Coordinated brain activity between individuals, or inter-brain synchrony, has been shown to increase during cooperation and correlate with cooperation success. However, few studies have examined parent-child inter-brain synchrony and whether it is associated with meaningful aspects of the parent-child relationship. Here, we measured inter-brain synchrony in the right prefrontal (PFC) and temporal cortices in mother-child dyads while they engaged in a cooperative and independent task. We tested whether inter-brain synchrony in mother-child dyads (1) increases during cooperation, (2) differs in mother-son versus mother-daughter dyads, and (3) is related to cooperation performance and the attachment relationship. Overall inter-brain synchrony in the right hemisphere, and the right dorsolateral and frontopolar PFC in particular, was higher during cooperation. Mother-son dyads showed less inter-brain synchrony during the independent task and a stronger increase in synchrony in response to cooperation than mother-daughter dyads. Lastly, we did not find strong evidence for links between inter-brain synchrony and child attachment. Mother-child cooperation may increase overall inter-brain synchrony, although differently for mother-son versus mother-daughter dyads. More research is needed to better understand the potential role of overall inter-brain synchrony in mother-child cooperation, and the potential link between inter-brain synchrony and attachment.

In both Turner syndrome (TS) and Klinefelter syndrome (KS) copy number aberrations of the X chromosome lead to various developmental symptoms. We report a comparative analysis of TS vs. KS regarding differences at the genomic network level measured in primary samples by analyzing gene expression, DNA methylation, and chromatin conformation. X-chromosome inactivation (XCI) silences transcription from one X chromosome in female mammals, on which most genes are inactive, and some genes escape from XCI. In TS, almost all differentially expressed escape genes are down-regulated but most differentially expressed inactive genes are up-regulated. In KS, differentially expressed escape genes are up-regulated while the majority of inactive genes appear unchanged. Interestingly, 94 differentially expressed genes (DEGs) overlapped between TS and female and KS and male comparisons; and these almost uniformly display expression changes into opposite directions. DEGs on the X chromosome and the autosomes are coexpressed in both syndromes, indicating that there are molecular ripple effects of the changes in X chromosome dosage. Six potential candidate genes (RPS4X,SEPT6,NKRF,CX0rf57,NAA10, andFLNA) for KS are identified on Xq, as well as candidate central genes on Xp for TS. Only promoters of inactive genes are differentially methylated in both syndromes while escape gene promoters remain unchanged. The intrachromosomal contact map of the X chromosome in TS exhibits the structure of an active X chromosome. The discovery of shared DEGs indicates the existence of common molecular mechanisms for gene regulation in TS and KS that transmit the gene dosage changes to the transcriptome.

Objective To identify distinct behavioral and cognitive profiles associated with ADHD in Turner syndrome (TS), relative to idiopathic ADHD and neurotypical controls, in order to elucidate X-linked influences contributing to ADHD. Methods We used a multilevel-model approach to compare 49 girls with TS to 37 neurotypical females, aged 5–12, on established measures of behavior (BASC-2) and neurocognitive function (NEPSY). We further compared girls with TS to BASC-2 and NEPSY age-matched reference data obtained from children with idiopathic ADHD. Results Within the TS group, 51% scored at or above the “at-risk” range for ADHD-associated behaviors on the BASC-2 (TS/+ADHD). The BASC-2 behavioral profile in this TS/+ADHD-subgroup was comparable to a reference group of boys with ADHD with respect to attentional problems and hyperactivity. However, the TS/+ADHD-subgroup had significantly higher hyperactivity scores relative to a reference sample of girls with ADHD (p=0.016). The behavioral profile in TS was associated with significantly lower attention and executive function scores on the NEPSY relative to neurotypical controls (p=0.015); but was comparable to scores from a reference sample of children with idiopathic ADHD. Deficits in attention and executive function were not observed in girls with TS having low levels of ADHD-associated behavior (TS/−ADHD). Conclusions ADHD-associated behavioral and cognitive problems in TS are prevalent and comparable in severity to those found in children with idiopathic ADHD. The ADHD phenotype in TS also appears relatively independent of cognitive features typically associated with TS, like visuospatial weaknesses. These findings suggest that X-linked haploinsufficiency and downstream biological effects contribute to increased risk for ADHD.

AimWe investigated neuropsychiatric outcomes in children with Noonan syndrome and addressed limitations in previous research with a focus on prepubertal children, comparison to typically developing children, comprehensive neuropsychiatric evaluation, and controlling for overall cognitive abilities.MethodForty‐five children with Noonan syndrome (mean = 8 years 6 months, SD = 2 years 2 months; 29 females) and 40 typically developing children (mean = 8 years 9 months, SD = 2 years; 22 females) were evaluated with objective, parent‐report, and psychiatric interview measures.ResultsChildren with Noonan syndrome demonstrated elevated symptoms across attention‐deficit/hyperactivity disorder (ADHD) (attention, hyperactivity, and inhibition), autism spectrum disorder (ASD) (maintaining social relationships, behavioral rigidity, and sensory sensitivity), and oppositional defiant disorder (ODD) (aggression) symptom clusters relative to typically developing children (all p < 0.05). Group differences in nearly all parent‐report measures were significant after accounting for variations in intellectual functioning, suggesting that increased neurodevelopmental symptoms are not simply driven by overall intelligence. Twenty out of 42 children with Noonan syndrome met criteria for ADHD, eight out of 42 for ODD, and 11 out of 43 demonstrated clinically significant symptoms seen in children with ASD.InterpretationChildren with Noonan syndrome are at increased risk for a range of ADHD, ASD, and ODD associated symptoms. A dimensional approach reveals significant ASD symptoms in Noonan syndrome that do not emerge when using the currently accepted categorical diagnostic approach.

Attachment plays a key role in how children process information about the self and others. Here, we examined the neural bases of interindividual differences in attachment in late childhood and tested whether social cognition-related neural activity varies as function of age. In a small sample of 8-year-old to 12-year-old children (n = 21/19), we used functional magnetic resonance imaging to measure neural responses during social feedback processing and self-other distinction. Attachment was assessed using child self-report. The social feedback processing task presented smiling and angry faces either confirming or disconfirming written information about participant performance on a perceptual game. In addition to observing main effects of facial emotion and performance, an increase in age was related to a shift from negative (i.e., angry faces/bad performance) to positive (i.e., smiling faces/good performance) information processing in the left amygdala/hippocampus, bilateral fusiform face area, bilateral anterior temporal pole (ATP), and left anterior insula. There were no effects of attachment on social feedback processing. The self-other distinction task presented digital morphs between children's own faces and faces of their mother or stranger females. We observed differential activation in face processing and mentalizing regions in response to self and mother faces versus morphed faces. Furthermore, left ATP activity was associated with attachment anxiety such that greater attachment anxiety was related to a shift from heightened processing of self and mother faces to morphed faces. There were no effects of age on self-other distinction. We discuss our preliminary findings in the context of attachment theory and previous work on social evaluation and self-other processing. Keywords Social cognitive affective neuroscience. Late childhood. fMRI. Attachment. Age The parent-child relationship provides the foundation for children's learning about the self and others. The quality of this relationship is reflected in children's attachment orientation to their parents, which, in turn, shapes how children respond to social situations (Bowlby, 1982). More specifically, attachment theory posits that sensitive versus insensitive caregiving experiences contribute to the development of different attachment-derived internal working models (IWMs)-cognitive schemas about the self, others, and social relationships in general-that have extended implications for social and emotional development (Bretherton & Munholland, 2008). In line with this perspective, a more secure attachment emerges from sensitive caregiving experiences and leads to an IWM that represents others as safe and dependable, and the self as worthy and capable of eliciting care when needed. Secure IWMs have consistently been associated with children's positive development, including greater social competence and emotion understanding (

ABBREVIATIONS NEPSYDevelopmental NEuroPSYchological Assessment SCA Sex chromosome aneuploidy AIM To study sex differences in attention-deficit/hyperactivity disorder (ADHD) symptoms, we explored whether X chromosome absence or excess is independently associated with deficits in attention and hyperactivity, executive function, and processing speed. METHOD We assessed 116 children (ages 3y 10mo-11y 11mo, mean 8y 5mo, SD 1y 11mo) with a variable number of sex chromosomes: 36 females with Turner syndrome (45, X0), 20 males with Klinefelter syndrome (47, XXY), 37 typically developing females (XX), and 23 typically developing males (XY).RESULTS X chromosome absence was associated with increased attention problems, hyperactivity, and deficits in inhibitory control, compared with female children with XX (all p<0.003). Conversely, X chromosome excess was associated with weakness in working memory (p=0.018) and approached significance for attention problems (p=0.071) but not with hyperactivity, or weakness in inhibitory control relative to male children with XY. Using nonparametric effect size to quantify the clinical effect revealed that X chromosome absence affected attention, hyperactivity, executive function, and processing speed (all r>0.4), while X excess affected in-laboratory as well as parent-reported working memory (all r>0.4).

Mounting evidence supports the role of the Ras/mitogen-activated protein kinase (Ras/MAPK) pathway in neurodevelopmental disorders. Here, the authors used a genetics-first approach to examine how Ras/MAPK pathogenic variants affect the functional organization of the brain and cognitive phenotypes including weaknesses in attention and inhibition. Functional MRI was used to examine resting state functional connectivity (RSFC) in association with Ras/MAPK pathogenic variants in children with Noonan syndrome (NS). Participants (age 4–12 years) included 39 children with NS (mean age 8.44, SD=2.20, 25 females) and 49 typically developing (TD) children (mean age 9.02, SD=9.02, 33 females). Twenty-eight children in the NS group and 46 in the TD group had usable MRI data and were included in final analyses. The results indicated significant hyperconnectivity for the NS group within canonical visual, ventral attention, left frontoparietal and limbic networks (p<0.05 FWE). Higher connectivity within canonical left frontoparietal and limbic networks positively correlated with cognitive function within the NS but not the TD group. Further, the NS group demonstrated significant group differences in seed-based striatal-frontal connectivity (Z>2.6, p<0.05 FWE). Hyperconnectivity within canonical brain networks may represent an intermediary phenotype between Ras/MAPK pathogenic variants and cognitive phenotypes, including weaknesses in attention and inhibition. Altered striatal-frontal connectivity corresponds with smaller striatal volume and altered white matter connectivity previously documented in children with NS. These results may indicate delayed maturation and compensatory mechanisms and they are important for understanding the pathophysiology underlying cognitive phenotypes in NS and in the broader population of children with neurodevelopmental disorders.

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