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Pregnant women in poverty may be especially likely to experience sleep and circadian rhythm disturbances, which may have downstream effects on fetal neurodevelopment. However, the associations between sleep and circadian rhythm disturbances, social disadvantage during pregnancy, and neonatal brain structure remains poorly understood. The current study explored the association between maternal sleep and circadian rhythm disturbances during pregnancy and neonatal brain outcomes, examining sleep and circadian rhythm disturbances as a mediator of the effect of social disadvantage during pregnancy on infant structural brain outcomes. The study included 148 mother‐infant dyads, recruited during early pregnancy, who had both actigraphy and neuroimaging data. Mothers' sleep was assessed throughout their pregnancy using actigraphy, and neonates underwent brain magnetic resonance imaging in the first weeks of life. Neonatal structural brain outcomes included cortical gray matter, subcortical gray matter, and white matter volumes along with a measure of the total surface area of the cortex. Neonates of mothers who experienced greater inter‐daily deviations in sleep duration had smaller total cortical gray and white matter volumes and reduced cortical surface areas. Neonates of mothers who had higher levels of circadian misalignment and later sleep timing during pregnancy showed smaller subcortical gray matter volumes. Inter‐daily deviations in sleep duration during pregnancy mediated the association between maternal social disadvantage and neonatal structural brain outcomes. Findings highlight the importance of regularity and rhythmicity in sleep schedules during pregnancy and bring to light the role of chronodisruption as a potential mechanism underlying the deleterious neurodevelopmental effects of prenatal adversity. Research Highlights: Social disadvantage was associated with sleep and circadian rhythm disturbances during pregnancy, including later sleep schedules, increased variability in sleep duration, circadian misalignment, and a higher proportion of the sleep period spent awake.Maternal sleep and circadian rhythm disturbances during pregnancy were associated with decreased brain volume and reduced cortical surface area in neonates.Maternal inter‐daily deviations in sleep duration during pregnancy mediated the association between social disadvantage and neonatal brain volume and cortical surface area. [ABSTRACT FROM AUTHOR]

Human studies of early brain development have been limited by extant neuroimaging methods. MRI scanners present logistical challenges for imaging young children, while alternative modalities like functional near‐infrared spectroscopy have traditionally been limited by image quality due to sparse sampling. In addition, conventional tasks for brain mapping elicit low task engagement, high head motion, and considerable participant attrition in pediatric populations. As a result, typical and atypical developmental trajectories of processes such as language acquisition remain understudied during sensitive periods over the first years of life. We evaluate high‐density diffuse optical tomography (HD‐DOT) imaging combined with movie stimuli for high resolution optical neuroimaging in awake children ranging from 1 to 7 years of age. We built an HD‐DOT system with design features geared towards enhancing both image quality and child comfort. Furthermore, we characterized a library of animated movie clips as a stimulus set for brain mapping and we optimized associated data analysis pipelines. Together, these tools could map cortical responses to movies and contained features such as speech in both adults and awake young children. This study lays the groundwork for future research to investigate response variability in larger pediatric samples and atypical trajectories of early brain development in clinical populations. [ABSTRACT FROM AUTHOR]

Irritability refers to the dispositional tendency to respond with anger and frustration to environmental challenges or limits, with both mood and behavioral elements. The dimensional spectrum of irritability is an RDoC‐informed transdiagnostic marker of psychopathology risk, specifically for the common and modifiable internalizing and externalizing disorders. Despite substantial interest in this robust developmentally based transdiagnostic indicator of psychopathology risk, its early brain markers are understudied. Here, we leveraged high‐quality, longitudinal behavioral phenotyping of irritability within an imaging substudy (n = 31) of toddlers, from the When to Worry (W2W) study. We examined prospective associations between volume in three subcortical regions implicated in irritability (the caudate, putamen, and amygdala) around the infants' first birthday (Baseline) and the dimensional spectrum of observed irritability using the Disruptive Behavior Diagnostic Observation Schedule (DB‐DOS) around toddlers' second birthday (Follow‐up). Both left (q =.04, FDR corrected) and right caudate volumes (q =.04, FDR corrected) at Baseline were negatively associated with observed irritability at Follow‐up. We did not find support for associations between putamen and amygdala volumes at Baseline and observed irritability at Follow‐up. These findings identify early prospective neuroanatomical correlates of toddler irritability and provide preliminary support for the caudate being one important brain region for further investigation regarding the early neural correlates of irritability. [ABSTRACT FROM AUTHOR]

Objective: To investigate resting‐state functional connectivity (FC) in pediatric patients with tuberous sclerosis complex and intractable epilepsy requiring surgery. Methods: Resting‐state functional MRI was utilized to investigate functional connectivity in 13 pediatric patients with tuberous sclerosis complex (TSC) and intractable epilepsy requiring surgery. Results: The majority of patients demonstrated a resting‐state network architecture similar to those reported in healthy individuals. However, preoperative differences were evident between patients with high versus low tuber burden, as well as those with good versus poor neurodevelopmental outcomes, most notably in the cingulo‐opercular and visual resting‐state networks. One patient with high tuber burden and poor preoperative development and seizure control had nearly normal development and seizure resolution after surgery. This was accompanied by significant improvement in resting‐state network architecture just one day postoperatively. Significance: Although many patients with tuberous sclerosis complex and medically refractory epilepsy demonstrate functional connectivity patterns similar to healthy children, relationships within and between RSNs demonstrate clear differences in patients with higher tuber burden and worse outcomes. Improvements in resting‐state network organization postoperatively may be related to epilepsy surgery outcomes, providing candidate biomarkers for clinical management in this high‐risk population. [ABSTRACT FROM AUTHOR]

Objective: Children with sickle cell disease (SCD) experience cognitive deficits even when unaffected by stroke. Using functional connectivity magnetic resonance imaging (MRI) as a potential biomarker of cognitive function, we tested our hypothesis that children with SCD would have decreased functional connectivity, and that children experiencing the greatest metabolic stress, indicated by elevated oxygen extraction fraction, would have the lowest connectivity. Methods: We prospectively obtained brain MRIs and cognitive testing in healthy controls and children with SCD. Results: We analyzed data from 60 participants (20 controls and 40 with sickle cell disease). There was no difference in global cognition or cognitive subdomains between cohorts. However, we found decreased functional connectivity within the sensory‐motor, lateral sensory‐motor, auditory, salience, and subcortical networks in participants with SCD compared with controls. Further, as white matter oxygen extraction fraction increased, connectivity within the visual (p = 0.008, parameter estimate = −0.760 [95% CI = −1.297, −0.224]), default mode (p = 0.012, parameter estimate = −0.417 [95% CI = −0.731, −0.104]), and cingulo‐opercular (p = 0.009, parameter estimate = −0.883 [95% CI = −1.517, −0.250]) networks decreased. Interpretation: We conclude that there is diminished functional connectivity within these anatomically contiguous networks in children with SCD compared with controls, even when differences are not seen with cognitive testing. Increased white matter oxygen extraction fraction was associated with decreased connectivity in select networks. These data suggest that elevated oxygen extraction fraction and disrupted functional connectivity are potentially presymptomatic neuroimaging biomarkers for cognitive decline in SCD. ANN NEUROL 2020;88:995–1008 [ABSTRACT FROM AUTHOR]

Motion‐induced artifacts can significantly corrupt optical neuroimaging, as in most neuroimaging modalities. For high‐density diffuse optical tomography (HD‐DOT) with hundreds to thousands of source‐detector pair measurements, motion detection methods are underdeveloped relative to both functional magnetic resonance imaging (fMRI) and standard functional near‐infrared spectroscopy (fNIRS). This limitation restricts the application of HD‐DOT in many challenging imaging situations and subject populations (e.g., bedside monitoring and children). Here, we evaluated a new motion detection method for multi‐channel optical imaging systems that leverages spatial patterns across measurement channels. Specifically, we introduced a global variance of temporal derivatives (GVTD) metric as a motion detection index. We showed that GVTD strongly correlates with external measures of motion and has high sensitivity and specificity to instructed motion—with an area under the receiver operator characteristic curve of 0.88, calculated based on five different types of instructed motion. Additionally, we showed that applying GVTD‐based motion censoring on both hearing words task and resting state HD‐DOT data with natural head motion results in an improved spatial similarity to fMRI mapping. We then compared the GVTD similarity scores with several commonly used motion correction methods described in the fNIRS literature, including correlation‐based signal improvement (CBSI), temporal derivative distribution repair (TDDR), wavelet filtering, and targeted principal component analysis (tPCA). We find that GVTD motion censoring on HD‐DOT data outperforms other methods and results in spatial maps more similar to those of matched fMRI data. [ABSTRACT FROM AUTHOR]

Background: Very preterm (VPT; <30 weeks gestation) children are a heterogeneous group, yet the co‐occurrence of psychiatric and neurodevelopmental impairments remains unclear. Moreover, the clinical and socio‐environmental factors that promote resilient developmental outcomes among VPT children are poorly understood. Methods: One hundred and twenty five children (85 VPT and 40 full‐term) underwent neurodevelopmental evaluation at age 5‐years. Parents and teachers completed measures of internalizing, externalizing, attention‐deficit/hyperactivity (ADHD), and autism symptoms. Psychiatric and neurodevelopmental measures were analyzed using Latent Profile Analysis. Multinomial regression examined the extent that infant, sociodemographic, and family factors, collected prospectively from birth to follow‐up, independently differentiated resilient and impaired children. Results: Four latent profiles were identified, including a Typically Developing Group which represented 27.1% of the VPT group and 65.0% of the full‐term group, an At‐Risk Group with mild psychiatric and neurodevelopmental problems (VPT 44.7%, full‐term 22.5%), a Psychiatric Group with moderate‐to‐severe psychiatric ratings (VPT 12.9%, full‐term 10.0%), and a school‐based Inattentive/Hyperactive Group (VPT 15.3%, full‐term 2.5%). Clinical diagnoses were highest among the Psychiatric Group (80%). Factors that differentiated resilient and impaired subgroups of VPT children included prolonged exposure to maternal psychosocial distress (p ≤.04), current family dysfunction (p ≤.05), and maternal ADHD symptoms (p ≤.02), whereas social risk index scores differentiated resilient and impaired full‐term children (p <.03). Conclusions: Lower levels of maternal distress, family dysfunction, and maternal ADHD symptoms were associated with resilience among VPT children. Maternal distress and family dysfunction are modifiable factors to be targeted as part of psychiatric interventions embedded in the long‐term care of VPT children. [ABSTRACT FROM AUTHOR]

Background: Sociodemographic factors are linked to cognitive outcomes in children born very preterm (VPT; ≤30 weeks gestation). The influence of maternal intellectual ability, a heritable trait, is unknown. Also undetermined is the extent to which associations between maternal and child intellectual ability vary according to parenting behaviors that target cognitive stimulation in the home. Methods: At age 5 years, 84 VPT and 38 demographically matched full-term (FT) children underwent neurodevelopmental assessment. Children's intellectual ability was assessed using The Wechsler Preschool Primary Scale of Intelligence-III, and language was assessed with the Clinical Evaluation of Language Fundamentals Preschool-2. The Wechsler Test of Adult Reading estimated maternal intellectual ability. The StimQ-Preschool questionnaire provided a measure of cognitive stimulation in the home. Linear mixed-effects models examined independent effects and interactions between maternal intellectual ability and cognitive stimulation on children's outcomes. Results: After covariate adjustment, maternal intellectual ability was associated with child intellectual (p < .001) and language (p = .002) abilities. Stronger associations were observed in FT mother–child dyads (B = .63, p = .04) than VPT dyads (B = .42, p = .01). Mothers of VPT children reported lower levels of Parental Involvement in Developmental Advance (p = .007) and Parental Verbal Responsiveness (p = .04). Group differences in Parental Involvement in Developmental Advance, but not Parental Verbal Responsivity, persisted after adjusting for social background (p = .03). There was no evidence of an interaction between maternal intellectual ability and Parental Involvement in Developmental Advance (p = .34). Instead, maternal intellectual ability (p < .001) and Parental Involvement in Developmental Advance (p = .05) independently predicted VPT children's outcomes. Conclusions: Maternal intellectual ability is an important trait linked to VPT and FT children's intellectual and language outcomes. Prematurity increases variation in the heritability of intellectual ability and shifts children from the expected range based on maternal ability. Parental involvement in activities that help children master new skills may promote cognitive development in VPT children born to mothers of lower intellectual ability. [ABSTRACT FROM AUTHOR]

Can babies think? A fundamental challenge for cognitive neuroscience is to answer when brain functions begin and in what form they first emerge. This is challenging with behavioral tasks, as it is difficult to communicate to an infant what a task requires, and motor function is impoverished, making execution of the appropriate response difficult. To circumvent these requirements, neuroimaging provides a complementary route for assessing the emergence of cognition. Starting from the prerequisites of cognitive function and building stepwise, we review when the cortex forms and when it becomes gyrated and regionally differentiated. We then discuss when white matter tracts mature and when functional brain networks arise. Finally, we assess the responsiveness of these brain systems to external events. We find that many cognitive systems are observed surprisingly early. Some emerge before birth, with activations in the frontal lobe even in the first months of gestation. These discoveries are changing our understanding of the nature of cognitive networks and their early function, transforming cognitive neuroscience, and opening new windows for education and investigation. Infant neuroimaging also has tremendous clinical potential, for both detecting atypical development and facilitating earlier intervention. Finally, we discuss the key technical developments that are enabling this nascent field. [ABSTRACT FROM AUTHOR]

Allometry has been used to demonstrate a power-law scaling relationship in the brain of premature born infants. Forty-nine preterm infants underwent neonatal MRI scans and neurodevelopmental testing at age 2 . Measures of cortical surface area and total cerebral volume demonstrated a power-law scaling relationship ( α = 1.27). No associations were identified between these measures and investigated clinical variables. Term equivalent cortical surface area and total cerebral volume measures and scaling exponents were not related to outcome. These findings confirm a previously reported allometric scaling relationship in the preterm brain, and suggest that scaling is not a sensitive indicator of aberrant cortical maturation. [ABSTRACT FROM AUTHOR]

The typical chromosome 16p11.2 rearrangements are estimated to occur at a frequency of approximately 0.6% of all samples tested clinically and have been identified as a major cause of autism spectrum disorders, developmental delay, behavioral abnormalities, and seizures. Careful examination of patients with these rearrangements revealed association with abnormal head size, obesity, dysmorphism, and congenital abnormalities. In this report, we extend this list of phenotypic abnormalities to include scoliosis and vertebral anomalies. We present detailed characterization of phenotypic and radiological data of 10 new patients, nine with the 16p11.2 deletion and one with the duplication within the coordinates chr16:29,366,195 and 30,306,956 (hg19) with a minimal size of 555 kb. We discuss the phenotypical and radiological findings in our patients and review 5 previously reported patients with 16p11.2 rearrangement and similar skeletal abnormalities. Our data suggest that patients with the recurrent 16p11.2 rearrangement have increased incidence of scoliosis and vertebral anomalies. However, additional studies are required to confirm this observation and to establish the incidence of these anomalies. We discuss the potential implications of our findings on the diagnosis, surveillance and genetic counseling of patients with 16p11.2 rearrangement. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

In the last decade, the role of magnetic resonance imaging (MRI) in neonatal care for prematurely born infants has rapidly expanded and evolved. Recent investigations addressed many of the practical issues pertaining to image acquisition and interpretation, enabling high-quality MR images to be obtained without sedating medications in preterm infants at any institution. Expanded application has demonstrated that MRI provides superior ability to assess cerebral development and identify and define cerebral injury in comparison to other imaging modalities. Term equivalent MRI results have been shown to correlate with neurodevelopmental outcomes, providing improved predictive ability over other neuroimaging, clinical or physical examination measures. Regular utilisation of MRI in this population is fundamental to gaining the knowledge and expertise necessary for rational, accurate application. Ongoing experiences will continue to shape the nature and type of information available to clinicians and families using MRI, further refining its role as a routine element of neonatal care. [ABSTRACT FROM AUTHOR]

Objective: Although many perinatal factors have been linked to adverse neurodevelopmental outcomes in very premature infants, much of the variation in outcome remains unexplained. The impact on brain development of 1 potential factor, exposure to stressors in the neonatal intensive care unit, has not yet been studied in a systematic, prospective manner.Methods: In this prospective cohort study of infants born at <30 weeks gestation, nurses were trained in recording procedures and cares. These recordings were used to derive Neonatal Infant Stressor Scale scores, which were employed to measure exposure to stressors. Magnetic resonance imaging (brain metrics, diffusion, and functional magnetic resonance imaging) and neurobehavioral examinations at term equivalent postmenstrual age were used to assess cerebral structure and function. Simple and partial correlations corrected for confounders, including immaturity and severity of illness, were used to explore these relations.Results: Exposure to stressors was highly variable, both between infants and throughout a single infant's hospital course. Exposure to a greater number of stressors was associated with decreased frontal and parietal brain width, altered diffusion measures and functional connectivity in the temporal lobes, and abnormalities in motor behavior on neurobehavioral examination.Interpretation: Exposure to stressors in the Neonatal Intensive Care Unit is associated with regional alterations in brain structure and function. Further research into interventions that may decrease or mitigate exposure to stressors in the neonatal intensive care unit is warranted. [ABSTRACT FROM AUTHOR]

We report on three children from two families with a new pattern recognition malformation syndrome consisting of severe congenital microcephaly (MIC), intractable epilepsy including infantile spasms, and generalized capillary malformations that was first reported recently in this journal [Carter et al. (2011); Am J Med Genet A 155: 301-306]. Two of our reported patients are an affected brother and sister, suggesting this is an autosomal recessive severe congenital MIC syndrome. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The author reflects on the study by K. Mevel and P. Fransson on the role of connectome-based analysis methods in examining neurodevelopmental disorders. The study reportedly involved an examination of studies using resting-state functional magnetic resonance imaging to analyze the brain's large-scale functional networks, cerebral development, and disease. Also discussed are the importance of further studies to improve physicians' ability to interpret reports.