While allowing for rapid recruitment of large samples, online research relies heavily on participants’ self-reports of neuropsychiatric traits, foregoing the clinical characterizations available in laboratory settings. Autism spectrum disorder (ASD) research is one example for which the clinical validity of such an approach remains elusive. Here we compared 56 adults with ASD recruited in person and evaluated by clinicians to matched samples of adults recruited through an online platform (Prolific; 56 with high autistic traits and 56 with low autistic traits) and evaluated via self-reported surveys. Despite having comparable self-reported autistic traits, the online high-trait group reported significantly more social anxiety and avoidant symptoms than in-person ASD participants. Within the in-person sample, there was no relationship between self-rated and clinician-rated autistic traits, suggesting they may capture different aspects of ASD. The groups also differed in their social tendencies during two decision-making tasks; the in-person ASD group was less perceptive of opportunities for social influence and acted less affiliative toward virtual characters. These findings highlight the need for a differentiation between clinically ascertained and trait-defined samples in autism research. Comparing clinically diagnosed adults with autism spectrum disorder (ASD) with online participants with self-reported high autistic traits, this study detected higher rates of social anxiety and avoidance symptoms in online participants, emphasizing the potential distinctions between clinically ascertained autism and self-reported trait-based samples.

BackgroundThe prevalence of depression is elevated in individuals with autism spectrum disorder (ASD) compared to the general population, yet the reasons for this disparity remain unclear. While social deficits central to ASD may contribute to depression, it is uncertain whether social interaction behavior themselves or individuals' introspection about their social behaviors are more impactful. Although the anterior cingulate cortex (ACC) is frequently implicated in ASD, depression, and social functioning, it is unknown if it explains differences between ASD adults with and without co-occurring depression.MethodsThe present study contrasted observed vs. subjective perception of autism symptoms and social interaction assessed with both standardized measures and a lab task, in 65 sex-balanced (52.24% male) autistic young adults. We also quantified ACC and amygdala volume with 7-Tesla structural neuroimaging to examine correlations with self-reported depression and social functioning.ResultsWe found that ASD individuals with self-reported depression exhibited differences in subjective evaluations including heightened self-awareness of ASD symptoms, lower subjective satisfaction with social relations, and less perceived affiliation during the social interaction task, yet no differences in corresponding observed measures, compared to those without depression. Larger ACC volume was related to depression, greater self-awareness of ASD symptoms, and worse subjective satisfaction with social relations. In contrast, amygdala volume, despite its association with clinician-rated ASD symptoms, was not related to depression.LimitationsDue to the cross-sectional nature of our study, we cannot determine the directionality of the observed relationships. Additionally, we included only individuals with an IQ over 60 to ensure participants could complete the social task. We also utilized self-reported depression indices instead of clinically diagnosed depression, which may limit the comprehensiveness of the findings.ConclusionsOur approach highlights the unique role of subjective perception of autism symptoms and social interactions, beyond the observable manifestation of social impairment in ASD, in contributing to self-reported depression, with the ACC playing a crucial role. These findings imply possible heterogeneity of ASD concerning co-occurring depression. Using neuroimaging, we were able to demarcate depressive phenotypes co-occurring alongside autistic phenotypes.

While allowing for rapid recruitment of large samples, online psychiatric and neurodevelopmental research relies heavily on participants' self-report of neuropsychiatric symptoms, foregoing the rigorous clinical characterization of laboratory settings. Autism spectrum disorder (ASD) research is one example where the clinical validity of such an approach remains elusive. Here, we compared participants characterized online via self-reports against in-person participants evaluated by clinicians. Despite having comparable self-reported autism symptoms, the online high-trait group reported significantly more social anxiety and avoidant behavior than in-person ASD subjects. Within the in-person sample, there was no relationship between self-rated and clinician-rated autism symptoms, suggesting these approaches may capture different aspects of ASD. The online high-trait and in-person ASD participants also differed in their behavior in well-validated social decision-making tasks: the in-person group perceived having less social control and acted less affiliative towards virtual characters. Our study aimed to draw comparisons at three levels: methodological platform (online versus in-person), symptom measurement (self- versus clinician-report), and social behavior. We identified a lack of agreement between self- and clinician-rated measures of symptoms and divergent social tendencies in groups ascertained by each method, highlighting the need for differentiation between in-person versus online samples in autism research.

Misophonia is a disorder in which certain sounds produced by other people lead to intense negative reactions. It remains unknown how misophonia relates to other psychiatric conditions or impairments. To identify latent constructs under-lying symptoms, we conducted a factor analysis consisting of items from ques-tionnaires assessing symptoms of misophonia and other psychiatric conditions. One thousand forty-two participants completed the questionnaires and a social exchange task in which they either could (''controllable'') or could not (''uncon-trollable'') influence future monetary offers from other people. Misophonia and obsessive-compulsive (OC) symptoms loaded onto the same factor. Compared with individuals with low Miso-OC factor scores, individuals with high scores reported higher perceived controllability of their social interactions during the uncontrollable condition and stronger aversion to social norm violations in the un-controllable compared with the controllable condition. Together, these results suggest misophonia, and OC symptoms share a latent psychiatric dimension char-acterized by aberrant computations of social controllability.

Humans constantly navigate complex social environments, where the controllability of these environments has a profound impact on our behavior and mental health. For instance, illusion of control, which refers to a false sense of control when in fact one does not have it, has been conceptually linked to delusional ideation. However, the neurocomputational mechanisms of social controllability, and how they might go awry in delusional individuals, are poorly understood.

Misophonia is a debilitating condition in which certain sounds produced by other people lead to intense negative reactions. It remains unknown how misophonia relates to other diagnostic conditions or specific functional impairments. A total of 1,175 participants completed online questionnaires assessing symptoms of misophonia and other psychiatric conditions. To identify latent constructs underlying symptoms, we conducted a factor analysis consisting of all psychiatric questionnaire items. 1,042 of the participants also completed a social exchange task in which they either could (‘controllable') or could not (‘uncontrollable’) influence the future monetary offers from other people. Misophonia and obsessive-compulsive disorder (OCD) symptoms loaded most heavily onto the same factor. Examination of participants’ task behaviors revealed that, compared to individuals with low Miso-OCD factor scores, individuals with high scores reported higher perceived controllability of their social interactions and a larger discrepancy between their perceived and actual controllability during the uncontrollable condition. Additionally, the high Miso-OCD group showed stronger aversion to social norm violation in the uncontrollable compared to the controllable condition. Together, these results suggest misophonia and OCD symptoms share a latent psychiatric dimension characterized by aberrant computations of controllability of their social environment.

Humans navigate complex situations that require the accurate estimation of the controllability of the environment. Aberrant controllability computation might lead to maladaptive behaviors and poor mental health outcomes. Illusion of control, which refers to a heightened sense of control while the environment is uncontrollable, is one such manifestation and has been conceptually associated with delusional ideation. Nevertheless, this association has not yet been formally characterized in a computational framework. To address this, we used a computational psychiatry approach to quantify illusion of control in human participants with high (n = 125) or low (n = 126) trait delusion. Participants played a two-party exchange game in which their choices either did ( "Controllable condition ") or did not ( "Uncontrollable condition ") influence the future monetary offers made by simulated partners. We found that the two groups behaved similarly in model-agnostic measures (i.e., offer size, rejection rate). However, computational modeling revealed that compared to the low trait delusion group, the high delusion group overestimated their influence ( "expected influence " parameter) over the offers made by their partners under the Uncontrollable condition. Highly delusional individuals also reported a stronger sense of control than those with low trait delusion in the Uncontrollable condition. Furthermore, the expected influence parameter and self-reported beliefs about controllability were significantly correlated in the Controllable condition in individuals with low trait delusion, whereas this relationship was diminished in those with high trait delusion. Collectively, these findings demonstrate that delusional ideation is associated with aberrant computation of and belief about environmental controllability, as well as a belief-behavior disconnect.

Individuals with Autism Spectrum Disorder (ASD) are thought to show alterations in social decision-making, but the neural underpinnings of these impairments remain poorly understood. To investigate this, we utilized novel, proactive social tasks akin to the types of interactions with which people with ASD struggle daily.

BACKGROUND AND OBJECTIVES:Prenatal exposure to environmental tobacco smoke (ETS) is associated with increased attention problems in children, however, the effects of such exposure on children's brain structure and function have not been studied. Herein, we probed effects of prenatal ETS on children's cognitive control circuitry and behavior. METHODS:Forty-one children (7-9 years) recruited from a prospective longitudinal birth cohort of non-smoking mothers completed structural and task-functional magnetic resonance imaging to evaluate effects of maternal ETS exposure, measured by maternal prenatal urinary cotinine. Attention problems and externalizing behaviors were measured by parent report on the Child Behavior Checklist. RESULTS:Compared to non-exposed children, exposed children had smaller left and right thalamic and inferior frontal gyrus (IFG) volumes, with large effect sizes (p-FDR < .05, Cohen's D range from 0.79 to 1.07), and increased activation in IFG during the resolution of cognitive conflict measured with the Simon Spatial Incompatibility Task (38 voxels; peak t(25) = 5.25, p-FWE = .005). Reduced thalamic volume was associated with increased IFG activation and attention problems, reflecting poor cognitive control. Mediation analyses showed a trend toward left thalamic volume mediating the association between exposure and attention problems (p = .05). CONCLUSIONS:Our findings suggest that maternal ETS exposure during pregnancy has deleterious effects on the structure and function of cognitive control circuitry which in turn affects attentional capacity in school-age children. These findings are consistent with prior findings documenting the effects of active maternal smoking on chidlren's neurodevleoment, pointing to the neurotixicity of nicotine regardless of exposure pathway.

BACKGROUND:Prenatal air pollution exposure is associated with reductions in self-regulation and academic achievement. Self-regulation has been separately linked with academic achievement. Understudied, however, are the contributions of pollution exposure to inhibitory control, a facet of self-regulation, and whether pollution-related inhibitory control deficits are associated with impairment in academic achievement. METHODS:Participants were recruited from a prospective birth cohort. Measures of prenatal airborne polycyclic aromatic hydrocarbons (PAH) during the third trimester of pregnancy, inhibitory control (NEPSY Inhibition) at mean age = 10.4 years, and Woodcock-Johnson Tests of Achievement-III at mean age = 13.7 were available for N = 200 participants. Multiple linear regression examined sex-dependent and sex independent associations among prenatal PAH, childhood inhibitory control, and academic achievement during adolescence, and whether childhood inhibitory control mediated associations between prenatal PAH and academic achievement during adolescence, controlling for ethnicity, maternal country of birth, language of prenatal interview, maternal marital status, maternal years of education, material hardship, quality of home caregiving environment, and early life stress. RESULTS:Across all participants, higher prenatal PAH was significantly associated with worse spelling skills (WJ-III Spelling, β = -0.16, 95%Confidence Interval [CI]: 0.30, -0.02, p = .02). Trend level associations between higher prenatal PAH and worse reading comprehension (WJ-III Passage Comprehension, β = -0.13, 95%CI: 0.28, 0.01, p = .07) and math skills (WJ-III Broad Math, β = -0.11, 95%CI: 0.25, 0.03, p = .11) were detected. Across all participants, higher PAH was significantly associated with worse inhibitory control (β = -0.15, 95%CI: 0.29,-0.01 p = .03). Better inhibitory control was significantly associated with better reading comprehension (WJ-III Passage Comprehension, β = 0.22, 95%CI: 0.09, 0.36, p < .002) and math skills (WJ-III Broad Math Index, β = 0.32, 95%CI: 0.19, 0.45, p < .001), and trend level associations with better spelling skills (WJ-III Spelling, β = 0.12, 95%CI: 0.02, 0.26, p = .10). Inhibitory control significantly mediated PAH-related achievement effects for Passage Comprehension (β = -0.61, 95%CI: 1.49, -0.01) and Broad Math Index (β = -1.09, 95%CI: 2.36, -0.03). CONCLUSIONS:Higher prenatal PAH exposure and lower childhood inhibitory control were associated with worse spelling, passage comprehension, and math in adolescence. Notably, childhood inhibitory control mediated PAH exposure-related effects on achievement in adolescents. Identifying these potential exposure-related phenotypes of learning problems may promote interventions that target inhibitory control deficits rather than content specific deficits.

Autism spectrum disorder (ASD) is characterized by hallmark impairments in social functioning. Nevertheless, nonsocial cognition, including hippocampus-dependent spatial reasoning and episodic memory, is also commonly impaired in ASD. ASD symptoms typically emerge between 12 and 24 months of age, a time window associated with critical developmental events in the hippocampus. Despite this temporal overlap and evidence of hippocampal structural abnormalities in ASD individuals, relatively few human studies have focused on hippocampal function in ASD. Herein, we review the existing evidence for the involvement of the hippocampus in ASD and highlight the hippocampus as a promising area of interest for future research in ASD.

Objective: The current study examined how the opposing effects of bilingualism and attention problems operate on executive functioning, visual processing, and verbal fluency in children with clinically significant levels of attention problems. Method: We tested whether bilingualism moderated associations between attention problems and visual processing, executive functioning, and verbal fluency. Results: Bilingual children (n = 331) showed visual processing advantages relative to their monolingual peers (n = 165), but only at higher, and not lower, levels of attention problems. Bilingualism did not moderate the association between attention problems and interference control; however, across all children, those with higher levels of attention problems had more difficulty with interference control. Monolingual children demonstrated advantages in verbal fluency relative to bilingual children, but this did not vary with attention problems. Conclusion: Visual processing advantages in bilinguals are detected among children with heightened attention problems, but advantages in interference control are not; findings may have implications for classroom interventions.

Importance:Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by deficits in visual-spatial processing but not in reading or verbal ability; in addition, problems in math calculation, visual executive functioning, fine-motor skills, and social skills are often present. To our knowledge, there are no population-based estimates of the prevalence of NVLD in community samples. Objective:To estimate the prevalence of the NVLD cognitive profile in 3 independent samples of children and adolescents from studies centered around brain imaging in the US and Canada. Design, Setting, and Participants:This cross-sectional study used data from 2 samples recruited from the community and overselected for children with psychiatric disorders (Healthy Brain Network [HBN], January 1, 2015, to December 31, 2019, and Nathan Kline Institute-Rockland Sample [NKI], January 1, 2011, to December 31, 2018) and 1 community-ascertained population sample (Saguenay Youth Study [SYS], January 1, 2003, to December 31, 2012) overselected for active maternal smoking during pregnancy. Main Outcomes and Measures:Prevalence of NVLD. Criteria for NVLD were based on clinical records of deficits in visual-spatial reasoning and impairment in 2 of 4 domains of function (fine-motor skills, math calculation, visual executive functioning, and social skills). Sample weighting procedures adjusted for demographic differences in sample frequencies compared with underlying target populations. Inflation factor weights accounted for overrepresentation of psychiatric disorders (HBN and NKI samples). Results:Across 3 independent samples, the prevalence of NVLD was estimated among 2596 children and adolescents aged 6 to 19 years (mean [SD] age, 12.5 [3.4] years; 1449 male [55.8%]). After sample and inflation weights were applied, the prevalence of NVLD was 2.78% (95% CI, 2.03%-3.52%) in the HBN sample and 3.9% (95% CI, 1.96%-5.78%) in the NKI sample. In the SYS sample, the prevalence of NVLD was 3.10% (95% CI, 1.93%-4.27%) after applying the sample weight. Across samples and estimation strategies, the population prevalence of NVLD was estimated to range from 3% to 4%. When applied to the US population younger than 18 years, 2.2 million to 2.9 million children and adolescents were estimated to have NVLD. Conclusions and Relevance:The findings suggest that the prevalence of NVLD in children and adolescents may be 3% to 4%. Given that few youths are diagnosed with NVLD and receive treatment, increased awareness, identification of the underlying neurobiological mechanisms, and development and testing interventions for the disorder are needed.

The hippocampus is known to play a critical role in a variety of complex abilities, including visual-spatial reasoning, social functioning, and math. Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by deficits in visual-spatial reasoning that are accompanied by impairment in social function or mathematics, as well as motor or executive function skills. Despite the overlap between behaviors supported by the hippocampus and impairments in NVLD, the structure and function of the hippocampus in NVLD has not been studied. To address this gap in the literature, we first compared hippocampal volume and resting-state functional connectivity in children with NVLD (n = 24) and typically developing (TD) children (n = 20). We then explored associations between hippocampal structure, connectivity, and performance on measures of spatial, social, and mathematical ability. Relative to TD children, those with NVLD showed significant reductions in left hippocampal volume and greater hippocampal-cerebellar connectivity. In children with NVLD, reduced hippocampal volume associated with worse mathematical problem solving. Although children with NVLD exhibited more social problems (social responsiveness scale [SRS]) and higher hippocampal-cerebellar connectivity relative to TD children, greater connectivity was associated with fewer social problems among children with NVLD but not TD children. Such an effect may suggest a compensatory mechanism. These structural and functional alterations of the hippocampus may disrupt its putative role in organizing conceptual frameworks through cognitive mapping, thus contributing to the cross-domain difficulties that characterize NVLD.

Nonverbal Learning Disability (NVLD) is characterized by deficits in visual-spatial, but not verbal, reasoning. Nevertheless, the functioning of the neural circuits supporting spatial processing have yet to be assessed in children with NVLD. We compared the resting state functional connectivity of a spatial brain network among children with NVLD, children with reading disorder (RD), and typically developing (TD) children. Seventy-five participants (7–15 years old) were included in the study (20 TD, 24 NVLD, and 31 RD). Group differences in global efficiency and functional connectivity among 12 regions comprising a previously defined spatial network were evaluated. Associations with behavior were explored. Global efficiency of the spatial network associated positively with spatial ability and inversely with socioemotional problems. Within the spatial network, associations between left posterior cingulate (PCC) and right retrosplenial cortical activity were reduced in children with NVLD relative to those without spatial deficits (RD and TD). Connectivity between left PCC and right posterior cerebellum (Crus I and II) was reduced in both groups of children with learning disabilities (NVLD and RD) relative to TD children. Functional connectivity of the spatial network was atypically associated with cognitive and socioemotional performance in children with NVLD. Identifying a neurobiological substrate for NVLD provides evidence that it is a discrete clinical entity and suggests targets for treatment.

Converging evidence suggests that early life adversity precipitates altered maturation of emotion regulation neurocircuitry, which may underlie increased psychiatric risk in adversity-exposed individuals. However, it is unknown whether neighborhood poverty, a more protracted form of adversity, has a similar effect on emotion regulation circuitry.

Reading disorder (RD) is characterized by deficient phonological processing, but children with RD also have cognitive control deficits, the neural correlates of which are not fully understood. We used fMRI to assess neural activity during the resolution of cognitive conflict on the Simon Spatial Incompatibility task and patterns of resting-state functional connectivity (RSFC) from task control (TC) regions in 7–12-year-old children with RD compared to their typically developing (TD) peers. Relative to TD children ( n = 17), those with RD ( n = 16) over-engaged a right superior/medial frontal cluster during the resolution of conflict ( p = .05). Relative to TD children ( n = 18), those with RD ( n = 17) also showed reduced RSFC (voxel-wise p < .001; cluster-size p < .05, FDR corrected) from cingulo-opercular seeds to left hemisphere fronto-parietal and temporo-parietal reading-related regions, perhaps reflecting reduced organization of TC circuits and reduced integration with reading-related regions. Children with RD additionally showed reduced RSFC between fronto-parietal and default mode network regions. Follow-up analyses in a subset of children with both useable task and resting state data (RD = 13; TD = 17) revealed that greater conflict-related activation of the right frontal Simon task ROI associated with better word-reading, perhaps suggesting a compensatory role for this over-engagement. Connectivity from fronto-parietal seeds significantly associated with Simon task performance and word-reading accuracy in RD children. These findings suggest that altered functioning and connectivity of control circuits may contribute to cognitive control deficits in children with RD. Future studies should assess the utility of adding cognitive control training to reading remediation programs.

Children from language minority (LM) environments speak a language at home that differs from that at school, are often from socioeconomically disadvantaged backgrounds, and are at risk for reading impairment. We evaluated the main effects and interaction of language status and phonological memory and awareness on reading disorder in 352 children from socioeconomically disadvantaged backgrounds. A significant phonological memory by language status interaction indicated that phonological memory problems were magnified in predicting reading impairment in children from LM versus English dominant (ED) homes. Among children without reading disorder, language minority status was unrelated to phonological processing.

Genetic factors explain 60 percent of variance in reading disorder. Exposure to neurotoxicants, including polybrominated diphenyl ethers (PBDEs), may be overlooked risk factors for reading problems. We used resting-state functional magnetic resonance imaging (rs-fMRI) to examine associations between prenatal PBDE concentrations and functional connectivity of a reading-related network (RN) in a community sample of 5-year-old children (N = 33). Maternal serum PBDE concentrations (SPBDE) were measured at 12.2 +/- 2.8 weeks gestation (mean +/- SD). The RN was defined by 12 regions identified in prior task-based fMRI meta-analyses; global efficiency (GE) was used to measure network integration. Linear regression evaluated associations between SPBDE, word reading, and GE of the RN and the default mode network (DMN); the latter to establish specificity of findings. Weighted quantile sum regression analyses evaluated the contributions of specific PBDE congeners to observed associations. Greater RN efficiency was associated with better word reading in these novice readers. Children with higher SPBDE showed reduced GE of the RN; SPBDE was not associated with DMN efficiency, demonstrating specificity of our results. Consistent with prior findings, SPBDE was not associated word reading at 5-years-old. Altered efficiency and integration of the RN may underlie associations between SPBDE concentrations and reading problems observed previously in older children.