segments and in the subthalamic nucleus tended to fire in repeating sequences, typically two ISIs long (i.e., involving three spikes). In recordings that were 5,000 interspike intervals long, 20%-40% of spikes participated in one of many sequences with each ISI replicating the sequence pattern with a timing error of ≤1%. Compared with similar analyses in shuffled representations of the same data, sequences were more common in the original representation of ISIs in all of the tested structures. Induction of parkinsonism reduced the proportion of sequence spikes in the external pallidum but increased it in the subthalamic nucleus. We found no relation between the sequence generation and the firing rate of neurons, and, at most, a weak correlation between sequence generation and the incidence of bursts. We conclude that basal ganglia neurons fire in recognizable sequences of ISIs, whose incidence is influenced by the induction of parkinsonism.NEW & NOTEWORTHY Previous work has shown that the timing of the electrical activity of basal ganglia neurons has nonstochastic properties, resulting in oscillatory firing patterns, or bursting. This article describes another such property in the monkey brain; a surprisingly large proportion of action potentials generated by cells in the extrastriatal basal ganglia are part of precisely timed recurring sequences of spiking events. We also found that the generation of these sequences changes substantially in the parkinsonian state.

A data-driven approach to categorizing early life adversity exposure in the ABCD Study.

BACKGROUND: Adversity occurring during development is associated with detrimental health and quality of life outcomes, not just following exposure but throughout the lifespan. Despite increased research, there exists both overlapping and distinct definitions of early life adversity exposure captured by over 30 different empirically validated tools. A data-driven approach to defining and cataloging exposure is needed to better understand associated outcomes and advance the field. METHODS: We utilized baseline data on 11,566 youth enrolled in the ABCD Study to catalog youth and caregiver-reported early life adversity exposure captured across 14 different measures. We employed an exploratory factor analysis to identify the factor domains of early life adversity exposure and conducted a series of regression analyses to examine its association with problematic behavioral outcomes. RESULTS: The exploratory factor analysis yielded a 6-factor solution corresponding to the following distinct domains: 1) physical and sexual violence; 2) parental psychopathology; 3) neighborhood threat; 4) prenatal substance exposure; 5) scarcity; and 6) household dysfunction. The prevalence of exposure among 9-and 10-year-old youth was largely driven by the incidence of parental psychopathology. Sociodemographic characteristics significantly differed between youth with adversity exposure and controls, depicting a higher incidence of exposure among racial and ethnic minoritized youth, and among those identifying with low socioeconomic status. Adversity exposure was significantly associated with greater problematic behaviors and largely driven by the incidence of parental psychopathology, household dysfunction and neighborhood threat. Certain types of early life adversity exposure were more significantly associated with internalizing as opposed to externalizing problematic behaviors. CONCLUSIONS: We recommend a data-driven approach to define and catalog early life adversity exposure and suggest the incorporation of more versus less data to capture the nuances of exposure, e.g., type, age of onset, frequency, duration. The broad categorizations of early life adversity exposure into two domains, such as abuse and neglect, or threat and deprivation, fail to account for the routine co-occurrence of exposures and the duality of some forms of adversity. The development and use of a data-driven definition of early life adversity exposure is a crucial step to lessening barriers to evidence-based treatments and interventions for youth.

Arsenic in medicine: past, present and future.

Arsenicals are one of the oldest treatments for a variety of human disorders. Although infamous for its toxicity, arsenic is paradoxically a therapeutic agent that has been used since ancient times for the treatment of multiple diseases. The use of most arsenic-based drugs was abandoned with the discovery of antibiotics in the 1940s, but a few remained in use such as those for the treatment of trypanosomiasis. In the 1970s, arsenic trioxide, the active ingredient in a traditional Chinese medicine, was shown to produce dramatic remission of acute promyelocytic leukemia similar to the effect of all-trans retinoic acid. Since then, there has been a renewed interest in the clinical use of arsenicals. Here the ancient and modern medicinal uses of inorganic and organic arsenicals are reviewed. Included are antimicrobial, antiviral, antiparasitic and anticancer applications. In the face of increasing antibiotic resistance and the emergence of deadly pathogens such as the severe acute respiratory syndrome coronavirus 2, we propose revisiting arsenicals with proven efficacy to combat emerging pathogens. Current advances in science and technology can be employed to design newer arsenical drugs with high therapeutic index. These novel arsenicals can be used in combination with existing drugs or serve as valuable alternatives in the fight against cancer and emerging pathogens. The discovery of the pentavalent arsenic-containing antibiotic arsinothricin, which is effective against multidrug-resistant pathogens, illustrates the future potential of this new class of organoarsenical antibiotics.

Frontopolar Cortex Response to Positive Feedback Relates to Nonincentivized Task Persistence.

When individuals make decisions whether to persist at a task, their decision-making is informed by whether success is pending or accomplished. If pending, the brain facilitates behavioral persistence; if the goal is accomplished or no longer desired, the brain enables switching away from the current task. Feedback, which is known to differentially engage reward neurocircuitry, may modulate goal-directed behavior such as task persistence. However, prior studies are confounded by offering external incentives for persistence. This study tested whether neural response to feedback differed as a function of nonincentivized task persistence in 99 human participants ages 13-30 (60 females). Individuals who persisted engaged the frontopolar cortex (FPC) to a greater extent during receipt of task-relevant positive feedback compared with negative feedback. For individuals who quit, task-irrelevant monetary reward engaged the FPC to a greater extent compared with positive feedback. FPC activation in response to positive feedback is identified as a key contributor to task persistence.

Characterizing trajectories of anxiety, depression, and criminal offending in male adolescents over the 5 years following their first arrest.

Youth in the juvenile justice system evince high rates of mental health symptoms, including anxiety and depression. How these symptom profiles change after first contact with the justice system and - importantly - how they are related to re-offending remains unclear. Here, we use latent growth curve modeling to characterize univariate and multivariate growth of anxiety, depression, and re-offending in 1216 male adolescents over 5 years following their first arrest. Overall, the group showed significant linear and quadratic growth in internalizing symptoms and offending behaviors over time such that levels decreased initially after first arrest followed by a small but significant upturn occurring a few years later. Crucially, multivariate growth models revealed strong positive relationships between the rates of growth in internalizing symptoms and offending behaviors such that improvements in mental health related to greater decreases in offending, and vice versa. These results highlight the reciprocal nature of internalizing and externalizing problems in adolescence, underscoring the importance of considering mental health alongside offending in the juvenile justice system.

Connectivity of the corticostriatal and thalamostriatal systems in normal and parkinsonian states: An update.

The striatum receives abundant glutamatergic afferents from the cortex and thalamus. These inputs play a major role in the functions of the striatal neurons in normal conditions, and are significantly altered in pathological states, such as Parkinson's disease. This review summarizes the current knowledge of the connectivity of the corticostriatal and thalamostriatal pathways, with emphasis on the most recent advances in the field. We also discuss novel findings regarding structural changes in cortico- and thalamostriatal connections that occur in these connections as a consequence of striatal loss of dopamine in parkinsonism.

An ArsRC fusion protein enhances arsenate sensing and detoxification.

Arsenical resistance (ars) operons encode genes for arsenic resistance and biotransformation. The majority are composed of individual genes, but fusion of ars genes is not uncommon, although it is not clear if the fused gene products are functional. Here we report identification of a four-gene ars operon from Paracoccus sp. SY that has two arsR-arsC gene fusions. ArsRC1 and ArsRC2 are related proteins that consist of an N-terminal ArsR arsenite (As(III))-responsive repressor with a C-terminal ArsC arsenate reductase. The other two genes in the operon are gapdh and arsJ. GAPDH, glyceraldehyde 3-phosphate dehydrogenase, forms 1-arseno-3-phosphoglycerate (1As3PGA) from 3-phosphoglyceraldehyde and arsenate (As(V)), ArsJ is an efflux permease for 1As3PGA that dissociates into extracellular As(V) and 3-phosphoglycerate. The net effect is As(V) extrusion and resistance. ArsRs are usually selective for As(III) and do not respond to As(V). However, the substrates and products of this operon are pentavalent, which would not be inducers of the operon. We propose that ArsRC fusions overcome this limitation by channelling the ArsC product into the ArsR binding site without diffusion through the cytosol, a de facto mechanism for As(V) induction. This novel mechanism for arsenate sensing can confer an evolutionary advantage for detoxification of inorganic arsenate.