The parietal cortex has a causal role in ambiguity computations in humans.

Humans often face the challenge of making decisions between ambiguous options. The level of ambiguity in decision-making has been linked to activity in the parietal cortex, but its exact computational role remains elusive. To test the hypothesis that the parietal cortex plays a causal role in computing ambiguous probabilities, we conducted consecutive fMRI and TMS-EEG studies. We found that participants assigned unknown probabilities to objective probabilities, elevating the uncertainty of their decisions. Parietal cortex activity correlated with the objective degree of ambiguity and with a process that underestimates the uncertainty during decision-making. Conversely, the midcingulate cortex (MCC) encodes prediction errors and increases its connectivity with the parietal cortex during outcome processing. Disruption of the parietal activity increased the uncertainty evaluation of the options, decreasing cingulate cortex oscillations during outcome evaluation and lateral frontal oscillations related to value ambiguous probability. These results provide evidence for a causal role of the parietal cortex in computing uncertainty during ambiguous decisions made by humans.

Risk-Taking Is Associated with Decreased Subjective Value Signals and Increased Prediction Error Signals in the Hot Columbia Card Task.

It remains a pressing concern to understand how neural computations relate to risky decisions. However, most observations of brain-behavior relationships in the risk-taking domain lack a rigorous computational basis or fail to emulate of the dynamic, sequential nature of real-life risky decision-making. Recent advances emphasize the role of neural prediction error (PE) signals. We modeled, according to prospect theory, the choices of n = 43 human participants (33 females, 10 males) performing an EEG version of the hot Columbia Card Task, featuring rounds of sequential decisions between stopping (safe option) and continuing with increasing odds of a high loss (risky option). Single-trial regression EEG analyses yielded a subjective value signal at centroparietal (300-700 ms) and frontocentral (>800 ms) electrodes and in the delta band, as well as PE signals tied to the feedback-related negativity, P3a, and P3b, and in the theta band. Higher risk preference (total number of risky choices) was linked to attenuated subjective value signals but increased PE signals. Higher P3-like activity associated with the most positive PE in each round predicted stopping in the present round but not risk-taking in the subsequent round. Our findings indicate that decreased representation of decision values and increased sensitivity to winning despite low odds (positive PE) facilitate risky choices at the subject level. Strong neural responses when gains are least expected (the most positive PE on each round) adaptively contribute to safer choices at the trial-by-trial level but do not affect risky choice at the round-by-round level.

Ventral Pallidum and Amygdala Cooperate to Restrain Reward Approach under Threat.

Foraging decisions involve assessing potential risks and prioritizing food sources, which can be challenging when confronted with changing and conflicting circumstances. A crucial aspect of this decision-making process is the ability to actively overcome defensive reactions to threats and focus on achieving specific goals. The ventral pallidum (VP) and basolateral amygdala (BLA) are two brain regions that play key roles in regulating behavior motivated by either rewards or threats. However, it is unclear whether these regions are necessary in decision-making processes involving competing motivational drives during conflict. Our aim was to investigate the requirements of the VP and BLA for foraging choices in conflicts involving overcoming defensive responses. Here, we used a novel foraging task and pharmacological techniques to inactivate either the VP or BLA or to disconnect these brain regions before conducting a conflict test in male rats. Our findings showed that BLA is necessary for making risky choices during conflicts, whereas VP is necessary for invigorating the drive to obtain food, regardless of the presence of conflict. Importantly, our research revealed that the connection between VP and BLA is critical in controlling risky food-seeking choices during conflict situations. This study provides a new perspective on the collaborative function of VP and BLA in driving behavior, aimed at achieving goals in the face of dangers.

Pre-acquired Functional Connectivity Predicts Choice Inconsistency.

Economic choice theories usually assume that humans maximize utility in their choices. However, studies have shown that humans make inconsistent choices, leading to suboptimal behavior, even without context-dependent manipulations. Previous studies showed that activation in value and motor networks are associated with inconsistent choices at the moment of choice. Here, we investigated if the neural predispositions, measured before a choice task, can predict choice inconsistency in a later risky choice task. Using functional connectivity (FC) measures from resting-state functional magnetic resonance imaging (rsfMRI), derived before any choice was made, we aimed to predict subjects' inconsistency levels in a later-performed choice task. We hypothesized that rsfMRI FC measures extracted from value and motor brain areas would predict inconsistency. Forty subjects (21 females) completed a rsfMRI scan before performing a risky choice task. We compared models that were trained on FC that included only hypothesized value and motor regions with models trained on whole-brain FC. We found that both model types significantly predicted inconsistency levels. Moreover, even the whole-brain models relied mostly on FC between value and motor areas. For external validation, we used a neural network pretrained on FC matrices of 37,000 subjects and fine-tuned it on our data and again showed significant predictions. Together, this shows that the tendency for choice inconsistency is predicted by predispositions of the nervous system and that synchrony between the motor and value networks plays a crucial role in this tendency.

Foraging in a non-foraging task: Fitness maximization explains human risk preference dynamics under changing environment.

Changes in risk preference have been reported when making a series of independent risky choices or non-foraging economic decisions. Behavioral economics has put forward various explanations for specific changes in risk preference in non-foraging tasks, but a consensus regarding the general principle underlying these effects has not been reached. In contrast, recent studies have investigated human economic risky choices using tasks adapted from foraging theory, which require consideration of past choices and future opportunities to make optimal decisions. In these foraging tasks, human economic risky choices are explained by the ethological principle of fitness maximization, which naturally leads to dynamic risk preference. Here, we conducted two online experiments to investigate whether the principle of fitness maximization can explain risk preference dynamics in a non-foraging task. Participants were asked to make a series of independent risky economic decisions while the environmental richness changed. We found that participants' risk preferences were influenced by the current and past environments, making them more risk-averse during and after the rich environment compared to the poor environment. These changes in risk preference align with fitness maximization. Our findings suggest that the ethological principle of fitness maximization might serve as a generalizable principle for explaining dynamic preferences, including risk preference, in human economic decision-making.

Older adults select different but not simpler strategies than younger adults in risky choice.

Younger and older adults often differ in their risky choices. Theoretical frameworks on human aging point to various cognitive and motivational factors that might underlie these differences. Using a novel computational model based on the framework of resource rationality, we find that the two age groups rely on different strategies. Importantly, older adults did not use simpler strategies than younger adults, they did not select among fewer strategies, they did not make more errors, and they did not put more weight on cognitive costs. Instead, older adults selected strategies that had different risk propensities than those selected by younger adults. Our modeling approach suggests that age differences in risky choice are not necessarily a consequence of cognitive decline; instead, they may reflect motivational differences between age groups.

Distinct neural dynamics of the observed ostracism effect in decision-making under risk and ambiguity.

Observational ostracism, as a form of social exclusion, can significantly affect human behavior. However, the effects of observed ostracism on risky and ambiguous decision-making and the underlying neural mechanisms remain unclear. This event-related potential study investigated these issues by involving participants in a wheel-of- fortune task, considering observed ostracism and inclusion contexts. The results showed that the cue-P3 component was more enhanced during the choice phase for risky decisions than for ambiguous decisions in the observed inclusion contexts but not in the observed ostracism contexts. During the outcome evaluation phase, feedback-related negativity amplitudes following both risky and ambiguous decisions were higher in the no-gain condition than in the gain condition in the observed inclusion context. In contrast, this effect was only observed following risky decisions in the observed ostracism context. The feedback-P3 component did not exhibit an observed ostracism effect in risky and ambiguous decision-making tasks. Risk levels further modulated the cue-P3 and feedback-related negativity components, while ambiguity levels further modulated the feedback-P3 components. These findings demonstrate a neural dissociation between risk and ambiguity decision-making during observed ostracism that unfolds from the choice phase to the outcome evaluation phase.

Decision-making under conditions of explicit risk and uncertainty in autistic and typically developing adolescents and young adults.

Adolescence has been characterized as a period of risky and possibly suboptimal decision-making, yet the development of decision-making in autistic adolescents is not well understood. To investigate decision-making in autism, we evaluated performance on 2 computerized tasks capturing decision-making under explicit risk and uncertainty in autistic and non-autistic adolescents/young adults ages 12-22 years. Participants completed the Game of Dice Task (32 IQ-matched participant pairs) to assess decision-making under explicit risk and the modified Iowa Gambling Task (35 IQ-matched pairs) to assess decision-making under uncertainty. Autistic participants overall made riskier decisions than non-autistic participants on the Game of Dice Task, and the odds of making riskier decisions varied by age and IQ. In contrast, the autistic group showed comparable levels of learning over trial blocks to the non-autistic group on the modified Iowa Gambling Task. For both tasks, younger autistic participants performed poorer than their non-autistic counterparts, while group differences diminished in older ages. This age-related pattern suggests positive development during adolescence on risk assessment and decision-making in autism but also implies differential developmental trajectories between groups. These findings also suggest differential performance by the risk type, with additional complex influences of IQ and fluid cognition, which warrants further investigations.

Intestine-to-neuronal signaling alters risk-taking behaviors in food-deprived Caenorhabditis elegans.

Animals integrate changes in external and internal environments to generate behavior. While neural circuits detecting external cues have been mapped, less is known about how internal states like hunger are integrated into behavioral outputs. Here, we use the nematode C. elegans to examine how changes in internal nutritional status affect chemosensory behaviors. We show that acute food deprivation leads to a reversible decline in repellent, but not attractant, sensitivity. This behavioral change requires two conserved transcription factors MML-1 (MondoA) and HLH-30 (TFEB), both of which translocate from the intestinal nuclei to the cytoplasm during food deprivation. Next, we identify the insulin-like peptide INS-31 as a candidate ligand relaying food-status signals from the intestine to other tissues. Further, we show that neurons likely use the DAF-2 insulin receptor and AGE-1/PI-3 Kinase, but not DAF-16/FOXO to integrate these intestine-released peptides. Altogether, our study shows how internal food status signals are integrated by transcription factors and intestine-neuron signaling to generate flexible behaviors via the gut-brain axis.

Early-life exposure to hardship increased risk tolerance and entrepreneurship in adulthood with gender differences.

Many entrepreneurs credit their success to early hardship. Here, we exploit geographical differences in the intensity of China's Great Famine to investigate the effect of hardship during formative years on individual personality and engagement in business entrepreneurship. To exclude factors that might confound the relation between famine intensity and entrepreneurship, we model famine intensity by random weather shocks. We find robust evidence that individuals who experienced more hardship were subsequently more likely to become entrepreneurs (defined broadly as self-employed or business owners). Importantly, the increase in entrepreneurship was at least partly due to conditioning rather than selection. Regarding the behavioral mechanism, hardship was associated with greater risk tolerance among men and women but increased business ownership only among men. The gender differences were possibly due to the intricate relationship between a Chinese social norm­men focus more on market work, while women focus more on domestic work­and interspousal risk pooling associated with occupational choices. Scientifically, these findings contribute to a long-standing debate on whether entrepreneurship is due to nature or nurture, particularly how hardship conditions people to be entrepreneurial. The findings also highlight the importance of gender differences in shaping the effect of early-life experience on life cycle outcomes.

Listening to the Data: Computational Approaches to Addiction and Learning.

Computational approaches hold great promise for identifying novel treatment targets and creating translational therapeutics for substance use disorders. From circuitries underlying decision-making to computationally derived neural markers of drug-cue reactivity, this review is a summary of the approaches to data presented at our 2023 Society for Neuroscience Mini-Symposium. Here, we highlight data- and hypothesis-driven computational approaches that recently afforded advancements in addiction and learning neuroscience. First, we discuss the value of hypothesis-driven algorithmic modeling approaches, which integrate behavioral, neural, and cognitive outputs to refine hypothesis testing. Then, we review the advantages of data-driven dimensionality reduction and machine learning methods for uncovering novel predictor variables and elucidating relationships in high-dimensional data. Overall, this review highlights recent breakthroughs in cognitive mapping, model-based analysis of behavior/risky decision-making, patterns of drug taking, relapse, and neuromarker discovery, and showcases the benefits of novel modeling techniques, across both preclinical and clinical data.

Temporal Dynamics Underlying Prelimbic Prefrontal Cortical Regulation of Action Selection and Outcome Evaluation during Risk/Reward Decision-Making.

Risk/reward decision-making is a dynamic process that includes periods of deliberation before action selection and evaluation of the action outcomes that bias subsequent choices. Inactivation of the prelimbic (PL) cortex has revealed its integral role in updating decision biases in the face of changes in probabilistic reward contingencies, yet how phasic PL signals during different phases of the decision process influence choice remains unclear. We used temporally specific optogenetic inhibition to selectively disrupt PL activity coinciding with action selection and outcome phases to examine how these signals influence choice. Male rats expressing the inhibitory opsin eArchT within PL excitatory neurons were well trained on a probabilistic discounting task, entailing choice between small/certain versus large/risky rewards, the probability of which varied over a session (50-12.5%). During testing, brief light pulses suppressed PL activity before choice or after different outcomes. Prechoice suppression reduced bias toward more preferred/higher utility options and disrupted how recent outcomes influenced subsequent choice. Inhibition during risky losses induced a similar profile, but here, the impact of reward omissions were either amplified or diminished, relative to the context of the estimated profitability of the risky option. Inhibition during large or small reward receipt reduced risky choice when this option was more profitable, suggesting these signals can both reinforce rewarded risky choices and also act as a relative value comparator signal that augments incentive for larger rewards. These findings reveal multifaceted contributions by the PL in implementing decisions and integrating action-outcome feedback to assign context to the decision space.SIGNIFICANCE STATEMENT The PL prefrontal cortex plays an integral role in guiding risk/reward decisions, but how activity in this region during different phases of the decision process influences choice is unclear. By using temporally specific optogenetic manipulations of this activity, the present study unveiled previously uncharacterized and differential contributions by PL in implementing decision policies and how evaluation of decision outcomes shape subsequent choice. These findings provide novel insight into the dynamic processes engaged by the PL that underlie action selection in situations involving reward uncertainty that may aid in understanding the mechanism underlying normal and aberrant decision-making processes.

Linking Impulsivity to Activity Levels in Pre-Supplementary Motor Area during Sequential Gambling.

Impulsivity refers to the tendency to act prematurely or without forethought, and excessive impulsivity is a key problem in many neuropsychiatric disorders. Since the pre-supplementary motor area (pre-SMA) has been implicated in inhibitory control, this region may also contribute to impulsivity. Here, we examined whether functional recruitment of pre-SMA may contribute to risky choice behavior (state impulsivity) during sequential gambling and its relation to self-reported trait impulsivity. To this end, we performed task-based functional MRI (fMRI) after low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of the pre-SMA. We expected low-frequency rTMS to modulate task-related engagement of the pre-SMA and, hereby, tune the tendency to make risky choices. Twenty-four healthy volunteers (12 females; age range, 19-52 years) received real or sham-rTMS on separate days in counterbalanced order. Thereafter, participants performed a sequential gambling task with concurrently increasing stakes and risk during whole-brain fMRI. In the sham-rTMS session, self-reported trait impulsivity scaled positively with state impulsivity (riskier choice behavior) during gambling. The higher the trait impulsivity, the lower was the task-related increase in pre-SMA activity with increasingly risky choices. Following real-rTMS, low-impulsivity participants increased their preference for risky choices, while the opposite was true for high-impulsivity participants, resulting in an overall decoupling of trait impulsivity and state impulsivity during gambling. This rTMS-induced behavioral shift was mirrored in the rTMS-induced change in pre-SMA activation. These results provide converging evidence for a causal link between the level of task-related pre-SMA activity and the propensity for impulsive risk-taking behavior in the context of sequential gambling.SIGNIFICANCE STATEMENT Impulsivity is a personal trait characterized by a tendency to act prematurely or without forethought, and excessive impulsivity is a key problem in many neuropsychiatric disorders. Here we provide evidence that the pre-supplementary motor area (pre-SMA) is causally involved in implementing general impulsive tendencies (trait impulsivity) into actual behavior (state impulsivity). Participants' self-reported impulsivity levels (trait impulsivity) were reflected in their choice behavior (state impulsivity) when involved in a sequential gambling task. This relationship was uncoupled after perturbing the pre-SMA with repetitive transcranial stimulation (rTMS). This effect was contingent on trait impulsivity and was echoed in rTMS-induced changes in pre-SMA activity. Pre-SMA is key in translating trait impulsivity into behavior, possibly by integrating prefrontal goals with corticostriatal motor control.

Changes in decision-making function in patients with subacute mild traumatic brain injury.

Although awareness regarding patients with mild traumatic brain injury has increased, they have not received sufficient attention in clinics; hence, many patients still experience only partial recovery. Deficits in decision-making function are frequently experienced by these patients. Accurate identification of impairment in the early stages after brain injury is particularly crucial for timely intervention and the prevention of long-term cognitive consequences. Therefore, we investigated the changes in decision-making ability under tasks of ambiguity and risk in patients with mild traumatic brain injury with a rule-based neuropsychological paradigm. In this study, patients (n = 39) and matched healthy controls (n = 38) completed general neuropsychological background tests and decision-making tasks (Iowa Gambling Task and Game of Dice Task). We found that patients had extensive cognitive impairment in general attention, memory and information processing speed in the subacute phase, and confirmed that patients had different degrees of impairment in decision-making abilities under ambiguity and risk. Furthermore, the decline of memory and executive function may be related to decision-making dysfunction.

Opportunities for risk-taking during play alters cognitive performance and prefrontal inhibitory signalling in rats of both sexes.

Social play behaviour is a rewarding activity that can entail risks, thus allowing young individuals to test the limits of their capacities and to train their cognitive and emotional adaptability to challenges. Here, we tested in rats how opportunities for risk-taking during play affect the development of cognitive and emotional capacities and medial prefrontal cortex (mPFC) function, a brain structure important for risk-based decision making. Male and female rats were housed socially or social play-deprived (SPD) between postnatal day (P)21 and P42. During this period, half of both groups were daily exposed to a high-risk play environment. Around P85, all rats were tested for cognitive performance and emotional behaviour after which inhibitory currents were recorded in layer 5 pyramidal neurons in mPFC slices. We show that playing in a high-risk environment altered cognitive flexibility in both sexes and improved behavioural inhibition in males. High-risk play altered anxiety-like behaviour in the elevated plus maze in males and in the open field in females, respectively. SPD affected cognitive flexibility in both sexes and decreased anxiety-like behaviour in the elevated plus maze in females. We found that synaptic inhibitory currents in the mPFC were increased in male, but not female, rats after high-risk play, while SPD lowered prefrontal cortex (PFC) synaptic inhibition in both sexes. Together, our data show that exposure to risks during play affects the development of cognition, emotional behaviour and inhibition in the mPFC. Furthermore, our study suggests that the opportunity to take risks during play cannot substitute for social play behaviour.

Lateralization of self-control over the dorsolateral prefrontal cortex in decision-making: a systematic review and meta-analytic evidence from noninvasive brain stimulation.

The dorsolateral prefrontal cortex (DLPFC) has been widely recognized as a crucial brain "control area." Recently, its causal role in promoting deliberate decision-making through self-control and the asymmetric performance of the left and right DLPFC in control functions have attracted the interest of many researchers. This study was designed to investigate the role of DLPFC in decision-making behaviors and lateralization of its control function by systematically examining the effects of noninvasive brain stimulation (NIBS) over the DLPFC on intertemporal choice, risk decision-making, and social fairness-related decision-making tasks. Literature searches were implemented at PubMed, Embase, Cochrane, Web of Science, Wanfang Data, China Science and Technology Journal Database, and China National Knowledge Infrastructure until May 10, 2022. Meta-analytic results for included studies were estimated by random-effect models. A total of 33 eligible studies were identified, yielding 130 effect sizes. Our results indicated that compared to sham group, excitatory NIBS over the left DLPFC reduced delay discounting rate (standardized mean differences, SMD = -0.51; 95% confidence interval, 95% CI: [-0.81, -0.21]) and risk-taking performance (SMD = -0.39, 95% CI [-0.68, -0.10]), and inhibitory NIBS over the right DLPFC increased self-interested choice of unfair offers (SMD = 0.50, 95% CI [0.04, 0.97]). Finding of current work indicated that neural excitement of the DLPFC activation improve individuals' self-control during decision-makings, whereas neural inhibition results in impaired control. In addition, our analyses furnish causal evidence for the presence of functional lateralization in the left and right DLPFC in monetary impulsive decision-making and social decision-making, respectively.

Humanized dopamine D4.7 receptor male mice display risk-taking behavior and deficits of social recognition and working memory in light/dark-dependent manner.

The dopamine D4 receptor 7-repeat allele (D4.7 R) has been linked with psychiatric disorders such as attention-deficit-hyperactivity disorder, autism, and schizophrenia. However, the highly diverse study populations and often contradictory findings make it difficult to draw reliable conclusions. The D4.7 R has the potential to explain individual differences in behavior. However, there is still a great deal of ambiguity surrounding whether it is causally connected to the etiology of psychiatric disorders. Therefore, humanized D4.7 R mice, with the long third intracellular domain of the human D4.7 R, may provide a valuable tool to examine the relationship between the D4.7 R variant and specific behavioral phenotypes. We report that D4.7 R male mice carrying the humanized D4.7 R variant exhibit distinct behavioral features that are dependent on the light-dark cycle. The behavioral phenotype was characterized by a working memory deficit, delayed decision execution in the light phase, decreased stress and anxiety, and increased risk behavior in the dark phase. Further, D4.7 R mice displayed impaired social recognition memory in both the light and dark phases. These findings provide insight into the potential causal relationship between the human D4.7 R variant and specific behaviors and encourage further consideration of dopamine D4 receptor (DRD4) ligands as novel treatments for psychiatric disorders in which D4.7 R has been implicated.

Assessing Direct and Spillover Effects of Intervention Packages in Network-randomized Studies.

BACKGROUND: Intervention packages may result in a greater public health impact than single interventions. Understanding the separate impact of each component on the overall package effectiveness can improve intervention delivery. METHODS: We adapted an approach to evaluate the effects of a time-varying intervention package in a network-randomized study. In some network-randomized studies, only a subset of participants in exposed networks receive the intervention themselves. The spillover effect contrasts average potential outcomes if a person was not exposed to themselves under intervention in the network versus no intervention in a control network. We estimated the effects of components of the intervention package in HIV Prevention Trials Network 037, a Phase III network-randomized HIV prevention trial among people who inject drugs and their risk networks using marginal structural models to adjust for time-varying confounding. The index participant in an intervention network received a peer education intervention initially at baseline, then boosters at 6 and 12 months. All participants were followed to ascertain HIV risk behaviors. RESULTS: There were 560 participants with at least one follow-up visit, 48% of whom were randomized to the intervention, and 1,598 participant visits were observed. The spillover effect of the boosters in the presence of initial peer education training was a 39% rate reduction (rate ratio = 0.61; 95% confidence interval = 0.43, 0.87). CONCLUSIONS: These methods will be useful for evaluating intervention packages in studies with network features.

In the fight against HIV/AIDS: the arduous implementation of government-funded pre-exposure prophylaxis programme in Taiwan.

INTRODUCTION: The government-funded pre-exposure prophylaxis (PrEP) programme was targeted to those aged under 30 years or serodiscordant couples and implemented in September 2018-October 2020 in Taiwan. The study aimed to examine the effectiveness of the programme and the relationship between sexually transmitted disease (STD) and HIV seroconversion. METHODS: This study was a retrospective cohort analysis with questionnaires designed for participants who joined the aforementioned programme in the PrEP-designated hospitals. The questionnaires included sociodemographic factors, sexual risk behaviours, number and types of sexual partners, and usage of narcotics filled in at the beginning of the programme and every 3 months. The McNemar test was used for the paired questionnaire analysis. The HIV seroconversion status among STD-notified patients nationwide was confirmed by using the data linkage method, followed up until October 2021 with stratification of PrEP programme participation or not. RESULTS: The programme recruited 2155 people. 11 participants (0.5%) had seroconversion within the programme, while 26 (1.2%) had seroconversion after withdrawing from the programme. Overall, 1892 subjects with repeated questionnaires were included in the analysis for behaviour changes with median follow-up of 289 days. After joining the programme, 94.7% of them claimed that they had sexual behaviours: the rate of those who had condomless sex rose to 5.5% (p<0.001) and the rate of those who used narcotics decreased to 2% (p<0.001), compared with their response in the pre-questionnaire. Notably, the frequency of non-use of narcotics in recent 3 months increased from 16.9% to 38.4% in the pre-questionnaire and post-questionnaire responses, among the 177 who had claimed narcotics usage in recent 12 months (p=0.003). More HIV seroconversion was found among patients with STD who did not join the programme than those who joined the programme (8.7% vs 4.9%, p=0.031). CONCLUSIONS: The government-funded programme showed HIV case reduction and positive changes in health behaviours except for condomless sex which had increased prevalence. The reduction of HIV cases was also observed among people with STD. More resources should be allocated to the PrEP programme.

Health-related risk behaviors among U.S. childhood cancer survivors: a nationwide estimate.

BACKGROUND: Childhood cancer survivors (CCS) are subject to a substantial burden of treatment-related morbidity. Engaging in health protective behaviors and eliminating risk behaviors are critical to preventing chronic diseases and premature deaths. This study is aimed to provide updated information on currently smoking, physical inactivity, binge drinking patterns and associated factors among CCS using a nationwide dataset. METHODS: We constructed a sample of CCS (cancer diagnosis at ages < 21y) and healthy controls (matched on age, sex, residency, race/ethnicity) using 2020 Behavioral Risk Factor Surveillance System. We used Chi-square tests and Wilcoxon rank-sum test to examine differences in sociodemographics and clinical characteristics between two groups. Logistic, ordinal regression and multivariable models (conditional models for matching) were used to determine factors associated with risk behaviors. RESULTS: The final sample (18-80y) included 372 CCS and 1107 controls. Compared to controls, CCS had a similar proportion of binge drinking (~ 18%) but higher prevalence of currently smoking (26.6% vs. 14.4%, p < 0.001), physical inactivity (23.7% vs. 17.7%, p = 0.012), and of having 2-or-3 risk behaviors (17.2% vs. 8.1%, p < 0.001). Younger age, lower educational attainment, and having multiple chronic health conditions were associated with engaging in more risk behaviors among CCS. Females, compared to male counterparts, had lower odds of binge drinking (adjusted odds ratio (aOR) = 0.30, 95% confidence interval (CI): 0.16-0.57) among CCS but not in all sample. Having multiple chronic health conditions increased odds of both currently smoking (aOR = 3.52 95%CI: 1.76-7.02) and binge drinking (aOR = 2.13 95%CI: 1.11-4.08) among CCS while it only increased odds of currently smoking in all sample. DISCUSSION: Our study provided risk behavior information for wide age-range CCS, which is currently lacking. Every one in four CCS was currently smoking. Interventions targeting risk behavior reduction should focus on CCS with multiple chronic health conditions.