Wave-like dopamine dynamics as a mechanism for spatiotemporal credit assignment.

Significant evidence supports the view that dopamine shapes learning by encoding reward prediction errors. However, it is unknown whether striatal targets receive tailored dopamine dynamics based on regional functional specialization. Here, we report wave-like spatiotemporal activity patterns in dopamine axons and release across the dorsal striatum. These waves switch between activational motifs and organize dopamine transients into localized clusters within functionally related striatal subregions. Notably, wave trajectories were tailored to task demands, propagating from dorsomedial to dorsolateral striatum when rewards are contingent on animal behavior and in the opponent direction when rewards are independent of behavioral responses. We propose a computational architecture in which striatal dopamine waves are sculpted by inference about agency and provide a mechanism to direct credit assignment to specialized striatal subregions. Supporting model predictions, dorsomedial dopamine activity during reward-pursuit signaled the extent of instrumental control and interacted with reward waves to predict future behavioral adjustments.

The gender agency gap in fiction writing (1850 to 2010).

Works of fiction play a crucial role in the production of cultural stereotypes. Concerning gender, a widely held presumption is that many such works ascribe agency to men and passivity to women. However, large-scale diachronic analyses of this notion have been lacking. This paper provides an assessment of agency attributions in 87,531 fiction works written between 1850 and 2010. It introduces a syntax-based approach for extracting networks of character interactions. Agency is then formalized as a dyadic property: Does a character primarily serve as an agent acting upon the other character or as recipient acted upon by the other character? Findings indicate that female characters are more likely to be passive in cross-gender relationships than their male counterparts. This difference, the gender agency gap, has declined since the 19th century but persists into the 21st. Male authors are especially likely to attribute less agency to female characters. Moreover, certain kinds of actions, especially physical and villainous ones, have more pronounced gender disparities.

Meaning from movement and stillness: Signatures of coordination dynamics reveal infant agency.

How do human beings make sense of their relation to the world and realize their ability to effect change? Applying modern concepts and methods of coordination dynamics, we demonstrate that patterns of movement and coordination in 3 to 4-mo-olds may be used to identify states and behavioral phenotypes of emergent agency. By means of a complete coordinative analysis of baby and mobile motion and their interaction, we show that the emergence of agency can take the form of a punctuated self-organizing process, with meaning found both in movement and stillness.

Emergence and collapse of reciprocity in semiautomatic driving coordination experiments with humans.

Forms of both simple and complex machine intelligence are increasingly acting within human groups in order to affect collective outcomes. Considering the nature of collective action problems, however, such involvement could paradoxically and unintentionally suppress existing beneficial social norms in humans, such as those involving cooperation. Here, we test theoretical predictions about such an effect using a unique cyber-physical lab experiment where online participants (N = 300 in 150 dyads) drive robotic vehicles remotely in a coordination game. We show that autobraking assistance increases human altruism, such as giving way to others, and that communication helps people to make mutual concessions. On the other hand, autosteering assistance completely inhibits the emergence of reciprocity between people in favor of self-interest maximization. The negative social repercussions persist even after the assistance system is deactivated. Furthermore, adding communication capabilities does not relieve this inhibition of reciprocity because people rarely communicate in the presence of autosteering assistance. Our findings suggest that active safety assistance (a form of simple AI support) can alter the dynamics of social coordination between people, including by affecting the trade-off between individual safety and social reciprocity. The difference between autobraking and autosteering assistance appears to relate to whether the assistive technology supports or replaces human agency in social coordination dilemmas. Humans have developed norms of reciprocity to address collective challenges, but such tacit understandings could break down in situations where machine intelligence is involved in human decision-making without having any normative commitments.

Impaired perception of temporal contiguity between action and effect is associated with disorders of agency in schizophrenia.

Delusions of control in schizophrenia are characterized by the striking feeling that one's actions are controlled by external forces. We here tested qualitative predictions inspired by Bayesian causal inference models, which suggest that such misattributions of agency should lead to decreased intentional binding. Intentional binding refers to the phenomenon that subjects perceive a compression of time between their intentional actions and consequent sensory events. We demonstrate that patients with delusions of control perceived less self-agency in our intentional binding task. This effect was accompanied by significant reductions of intentional binding as compared to healthy controls and patients without delusions. Furthermore, the strength of delusions of control tightly correlated with decreases in intentional binding. Our study validated a critical prediction of Bayesian accounts of intentional binding, namely that a pathological reduction of the prior likelihood of a causal relation between one's actions and consequent sensory events-here captured by delusions of control-should lead to lesser intentional binding. Moreover, our study highlights the import of an intact perception of temporal contiguity between actions and their effects for the sense of agency.

The Role of Agentive and Physical Forces in the Neural Representation of Motion Events.

How does the brain represent information about motion events in relation to agentive and physical forces? In this study, we investigated the neural activity patterns associated with observing animated actions of agents (e.g., an agent hitting a chair) in comparison to similar movements of inanimate objects that were either shaped solely by the physics of the scene (e.g., gravity causing an object to fall down a hill and hit a chair) or initiated by agents (e.g., a visible agent causing an object to hit a chair). Using an fMRI-based multivariate pattern analysis (MVPA), this design allowed testing where in the brain the neural activity patterns associated with motion events change as a function of, or are invariant to, agentive versus physical forces behind them. A total of 29 human participants (nine male) participated in the study. Cross-decoding revealed a shared neural representation of animate and inanimate motion events that is invariant to agentive or physical forces in regions spanning frontoparietal and posterior temporal cortices. In contrast, the right lateral occipitotemporal cortex showed a higher sensitivity to agentive events, while the left dorsal premotor cortex was more sensitive to information about inanimate object events that were solely shaped by the physics of the scene.

Neural correlates of an illusionary sense of agency caused by virtual reality.

Sense of agency (SoA) is the sensation that self-actions lead to ensuing perceptual consequences. The prospective mechanism emphasizes that SoA arises from motor prediction and its comparison with actual action outcomes, while the reconstructive mechanism stresses that SoA emerges from retrospective causal processing about the action outcomes. Consistent with the prospective mechanism, motor planning regions were identified by neuroimaging studies using the temporal binding (TB) effect, a behavioral measure often linked to implicit SoA. Yet, TB also occurs during passive observation of another's action, lending support to the reconstructive mechanism, but its neural correlates remain unexplored. Here, we employed virtual reality (VR) to modulate such observation-based SoA and examined it with functional magnetic resonance imaging (fMRI). After manipulating an avatar hand in VR, participants passively observed an avatar's "action" and showed a significant increase in TB. The binding effect was associated with the right angular gyrus and inferior parietal lobule, which are critical nodes for inferential and agency processing. These results suggest that the experience of controlling an avatar may potentiate inferential processing within the right inferior parietal cortex and give rise to the illusionary SoA without voluntary action.

My choice, my actions: self-determination, not instrumental value of outcomes enhances outcome monitoring during learning.

Freedom of choice enhances our sense of agency. During goal-directed behavior, the freedom to choose between different response options increases the neural processing of positive and negative feedback, indicating enhanced outcome monitoring under conditions of high agency experience. However, it is unclear whether this enhancement is predominantly driven by an increased salience of self- compared to externally determined action outcomes or whether differences in the perceived instrumental value of outcomes contribute to outcome monitoring in goal-directed tasks. To test this, we recorded electroencephalography while participants performed a reinforcement learning task involving free choices, action-relevant forced choices, and action-irrelevant forced choices. We observed larger midfrontal theta power and N100 amplitudes for feedback following free choices compared with action-relevant and action-irrelevant forced choices. In addition, a Reward Positivity was only present for free but not forced choice outcomes. Crucially, our results indicate that enhanced outcome processing is not driven by the relevance of outcomes for future actions but rather stems from the association of outcomes with recent self-determined choice. Our findings highlight the pivotal role of self-determination in tracking the consequences of our actions and contribute to an understanding of the cognitive processes underlying the choice-induced facilitation in outcome monitoring.

The importance of race, gender, and religion in naturalization adjudication in the United States.

This study presents an empirical investigation of naturalization adjudication in the United States using new administrative data on naturalization applications decided by the US Citizenship and Immigration Services between October 2014 and March 2018. We find significant group disparities in naturalization approvals based on applicants' race/ethnicity, gender, and religion, controlling for individual applicant characteristics, adjudication years, and variation between field offices. Non-White applicants and Hispanic applicants are less likely to be approved than non-Hispanic White applicants, male applicants are less likely to be approved than female applicants, and applicants from Muslim-majority countries are less likely to be approved than applicants from other countries. In addition, race/ethnicity, gender, and religion interact to produce a certain group hierarchy in naturalization approvals. For example, the probability of approval for Black males is 5 percentage points smaller than that of White females. The probability of approval for Blacks from Muslim-majority countries is 9 percentage points smaller than that of Whites from other countries. The probability of approval for females from Muslim-majority countries is 6 percentage points smaller than that of females from other countries. This study contributes to our understanding of the nature of inequalities present in agency decision-making in the naturalization process.

Temporal Dynamics of Brain Activity Predicting Sense of Agency over Muscle Movements.

Our muscles are the primary means through which we affect the external world, and the sense of agency (SoA) over the action through those muscles is fundamental to our self-awareness. However, SoA research to date has focused almost exclusively on agency over action outcomes rather than over the musculature itself, as it was believed that SoA over the musculature could not be manipulated directly. Drawing on methods from human-computer interaction and adaptive experimentation, we use human-in-the-loop Bayesian optimization to tune the timing of electrical muscle stimulation so as to robustly elicit a SoA over electrically actuated muscle movements in male and female human subjects. We use time-resolved decoding of subjects' EEG to estimate the time course of neural activity which predicts reported agency on a trial-by-trial basis. Like paradigms which assess SoA over action consequences, we found that the late (post-conscious) neural activity predicts SoA. Unlike typical paradigms, however, we also find patterns of early (sensorimotor) activity with distinct temporal dynamics predicts agency over muscle movements, suggesting that the "neural correlates of agency" may depend on the level of abstraction (i.e., direct sensorimotor feedback versus downstream consequences) most relevant to a given agency judgment. Moreover, fractal analysis of the EEG suggests that SoA-contingent dynamics of neural activity may modulate the sensitivity of the motor system to external input.SIGNIFICANCE STATEMENT The sense of agency, the feeling of "I did that," when directing one's own musculature is a core feature of human experience. We show that we can robustly manipulate the sense of agency over electrically actuated muscle movements, and we investigate the time course of neural activity that predicts the sense of agency over these actuated movements. We find evidence of two distinct neural processes: a transient sequence of patterns that begins in the early sensorineural response to muscle stimulation and a later, sustained signature of agency. These results shed light on the neural mechanisms by which we experience our movements as volitional.

Decision-Making at Swissmedic, the Swiss Regulatory Agency, with a Focus on (Neo)adjuvant Cancer Treatments.

INTRODUCTION: Additional considerations are required for the benefit-risk assessment of new drugs or indications in the setting of (neo)adjuvant cancer treatment as compared to the metastatic/advanced setting, possibly leading to different decision patterns for the (neo)adjuvant versus the metastatic and advanced setting within a health authority but also among different health authorities. METHODS: We analyzed regulatory decisions at the Swiss Agency for Therapeutic Products Swissmedic (SMC) for all oncology indications (mostly metastatic indications) and indications in the (neo)adjuvant setting and compared these to decisions taken by the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA). RESULTS: Comparing the positive and negative decisions within SMC between July 2017 and December 2021, the approval rates were with 66.7% lower for (neo)adjuvant indications versus 88.4% in the metastatic and advanced indications. While the approval rates for metastatic and advanced new active substances (NAS) applications were similar at SMC as compared to the EMA and the FDA, they were lower for (neo)adjuvant applications at SMC as compared to the EMA and the FDA. The underlying reason in all cases with divergent decisions at SMC as compared to EMA and FDA was that no overall survival benefit as compared to control arm has been observed in the submitted data package. CONCLUSION: Approval and consensus decision rates at SMC in comparison to EMA and FDA were lower for (neo)adjuvant indications but not for advanced and metastastic NAS oncology indications.

Sensitivity to the Instrumental Value of Choice Increases Across Development.

Across development, people tend to demonstrate a preference for contexts in which they have the opportunity to make choices. However, it is not clear how children, adolescents, and adults learn to calibrate this preference based on the costs and benefits of agentic choice. Here, in both a primary, in-person, reinforcement-learning experiment (N = 92; age range = 10-25 years) and a preregistered online replication study (N = 150; age range = 8-25 years), we found that participants overvalued agentic choice but also calibrated their agency decisions to the reward structure of the environment, increasingly selecting agentic choice when choice had greater instrumental value. Regression analyses and computational modeling of participant choices revealed that participants' bias toward agentic choice-reflecting its intrinsic value-remained consistent across age, whereas sensitivity to the instrumental value of agentic choice increased from childhood to early adulthood.

Testosterone, gender identity and gender-stereotyped personality attributes.

Sex/gender differences in personality associated with gender stereotyped behavior are widely studied in psychology yet remain a subject of ongoing debate. Exposure to testosterone during developmental periods is considered to be a primary mediator of many sex/gender differences in behavior. Extensions of this research has led to both lay beliefs and initial research about individual differences in basal testosterone in adulthood relating to "masculine" personality. In this study, we explored the relationships between testosterone, gender identity, and gender stereotyped personality attributes in a sample of over 400 university students (65 % female assigned at birth). Participants provided ratings of their self-perceived masculinity and femininity, resulting in a continuous measure of gender identity, and a set of agentic and communal personality attributes. A saliva sample was also provided for assay of basal testosterone. Results showed no compelling evidence that basal testosterone correlates with gender-stereotyped personality attributes or explains the relationship between sex/gender identity and these attributes, across, within, or covarying out sex assigned at birth. Contributing to a more gender diverse approach to assessing sex/gender relationships with personality and testosterone, our continuous measure of self-perceived masculinity and femininity predicted additional variance in personality beyond binary sex and showed some preliminary but weak relationships with testosterone. Results from this study cast doubt on the activational testosterone-masculinity hypothesis for explaining sex differences in gender stereotyped traits and within-sex/gender variation in attributes associated with agency and communality.

What AHRQ Learned While Working to Transform Primary Care.

Building on previous efforts to transform primary care, the Agency for Healthcare Research and Quality (AHRQ) launched EvidenceNOW: Advancing Heart Health in 2015. This 3-year initiative provided external quality improvement support to small and medium-size primary care practices to implement evidence-based cardiovascular care. Despite challenges, results from an independent national evaluation demonstrated that the EvidenceNOW model successfully boosted the capacity of primary care practices to improve quality of care, while helping to advance heart health. Reflecting on AHRQ's own learnings as the funder of this work, 3 key lessons emerged: (1) there will always be surprises that will require flexibility and real-time adaptation; (2) primary care transformation is about more than technology; and (3) it takes time and experience to improve care delivery and health outcomes. EvidenceNOW taught us that lasting practice transformation efforts need to be responsive to anticipated and unanticipated changes, relationship-oriented, and not tied to a specific disease or initiative. We believe these lessons argue for a national primary care extension service that provides ongoing support for practice transformation.

Brain Networks, Neurotransmitters and Psychedelics: Towards a Neurochemistry of Self-Awareness.

PURPOSE OF REVIEW: Self-awareness can be defined as the capacity of becoming the object of one's own awareness and, increasingly, it has been the target of scientific inquiry. Self-awareness has important clinical implications, and a better understanding of the neurochemical basis of self-awareness may help clarifying causes and developing interventions for different psychopathological conditions. The current article explores the relationship between neurochemistry and self-awareness, with special attention to the effects of psychedelics. RECENT FINDINGS: The functioning of self-related networks, such as the default-mode network and the salience network, and how these are influenced by different neurotransmitters is discussed. The impact of psychedelics on self-awareness is reviewed in relation to specific processes, such as interoception, body ownership, agency, metacognition, emotional regulation and autobiographical memory, within a framework based on predictive coding. Improved outcomes in emotional regulation and autobiographical memory have been observed in association with the use of psychedelics, suggesting higher-order self-awareness changes, which can be modulated by relaxation of priors and improved coping mechanisms linked to cognitive flexibility. Alterations in bodily self-awareness are less consistent, being potentially impacted by doses employed, differences in acute/long-term effects and the presence of clinical conditions. Future studies investigating the effects of different molecules in rebalancing connectivity between resting-state networks may lead to novel therapeutic approaches and the refinement of existing treatments.

Recent advances in hepatitis E virus research and the Japanese clinical practice guidelines for hepatitis E virus infection.

Acute hepatitis E was considered rare until reports emerged affirming the existence of hepatitis E virus (HEV) genotypes 3 and 4 infections in Japan in the early 2000s. Extensive studies by Japanese researchers have highlighted the pivotal role of pigs and wild animals, such as wild boars and deer, as reservoirs for HEV, linking them to zoonotic infections in Japan. Currently, when hepatitis occurs subsequent to the consumption of undercooked or grilled pork, wild boar meat, or offal (including pig liver and intestines), HEV infection should be considered. Following the approval of anti-HEV immunoglobulin A antibody as a diagnostic tool for hepatitis E by Japan's Health Insurance System in 2011, the annual number of diagnosed cases of HEV infection has surged. Notably, the occurrence of post-transfusion hepatitis E promoted nationwide screening of blood products for HEV using nucleic acid amplification tests since 2020. Furthermore, chronic hepatitis E has been observed in immunosuppressed individuals. Considering the significance of hepatitis E, heightened preventive measures are essential. The Japan Agency for Medical Research and Development Hepatitis A and E viruses (HAV and HEV) Study Group, which includes special virologists and hepatologists, held a virtual meeting on February 17, 2024. Discussions encompassed pathogenesis, transmission routes, diagnosis, complications, severity factors, and ongoing and prospective vaccination or treatments for hepatitis E. Rigorous assessment of referenced studies culminated in the formulation of recommendations, which are detailed within this review. This comprehensive review presents recent advancements in HEV research and Japanese clinical practice guidelines for HEV infection.

Effect of multidisciplinary cooperative continuous nursing and psychological nursing on multiple myeloma with a peripherally inserted central catheter.

Objective: This study was conducted to analyze the effectiveness of multidisciplinary cooperative continuous nursing combined with psychological nursing intervention in multiple myeloma (MM) patients undergoing peripherally inserted central catheter (PICC). Methods: The Numerical Pain Rating Scale (NPRS), Anxiety Self-Assessment Scale (SAS), Depression Self-Assessment Scale (SDS) and Revised Piper Fatigue Scale (PFS-R), Self-Care Ability Scale (ESCA), Quality of Life Core Questionnaire (QLQ-C30), incidence of unplanned extubation of PICC, total incidence of catheter-related complications and satisfaction with nursing were compared between the two groups of patients in a prospective study. Results: Patients in the observation group had reduced NPRS, SAS, SDS and PFS-R scores, total incidence of unplanned extubation of PICC and the total incidence of catheter-related complications, and a higher nursing satisfaction rate in comparison to those in the control group. Conclusion: Multidisciplinary cooperative continuous nursing combined with psychological nursing interventions can relieve pain in MM patients.

Financial incentives and prescribing behavior in primary care.

Many healthcare systems prohibit primary care physicians from dispensing the drugs they prescribe due to concerns that this encourages excessive, ineffective or unnecessarily costly prescribing. Using data from the English National Health Service for 2011-2018, we estimate the impact of physician dispensing rights on prescribing behavior at the extensive margin (comparing practices that dispense and those that do not) and the intensive margin (comparing practices with different proportions of patients to whom they dispense). We control for practices selecting into dispensing based on observable (OLS, entropy balancing) and unobservable practice characteristics (2SLS). We find that physician dispensing increases drug costs per patient by 3.1%, due to more, and more expensive, drugs being prescribed. Reimbursement is partly based on a fixed fee per package dispensed and we find that dispensing practices prescribe smaller packages. As the proportion of the practice population for whom they can dispense increases, dispensing practices behave more like non-dispensing practices.

Harmonizing regulatory market approval of products with high safety requirements: Evidence from the European pharmaceutical market.

We causally analyzed whether being a member of the European Union (EU) and having access to a centralized marketing authorization procedure (centralized procedure [CP]) affects availability and time to launch of new pharmaceuticals. We employed multiple difference-in-differences models, exploiting the eastern enlargement of the EU as well as changes in the indications that fall within the compulsory or voluntary scope of the CP. Results showed that countries experienced a mean decrease in launch delay of 10.9 months (p = 0.004) after joining the EU. Effects were higher among pharmaceuticals that belong to indications that might voluntarily participate in the CP but are not obliged to. These are often financially less attractive to manufacturers than pharmaceuticals within the compulsory scope. Availability of new pharmaceuticals launched remained unaffected. We found signs that the magnitude of the country-specific effect of centralized marketing authorization on launch delay may be influenced by strategic decisions of manufacturers at the national level (e.g., parallel trade or reference pricing).

An investigation of the experience of control through the sense of agency in people with obsessive-compulsive disorder: a review and meta-analysis.

The construct of sense of agency (SoA) has proven useful for understanding mechanisms underlying obsessive-compulsive disorder (OCD) phenomenology, especially in explaining the apparent dissociation in OCD between actual and perceived control over one's actions. Paradoxically, people with OCD appear to experience both diminished SoA (feeling unable to control their actions) and inflated SoA (having "magical" control over events). The present review investigated the extent to which the SoA is distorted in OCD, in terms of both implicit (ie, inferred from correlates and outcomes of voluntary actions) and explicit (ie, subjective judgment of one's control over an outcome) measures of SoA. Our search resulted in 15 studies that met the criteria for inclusion in a meta-analysis, where we also examined the potential moderating effects of the type of measure (explicit versus implicit) and of the actual control participants had over the outcome. We found that participants with OCD or with high levels of OCD symptoms show lower implicit measures of SoA and at the same time tend to overestimate their control in situations where they do not actually have it. Together, these findings support the hypothesized dissociation in OCD between actual and perceived control over one's actions.