PACE: a Novel Eating Behavior Phenotype to Assess Risk for Obesity in Middle Childhood.

BACKGROUND: Behavioral phenotypes that predict future weight gain are needed to identify children susceptible to obesity. OBJECTIVES: This prospective study developed an eating behavior risk score to predict change in adiposity over 1 y in children. METHODS: Data from 6 baseline visits (Time 1, T1) and a 1-y follow-up visit (Time 2, T2) were collected from 76, 7- to 8-y-old healthy children recruited from Central Pennsylvania. At T1, children had body mass index (BMI) percentiles <90 and were classified with either high (n = 33; maternal BMI ≥30 kg/m2) or low (n = 43; maternal BMI ≤25 kg/m2) familial risk for obesity. Appetitive traits and eating behaviors were assessed at T1. Adiposity was measured at T1 and T2 using dual-energy x-ray absorptiometry, with a main outcome of fat mass index (FMI; total body fat mass divided by height in meters squared). Hierarchical linear regressions determined which eating measures improved prediction of T2 FMI after adjustment for covariates in the baseline model (T1 FMI, sex, income, familial risk, and Tanner stage). RESULTS: Four eating measures-Portion susceptibility, Appetitive traits, loss of control eating, and eating rate-were combined into a standardized summary score called PACE. PACE improved the baseline model to predict 80% variance in T2 FMI. PACE was positively associated with the increase in FMI in children from T1 to T2, independent of familial risk (r = 0.58, P < 0.001). Although PACE was higher in girls than boys (P < 0.05), it did not differ by familial risk, income, or education. CONCLUSIONS: PACE represents a cumulative eating behavior risk score that predicts adiposity gain over 1 y in middle childhood. If PACE similarly predicts adiposity gain in a cohort with greater racial and socioeconomic diversity, it will inform the development of interventions to prevent obesity. This trial was registered at clinicaltrials.gov as NCT03341247.

Strengthening through adversity: The hormesis model in developmental psychopathology.

BACKGROUND: Employing a developmental psychopathology framework, we tested the utility of the hormesis model in examining the strengthening of children and youth through limited levels of adversity in relation to internalizing and externalizing outcomes within a brain-by-development context. METHODS: Analyzing data from the Adolescent Brain and Cognitive Development study (N = 11,878), we formed latent factors of threat, deprivation, and unpredictability. We examined linear and nonlinear associations between adversity dimensions and youth psychopathology symptoms and how change of resting-state functional connectivity (rsFC) in the default mode network (DMN) from Time 1 to Time 5 moderates these associations. RESULTS: A cubic association was found between threat and youth internalizing problems; low-to-moderate family conflict levels reduced these problems. Deprivation also displayed a cubic relation with youth externalizing problems, with moderate deprivation levels associated with fewer problems. Unpredictability linearly increased both problem types. Change in DMN rsFC significantly moderated the cubic link between threat levels and internalizing problems, with declining DMN rsFC levels from Time 1 to Time 5 facilitating hormesis. Hormetic effects peaked earlier, emphasizing the importance of sensitive periods and developmental timing of outcomes related to earlier experiences. CONCLUSIONS: Strengthening through limited environmental adversity is crucial for developing human resilience. Understanding this process requires considering both linear and nonlinear adversity-psychopathology associations. Testing individual differences by brain and developmental context will inform preventive intervention programming.

Does 'portion size' matter? Brain responses to food and non-food cues presented in varying amounts.

Larger portions of food elicit greater intake than smaller portions of food, particularly when foods are high in energy density (kcal/g; ED). The neural mechanisms underlying this effect remain unclear. The present study used fMRI to assess brain activation to food (higher-ED, lower-ED) and non-food (office supplies) images presented in larger and smaller (i.e., age-appropriate) amounts in 61, 7-8-year-olds (29 male, 32 female) without obesity. Larger amounts of food increased activation in bilateral visual and right parahippocampal areas compared to smaller amounts; greater activation to food amount (larger > smaller) in this cluster was associated with smaller increases in food intake as portions increased. Activation to amount (larger > smaller) was stronger for food than office supplies in primary and secondary visual areas, but, for office supplies only, extended into bilateral parahippocampus, inferior parietal cortex, and additional visual areas (e.g., V7). Activation was greater for higher-vs. lower-ED food images in ventromedial prefrontal cortex for both larger and smaller amounts of food; however, this activation extended into left lateral orbital frontal cortex for smaller amounts only. Activation to food cues did not differ by familial risk for obesity. These results highlight potentially distinct neural pathways for encoding food energy content and quantity.

Testing the efficacy of real-time fMRI neurofeedback for training people who smoke daily to upregulate neural responses to nondrug rewards.

Although the use of nondrug rewards (e.g., money) to facilitate smoking cessation is widespread, recent research has found that such rewards may be least effective when people who smoke cigarettes are tempted to do so. Specifically, among people who smoke, the neural response to nondrug rewards appears blunted when access to cigarettes is anticipated, and this blunting is linked to a decrease in willingness to refrain from smoking to earn a monetary incentive. Accordingly, methods to enhance the value of nondrug rewards may be theoretically and clinically important. The current proof-of-concept study tested if real-time fMRI neurofeedback training augments the ability to upregulate responses in reward-related brain areas relative to a no-feedback control condition in people who smoke. Adults (n = 44, age range = 20-44) who reported smoking >5 cigarettes per day completed the study. Those in the intervention group (n = 22, 5 females) were trained to upregulate brain responses using feedback of ongoing striatal activity (i.e., a dynamic "thermometer" that reflected ongoing changes of fMRI signal intensity in the striatum) in a single neurofeedback session with three training runs. The control group (n = 22, 5 females) underwent a nearly identical procedure but received no neurofeedback. Those who received neurofeedback training demonstrated significantly greater increases in striatal BOLD activation while attempting to think about something rewarding compared to controls, but this effect was present only during the first training run. Future neurofeedback research with those who smoke should explore how to make neurofeedback training more effective for the self-regulation of reward-related brain activities.

Incentives facilitate developmental improvement in inhibitory control by modulating control-related networks.

Adolescence is a period of heightened sensitivity to incentives and relatively weak cognitive control, which may contribute to risky behaviors. Studies of brain activity have generally identified greater activation of the ventral striatum to rewards and less activation of prefrontal regions during control tasks in adolescents compared to adults. Little is known, however, about age-related changes in the functional brain networks underlying incentive processing and cognitive control. This cross-sectional study characterized the effects of incentives on inhibitory control during an oculomotor task using whole-brain functional connectivity analyses. During an fMRI scan, one hundred forty typically developing individuals completed an incentivized antisaccade task consisting of incentive cue, preparation, and response phases. We found that task modulation of control networks increased gradually from childhood to adulthood, whereas a network including ventral striatum and ventromedial prefrontal cortex displayed an adolescent-specific peak in response to the receipt of outcomes, consistent with dual-systems models. Notably, however, greater modulation of salience and motor networks during the preparation phase mediated age-related improvements in antisaccade accuracy, whereas adolescent enhancement of value-related circuitry did not. Relative to neutral cues, both reward and loss cues enhanced task-related connectivity of the salience network when preparing to inhibit a saccade. Altogether, our findings suggest that incentives facilitate inhibitory control by enhancing the salience of one's responses and that over development, the recruitment of functional networks involved in saliency and motor preparation supports better performance.

Is brain response to food rewards related to overeating? A test of the reward surfeit model of overeating in children.

The reward surfeit model of overeating suggests that heightened brain response to rewards contributes to overeating and subsequent weight gain. However, previous studies have not tested whether brain response to reward is associated with food intake, particularly during childhood, a period of dynamic development in reward and inhibitory control neurocircuitry. We conducted functional magnetic resonance imaging (fMRI) with 7-11-year-old children (n = 59; healthy weight, n = 31; overweight, n = 28; 54% female) while they played a modified card-guessing paradigm to examine blood-oxygen-level-dependent (BOLD) response to anticipating and winning rewards (food, money, neutral). Food intake was assessed at three separate meals that measured different facets of eating behavior: 1) typical consumption (baseline), 2) overindulgence (palatable buffet), and 3) eating in the absence of hunger (EAH). A priori regions of interest included regions implicated in both reward processing and inhibitory control. Multiple stepwise regressions were conducted to examine the relationship between intake and BOLD response to rewards. Corrected results showed that a greater BOLD response in the medial prefrontal cortex for anticipating food compared to money positively correlated with how much children ate at the baseline and palatable buffet meals. BOLD response in the dorsolateral prefrontal cortex for winning food compared to money was positively correlated with intake at the palatable buffet meal and EAH. All aforementioned relationships were independent of child weight status. Findings support the reward surfeit model by showing that increased brain response to food compared to money rewards positively correlates with laboratory measures of food intake in children.

Age-Varying Associations Between Cigarette Smoking, Sensation Seeking, and Impulse Control Through Adolescence and Young Adulthood.

Sensation seeking (SS) and impulse control (IC) are constructs at the core of dual systems models of adolescent risk taking. Using data from the National Longitudinal Study of Adolescent to Adult Health, age-varying associations between SS and IC (predictors) and both any smoking in the previous 30 days and daily smoking (outcomes) were examined. The association between SS and both any smoking in the previous 30 days and daily smoking was strongest during adolescence. IC was consistently associated with any smoking in the previous 30 days and daily smoking, with the strongest association emerging during the mid-20s to early 30s. The results provide a nuanced perspective on when the components of dual systems models may be most related to smoking.

Modulation of reward-related neural activation on sensation seeking across development.

Sensation seeking is a personality construct associated with an increased propensity for engaging in risk-taking. Associations with deleterious outcomes ranging from mental health impairments to increased mortality rates highlight important public health concerns related to this construct. Although some have suggested that increased neural responsivity to reward within the ventral striatum (e.g., nucleus accumbens) may drive sensation seeking behaviors, few studies have examined the neural mechanisms associated with stable individual differences in sensation seeking across development. To address this issue, the current study used functional magnetic resonance imaging to examine the association between neural responding to reward and stable patterns of sensation seeking across a three-year follow-up period among healthy adolescents and young adults (N = 139). Results indicated that during early adolescence (~ages 10-12), increased reactivity to reward within the nucleus accumbens (NAcc) was associated with lower levels of sensation seeking across a three-year follow-up. In middle adolescence (~ages 12-16), there was no evidence of a relationship between NAcc reactivity and sensation seeking. However, during the transition from late adolescence into adulthood (~ages 17-25), heightened reward-related reactivity in the NAcc was linked to increased sensation seeking. Findings suggest that the neural mechanisms underlying individual differences in trait-like levels of sensation seeking change from early to late adolescence.

Reduced Influence of Monetary Incentives on Go/NoGo Performance During Smoking Abstinence.

INTRODUCTION: Smokers may experience decreased sensitivity to nondrug incentives during acute smoking deprivation. This decreased sensitivity may undermine attempts to encourage continued abstinence by enhancing cognitive processes through the use of monetary incentives. This study assessed whether the capacity for monetary incentives to enhance cognitive performance was compromised in nicotine-deprived smokers. METHOD: Eighteen smokers performed an incentivized Go/NoGo task on 2 occasions, once after smoking as usual prior to the session, and once after undergoing 12-hr abstinence. Participants could earn up to $5.00 ($2.50 per session) based on their performance on reward blocks of the Go/NoGo task. RESULTS: Performance was significantly more accurate on incentivized NoGo, frequent-Go, and infrequent-Go trials relative to neutral trials during the smoke as usual session. Participants also produced fewer premature, impulsive responses on rewarded versus neutral blocks during the smoke as usual session. No significant difference between reward and neutral blocks was observed on any of the 4 performance indices during the abstinent session. CONCLUSIONS: The ability for monetary incentives to enhance inhibitory control may be compromised during acute abstinence in smokers. These findings may have implications for contingency management treatment programs which are thought to promote continued abstinence partly by facilitating the allocation of cognitive resources to processes that encourage continued abstinence by increasing the value associated with continued abstinence.

What ergodicity means for you.

This paper explores the relation between within-person and between-person research designs using the concept of ergodicity from statistical mechanics in physics. We demonstrate the consequences of ergodicity using several real data examples from previously published studies. We then create several simulated examples that illustrate the independence of within-person processes from between-person differences, and pair these examples with analytic results that reinforce our conclusions. Finally, we discuss the plausibility of ergodicity being the general rule rather than the exception for social and behavioral processes, address common arguments against heeding the implications of ergodicity for behavioral research, and offer several possible solutions.

Social visual attention as a treatment outcome: evaluating the social games for autistic adolescents (SAGA) intervention.

A core feature of autism involves difficulty perceiving and interpreting eye gaze shifts as nonverbal communicative signals. A hypothesis about the origins of this phenotype is that it emerges from developmentally different social visual attention (SVA). We developed Social Games for Autistic Adolescents (SAGA; Scherf et al. BMJ Open 8(9):e023682, 2018) as a serious game intervention for autistic individuals to discover the significance of eye gaze cues. Previously, we demonstrated the effectiveness of SAGA to improve the perception and understanding of eye gaze cues and social skills for autistic adolescents (Griffin et al. JCPP Adv 1(3):e12041, 2021). Here, we determine whether increases in social visual attention to faces and/or target gazed-at objects, as measured via eye tracking during the same Gaze Perception task in the same study sample, moderated this improvement. In contrast to predictions, SVA to faces did not differentially increase for the treatment group. Instead, both groups evinced a small increase in SVA to faces over time. Second, Prior to the SAGA intervention, attention to faces failed to predict performance in the Gaze Perception task for both the treatment and standard care control groups. However, at post-test, autistic adolescents in the treatment group were more likely to identify the object of directed gaze when they attended longer to faces and longer to target objects. Importantly, this is the first study to measure social visual attention via eye tracking as a treatment response in an RCT for autism. NCT02968225.

Associations between somatomotor-putamen resting state connectivity and obsessive-compulsive symptoms vary as a function of stress during early adolescence: Data from the ABCD study.

Obsessive-compulsive symptoms (OCS) are relatively common during adolescence although most individuals do not meet diagnostic criteria for obsessive-compulsive disorder (OCD). Nonetheless, OCS during adolescence are associated with comorbid psychopathologies and behavioral problems. Heightened levels of environmental stress and greater functional connectivity between the somatomotor network and putamen have been previously associated with elevated OCS in OCD patients relative to healthy controls. However, the interaction of these factors within the same sample of individuals has been understudied. This study examined somatomotor-putamen resting state connectivity, stress, and their interaction on OCS in adolescents from 9-12 years of age. Participants (n = 6386) were drawn from the ABCD Study 4.0 release. Multilevel modeling was used to account for nesting in the data and to assess changes in OCS in this age range. Stress moderated the association between somatomotor-putamen connectivity and OCS (ß = 0.35, S.E. = 0.13, p = 0.006). Participants who reported more stress than their average and had greater somatomotor-left putamen connectivity reported more OCS, whereas participants who reported less stress than their average and had greater somatomotor-left putamen connectivity reported less OCS. These data suggest that stress differentially affects the direction of association between somatomotor-putamen connectivity and OCS. Individual differences in the experience or perception of stress may contribute to more OCS in adolescents with greater somatomotor-putamen connectivity.

The Cerebellar Response to Visual Portion Size Cues Is Associated with the Portion Size Effect in Children.

The neural mechanisms underlying susceptibility to eating more in response to large portions (i.e., the portion size effect) remain unclear. Thus, the present study examined how neural responses to portion size relate to changes in weight and energy consumed as portions increase. Associations were examined across brain regions traditionally implicated in appetite control (i.e., an appetitive network) as well as the cerebellum, which has recently been implicated in appetite-related processes. Children without obesity (i.e., BMI-for-age-and-sex percentile < 90; N = 63; 55% female) viewed images of larger and smaller portions of food during fMRI and, in separate sessions, ate four meals that varied in portion size. Individual-level linear and quadratic associations between intake (kcal, grams) and portion size (i.e., portion size slopes) were estimated. The response to portion size in cerebellar lobules IV-VI was associated with the quadratic portion size slope estimated from gram intake; a greater response to images depicting smaller compared to larger portions was associated with steeper increases in intake with increasing portion sizes. Within the appetitive network, neural responses were not associated with portion size slopes. A decreased cerebellar response to larger amounts of food may increase children's susceptibility to overeating when excessively large portions are served.

Racial Discrimination and Risk for Internalizing and Externalizing Symptoms Among Black Youths.

Importance: Racial discrimination is a psychosocial stressor associated with youths' risk for psychiatric symptoms. Scarce data exist on the moderating role of amygdalar activation patterns among Black youths in the US. Objective: To investigate the association between racial discrimination and risk for psychopathology moderated by neuroaffective processing. Design, Setting, and Participants: This cohort study used longitudinal self-report and functional magnetic resonance imaging (fMRI) data from Black youth participants in the US from the Adolescent Brain Cognitive Development (ABCD) study. Data were analyzed from January 2023 to May 2024. Exposures: At time 1 of the current study (12 months after baseline), youths self-reported on their experiences of interpersonal racial discrimination and their feelings of marginalization. Amygdalar response was measured during an emotionally valenced task that included blocks of faces expressing either neutral or negative emotion. Main Outcomes and Measures: At 24 and 36 months after baseline, youths reported their internalizing (anxiety and depressive symptoms) and externalizing symptoms (aggression and rule-breaking symptoms). Results: A total of 1596 youths were a mean (SD) age of 10.92 (0.63) years, and 803 were female (50.3%). Families in the study had a mean annual income range of $25 000 to $34 999. Two factors were derived from factor analysis: interpersonal racial discrimination and feelings of marginalization (FoM). Using structural equation modeling in a linear regression, standardized ß coefficients were obtained. Neural response to faces expressing negative emotion within the right amygdala significantly moderated the association between FoM and changes in internalizing symptoms (ß = -0.20; 95% CI, -0.32 to -0.07; P < .001). The response to negative facial emotion within the right amygdala significantly moderated the association between FoM and changes in externalizing symptoms (ß = 0.24; 95% CI, 0.04 to 0.43; P = .02). Left amygdala response to negative emotion significantly moderated the association between FoM and changes in externalizing symptoms (ß = -0.16; 95% CI, -0.32 to -0.01; P = .04). Conclusions and Relevance: In this cohort study of Black adolescents in the US, findings suggest that amygdala function in response to emotional stimuli can both protect and intensify the affective outcomes of feeling marginalized on risk for psychopathology, informing preventive interventions aimed at reducing the adverse effects of racism on internalizing and externalizing symptoms among Black youths.

Adolescent cognitive control and reward processing: implications for risk taking and substance use.

Adolescence is a unique, transitional period of human development. Once hallmark of this period is progressive improvements (relative to children) in cognitive control, core mental abilities enabling the 'top-down', endogenous control over behavior. However, as adolescents transition to more mature (adult) levels of functioning, limitations still exist in the ability to consistently and flexibly exert cognitive control across various contexts into the early twenties. Adolescence is also marked by peaks in sensation, novelty, and reward seeking behaviors thought to stem from normative increases in responsiveness in limbic and paralimbic brain structures, beginning around the onset of puberty. Asynchronous maturation in these systems during the adolescent period likely contributes to immature decision-making, strongly influenced by 'bottom-up' reward processes, and may help explain noted increases in risk taking behavior during adolescence. In this paper, structural and functional maturation in brain systems supporting reward and cognitive control processing are reviewed as a means to better understand risk taking. Particular emphasis is placed on adolescents' experimentation with drugs as a specific example of a risky behavior.

Children at high familial risk for obesity show executive functioning deficits prior to development of excess weight status.

OBJECTIVE: The objective of this study was to determine whether children with healthy weight who vary by familial risk for obesity differ in executive functioning. METHODS: Children (age 7-8 years) without obesity (n = 93, 52% male) who differed by familial risk for obesity (based on maternal weight status) completed go/no-go and stop-signal tasks to assess inhibitory control and an N-back task to assess working memory. Dual energy x-ray absorptiometry measured adiposity. Linear and mixed-effect models assessed unique effects and relative importance analysis-quantified relative effects of familial risk and percent body fat. RESULTS: Children at high compared with low familial risk showed worse inhibitory control; however, child adiposity was not associated with inhibitory control. Both high familial risk and greater child adiposity were associated with worse N-back performance when cognitive demand was high (2-back), but not low (0- and 1-back). The relative effect of familial risk on executive functioning was 2.7 to 16 times greater than the relative effect of percent body fat. CONCLUSIONS: These findings provide initial evidence that deficits in executive functioning may precede the development of obesity in children at high familial risk for this disease. Additional family risk studies are needed to elucidate the pathways through which maternal obesity influences child executive functioning and risk for obesity.

Developmental effects of incentives on response inhibition.

Inhibitory control and incentive processes underlie decision making, yet few studies have explicitly examined their interaction across development. Here, the effects of potential rewards and losses on inhibitory control in 64 adolescents (13- to 17-year-olds) and 42 young adults (18- to 29-year-olds) were examined using an incentivized antisaccade task. Notably, measures were implemented to minimize age-related differences in reward valuation and potentially confounding motivation effects. Incentives affected antisaccade metrics differently across the age groups. Younger adolescents generated more errors than adults on reward trials, but all groups performed well on loss trials. Adolescent saccade latencies also differed from adults across the range of reward trials. Overall, results suggest persistent immaturities in the integration of reward and inhibitory control processes across adolescence.

Effective Connectivity during an Avoidance-Based Pavlovian-to-Instrumental Transfer Task.

Pavlovian-to-instrumental transfer (PIT) refers to a phenomenon whereby a classically conditioned stimulus (CS) impacts the motivational salience of instrumental behavior. We examined behavioral response patterns and functional magnetic resonance imaging (fMRI) based effective connectivity during an avoidance-based PIT task. Eleven participants (8 females; Mage = 28.2, SD = 2.8, range = 25-32 years) completed the task. Effective connectivity between a priori brain regions engaged during the task was determined using hemodynamic response function group iterative multiple model estimation (HRF-GIMME). Participants exhibited behavior that was suggestive of specific PIT, a CS previously associated with a reinforcing outcome increased instrumental responding directed at the same outcome. We did not find evidence for general PIT; a CS did not significantly increase instrumental responding towards a different but related outcome. Using HRF-GIMME, we recovered effective connectivity maps among corticostriatal circuits engaged during the task. Group-level paths revealed directional effects from left putamen to right insula and from right putamen to right cingulate. Importantly, a direct effect of specific PIT stimuli on blood-oxygen-level-dependent (BOLD) activity in the left putamen was found. Results provide initial evidence of effective connectivity in key brain regions in an avoidance-based PIT task network. This study adds to the literature studying PIT effects in humans and employing GIMME models to understand how psychological phenomena are supported in the brain.

Cracking the Code of Live Human Social Interactions in Autism: A Review of the Eye-Tracking Literature.

Human social interaction involves a complex, dynamic exchange of verbal and non-verbal information. Over the last decade, eye-tracking technology has afforded unique insight into the way eye gaze information, including both holding gaze and shifting gaze, organizes live human interactions. For example, while playing a social game together, speakers end their turn by directing gaze at the listener, who begins to speak with averted gaze (Ho et al., 2015). These findings reflect how eye gaze can be used to signal important turn-taking transitions in social interactions. Deficits in conversational turn-taking is a core feature of autism spectrum disorders. Individuals on the autism spectrum also have notable difficulties processing eye gaze information (Griffin & Scherf, 2020). A central hypothesis in the literature is that the difficulties in processing eye gaze information are foundational to the social communication deficits that make social interactions so challenging for individuals on the autism spectrum. Although eye-tracking technology has been used extensively to assess the way individuals on the spectrum attend to stimuli presented on computer screens (for review see Papagiannopoulou et al., 2014), it has rarely been used to evaluate the critical question regarding whether and how autistic individuals process non-verbal social cues from their partners during live social interactions. Here, we review this emerging literature with a focus on characterizing the experimental paradigms and eye-tracking procedures to understand the scope (and limitations) of research questions and findings. We discuss the theoretical implications of the findings from this review and provide recommendations for future work that will be essential to understand whether and how fundamental difficulties in perceiving and processing information about eye gaze cues interfere with social communication skills in autism.

Improving sensitivity to eye gaze cues in adolescents on the autism spectrum using serious game technology: A randomized controlled trial.

Background: Perceiving and interpreting eye gaze cues is foundational for social cognition and social interactions because it involves the ability to use eye gaze direction to predict the actions and intentions of others. Autism is a disability that impacts social interactions. A diagnostic symptom of autism is difficulty understanding eye gaze cues as social signals. This deficit has long-term consequences for understanding goal-directed behavior, language learning, and social communication. We hypothesize that targeted intervention methods designed to improve sensitivity to eye gaze cues may begin to treat core symptoms of autism and potentially alter multiple aspects of social functioning. Social Games for Autistic Adolescents (SAGA) is a serious computer game intervention designed to improve sensitivity to eye gaze cues. Serious games improve targeted skills with the goal of enhancing real life outcomes. In SAGA, participants progress through a narrative storyline and interact with animated characters. In so doing, they implicitly discover that eye gaze cues are useful for guiding their own goal-directed behavior to solve problems in the game. Methods: We evaluated the feasibility and effectiveness of SAGA in a hybrid phase 1/2, randomized controlled trial. Forty adolescents on the autism spectrum were randomized to either the treatment or standard care control group. Adolescents in the treatment group were asked to play SAGA for 30-minute sessions at home 3 times a week over 10 weeks. Results: A group × time interaction revealed that the treatment group developed increasing sensitivity to human eye gaze cues, whereas the standard care group did not. Participants who experienced a sufficient dose of gameplay showed larger treatment-related improvements. Critically, increases in sensitivity to human eye gaze cues were associated with improvements in social skills. Conclusions: This accessible, scalable, and affordable intervention shows promise as an effective tool for improving the ability to interpret and understand eye gaze cues and social skills in adolescents on the autism spectrum.