Sex- and age-based differences in fetal and early childhood hippocampus maturation: a cross-sectional and longitudinal analysis.

The hippocampus, essential for cognitive and affective processes, develops exponentially with differential trajectories seen in girls and boys, yet less is known about its development during early fetal life until early childhood. In a cross-sectional and longitudinal study, we examined the sex-, age-, and laterality-related developmental trajectories of hippocampal volumes in fetuses, infants, and toddlers associated with age. Third trimester fetuses (27-38 weeks' gestational age), newborns (0-4 weeks' postnatal age), infants (5-50 weeks' postnatal age), and toddlers (2-3 years postnatal age) were scanned with magnetic resonance imaging. A total of 133 datasets (62 female, postmenstrual age [weeks] M = 69.38, SD = 51.39, range = 27.6-195.3) were processed using semiautomatic segmentation methods. Hippocampal volumes increased exponentially during the third trimester and the first year of life, beginning to slow at approximately 2 years. Overall, boys had larger hippocampal volumes than girls. Lateralization differences were evident, with left hippocampal growth beginning to plateau sooner than the right. This period of rapid growth from the third trimester, continuing through the first year of life, may support the development of cognitive and affective function during this period.

Default mode network functional connectivity strength in utero and the association with fetal subcortical development.

The default mode network is essential for higher-order cognitive processes and is composed of an extensive network of functional and structural connections. Early in fetal life, the default mode network shows strong connectivity with other functional networks; however, the association with structural development is not well understood. In this study, resting-state functional magnetic resonance imaging and anatomical images were acquired in 30 pregnant women with singleton pregnancies. Participants completed 1 or 2 MR imaging sessions, on average 3 weeks apart (43 data sets), between 28- and 39-weeks postconceptional ages. Subcortical volumes were automatically segmented. Activation time courses from resting-state functional magnetic resonance imaging were extracted from the default mode network, medial temporal lobe network, and thalamocortical network. Generalized estimating equations were used to examine the association between functional connectivity strength between default mode network-medial temporal lobe, default mode network-thalamocortical network, and subcortical volumes, respectively. Increased functional connectivity strength in the default mode network-medial temporal lobe network was associated with smaller right hippocampal, left thalamic, and right caudate nucleus volumes, but larger volumes of the left caudate. Increased functional connectivity strength in the default mode network-thalamocortical network was associated with smaller left thalamic volumes. The strong associations seen among the default mode network functional connectivity networks and regionally specific subcortical volume development indicate the emergence of short-range connectivity in the third trimester.

Age-related effects on the anterior and posterior hippocampal volumes in 6-21 year olds: A model selection approach.

Although recent studies support significant differences in intrinsic structure, function, and connectivity along the longitudinal axis of the hippocampus, few studies have investigated the normative development of this dimension. In addition, factors known to influence hippocampal structure, such as sex or puberty, have yet to be characterized when assessing age-related effects on its subregions. This study addresses this gap by investigating the relationship of the anterior (antHC) and posterior (postHC) hippocampus volumes with age, and how these are moderated by sex or puberty, in structural magnetic resonance imaging scans from 183 typically developing participants aged 6-21 years. Based on previous literature, we first anticipated that non-linear models would best represent the relationship between age and the antHC and postHC volumes. We found that age-related effects are region-specific, such that the antHC volume remains stable with increasing age, while the postHC shows a cubic function characterized by overall volume increase with age but a slower rate during adolescence. Second, we hypothesized that models, which include biological sex or pubertal status would best describe these relationships. Contrary to expectation, models comprising either biological sex or pubertal status did not significantly improve model performance. Further longitudinal research is needed to evaluate their effects on the antHC and postHC development.

Hippocampus long-axis specialization throughout development: A meta-analysis.

The human adult hippocampus can be subdivided into the head, or anterior hippocampus and its body and tail, or posterior hippocampus, and a wealth of functional differences along the longitudinal axis have been reported. One line of literature emphasizes specialization for different aspects of cognition, whereas another emphasizes the unique role of the anterior hippocampus in emotional processing. While some research suggests that functional differences in memory between the anterior and posterior hippocampus appear early in development, it remains unclear whether this is also the case for functional differences in emotion processing. The goal of this meta-analysis was to determine whether the long-axis functional specialization observed in adults is present earlier in development. Using a quantitative meta-analysis, long-axis functional specialization was assessed using the data from 26 functional magnetic resonance imaging studies, which included 39 contrasts and 804 participants ranging in age from 4 to 21 years. Results indicated that emotion was more strongly localized to the anterior hippocampus, with memory being more strongly localized to the posterior hippocampus, demonstrating long-axis specialization with regard to memory and emotion in children similar to that seen in adults. An additional analysis of laterality indicated that while memory was left dominant, emotion was processed bilaterally.

A radiofrequency coil for infants and toddlers.

Infants and toddlers are a challenging population upon which to perform magnetic resonance imaging (MRI) of the brain, both in research and clinical settings. Because of the large range in head size during the early years of development, paediatric neuro-MRI requires a radiofrequency (RF) coil, or set of coils, that is tailored to head size to provide the highest image quality. Mitigating techniques must also be employed to reduce and correct for subject motion. This manuscript describes an RF coil with a tailored mechanical-electrical design that can adapt to the head size of 3-month-old infants to 3-year-old toddlers. The RF coil was designed with tight-fitting coil elements to improve the signal-to-noise ratio (SNR) in comparison with commercially available adult head coils, while simultaneously aiding in immobilization. The coil was designed without visual obstruction to facilitate an unimpeded view of the child's face and the potential application of camera or motion-tracking systems. Despite the lack of elements over the face, the paediatric coil produced higher SNR over most of the brain compared with adult coils, including more than twofold in the periphery. Acceleration rates of fourfold in each Cartesian direction could be achieved. High SNR allowed for short acquisition times through accelerated imaging protocols and reduced the probability of motion during a scan. Modification of the acquisition protocol, with immobilization of the head through the adjustable coil geometry, and subsequently being combined with a motion-tracking system, provides a compelling platform for scanning paediatric populations without sedation and with improved image quality.

Subcortical brain volumes in neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Despite treatment with therapeutic hypothermia, hypoxic-ischemic encephalopathy (HIE) is associated with adverse developmental outcomes, suggesting the involvement of subcortical structures including the thalamus and basal ganglia, which may be vulnerable to perinatal asphyxia, particularly during the acute period. The aims were: (1) to examine subcortical macrostructure in neonates with HIE compared to age- and sex-matched healthy neonates within the first week of life; (2) to determine whether subcortical brain volumes are associated with HIE severity. METHODS: Neonates (n = 56; HIE: n = 28; Healthy newborns from the Developing Human Connectome Project: n = 28) were scanned with MRI within the first week of life. Subcortical volumes were automatically extracted from T1-weighted images. General linear models assessed between-group differences in subcortical volumes, adjusting for sex, gestational age, postmenstrual age, and total cerebral volumes. Within-group analyses evaluated the association between subcortical volumes and HIE severity. RESULTS: Neonates with HIE had smaller bilateral thalamic, basal ganglia and right hippocampal and cerebellar volumes compared to controls (all, p < 0.02). Within the HIE group, mild HIE severity was associated with smaller volumes of the left and right basal ganglia (both, p < 0.007) and the left hippocampus and thalamus (both, p < 0.04). CONCLUSIONS: Findings suggest that, despite advances in neonatal care, HIE is associated with significant alterations in subcortical brain macrostructure. IMPACT: Compared to their healthy counterparts, infants with HIE demonstrate significant alterations in subcortical brain macrostructure on MRI acquired as early as 4 days after birth. Smaller subcortical volumes impacting sensory and motor regions, including the thalamus, basal ganglia, and cerebellum, were seen in infants with HIE. Mild and moderate HIE were associated with smaller subcortical volumes.

Amygdala subnuclei volumes and anxiety behaviors in children and adolescents with autism spectrum disorder, attention deficit hyperactivity disorder, and obsessive-compulsive disorder.

Alterations in the structural maturation of the amygdala subnuclei volumes are associated with anxiety behaviors in adults and children with neurodevelopmental and associated disorders. This study investigated the relationship between amygdala subnuclei volumes and anxiety in 233 children and adolescents (mean age = 11.02 years; standard deviation = 3.17) with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and children with obsessive compulsive disorder (OCD), as well as typically developing (TD) children. Parents completed the Child Behavior Checklist (CBCL), and the children underwent structural MRI at 3 T. FreeSurfer software was used to automatically segment the amygdala subnuclei. A general linear model revealed that children and adolescents with ASD, ADHD, and OCD had higher anxiety scores compared to TD children (p < .001). A subsequent interaction analysis revealed that children with ASD (B = 0.09, p < .0001) and children with OCD (B = 0.1, p < .0001) who had high anxiety had larger right central nuclei volumes compared with TD children. Similar results were obtained for the right anterior amygdaloid area. Amygdala subnuclei volumes may be key to identifying children with neurodevelopmental disorders or those with OCD who are at high risk for anxiety. Findings may inform the development of targeted behavioral interventions to address anxiety behaviors and to assess the downstream effects of such interventions.

Sex-Based Differences in Cortical and Subcortical Development in 436 Individuals Aged 4-54 Years.

Sex-based differences in brain development have long been established in ex vivo studies. Recent in vivo studies using magnetic resonance imaging (MRI) have offered considerable insight into sex-based variations in brain maturation. However, reports of sex-based differences in cortical volumes and thickness are inconsistent. We examined brain maturation in a cross-sectional, single-site cohort of 436 individuals (201 [46%] males) aged 4-54 years (median = 16 years). Cortical thickness, cortical surface area, subcortical surface area, volumes of the cerebral cortex, white matter (WM), cortical and subcortical gray matter (GM), including the thalamic subnuclei, basal ganglia, and hippocampi were calculated using automatic segmentation pipelines. Subcortical structures demonstrated distinct curvilinear trajectories from the cortex, in both volumetric maturation and surface-area expansion in relation to age. Surface-area analysis indicated that dorsal regions of the thalamus, globus pallidus and striatum, regions demonstrating structural connectivity with frontoparietal cortices, exhibited extensive expansion with age, and were inversely related to changes seen in cortical maturation, which contracted with age. Furthermore, surface-area expansion was more robust in males in comparison to females. Age- and sex-related maturational changes may reflect alterations in dendritic and synaptic architecture known to occur during development from early childhood through to mid-adulthood.

Early Procedural Pain Is Associated with Regionally-Specific Alterations in Thalamic Development in Preterm Neonates.

Very preterm human neonates are exposed to numerous invasive procedures as part of life-saving care. Evidence suggests that repetitive neonatal procedural pain precedes long-term alterations in brain development. However, to date the link between pain and brain development has limited temporal and anatomic specificity. We hypothesized that early exposure to painful stimuli during a period of rapid brain development, before pain modulatory systems reach maturity, will predict pronounced changes in thalamic development, and thereby cognitive and motor function. In a prospective cohort study, 155 very preterm neonates (82 males, 73 females) born 24-32 weeks' gestation underwent two MRIs at median postmenstrual ages 32 and 40 weeks that included structural, metabolic, and diffusion imaging. Detailed day-by-day clinical data were collected. Cognitive and motor abilities were assessed at 3 years, corrected age. The association of early (skin breaks, birth-Scan 1) and late pain (skin breaks, Scans 1-2) with thalamic volumes and N-acetylaspartate (NAA)/choline (Cho), and fractional anisotropy of white-matter pathways was assessed. Early pain was associated with slower thalamic macrostructural growth, most pronounced in extremely premature neonates. Deformation-based morphometry analyses confirmed early pain-related volume losses were localized to somatosensory regions. In extremely preterm neonates early pain was associated with decreased thalamic NAA/Cho and microstructural alterations in thalamocortical pathways. Thalamic growth was in turn related to cognitive and motor outcomes. We observed regionally-specific alterations in the lateral thalamus and thalamocortical pathways in extremely preterm neonates exposed to more procedural pain. Findings suggest a sensitive period leading to lasting alterations in somatosensory-system development.SIGNIFICANCE STATEMENT Early exposure to repetitive procedural pain in very preterm neonates may disrupt the development of regions involved in somatosensory processing, leading to poor functional outcomes. We demonstrate that early pain is associated with thalamic volume loss in the territory of the somatosensory thalamus and is accompanied by disruptions thalamic metabolic growth and thalamocortical pathway maturation, particularly in extremely preterm neonates. Thalamic growth was associated with cognitive and motor outcome at 3 years corrected age. Findings provide evidence for a developmentally sensitive period whereby subcortical structures in young neonates may be most vulnerable to procedural pain. Furthermore, results suggest that the thalamus may play a key role underlying the association between neonatal pain and poor neurodevelopmental outcomes in these high-risk neonates.

White matter injury in term neonates with congenital heart diseases: Topology & comparison with preterm newborns.

BACKGROUND: Neonates with congenital heart disease (CHD) are at high risk of punctate white matter injury (WMI) and impaired brain development. We hypothesized that WMI in CHD neonates occurs in a characteristic distribution that shares topology with preterm WMI and that lower birth gestational age (GA) is associated with larger WMI volume. OBJECTIVE: (1) To quantitatively assess the volume and location of WMI in CHD neonates across three centres. (2) To compare the volume and spatial distribution of WMI between term CHD neonates and preterm neonates using lesion mapping. METHODS: In 216 term born CHD neonates from three prospective cohorts (mean birth GA: 39 weeks), WMI was identified in 86 neonates (UBC: 29; UCSF: 43; UCZ: 14) on pre- and/or post-operative T1 weighted MRI. WMI was manually segmented and volumes were calculated. A standard brain template was generated. Probabilistic WMI maps (total, pre- and post-operative) were developed in this common space. Using these maps, WMI in the term CHD neonates was compared with that in preterm neonates: 58 at early-in-life (mean postmenstrual age at scan 32.2 weeks); 41 at term-equivalent age (mean postmenstrual age at scan 40.1 weeks). RESULTS: The total WMI volumes of CHD neonates across centres did not differ (p = 0.068): UBC (median = 84.6 mm3, IQR = 26-174.7 mm3); UCSF (median = 104 mm3, IQR = 44-243 mm3); UCZ (median = 121 mm3, IQR = 68-200.8 mm3). The spatial distribution of WMI in CHD neonates showed strong concordance across centres with predilection for anterior and posterior rather than central lesions. Predominance of anterior lesions was apparent on the post-operative WMI map relative to the pre-operative map. Lower GA at birth predicted an increasing volume of WMI across the full cohort (41.1 mm3 increase of WMI per week decrease in gestational age; 95% CI 11.5-70.8; p = 0.007), when accounting for centre and heart lesion. While WMI in term CHD and preterm neonates occurs most commonly in the intermediate zone/outer subventricular zone there is a paucity of central lesions in the CHD neonates relative to preterms. CONCLUSIONS: WMI in term neonates with CHD occurs in a characteristic topology. The spatial distribution of WMI in term neonates with CHD reflects the expected maturation of pre-oligodendrocytes such that the central regions are less vulnerable than in the preterm neonates.

Converging function, structure, and behavioural features of emotion regulation in very preterm children.

Children born very preterm (VPT; <32 weeks' gestational age) are at high risk for emotional regulation and social communication impairments. However, the underlying neurobiological correlates of these difficulties remain poorly understood. Using a multimodal approach, including both magnetoencephalographic and structural magnetic resonance imaging, we investigated the functional, structural, and behavioural characteristics of socio-emotional processing in 19 school-age children born VPT and 21 age-matched term-born (TB) children (7-13 years). Structural MRI analyses were conducted on a subset of these groups (16 VPT and 21 age-matched TB). Results showed that the inhibition of aversive socio-emotional stimuli was associated with a sustained reduction of right frontoparietal functional brain activity in children born VPT children. Moreover, whole brain structural analyses showed that reductions of cortical thickness or volume in these regions were associated with poor socio-emotional performance in children born VPT. Hence, our results suggest that functional and structural alterations encompassing the frontoparietal areas might be a biological marker of less efficient emotion regulation processes/performance in school-age children born VPT. These findings open up novel avenues to investigate the potential impact of such atypicalities, and in particular, those related to the atypical maturation of the medial prefrontal regions, on the frequent development of psychiatric disorders in this vulnerable population.

Multiple Postnatal Infections in Newborns Born Preterm Predict Delayed Maturation of Motor Pathways at Term-Equivalent Age with Poorer Motor Outcomes at 3 Years.

OBJECTIVES: To evaluate whether the number of postnatal infections is associated with abnormal white matter maturation and poorer motor neurodevelopmental outcomes at 36 months of corrected age. STUDY DESIGN: A prospective longitudinal cohort study was undertaken of 219 newborns born preterm at 24-32 weeks of gestational age recruited between 2006 and 2013 with magnetic resonance imaging of the brain both early in life and at term-equivalent age. Postnatal infection was defined as any clinical infection or positive culture ≥72 hours after birth. White matter maturation was assessed by magnetic resonance spectroscopic imaging, magnetic resonance diffusion tensor imaging, and tract-based spatial statistics. Neurodevelopmental outcomes were assessed in 175 (82% of survivors) infants with Bayley Scales of Infant and Toddler Development-III composite scores and Peabody Developmental Motor Scales at 35 months of corrected age (IQR 34-37 months). Infection groups were compared via the Fisher exact test, Kruskal-Wallis test, and generalized estimating equations. RESULTS: Of 219 neonates born preterm (median gestational age 27.9 weeks), 109 (50%) had no postnatal infection, 83 (38%) had 1 or 2 infections, and 27 (12%) had ≥3 infections. Infants with postnatal infections had more cerebellar hemorrhage. Infants with ≥3 infections had lower N-acetylaspartate/choline in the white matter and basal ganglia regions, lower fractional anisotropy in the posterior limb of the internal capsule, and poorer maturation of the corpus callosum, optic radiations, and posterior limb of the internal capsule on tract-based spatial statistics analysis as well as poorer Bayley Scales of Infant and Toddler Development-III (P = .02) and Peabody Developmental Motor Scales, Second Edition, motor scores (P < .01). CONCLUSIONS: In newborns born preterm, ≥3 postnatal infections predict impaired development of the motor pathways and poorer motor outcomes in early childhood.

Clinical Risk Factors for Punctate White Matter Lesions on Early Magnetic Resonance Imaging in Preterm Newborns.

OBJECTIVE: To identify clinical risk factors for punctate white matter lesions (PWML) on early magnetic resonance imaging (MRI) in 2 cohorts of newborns born extremely preterm in different neonatal centers. STUDY DESIGN: A total of 250 newborns born preterm at less than 28 weeks of gestation (mean 26.4 ± 1.1 weeks) with an early MRI were identified from 2 neonatal centers, in Vancouver, Canada (cohort A, n = 100) and Utrecht, the Netherlands (cohort B, n = 150). Cohort A was imaged as part of a prospective research study and cohort B was imaged as part of routine clinical care. PWML were defined as cluster type foci of hyperintensity on T1-weighted imaging and were identified at a mean postmenstrual age of 31.1 (±1.9) weeks. Multivariable analysis was used to identify clinical factors predictive of PWML. RESULTS: Cluster type PWML were found in 47 newborns born extremely preterm (18.8%) and were more common in cohort A (32%) than in cohort B (10%). Newborns in cohort A generally were sicker than those in cohort B. Multivariable analyses revealed that greater birth weight (B = 0.002; P < .02), grade II-III intraventricular hemorrhage (B = 0.83; P < .02), and cohort A (B = 1.34; P < .0001) were independent predictors of PWML. CONCLUSION: Several risk factors for PWML on early MRI were identified. The interaction among birth weight, intraventricular hemorrhage, and other aspects of postnatal illness as risk factors for PWML warrants further investigation in newborns born extremely preterm and may help to identify modifiable risk factors for PWML.

Midazolam dose correlates with abnormal hippocampal growth and neurodevelopmental outcome in preterm infants.

OBJECTIVE: Very preterm-born neonates (24-32 weeks of gestation) are exposed to stressful and painful procedures during neonatal intensive care. Analgesic and sedation therapies are essential, and opiates and benzodiazepines are commonly used. These medications may negatively impact brain development. The hippocampus may be especially vulnerable to the effects of pain and analgesic and/or sedative therapies and contribute to adverse outcomes. The effect of invasive procedures and analgesic-sedative exposure on hippocampal growth was assessed, as was that of hippocampal growth on neurodevelopmental outcome. METHODS: A total of 138 neonates (51% male, median gestational age = 27.7 weeks) underwent magnetic resonance imaging and diffusion tensor imaging (DTI) scans, early in life (postmenstrual age [PMA] = 32.3 weeks) and at term-equivalent age (PMA = 40.2 weeks). Volumes and DTI measures of axial diffusivity, radial diffusivity, and mean diffusivity (MD) were obtained from the hippocampus. Cognitive, language, and motor abilities were assessed using the Bayley Scales of Infant Development-III at 18.7 months median corrected age. Models testing the association of invasive procedures with hippocampal volumes and DTI measures accounted for birth gestational age, sex, PMA, dose of analgesics/sedatives (fentanyl, morphine, midazolam), mechanical ventilation, hypotension, and surgeries. RESULTS: Total midazolam dose predicted decreased hippocampal volumes (ß = -1.8, p < 0.001) and increased MD (ß = 0.002, p = 0.02), whereas invasive procedures did not (ß = 0, p > 0.5 each). Lower cognitive scores were associated with hippocampal growth (ß = -0.31, p = 0.003), midazolam dose (ß = -0.27, p = 0.03), and surgery (ß = -8.32, p = 0.04). INTERPRETATION: Midazolam exposure was associated with macro- and microstructural alterations in hippocampal development and poorer outcomes consistent with hippocampal dysmaturation. Use of midazolam in preterm neonates, particularly those not undergoing surgery, is cautioned.

Structural Alterations of the Corpus Callosum in Children With Infantile Hydrocephalus.

This study investigates structural alterations of the corpus callosum in children diagnosed with infantile hydrocephalus. We aim to assess both macrostructural (volume) and microstructural (diffusion tensor imaging metrics) facets of the corpus callosum, providing insights into the nature and extent of alterations associated with this condition. Eighteen patients with infantile hydrocephalus (mean age = 9 years) and 18 age- and sex-matched typically developing healthy children participated in the study. Structural magnetic resonance imaging and diffusion tensor imaging were used to assess corpus callosum volume and microstructure, respectively. Our findings reveal significant alterations in corpus callosum volume, particularly in the posterior area, as well as distinct microstructural disparities, notably pronounced in these same segments. These results highlight the intricate interplay between macrostructural and microstructural aspects in understanding the impact of infantile hydrocephalus. Examining these structural alterations provides an understanding into the mechanisms underlying the effects of infantile hydrocephalus on corpus callosum integrity, given its pivotal role in interhemispheric communication. This knowledge offers a more nuanced perspective on neurologic disorders and underscores the significance of investigating the corpus callosum's health in such contexts.

A transdiagnostic examination of cognitive heterogeneity in children and adolescents with neurodevelopmental disorders.

Children and adolescents with neurodevelopmental disorders demonstrate extensive cognitive heterogeneity that is not adequately captured by traditional diagnostic systems, emphasizing the need for alternative assessment and classification techniques. Using a transdiagnostic approach, a retrospective cohort study of cognitive functioning was conducted using a large heterogenous sample (n = 1529) of children and adolescents 7 to 18 years of age with neurodevelopmental disorders. Measures of short-term memory, verbal ability, and reasoning were administered to participants with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), comorbid ADHD/ASD, and participants without neurodevelopmental disorders (non-NDD) using a 12-task, web-based neurocognitive testing battery. Unsupervised machine learning techniques were used to create a self-organizing map, an artificial neural network, in conjunction with k-means clustering to identify data-driven subgroups. The study aims were to: 1) identify cognitive profiles in the sample using a data-driven approach, and 2) determine their correspondence with traditional diagnostic statuses. Six clusters representing different cognitive profiles were identified, including participants with varying forms of cognitive impairment. Diagnostic status did not correspond with cluster-membership, providing evidence for the application of transdiagnostic approaches to understanding cognitive heterogeneity in children and adolescents with neurodevelopmental disorders. Additionally, the findings suggest that many typically developing participants may have undiagnosed learning difficulties, emphasizing the need for accessible cognitive assessment tools in school-based settings.

Identifying cognitive profiles in children with neurodevelopmental disorders using online cognitive testing.

Children with neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD) tend to exhibit similar deficits in attention and memory ability. Early screening of cognitive deficits in children with NDDs, particularly in preschool children, is fundamental to improving cognitive and academic outcomes. In order to determine cognitive profiles in children with ASD and ADHD, we developed accessible audiovisual instructions for an online battery of 13 cognitive tests. Children ages 4-16 who were diagnosed with ADHD (n = 83), or ASD (n = 37), or who were typically developing children (TD) (n = 86) were recruited. Data were analyzed using a stepwise Discriminant Analysis to determine which cognitive tasks were the strongest discriminators between the diagnostic groups. Results revealed four tasks reflective of working memory, reasoning, and attentional processes, which correctly classified approximately 53-60% of each group. The ADHD group had lower scores on attentional tasks compared to TD, while ASD group had lower scores on reasoning tasks compared to the TD children, and made more attempts across all four tasks. The results from this study stress the need for cognitive screening assessments that include domain-specific items to improve the characterization of executive function deficits and promote academic achievement in all children with NDDs.

Commonly diagnosed Neurodevelopmental disorders (NDDs) include autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD). Children with NDDs often experience a wide range of cognitive difficulties which can seriously impact their academic, emotional and behavioural outcomes at school. In this study, we used online cognitive tests that were developed for adults. These 'gamified' tasks assess a number of cognitive abilities including working memory, attention, verbal skills, and reasoning. We developed audiovisual instructions to make these tasks more suitable to children with and without NDDs. These tasks were then used in an online sample of children with ASD, ADHD, and typically developing children. We wanted to see how each group of children performed on the tasks, to assess their relative cognitive strengths and difficulties. We found that the tasks could successfully categorize each group of children based on their task performance. The ADHD group had lower scores on attentional tasks compared to TD children. The ASD group had lower scores on reasoning compared to TD children. The cognitive task battery may eventually be used to help identify cognitive difficulties and improve outcomes in children with NDDs.

Altered resting-state functional connectivity in newborns with hypoxic ischemic encephalopathy assessed using high-density functional near-infrared spectroscopy.

Hypoxic-ischemic encephalopathy (HIE) results from a lack of oxygen to the brain during the perinatal period. HIE can lead to mortality and various acute and long-term morbidities. Improved bedside monitoring methods are needed to identify biomarkers of brain health. Functional near-infrared spectroscopy (fNIRS) can assess resting-state functional connectivity (RSFC) at the bedside. We acquired resting-state fNIRS data from 21 neonates with HIE (postmenstrual age [PMA] = 39.96), in 19 neonates the scans were acquired post-therapeutic hypothermia (TH), and from 20 term-born healthy newborns (PMA = 39.93). Twelve HIE neonates also underwent resting-state functional magnetic resonance imaging (fMRI) post-TH. RSFC was calculated as correlation coefficients amongst the time courses for fNIRS and fMRI data, respectively. The fNIRS and fMRI RSFC maps were comparable. RSFC patterns were then measured with graph theory metrics and compared between HIE infants and healthy controls. HIE newborns showed significantly increased clustering coefficients, network efficiency and modularity compared to controls. Using a support vector machine algorithm, RSFC features demonstrated good performance in classifying the HIE and healthy newborns in separate groups. Our results indicate the utility of fNIRS-connectivity patterns as potential biomarkers for HIE and fNIRS as a new bedside tool for newborns with HIE.

Lateralization of affective processing in the insula.

Evidence from electrophysiological and functional neuroimaging studies has suggested strong lateralization of affective processing within the insular cortices; however, little is known about the spatial location of these processes in these regions. Using quantitative meta-analytic methods the laterality of: (1) emotional processing; (2) stimulus valence (positive vs. negative); (3) perception vs. experience of emotion; and (4) sex-differences were assessed using the data from 143 functional magnetic resonance imaging studies. Activation in response to all emotional stimuli occurred in bilateral anterior and mid-insula, and the left posterior insula. Positive emotional stimuli were associated with activation in the left anterior and mid-insula, while negative emotional stimuli activated bilateral anterior and mid-insula. Activation in response to the perception and experience of emotions was highest in bilateral anterior insula, and within the mid and posterior insula it was left lateralized. In males, emotional stimuli predominantly activated the left anterior/mid-insula and right posterior insula, whereas females activated bilateral anterior insula and the left mid and posterior insula. Spatial distinctions observed in emotional processing and its subcategories can provide a comprehensive account of the role of the insular cortices in affect processing, which could aid in understanding deficits seen in psychiatric or developmental disorders.