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Many decisions happen in social contexts such as negotiations, yet little is understood about how people balance fairness versus selfishness. Past investigations found that activation in brain areas involved in executive function and reward processing was associated with people offering less with no threat of rejection from their partner, compared to offering more when there was a threat of rejection. However, it remains unclear how trait reward sensitivity may modulate activation and connectivity patterns in these situations. To address this gap, we used task-based fMRI to examine the relation between reward sensitivity and the neural correlates of bargaining choices. Participants (N = 54) completed the Sensitivity to Punishment (SP)/Sensitivity to Reward (SR) Questionnaire and the Behavioral Inhibition System/Behavioral Activation System scales. Participants performed the Ultimatum and Dictator Games as proposers and exhibited strategic decisions by being fair when there was a threat of rejection, but being selfish when there was not a threat of rejection. We found that strategic decisions evoked activation in the Inferior Frontal Gyrus (IFG) and the Anterior Insula (AI). Next, we found elevated IFG connectivity with the Temporoparietal junction (TPJ) during strategic decisions. Finally, we explored whether trait reward sensitivity modulated brain responses while making strategic decisions. We found that people who scored lower in reward sensitivity made less strategic choices when they exhibited higher AI-Angular Gyrus connectivity. Taken together, our results demonstrate how trait reward sensitivity modulates neural responses to strategic decisions, potentially underscoring the importance of this factor within social and decision neuroscience., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aberrant levels of reward sensitivity have been linked to substance use disorder and are characterized by alterations in reward processing in the ventral striatum (VS). Less is known about how reward sensitivity and subclinical substance use relate to striatal function during social rewards (e.g. positive peer feedback). Testing this relation is critical for predicting risk for development of substance use disorder. In this pre-registered study, participants (N = 44) underwent fMRI while completing well-matched tasks that assess neural response to reward in social and monetary domains. Contrary to our hypotheses, aberrant reward sensitivity blunted the relationship between substance use and striatal activation during receipt of rewards, regardless of domain. Moreover, exploratory whole-brain analyses showed unique relations between substance use and social rewards in temporoparietal junction. Psychophysiological interactions demonstrated that aberrant reward sensitivity is associated with increased connectivity between the VS and ventromedial prefrontal cortex during social rewards. Finally, we found that substance use was associated with decreased connectivity between the VS and dorsomedial prefrontal cortex for social rewards, independent of reward sensitivity. These findings demonstrate nuanced relations between reward sensitivity and substance use, even among those without substance use disorder, and suggest altered reward-related engagement of cortico-VS responses as potential predictors of developing disordered behavior., (© The Author(s) 2024. Published by Oxford University Press.)

Although prior research has demonstrated enhanced striatal response when sharing rewards with close social connections, less is known about how individual differences affect ventral striatal (VS) activation and connectivity when experiencing rewards within social contexts. Given that self-reported reward sensitivity and level of substance use have been associated with differences in VS activation, we set out to investigate whether these factors would be independently associated with enhancements to neural reward responses within social contexts. In this pre-registered study, participants (N=45) underwent fMRI while playing a card guessing game in which correct or incorrect guesses resulted in monetary gains and losses that were shared evenly with either a close friend, stranger (confederate), or non-human partner. Consistent with our prior work, we found increased VS activation when sharing rewards with a socially close peer as opposed to an out-of-network stranger. As self-reported reward sensitivity increased, the difference in VS response to rewards shared with friends and strangers decreased. We also found enhanced connectivity between the VS and temporoparietal junction when sharing rewards with close friends as opposed to strangers. Finally, exploratory analyses revealed that as reward sensitivity and sub-clinical substance use increase, the difference in VS connectivity with the right fusiform face area increases as a function of social context. These findings demonstrate that responsivity to the context of close friends may be tied to individual reward sensitivity or sub-clinical substance use habits; together these factors may inform predictions of risk for future mental health disorders., Competing Interests: Conflict of interest statement The authors declare no competing financial interests.

Perturbations in dopamine system function may increase risk of substance use disorder (SUD). We recently demonstrated that neuromelanin (NM) MRI signal in the substantia nigra, a non-invasive index of dopamine system function, is elevated in long term cocaine users (Cassidy et al., 2020). However, it is unclear whether elevated NM-MRI signal is linked to risk of SUD, or is a byproduct of long-term drug use. Our prior work failed to show relations between NM-MRI signal and functional engagement of ventral striatum during a monetary reward task. However, social experiences are commonly linked to drug use and relapse. Given that, NM-MRI signal may be more closely linked to ventral striatal engagement during social, rather than monetary reward processing. Emerging adults ( n = 33, 21.88 ± 4.35 years) with varying levels of substance abuse, but without SUD, underwent NM-MRI and fMRI during social and monetary reward processing tasks. Voxelwise analysis within the substantia nigra (SN) demonstrated lower NM-MRI signal was associated with more severe substance abuse. Lower right ventral striatal engagement to social reward was also associated with more severe substance abuse. This relation was moderated by SN NM-MRI signal such that diminished striatal response to reward was associated with greater substance abuse among those with low NM-MRI signal, but lower substance abuse among those with high NM-MRI signal. Unexpectedly, higher right ventral striatal engagement during monetary reward was associated with more severe substance abuse. This relation was moderated by SN NM-MRI signal such that greater striatal response to reward was associated with greater substance abuse among those with low NM-MRI signal. Taken together, we provide preliminary evidence that, in emerging adults, low rather than high dopamine system function may increase risk of substance abuse, and strengthen the association between substance use and the brain's sensitivity to social and monetary outcomes in different ways.

This notice sets forth three actions to be taken by the Director, National Institutes of Health (NIH), under the May 7, 1986, NIH Guidelines for Research Involving Recombinant DNA Molecules (51 FR 16958).

The laboratory of which the National Institutes of Health (NIH) is a lineal descendant was founded in 1887. During discussions of our plans for a year-long centennial observance with members of our House and Senate appropriations subcommittees, congressional members urged us to set two specific objectives: making NIH better known to the American people, and presenting the attractions of the many roles in health-related research to young people who have not yet formulated career plans. When I was invited to prepare an article for Science dealing with my personal experiences as director of NIH since April 1982, it seemed an opportunity to address the same objectives for the scientific community, for in my view there is much misinformation and far too much pessimism throughout the country about the state of biomedical research and its support.

The National Institutes of Health has given its highest priority to funding investigator-initiated projects and to minimizing year-to-year fluctuations in the number of new and competing awards. Adequate funding for centers, research contracts, intramural research, and training is also necessary for creation of the science base essential to sustaining the powerful momentum of recent progress. The important question for the future is whether the present system is sufficiently flexible and imaginative to keep pace with the contemporary revolution in science.

The Colloquium on Scientific Authorship was held at the National Institutes of Health (NIH) at a time of extraordinary scrutiny by the public of the ethics of scientists, as represented by intense interest of the press and the Congress of the United States. Indeed, several regulations dealing with scientific misconduct have been proposed during the last year in the Federal Register, and new legislation has been proposed in the Congress. As a result of these concerns, conferences have been organized by the Institute of Medicine, the American Association for the Advancement of Science/American Bar Association, the Council of Biology Editors, and other groups. The colloquium at NIH, which was held May 31, 1988, and sponsored by the Intramural Scientists, focused on publication practices, especially multiple authorship, as contributing to perceived difficulties. The participants suggested various changes in conventions related to authorship that might help prevent future problems.

The origins of the National Institutes of Health (NIH) are linked with European science. Few Americans had participated in the advances in bacteriology led by Koch and Pasteur when a laboratory from which the NIH eventually developed was established in New York in 1887, but its first director patterned this laboratory after ones already established in Germany, France, and England. The era of modern biomedical research in the United States began during World War II with the cooperation of government and nongovernment (mostly academic) research laboratories. Today, the philosophical foundation underlying all research-supporting programs of the NIH is that a close connection exists between improved medical care and research and that any expansion of medical facilities must be accompanied by an expansion of medical training and research. In addition, government grants should not interfere with the freedom and integrity of academic institutions and should allow scientists complete independence in determining the nature, scope, and methodology of their investigations. Discoveries in genetics in the 1950's and 1960's heralded an era of science in which it was necessary to address major questions with immediate relevance to human health. Impelled by pressure from the public, the scientific community, and the Congress, the NIH participates in formulating safety guidelines regarding potential applications of biotechnology. The annual increase in funds appropriated by Congress to the NIH attests to a high level of public commitment to the support of biomedical research and underlines the degree of accountability to which the NIH is subject.

Amidophosphoribosyltransferase (EC 2.4.2.14) has been partially purified from pigeon liver, and ligand-induced alterations in molecular and kinetic properties have been studied. In Tris-HCl buffer the predominant form of the enzyme has an s20,w of 5.9 +/- 0.7, Stokes radium of 42 A, and estimated molecular weight of 102,000. Incubation with phosphoribosylpyrophosphate (PP-ribose-P) results in an increase in the s20,w to 7.9 +/- 0.6, Stokes radius to 53 A, and estimated molecular weight to 172,000. Incubation of this larger form with purine ribonucleotides leads to a decrease in the molecular weight of amidophosphoribosyltransferase that is proportional to the concentration of purine ribonucleotide. Purine ribonucleotides produce sigmoidal kinetics with respect to the substrate PP-ribose-P, with Hill coefficients of 1.4 to 1.6 and 1.8 to 2.0 in the presence of AMP and GMP, respectively. Incubation with 0.6 M KCl leads to sigmoidal kinetics. Hill coefficient of 1.8 and dissociation of the larger form of amidophosphoribosyltransferase. Inorganic phosphate has complex effects upon the enzyme. In 25 mM potassium phosphate buffer the enzyme aggregates to a large form with an s20,w of 8.3 +/- 0.2, Stokes radius of 53 A, and estimated molecular weight of 181,000. Inorganic phosphate and PP-ribose-P both stabilize the enzyme to storage in vitro at 4 degrees. However, inorganic phosphate is 4 times more effective than PP-ribose-P in preventing inactivation of the enzyme by sodium dodecyl sulfate. Inorganic phosphate produces sigmoidal kinetics with respect to PP-ribose-P, Hill coefficient of 1.5. The interaction coefficients for AMP and GMP are reduced from 1.8 to 1.2 and 2.2 to 1.4, respectively, in the presence of 25 mM potassium phosphate. It is concluded that pigeon liver amidophosphoribosyltransferase is a complex allosteric protein whose activity is regulated by a series of conformational changes induced by a number of ligands.