The ability to learn and apply rules lies at the heart of cognition. In a seminal study, Marcus et al.(1999) reported that 7-month-old infants learned abstract rules over syllable sequences and wereable to generalize those rules to novel syllable sequences. Dozens of studies have since replicatedthat finding and extended it using different rules, modalities, stimuli, participants (human adultsand non-human animals) and experimental procedures. Yet questions remain about thegeneralizability of Marcus et al.’s (1999) core findings, and sources of variation across thesefindings. In the current study, we address this issue by testing 839 infants of a wide age range(5;0-12;0 months) in a multi-laboratory (30 laboratories, [31 samples]) conceptual replication ofthe Marcus et al. (1999) study. This study and the analyses were submitted as a registered report.A mixed-model analysis of the looking times at consistent vs. inconsistent test trials indicated nosignificant effect. The current study therefore finds no evidence for rule-learning; to the contrary, aBayesian analysis of the data indicated strong evidence for a null effect. This was similarly thecase for the moderating factors that were part of the design: mono- vs. multilingualism, age, andexperimental paradigm; none of these factors showed significant effects. Robustness analysesindicated that the results were not different in the case of different choices in the (pre-)processingof the data. A follow-up analysis for single labs indicated that there was no evidence ofrule-learning in 30 of the 31 contributed samples. The current finding raises fundamental issuesabout rule-learning that are presented in Discussion.

Infants prefer infant-directed (ID) speech. Concerning talking faces, previous research showed that 3- and 5-month-olds prefer faces that produce native ID than native adult-directed (AD) speech, regardless of background speech being ID, AD or silent. Here, we explored whether infants also show a preference for non-native ID speech. We presented 3- and 6-month-old infants with pairs of talking faces, one producing non-native ID speech and the other non-native AD speech, either in silence (Experiment 1) or accompanied by non-native ID or AD background speech (Experiment 2). Results from Experiment 1 showed an overall preference for the silent ID talking faces across both age groups, suggesting a reliance on cross-linguistic, potentially universal cues for this preference. However, Experiment 2 showed that preference for ID faces was disrupted at 3 months when auditory speech was present (ID or AD). At 6 months, infants maintained a preference for ID talking faces, but only when accompanied by ID speech. These findings show that auditory non-native speech interferes with infants' processing of ID talking faces. They also suggest that by 6 months, infants start associating ID features from faces and voices irrespective of language familiarity, suggesting that infants' ID preference may be universal and amodal.

Mental rotation (MR) is an important feature of spatial cognition invoking mental imagery of an object’s appearance when viewed from a new orientation. Prior studies have revealed evidence of MR in infants, including a sex difference similar to that detected in older populations. Some of these studies used visual habituation methods whereby infants were familiarized with an object rotating through a 240° angle, followed by test trials showing either the habituation object or a mirror image object rotating through the previously unseen 120° angle. Significantly longer looking at either of these objects was taken to reflect infants’ ability to recognize the habituation object even when seen from a novel viewpoint, suggesting the capacity for MR. However, these infants’ responses could, in theory, be explained with reference to perceptual discrimination rather than MR, because the views of the habituation and test objects were very similar in some video frames. In the current study, we observed a diverse population of 5-month-olds (24 females, 24 males) for evidence of MR through 30° of arc. In this more challenging test, our stimuli left a 30° gap angle between critical video frames representing the habituation and test objects. Consistent with earlier reports, we found that relative to female infants, male infants looked significantly longer at the mirror image test stimulus immediately following habituation. These results add to an emerging consensus that some young infants are capable of MR, and that male and female infants on average behave differently in this type of MR task.

The communication of emotion is dynamic and occurs across multiple channels, such as facial expression and tone of voice. When cues are in conflict, interpreting emotion can become challenging. Here, we examined the effects of incongruent emotional cues on toddlers' interpretation of emotions. We presented 33 children (22-26 months, Mage = 23.8 months, 15 female) with side-by-side images of faces along with sentences spoken in a tone of voice that conflicted with semantic content. One of the two faces matched the emotional tone of the audio, whereas the other matched the semantic content. For both congruent and incongruent trials, toddlers showed no overall looking preference to either type of face stimuli. However, during the second exposure to the sentences of incongruent trials, older children tended to look longer to the face matching semantic content when listening to happy vs. angry content. Results inform our understanding of the early development of complex emotion understanding.

Statistical learning relies on detecting the frequency of co-occurrences of items and has been proposed to be crucial for a variety of learning problems, notably to learn and memorize words from fluent speech. Endress and Johnson (2021) (hereafter EJ) recently showed that such results can be explained based on simple memory-less correlational learning mechanisms such as Hebbian Learning. Tovar and Westermann (2022) (hereafter TW) reproduced these results with a different Hebbian model. We show that the main differences between the models are whether temporal decay acts on both the connection weights and the activations (in TW) or only on the activations (in EJ), and whether interference affects weights (in TW) or activations (in EJ). Given that weights and activations are linked through the Hebbian learning rule, the networks behave similarly. However, in contrast to TW, we do not believe that neurophysiological data are relevant to adjudicate between abstract psychological models with little biological detail. Taken together, both models show that different memory-less correlational learning mechanisms provide a parsimonious account of Statistical Learning results. They are consistent with evidence that Statistical Learning might not allow learners to learn and retain words, and Statistical Learning might support predictive processing instead.

Eye tracking (ET) experiments commonly record the continuous trajectory of a subject’s gaze on a two-dimensional screen throughout repeated presentations of stimuli (referred to as trials). Even though the continuous path of gaze is recorded during each trial, commonly derived outcomes for analysis collapse the data into simple summaries, such as looking times in regions of interest, latency to looking at stimuli, number of stimuli viewed, number of fixations, or fixation length. In order to retain information in trial time, we utilize functional data analysis (FDA) for the first time in literature in the analysis of ET data. More specifically, novel functional outcomes for ET data, referred to as viewing profiles, are introduced that capture the common gazing trends across trial time which are lost in traditional data summaries. Mean and variation of the proposed functional outcomes across subjects are then modeled using functional principal component analysis. Applications to data from a visual exploration paradigm conducted by the Autism Biomarkers Consortium for Clinical Trials showcase the novel insights gained from the proposed FDA approach, including significant group differences between children diagnosed with autism and their typically developing peers in their consistency of looking at faces early on in trial time.

The Selective Social Attention (SSA) task is a brief eye-tracking task involving experimental conditions varying along socio-communicative axes. Traditionally the SSA has been used to probe socially-specific attentional patterns in infants and toddlers who develop autism spectrum disorder (ASD). This current work extends these findings to preschool and school-age children. Children 4- to 12-years-old with ASD (N = 23) and a typically-developing comparison group (TD; N = 25) completed the SSA task as well as standardized clinical assessments. Linear mixed models examined group and condition effects on two outcome variables: percent of time spent looking at the scene relative to scene presentation time (%Valid), and percent of time looking at the face relative to time spent looking at the scene (%Face). Age and IQ were included as covariates. Outcome variables' relationships to clinical data were assessed via correlation analysis. The ASD group, compared to the TD group, looked less at the scene and focused less on the actress' face during the most socially-engaging experimental conditions. Additionally, within the ASD group, %Face negatively correlated with SRS total T-scores with a particularly strong negative correlation with the Autistic Mannerism subscale T-score. These results highlight the extensibility of the SSA to older children with ASD, including replication of between-group differences previously seen in infants and toddlers, as well as its ability to capture meaningful clinical variation within the autism spectrum across a wide developmental span inclusive of preschool and school-aged children. The properties suggest that the SSA may have broad potential as a biomarker for ASD.

Individuals with autism spectrum disorder (ASD) tend to experience greater difficulties with social communication and sensory information processing. Of particular interest in ASD biomarker research is the study of visual attention, effectively quantified in eye tracking (ET) experiments. Eye tracking offers a powerful, safe, and feasible platform for gaining insights into attentional processes by measuring moment-by-moment gaze patterns in response to stimuli. Even though recording is done with millisecond granularity, analyses commonly collapse data across trials into variables such as proportion time spent looking at a region of interest (ROI). In addition, looking times in different ROIs are typically analyzed separately. We propose a novel multivariate functional outcome that carries proportion looking time information from multiple regions of interest jointly as a function of trial type, along with a novel constrained multivariate functional principal components analysis procedure to capture the variation in this outcome. The method incorporates the natural constraint that the proportion looking times from the multiple regions of interest must sum up to one. Our approach is motivated by the Activity Monitoring task, a social-attentional assay within the ET battery of the Autism Biomarkers Consortium for Clinical Trials (ABC-CT). Application of our methods to the ABC-CT data yields new insights into dominant modes of variation of proportion looking times from multiple regions of interest for school-age children with ASD and their typically developing (TD) peers, as well as richer analysis of diagnostic group differences in social attention.

# CPSS-1. Abstract ID 108. Radiographic reporting in adolescent idiopathic scoliosis: Is there a discrepancy between radiologists’ reports and surgeons’ assessments? {#article-title-2} Cobb angle measurement is a standard method for quantification of scoliosis in patients with adolescent

Abstract Background Amino acid PET radiopharmaceutical, 18F-fluciclovine, shows increased uptake in brain tumors relative to normal tissue and may be a useful tool for detecting recurrent brain metastases. Here, we report results from a prospective pilot study evaluating the use of 18F-fluciclovine PET/CT to distinguish radiation necrosis from tumour progression among patients with brain metastases treated with stereotactic radiosurgery (SRS). Material and Methods The primary objective was to estimate the accuracy of 18F-fluciclovine PET/CT in distinguishing radiation necrosis from tumour progression. The trial included adults with brain metastases who underwent SRS and presented with a follow up MRI brain (with DSC MR perfusion) which was equivocal for radiation necrosis versus tumour progression. Within 30 days of equivocal MRI brain, patients underwent an 18F-fluciclovine PET/CT (Siemens mCT) acquired 5-15 min post-injection with images generated by PSF reconstruction. Quantitative metrics for each lesion were documented and lesion to normal brain SUVmean ratios were calculated. The reference standard for diagnosis of radiation necrosis vs tumour progression was clinical follow up with MRI brain every 2-4 months until multidisciplinary consensus or tissue confirmation. Results Of 16 patients enrolled between 7/2019-11/2020, 1 patient died prior to diagnosis, allowing 15 evaluable subjects with 20 lesions. Primary histology was NSCLC in 9 (45%) lesions, breast in 7 (35%), melanoma in 3 (15%), and endometrial in 1 (5%). The final diagnosis was radiation necrosis in 16 (80%) lesions and tumour progression in 4 (20%). SUVmax was a statistically significant predictor of tumour progression (P = 0.011), with higher SUVmax values indicative of tumour progression. The area under the ROC curve was 0.833 (95% CI: 0.590, 1.0). A cutoff of 4.3 provided a sensitivity to identify tumour progression of 1.0 (4/4) and specificity to rule out tumour progression of 0.63 (10/16). SUVmean (P = 0.018), SUVpeak (P = 0.007), and SUVpeak/normal (P = 0.002) also reached statistical significance as predictors of tumour progression, with higher SUVmax values indicative of tumour progression. SUVmax/normal (P = 0.1) and SUVmean/normal (P = 0.5) were not statistically significant. The AUC for SUVmax was not significantly higher than the AUCs for the other quantitative variables (P-values > 0.2). Conclusion In this prospective pilot study, 18F Fluciclovine PET/CT demonstrated promising accuracy to distinguish radiation necrosis from tumour progression among patients with brain metastases previously treated with SRS. Using SUVmax, a cutpoint of 4.3 provided a sensitivity of 1.0 and specificity of 0.63. Confirmatory phase II and III studies are ongoing.

Objective: Numerous candidate EEG biomarkers have been put forward for use in clinical research on autism spectrum disorder (ASD), but biomarker development has been hindered by limited attention to the psychometric properties of derived variables, inconsistent results across small studies, and variable methodology. The authors evaluated the basic psychometric properties of a battery of EEG assays for their potential suitability as biomarkers in clinical trials. Methods: This was a large, multisite, naturalistic study in 6- to 11-year-old children who either had an ASD diagnosis (N=280) or were typically developing (N=119). The authors evaluated an EEG battery composed of well-studied assays of resting-state activity, face perception (faces task), biological motion perception, and visual evoked potentials (VEPs). Biomarker psychometrics were evaluated in terms of acquisition rates, construct performance, and 6-week stability. Preliminary evaluation of use was explored through group discrimination and phenotypic correlations. Results: Three assays (resting state, faces task, and VEP) show promise in terms of acquisition rates and construct performance. Six-week stability values in the ASD group were moderate (intraclass correlations ≥0.66) for the faces task latency of the P1 and N170, the VEP amplitude of N1 and P1, and resting alpha power. Group discrimination and phenotype correlations were primarily observed for the faces task P1 and N170. Conclusions: In the context of a large-scale, rigorous evaluation of candidate EEG biomarkers for use in ASD clinical trials, neural response to faces emerged as a promising biomarker for continued evaluation. Resting-state activity and VEP yielded mixed results. The study’s biological motion perception assay failed to display construct performance. The results provide information about EEG biomarker performance that is relevant for the next stage of biomarker development efforts focused on context of use.

Language has been proposed as a potential mechanism for young children's developing understanding of emotion. However, much remains unknown about this relation at an individual difference level. The present study investigated 15- to 18-month-old infants' perception of emotions across multiple pairs of faces. Parents reported their child's productive vocabulary, and infants participated in a non-linguistic emotion perception task via an eye tracker. Infant vocabulary did not predict nonverbal emotion perception when accounting for infant age, gender, and general object perception ability (ss = 0.15, p =.300). However, we observed a gender difference: Only girls' vocabulary scores related to nonverbal emotion perception when controlling for age and general object perception ability ( ss = 0.42, p =.024). Further, boys showed a stronger preference for the novel emotion face vs. girls (t(48) = 2.35, p =.023, d= 0.67). These data suggest that pathways of processing emotional information (e.g., using language vs visual information) may differ for girls and boys in late infancy. Language has been proposed as a potential mechanism for young children's developing understanding of emotion. However, much remains unknown about this relation at an individual difference level. The present study investigated 15- to 18-month-old infants' perception of emotions across multiple pairs of faces. Parents reported their child's productive vocabulary, and infants participated in a non-linguistic emotion perception task via an eye tracker. Infant vocabulary did not predict nonverbal emotion perception when accounting for infant age, gender, and general object perception ability (beta = -0.15, p = .300). However, we observed a gender difference: Only girls' vocabulary scores related to nonverbal emotion perception when controlling for age and general object perception ability (beta = 0.42, p = .024). Further, boys showed a stronger preference for the novel emotion face vs. girls (t(48) = 2.35, p = .023, d= 0.67). These data suggest that pathways of processing emotional information (e.g., using language vs visual information) may differ for girls and boys in late infancy.

Visual exploration paradigms involving object arrays have been used to examine salience of social stimuli such as faces in ASD. Recent work suggests performance on these paradigms may associate with clinical features of ASD. We evaluate metrics from a visual exploration paradigm in 4-to-11-year-old children with ASD (n = 23; 18 males) and typical development (TD; n = 23; 13 males). Presented with arrays containing faces and nonsocial stimuli, children with ASD looked less at (p = 0.002) and showed fewer fixations to (p = 0.022) faces than TD children, and spent less time looking at each object on average (p = 0.004). Attention to the screen and faces correlated positively with social and cognitive skills in the ASD group (ps < .05). This work furthers our understanding of objective measures of visual exploration in ASD and its potential for quantifying features of ASD.

Abstract PURPOSE/OBJECTIVE(S) To assess the ability of 18F-Fluciclovine PET/CT to distinguish radiation necrosis (RN) from tumor progression (TP) among patients with brain metastases (BM) treated with stereotactic radiosurgery (SRS) in a prospective pilot study. MATERIALS/METHODS Adults with post-SRS BM presenting with follow-up brain MRI equivocal for RN versus TP underwent 18F-Fluciclovine PET/CT within 30 days of equivocal MRI. PET images were reconstructed using a point-spread-function algorithm. Three physician reviewers independently performed qualitative analyses of each lesion using a three-point visual score relative to PET-avidity of blood pool and parotid. Quantitative metrics for each lesion were documented. Reference standard was clinical follow-up with brain MRI until tumor board consensus or tissue confirmation. Nonparametric estimates of area under the receiver operating characteristic curve (AUC) for clustered data were estimated, with diagnostic performance based on visual score. RESULTS In 15 subjects with 20 lesions, final diagnosis was RN in 16 (80%) lesions and TP in 4 (20%). Visual score significantly correlated with final diagnosis (AUC range 0.836-0.906 [p≤0.037]). A threshold score of 2 (lesion 18F-fluciclovine uptake above blood pool to parotid) and higher produced sensitivities and specificities of 75-100% and 38-56% respectively among the reviewer majority. Conversely, a threshold of 3 (uptake higher than parotid) produced sensitivities and specificities of 50-75% and 100% respectively. CONCLUSION In this prospective pilot, basic visual analysis of 18F-Fluciclovine PET/CT provided high sensitivity and specificity in detection of TP in post-SRS BM based on different threshold scores, suggesting room for visual threshold optimization. A low TP event rate limited the ability to estimate sensitivity/specificity and to perform combined qualitative/quantitative analyses. Further study to refine interpretation criteria is ongoing.

We examined development of 5- and 10.5-month-old infants' face representations, focusing on infants' discrimination and categorization of female and male faces. We tested for gender-based preferences and categorization of female and male faces by presenting infants with pairs of faces and then habituating them to a series of majority female or male face ensembles. We then tested for gender preferences with new face pairs (one female and one male; Study 1) or new face ensembles (majority female and majority male; Study 2). We found that both 5- and 10.5-month-old infants discriminated female from male faces in face pairs, and both age groups looked more at female faces during habituation. Neither age group, however, provided evidence of gender-based categorization. We interpret these findings within a theoretical framework that stresses environmental exposure to different social categories, and infants' ability to detect commonalities of features within categories. We conclude that infants' gender-based categorization of faces is constrained by the set of features available in the input.

The ability to learn and apply rules lies at the heart of cognition. In a seminal study, Marcus, Vijayan, Rao, and Vishton (1999) reported that seven-month-old infants learned abstract rules over syllable sequences and were able to generalize those rules to novel syllable sequences. Dozens of studies have since extended on that research using different rules, modalities, stimuli, participants (human adults and non-human animals) and experimental procedures. Yet questions remain about the robustness of Marcus et al.’s (1999) core findings, as the presence of significant learning effects has been mixed. In the current study, we aimed to address this issue by testing XX infants of a wide age range (5;0-12;0 months) in a multi-laboratory (XX laboratories) replication of the Marcus et al. (1999) study.

Both the movements of people and inanimate objects are intimately bound up with physical causality. Furthermore, in contrast to object movements, causal relationships between limb movements controlled by humans and their body displacements uniquely reflect agency and goal-directed actions in support of social causality. To investigate the development of sensitivity to causal movements, we examined the looking behavior of infants between 9 and 18 months of age when viewing movements of humans and objects. We also investigated whether individual differences in gender and gross motor functions may impact the development of the visual preferences for causal movements. In Experiment 1, infants were presented with walking stimuli showing either normal body translation or a "moonwalk" that reversed the horizontal motion of body translations. In Experiment 2, infants were presented with unperformable actions beyond infants' gross motor functions (i.e., long jump) either with or without ecologically valid body displacement. In Experiment 3, infants were presented with rolling movements of inanimate objects that either complied with or violated physical causality. We found that female infants showed longer looking times to normal walking stimuli than to moonwalk stimuli, but did not differ in their looking time to movements of inanimate objects and unperformable actions. In contrast, male infants did not show sensitivity to causal movement for either category. Additionally, female infants looked longer at social stimuli of human actions than male infants. Under the tested circumstances, our findings indicate that female infants have developed a sensitivity to causal consistency between limb movements and body translations of biological motion, only for actions with previous visual and motor exposures, and demonstrate a preference toward social information.