Neural signals predict information sharing across cultures.

Information sharing influences which messages spread and shape beliefs, behavior, and culture. In a preregistered neuroimaging study conducted in the United States and the Netherlands, we demonstrate replicability, predictive validity, and generalizability of a brain-based prediction model of information sharing. Replicating findings in Scholz et al., Proc. Natl. Acad. Sci. U.S.A. 114, 2881-2886 (2017), self-, social-, and value-related neural signals in a group of individuals tracked the population sharing of US news articles. Preregistered brain-based prediction models trained on Scholz et al. (2017) data proved generalizable to the new data, explaining more variance in population sharing than self-report ratings alone. Neural signals (versus self-reports) more reliably predicted sharing cross-culturally, suggesting that they capture more universal psychological mechanisms underlying sharing behavior. These findings highlight key neurocognitive foundations of sharing, suggest potential target mechanisms for interventions to increase message effectiveness, and advance brain-as-predictor research.

Mindful attention promotes control of brain network dynamics for self-regulation and discontinues the past from the present.

Mindful attention is characterized by acknowledging the present experience as a transient mental event. Early stages of mindfulness practice may require greater neural effort for later efficiency. Early effort may self-regulate behavior and focalize the present, but this understanding lacks a computational explanation. Here we used network control theory as a model of how external control inputs-operationalizing effort-distribute changes in neural activity evoked during mindful attention across the white matter network. We hypothesized that individuals with greater network controllability, thereby efficiently distributing control inputs, effectively self-regulate behavior. We further hypothesized that brain regions that utilize greater control input exhibit shorter intrinsic timescales of neural activity. Shorter timescales characterize quickly discontinuing past processing to focalize the present. We tested these hypotheses in a randomized controlled study that primed participants to either mindfully respond or naturally react to alcohol cues during fMRI and administered text reminders and measurements of alcohol consumption during 4 wk postscan. We found that participants with greater network controllability moderated alcohol consumption. Mindful regulation of alcohol cues, compared to one's own natural reactions, reduced craving, but craving did not differ from the baseline group. Mindful regulation of alcohol cues, compared to the natural reactions of the baseline group, involved more-effortful control of neural dynamics across cognitive control and attention subnetworks. This effort persisted in the natural reactions of the mindful group compared to the baseline group. More-effortful neural states had shorter timescales than less effortful states, offering an explanation for how mindful attention promotes being present.

A neural signature of the vividness of prospective thought is modulated by temporal proximity during intertemporal decision making.

Why do people discount future rewards? Multiple theories in psychology argue that one reason is that future events are imagined less vividly than immediate events, thereby diminishing their perceived value. Here we provide neuroscientific evidence for this proposal. First, we construct a neural signature of the vividness of prospective thought, using an fMRI dataset where the vividness of imagined future events is orthogonal to their valence by design. Then, we apply this neural signature in two additional fMRI datasets, each using a different delay-discounting task, to show that neural measures of vividness decline as rewards are delayed farther into the future.

Overlapping Functional Representations of Self- and Other-Related Thought are Separable Through Multivoxel Pattern Classification.

Self-reflection and thinking about the thoughts and behaviors of others are important skills for humans to function in the social world. These two processes overlap in terms of the component processes involved, and share overlapping functional organizations within the human brain, in particular within the medial prefrontal cortex (MPFC). Several functional models have been proposed to explain these two processes, but none has directly explored the extent to which they are distinctly represented within different parts of the brain. This study used multivoxel pattern classification to quantify the separability of self- and other-related thought in the MPFC and expanded this question to the entire brain. Using a large-scale mega-analytic dataset, spanning three separate studies (n = 142), we find that self- and other-related thought can be reliably distinguished above chance within the MPFC, posterior cingulate cortex and temporal lobes. We highlight subcomponents of the ventral MPFC that are particularly important in representing self-related thought, and subcomponents of the orbitofrontal cortex robustly involved in representing other-related thought. Our findings indicate that representations of self- and other-related thought in the human brain are described best by a distributed pattern rather than stark localization or a purely ventral to dorsal linear gradient in the MPFC.

Causal effects of point-of-sale cigarette promotions and subjective social status on cigarette craving: a randomised within-person experiment.

BACKGROUND: Cigarette smoking continues to be a leading cause of preventable deaths in the USA, in part because the USA has not adopted the WHO Framework Convention on Tobacco Control. One way the tobacco industry counteracts tobacco control policies is by heavily advertising cigarettes at the point of sale in retailers (eg, at the cash register) and by offering discounts on cigarettes. DESIGN: A within-subject experimental design with adults who smoke cigarettes daily (n=281) investigated whether: (1) exposure to images of cigarette promotions in an online experiment is associated with greater cigarette craving relative to viewing images of non-smoking cues, and (2) if exposure to images of point-of-sale cigarette promotions with a discount (vs without) increases cigarette craving. The study also examined how participants' subjective social status (compared with others in the USA) relates to cigarette craving after exposure to images of cigarette promotions with and without a discount. RESULTS: In an online experiment, exposure to images of smoking cues, including point-of-sale cigarette promotions, elicited greater craving relative to non-smoking cues (all p<0.001). In addition, images of promotions with a discount elicited higher levels of craving compared with those without a discount (b=0.09, p=0.001). Although participants with a higher (vs lower) subjective social status craved cigarettes less overall (b=-0.12, p=0.012), there was no difference in their craving between images of promotions with and without a discount, while craving was higher for images of promotions with a discount than without for participants with higher subjective social status (b=0.06, p=0.021). CONCLUSION: Viewing images of point-of-sale cigarette promotions can causally increase cravings to smoke, which may also apply to real-world retail settings that display cigarette promotions. Restricting point-of-sale promotions generally, and discounts specifically, could help reduce cigarette smoking and address tobacco use disparities in the USA.

Evaluation of a telemedicine pilot program for the provision of HIV pre-exposure prophylaxis in the Southeastern United States.

Pre-exposure prophylaxis (PrEP) is a daily regimen that reduces the risk of acquiring HIV by up to 97%. There is limited information on the use of telehealth to provide PrEP in a program aimed toward the primary prevention of HIV. This was a 6-month telePrEP feasibility study that assessed process measures, clinical outcomes and patient satisfaction. Descriptive statistics and Chi-square analysis were used to evaluate measures and outcomes from the start to the end of the study. Twenty patients enrolled, and 80% completed the study. Participants were cisgender males (100%) with an average age of 35.6 years, white (95%), and were college graduates or higher (55%). The majority (75%) had very high comfort with video calls before the program. Self-reported adherence to PrEP medication remained high throughout the program (60%-70%). Without this program 31.2% of participants were unlikely to have received PrEP. For obtaining PrEP 56.3% preferred telemedicine only, and 31.2% preferred a combination of telemedicine and in-person office visits. PrEP is an effective method of preventing HIV infection for those at high risk. Our program shows that telemedicine can be useful to expand access to medication for patients at high risk.

Preventive Care Utilization by Patients Who Use Virtual Urgent Care.

Introduction: The use of direct to patient (DTP) telemedicine for common acute conditions is widespread. It provides certain advantages over in-person visits, but has led to concerns about fragmentation of care. It is unknown whether use of DTP telemedicine decreases use of primary care services in a way that leads to missed preventive screenings and immunizations. Methods: Virtual urgent care (VUC) is a DTP telemedicine service to treat common acute conditions. All VUC encounters completed at an academic health system from July 2018 to December 2019 were evaluated and analyzed in 2020. Only patients established with primary care (at least one primary care visit in the same year as VUC encounter) were included. Specific preventive screenings (breast cancer, gonorrhea/chlamydia, and cervical cancer) and immunizations (tetanus and influenza) were characterized as up to date based on national guidelines. Chi-squares and multivariate logistic regressions were used to assess receipt of screenings and immunizations. Regressions included VUC and primary care utilization and demographic factors. Results: Patients evaluated (N = 1025) were mostly 25-50 years old (69.7%), women (81.8%), and white (74.9%). More than half (56.5%) had only used VUC once. In multivariate analyses, VUC utilization was not negatively associated with any of the preventive services evaluated, whereas primary care utilization was associated with receipt of both immunizations and gonorrhea/chlamydia screening. Conclusions: Higher VUC utilization is not negatively associated with receipt of preventive services, as long as a primary care relationship is established. VUC may provide a useful method of encouraging receipt of preventive services, especially for younger patients.

Effects of self-transcendence on neural responses to persuasive messages and health behavior change.

Self-transcendence refers to a shift in mindset from focusing on self-interests to the well-being of others. We offer an integrative neural model of self-transcendence in the context of persuasive messaging by examining the mechanisms of self-transcendence in promoting receptivity to health messages and behavior change. Specifically, we posited that focusing on values and activities that transcend the self can allow people to see that their self-worth is not tied to a specific behavior in question, and in turn become more receptive to subsequent, otherwise threatening health information. To test whether inducing self-transcendent mindsets before message delivery would help overcome defensiveness and increase receptivity, we used two priming tasks, affirmation and compassion, to elicit a transcendent mindset among 220 sedentary adults. As preregistered, those who completed a self-transcendence task before health message exposure, compared with controls, showed greater increases in objectively logged levels of physical activity throughout the following month. In the brain, self-transcendence tasks up-regulated activity in a region of the ventromedial prefrontal cortex, chosen for its role in positive valuation and reward processing. During subsequent health message exposure, self-transcendence priming was associated with increased activity in subregions of the ventromedial prefrontal cortex, implicated in self-related processing and positive valuation, which predicted later decreases in sedentary behavior. The present findings suggest that having a positive self-transcendent mindset can increase behavior change, in part by increasing neural receptivity to health messaging.

No Effect of Commercial Cognitive Training on Brain Activity, Choice Behavior, or Cognitive Performance.

Increased preference for immediate over delayed rewards and for risky over certain rewards has been associated with unhealthy behavioral choices. Motivated by evidence that enhanced cognitive control can shift choice behavior away from immediate and risky rewards, we tested whether training executive cognitive function could influence choice behavior and brain responses. In this randomized controlled trial, 128 young adults (71 male, 57 female) participated in 10 weeks of training with either a commercial web-based cognitive training program or web-based video games that do not specifically target executive function or adapt the level of difficulty throughout training. Pretraining and post-training, participants completed cognitive assessments and functional magnetic resonance imaging during performance of the following validated decision-making tasks: delay discounting (choices between smaller rewards now vs larger rewards in the future) and risk sensitivity (choices between larger riskier rewards vs smaller certain rewards). Contrary to our hypothesis, we found no evidence that cognitive training influences neural activity during decision-making; nor did we find effects of cognitive training on measures of delay discounting or risk sensitivity. Participants in the commercial training condition improved with practice on the specific tasks they performed during training, but participants in both conditions showed similar improvement on standardized cognitive measures over time. Moreover, the degree of improvement was comparable to that observed in individuals who were reassessed without any training whatsoever. Commercial adaptive cognitive training appears to have no benefits in healthy young adults above those of standard video games for measures of brain activity, choice behavior, or cognitive performance.SIGNIFICANCE STATEMENT Engagement of neural regions and circuits important in executive cognitive function can bias behavioral choices away from immediate rewards. Activity in these regions may be enhanced through adaptive cognitive training. Commercial brain training programs claim to improve a broad range of mental processes; however, evidence for transfer beyond trained tasks is mixed. We undertook the first randomized controlled trial of the effects of commercial adaptive cognitive training (Lumosity) on neural activity and decision-making in young adults (N = 128) compared with an active control (playing on-line video games). We found no evidence for relative benefits of cognitive training with respect to changes in decision-making behavior or brain response, or for cognitive task performance beyond those specifically trained.

Neuroanatomy predicts individual risk attitudes.

Over the course of the last decade a multitude of studies have investigated the relationship between neural activations and individual human decision-making. Here we asked whether the anatomical features of individual human brains could be used to predict the fundamental preferences of human choosers. To that end, we quantified the risk attitudes of human decision-makers using standard economic tools and quantified the gray matter cortical volume in all brain areas using standard neurobiological tools. Our whole-brain analysis revealed that the gray matter volume of a region in the right posterior parietal cortex was significantly predictive of individual risk attitudes. Participants with higher gray matter volume in this region exhibited less risk aversion. To test the robustness of this finding we examined a second group of participants and used econometric tools to test the ex ante hypothesis that gray matter volume in this area predicts individual risk attitudes. Our finding was confirmed in this second group. Our results, while being silent about causal relationships, identify what might be considered the first stable biomarker for financial risk-attitude. If these results, gathered in a population of midlife northeast American adults, hold in the general population, they will provide constraints on the possible neural mechanisms underlying risk attitudes. The results will also provide a simple measurement of risk attitudes that could be easily extracted from abundance of existing medical brain scans, and could potentially provide a characteristic distribution of these attitudes for policy makers.

Brain activity in valuation regions while thinking about the future predicts individual discount rates.

People vary widely in how much they discount delayed rewards, yet little is known about the sources of these differences. Here we demonstrate that neural activity in ventromedial prefrontal cortex (VMPFC) and ventral striatum (VS) when human subjects are asked to merely think about the future--specifically, to judge the subjective length of future time intervals--predicts delay discounting. High discounters showed lower activity for longer time delays, while low discounters showed the opposite pattern. Our results demonstrate that the correlation between VMPFC and VS activity and discounting occurs even in the absence of choices about future rewards, and does not depend on a person explicitly evaluating future outcomes or judging their self-relevance. This suggests a link between discounting and basic processes involved in thinking about the future, such as temporal perception. Our results also suggest that reducing impatience requires not suppression of VMPFC and VS activity altogether, but rather modulation of how these regions respond to the present versus the future.

Neural correlates associated with conformity in adolescent and young adult men.

Social influence affects us throughout our lives, shaping our attitudes, behaviors, and preferences. Thus, the current study aimed to examine whether key age groups (adolescence versus young adulthood) were associated with differences in neural correlates associated with processing social feedback and conformity (i.e., conflict detection, positive valuation, and mentalizing) among young men. We recruited 153 participants across 5 studies, who completed a social influence task during an fMRI scan. Overall, participants were more likely to conform by changing their ratings when misaligned with others, and adolescents were more likely to conform when misaligned (compared to aligned) with others compared to young adults. Further, we found that adolescents showed increased activity in mentalizing (TPJ, dmPFC) and positive valuation regions (VS, vmPFC), compared to young adults, in response to misalignment with others. In contrast, young adults showed increased activity in conflict detection regions (AI, dACC) when exposed to feedback that they were misaligned with others and when conforming to that feedback. Overall, our results offer initial evidence that adolescent and young adult men engage different neural processes when they find out they are misaligned with others and when conforming to the recommendations of others, and this difference appears to track with brain responses in conflict detection, mentalizing and value regions. DATA STATEMENT: Raw data and analysis codes are available upon request.

Message self and social relevance increases intentions to share content: Correlational and causal evidence from six studies.

Information sharing within social networks can catalyze widespread attitudinal and behavioral change and the chance to share information with others has been characterized as inherently valuable to people. But what are the sources of value and how might they be leveraged to promote sharing? We test ideas from the value-based virality model that the value of sharing increases when people perceive messages as more relevant to themselves and to people they know, resulting in stronger intentions to share. We extend this work by considering how sharing context-broadcasting to a wide audience or narrowcasting directly to someone-may alter these relationships. Six online studies with adults in the United States (N participants = 3,727; messages = 362; message ratings = 30,954) showed robust evidence that self and social relevance are positively and uniquely related to sharing intentions within- and between-person. Specification curve analysis showed these relationships were consistent across message content (COVID-19, voting, general health, climate change), medium (social media post and news articles), and sharing context (broad- and narrowcasting). A preregistered experiment showed that manipulating the self and social relevance of messages through a framing manipulation causally increased sharing intentions. These causal effects were mediated by changes in both self and social relevance, but the relative strength of the causal pathways differed depending on sharing context. These findings extend existing models of information sharing, and highlight self and social relevance as psychological mechanisms that motivate information sharing that can be targeted to promote sharing across contexts. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Psychological distance intervention reminders reduce alcohol consumption frequency in daily life.

Modifying behaviors, such as alcohol consumption, is difficult. Creating psychological distance between unhealthy triggers and one's present experience can encourage change. Using two multisite, randomized experiments, we examine whether theory-driven strategies to create psychological distance-mindfulness and perspective-taking-can change drinking behaviors among young adults without alcohol dependence via a 28-day smartphone intervention (Study 1, N = 108 participants, 5492 observations; Study 2, N = 218 participants, 9994 observations). Study 2 presents a close replication with a fully remote delivery during the COVID-19 pandemic. During weeks when they received twice-a-day intervention reminders, individuals in the distancing interventions reported drinking less frequently than on control weeks-directionally in Study 1, and significantly in Study 2. Intervention reminders reduced drinking frequency but did not impact amount. We find that smartphone-based mindfulness and perspective-taking interventions, aimed to create psychological distance, can change behavior. This approach requires repeated reminders, which can be delivered via smartphones.

Retrieval of Chronically Implanted Dual-chamber Leadless Pacemakers in an Ovine Model.

BACKGROUND: The clinical utilization of leadless pacemakers (LPs) as an alternative to traditional transvenous pacemakers is likely to increase with the advent of dual-chamber LP systems. Since device retrieval to allow LP upgrade or replacement will become an important capability, the first such dual-chamber, helix-fixation LP system (Aveir DR; Abbott, Abbott Park, IL) was specifically designed to allow catheter-based retrieval. In this study, the preclinical performance and safety of retrieving chronically implanted dual-chamber LPs was evaluated. METHODS: Atrial and ventricular LPs were implanted in the right atrial appendage and right ventricular apex of 9 healthy ovine subjects. After ≈2 years, the LPs were retrieved using a dedicated transvenous retrieval catheter (Aveir Retrieval Catheter; Abbott) by snaring, docking, and unscrewing from the myocardium. Comprehensive necropsy/histopathology studies were conducted to evaluate device- and procedure-related outcomes. RESULTS: At a median of 1.9 years postimplant (range, 1.8-2.6), all 18 of 18 (100%) LPs were retrieved from 9 ovine subjects without complications. The median retrieval procedure duration for both LPs, from first-catheter-in to last-catheter-out, was 13.3 minutes (range, 2.5-36.4). Postretrieval, all right atrial, and right ventricular implant sites demonstrated minimal tissue disruption, with intact fibrous tissue limited to the distal device body. No significant device-related trauma, perforation, pericardial effusion, right heart or tricuspid valve injury, or chronic pulmonary thromboembolism were observed at necropsy. CONCLUSIONS: This preclinical study demonstrated the safe and effective retrieval of chronically implanted, helix-fixation, dual-chamber LP systems, paving the way for clinical studies of LP retrieval.

An evaluation of the impact for healthcare professionals after a leadership innovation fellowship program.

BACKGROUND: Leadership among healthcare professionals is required to address important healthcare challenges. The TAHSNp Health Professions Innovation Fellowship program ("Program") supports health professionals' leadership development by offering them an opportunity to lead a quality improvement project and participate in a curriculum focused on leading change. OBJECTIVE: As part of an outcome evaluation of the program, our objective was to determine the program's impact on leadership activities and roles undertaken by alumni. METHODS: A questionnaire was administered to participants who completed the program in 2019 and 2020 at 6 and 18 months post-program to assess their leadership activities, leadership roles and the program's impact. Prospectively, we conducted internal and LinkedIn searches to identify current roles and obtained personal statements from program alumni of medical imaging health professions as complementary data sources for our program evaluation. RESULTS: At 6 and 18 months post-program, 47% - 59% of alumni respondents reported participation in hospital/organization committees, mentoring fellows or students, and presenting scholarly work inside or outside their organizations (6 months: N = 25, response rate = 39.1%; 18 months: N = 17, response rate = 26.6%). Additionally, at 18 months post program, 35% - 41% of alumni reported leading a new quality improvement initiative, pursuing formal education, and having a new leadership role. Most alumni reported their leadership activities were influenced by the program, with the largest impact occurring after 18 months post-program for leading a new quality improvement initiative (100%), career plans for the next five years (94%), mentoring fellowship staff (91%), presenting at their healthcare organization (91%) and a new leadership role (90%). Alumni reported the program helped build their confidence, create networking opportunities, leadership skill-building and interest in pursuing other roles beyond their clinical role. More specifically, alumni reported that leadership skills gained from the program were used in subsequent roles and responsibilities. CONCLUSION/IMPLICATIONS: The program evaluation demonstrates engaged alumni who undertake informal and formal leadership activities and roles. Our results are illustrative of the value-add as a result of healthcare organizations' investment in developing leadership among healthcare professionals. As continued engagement and career development are known to be important for staff retention and succession planning strategies, our findings are highly relevant given the current staffing challenges in healthcare.

Sensory and motor innervation of the crural diaphragm by the vagus nerves.

BACKGROUND & AIMS: During gastroesophageal reflux, transient lower esophageal sphincter relaxation and crural diaphragm (CD) inhibition occur concomitantly. Modifying vagus nerve control of transient lower esophageal sphincter relaxation is a major focus of development of therapeutics for gastroesophageal reflux disease, but neural mechanisms that coordinate the CD are poorly understood. METHODS: Nerve tracing and immunolabeling were used to assess innervation of the diaphragm and lower esophageal sphincter in ferrets. Mechanosensory responses of vagal afferents in the CD and electromyography responses of the CD were recorded in novel in vitro preparations and in vivo. RESULTS: Retrograde tracing revealed a unique population of vagal CD sensory neurons in nodose ganglia and CD motor neurons in brainstem vagal nuclei. Anterograde tracing revealed specialized vagal endings in the CD and phrenoesophageal ligament-sites of vagal afferent mechanosensitivity recorded in vitro. Spontaneous electromyography activity persisted in the CD following bilateral phrenicotomy in vivo, while vagus nerve stimulation evoked electromyography responses in the CD in vitro and in vivo. CONCLUSIONS: We conclude that vagal sensory and motor neurons functionally innervate the CD and phrenoesophageal ligament. CD vagal afferents show mechanosensitivity to distortion of the gastroesophageal junction, while vagal motor neurons innervate both CD and distal esophagus and may represent a common substrate for motor control of the reflux barrier.

Industry-informed perspectives on the benefits of rideshare-based medical transportation.

Previous research on rideshare-based nonemergency medical transportation has limited generalizability due to the specific model studied, and the lack of trip-level data raises concerns of ecological fallacy.

Social networks and neural receptivity to persuasive health messages.

OBJECTIVE: Health-related norms in social networks can influence whether people are open to health behavior change. Yet, little is known about how social networks relate to the ways individual brains respond to persuasive health messaging. The current study focuses on ventromedial prefrontal cortex (VMPFC) activity as an index of neural receptivity to health messages that may be related to behavior change. The study tested whether health-related norms and perceived physical activity levels within participants' social networks are associated with neural receptivity to health messages. METHOD: Adults who initially reported under 200 minutes/week of physical activity (N = 146) rated the perceived physical activity levels of, and closeness to, each person in their core social network. VMPFC activity was monitored using fMRI while participants viewed persuasive health messages promoting physical activity. Longitudinal changes in sedentary behavior were objectively logged using wrist-worn accelerometers throughout a 2-week baseline and the month following the fMRI scan. RESULTS: Higher levels of perceived physical activity in participants' social networks were associated with greater VMPFC activity during message exposure, which in turn were associated with greater decreases in sedentary minutes. By contrast, greater closeness to physically inactive social ties was associated with lower VMPFC activity. CONCLUSIONS: Perceived norms in social networks relate to neural receptivity to health messaging. In particular, closeness to physically inactive ties is associated with lower neural receptivity to health messages encouraging physical activity, which may undermine the effectiveness of health messages. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Nitric oxide as an endogenous peripheral modulator of visceral sensory neuronal function.

Nitric oxide (NO) plays important roles in CNS and smooth muscle function. Here we reveal an additional function in peripheral sensory transmission. We hypothesized that endogenous NO modulates the function of gastrointestinal vagal afferent endings. The nonselective NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester hydrochloride increased responses to tactile mechanical stimuli of mucosal afferent endings in two species, in some cases severalfold. This was mimicked by a neuronal NOS inhibitor but not an endothelial NOS inhibitor. NOS inhibitors did not affect the responsiveness of smooth muscle afferent endings, suggesting that the endogenous source of NO is exclusively accessible to mucosal receptors. The role of the NO-soluble guanylyl cyclase (sGC)-cGMP pathway was confirmed using the sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one and the cGMP phosphodiesterase 5' inhibitor sildenafil. The first enhanced and the second inhibited mechanosensory function. Exogenous NO, from the donor S-nitroso-N-acetylpenicillamine, significantly reduced mechanosensitivity of both types of ending. Up to one-third of stomach-projecting afferent neurons in the nodose ganglia expressed neuronal NOS (nNOS). However, anterograde-traced vagal endings were nNOS negative, indicating NOS is not transported peripherally and there are alternative sources of NO for afferent modulation. A subpopulation of enteroendocrine cells in the gut mucosa were nNOS positive, which were found anatomically in close apposition with mucosal vagal afferent endings. These results indicate an inhibitory neuromodulatory role of epithelial NO, which targets a select population of vagal afferents. This interaction is likely to play a role in generation of symptoms and behaviors from the upper gastrointestinal system.