Obesity-Related Metabolic Risk in Sedentary Hispanic Adolescent Girls with Normal BMI

Hispanic adolescent girls with normal BMI frequently have high body fat %. Without knowledge of body fat content and distribution, their risk for metabolic complications is unknown. We measured metabolic risk indicators and abdominal fat distribution in post-pubertal Hispanic adolescent girls with Normal BMI (N-BMI: BMI < 85th percentile) and compared these indicators between girls with Normal BMI and High Fat content (N-BMI-HF: body fat ≥ 27%; n = 15) and Normal BMI and Normal Fat content (N-BMI-NF: body fat < 27%; n = 8). Plasma concentrations of glucose, insulin, adiponectin, leptin and Hs-CRP were determined. Insulin resistance was calculated using an oral glucose tolerance test. Body fat % was measured by DXA and subcutaneous, visceral and hepatic fat by MRI/MRS. The N-BMI-HF girls had increased abdominal and hepatic fat content and increased insulin resistance, plasma leptin and Hs-CRP concentrations (p < 0.05) as compared to their N-BMI-NF counterparts. In N-BMI girls, insulin resistance, plasma insulin and leptin correlated with BMI and body fat % (p < 0.05). This research confirms the necessity of the development of BMI and body fat % cut-off criteria per sex, age and racial/ethnic group based on metabolic risk factors to optimize the effectiveness of metabolic risk screening procedures

Superior Verbal Learning and Memory in Pediatric Brain Tumor Survivors Treated With Proton Versus Photon Radiotherapy

OBJECTIVE: Radiotherapy for pediatric brain tumor has been associated with late cognitive effects. Compared to conventional photon radiotherapy (XRT), proton radiotherapy (PRT) delivers lower doses of radiation to healthy brain tissue. PRT has been associated with improved long-term cognitive outcomes compared to XRT. However, there is limited research comparing the effects of XRT and PRT on verbal memory. METHOD: Survivors of pediatric brain tumor treated with either XRT ( RESULTS: Overall, patients receiving PRT demonstrated superior verbal learning and recall compared to those treated with XRT. Encoding and retrieval deficits were more common in the XRT group than the PRT group, with encoding problems being most prevalent. The PRT group was more likely to engage in semantic clustering strategies, which predicted better encoding and retrieval. Encoding ability was associated with higher intellectual and adaptive functioning, and fewer parent-reported concerns about day-to-day attention and cognitive regulation. CONCLUSION: Results suggest that PRT is associated with verbal memory sparing, driven by effective encoding and use of learning strategies. Future work may help to clarify underlying neural mechanisms associated with verbal memory decline, which will better inform treatment approaches

A Preliminary DTI Tractography Study of Developmental Neuroplasticity 5-15 Years After Early Childhood Traumatic Brain Injury

Plasticity is often implicated as a reparative mechanism when addressing structural and functional brain development in young children following traumatic brain injury (TBI); however, conventional imaging methods may not capture the complexities of post-trauma development. The present study examined the cingulum bundles and perforant pathways using diffusion tensor imaging (DTI) in 21 children and adolescents (ages 10-18 years) 5-15 years after sustaining early childhood TBI in comparison with 19 demographically-matched typically-developing children. Verbal memory and executive functioning were also evaluated and analyzed in relation to DTI metrics. Beyond the expected direction of quantitative DTI metrics in the TBI group, we also found qualitative differences in the streamline density of both pathways generated from DTI tractography in over half of those with early TBI. These children exhibited hypertrophic cingulum bundles relative to the comparison group, and the number of tract streamlines negatively correlated with age at injury, particularly in the late-developing anterior regions of the cingulum; however, streamline density did not relate to executive functioning. Although streamline density of the perforant pathway was not related to age at injury, streamline density of the left perforant pathway was significantly and positively related to verbal memory scores in those with TBI, and a moderate effect size was found in the right hemisphere. DTI tractography may provide insight into developmental plasticity in children post-injury. While traditional DTI metrics demonstrate expected relations to cognitive performance in group-based analyses, altered growth is reflected in the white matter structures themselves in some children several years post-injury. Whether this plasticity is adaptive or maladaptive, and whether the alterations are structure-specific, warrants further investigation

Postnatal Brain Trajectories and Maternal Intelligence Predict Childhood Outcomes in Complex CHD

Objective: To determine whether early structural brain trajectories predict early childhood neurodevelopmental deficits in complex CHD patients and to assess relative cumulative risk profiles of clinical, genetic, and demographic risk factors across early development. Study Design: Term neonates with complex CHDs were recruited at Texas Children’s Hospital from 2005–2011. Ninety-five participants underwent three structural MRI scans and three neurodevelopmental assessments. Brain region volumes and white matter tract fractional anisotropy and radial diffusivity were used to calculate trajectories: perioperative, postsurgical, and overall. Gross cognitive, language, and visuo-motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development and with the Wechsler Preschool and Primary Scale of Intelligence and Beery–Buktenica Developmental Test of Visual–Motor Integration. Multi-variable models incorporated risk factors. Results: Reduced overall period volumetric trajectories predicted poor language outcomes: brainstem ((β, 95% CI) 0.0977, 0.0382–0.1571; p = 0.0022) and white matter (0.0023, 0.0001–0.0046; p = 0.0397) at 5 years; brainstem (0.0711, 0.0157–0.1265; p = 0.0134) and deep grey matter (0.0085, 0.0011–0.0160; p = 0.0258) at 3 years. Maternal IQ was the strongest contributor to language variance, increasing from 37% at 1 year, 62% at 3 years, and 81% at 5 years. Genetic abnormality’s contribution to variance decreased from 41% at 1 year to 25% at 3 years and was insignificant at 5 years. Conclusion: Reduced postnatal subcortical–cerebral white matter trajectories predicted poor early childhood neurodevelopmental outcomes, despite high contribution of maternal IQ. Maternal IQ was cumulative over time, exceeding the influence of known cardiac and genetic factors in complex CHD, underscoring the importance of heritable and parent-based environmental factors

Cognitive Sparing in Proton versus Photon Radiotherapy for Pediatric Brain Tumor Is Associated with White Matter Integrity: An Exploratory Study

Radiotherapy for pediatric brain tumors is associated with reduced white matter structural integrity and neurocognitive decline. Superior cognitive outcomes have been reported following proton radiotherapy (PRT) compared to photon radiotherapy (XRT), presumably due to improved sparing of normal brain tissue. This exploratory study examined the relationship between white matter change and late cognitive effects in pediatric brain tumor survivors treated with XRT versus PRT. Pediatric brain tumor survivors treated with XRT

Effects of eight neuropsychiatric copy number variants on human brain structure

Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions

Metrics of brain network architecture capture the impact of disease in children with epilepsy

Background and objective: Epilepsy is associated with alterations in the structural framework of the cerebral network. The aim of this study was to measure the potential of global metrics of network architecture derived from resting state functional MRI to capture the impact of epilepsy on the developing brain. Methods: Pediatric patients were retrospectively identified with: 1. Focal epilepsy; 2. Brain MRI at 3 Tesla, including resting state functional MRI; 3. Full scale IQ measured by a pediatric neuropsychologist. The cerebral cortex was parcellated into approximately 700 gray matter network nodes. The strength of a connection between two nodes was defined as the correlation between their resting BOLD signal time series. The following global network metrics were then calculated: clustering coefficient, transitivity, modularity, path length, and global efficiency. Epilepsy duration was used as an index for the cumulative impact of epilepsy on the brain. Results: 45 patients met criteria (age: 4–19 years). After accounting for age of epilepsy onset, epilepsy duration was inversely related to IQ (p: 0.01). Epilepsy duration predicted by a machine learning algorithm on the basis of the five global network metrics was highly correlated with actual epilepsy duration (r: 0.95; p: 0.0001). Specifically, modularity and to a lesser extent path length and global efficiency were independently associated with epilepsy duration. Conclusions: We observed that a machine learning algorithm accurately predicted epilepsy duration based on global metrics of network architecture derived from resting state fMRI. These findings suggest that network metrics have the potential to form the basis for statistical models that translate quantitative imaging data into patient-level markers of cognitive deterioration

Normalization enhances brain network features that predict individual intelligence in children with epilepsy.

BACKGROUND AND PURPOSE:Architecture of the cerebral network has been shown to associate with IQ in children with epilepsy. However, subject-level prediction on this basis, a crucial step toward harnessing network analyses for the benefit of children with epilepsy, has yet to be achieved. We compared two network normalization strategies in terms of their ability to optimize subject-level inferences on the relationship between brain network architecture and brain function. MATERIALS AND METHODS:Patients with epilepsy and resting state fMRI were retrospectively identified. Brain network nodes were defined by anatomic parcellation, first in patient space (nodes defined for each patient) and again in template space (same nodes for all patients). Whole-brain weighted graphs were constructed according to pair-wise correlation of BOLD-signal time courses between nodes. The following metrics were then calculated: clustering coefficient, transitivity, modularity, path length, and global efficiency. Metrics computed on graphs in patient space were normalized to the same metric computed on a random network of identical size. A machine learning algorithm was used to predict patient IQ given access to only the network metrics. RESULTS:Twenty-seven patients (8-18 years) comprised the final study group. All brain networks demonstrated expected small world properties. Accounting for intrinsic population heterogeneity had a significant effect on prediction accuracy. Specifically, transformation of all patients into a common standard space as well as normalization of metrics to those computed on a random network both substantially outperformed the use of non-normalized metrics. CONCLUSION:Normalization contributed significantly to accurate subject-level prediction of cognitive function in children with epilepsy. These findings support the potential for quantitative network approaches to contribute clinically meaningful information in children with neurological disorders

Mutual Information Better Quantifies Brain Network Architecture in Children with Epilepsy

Purpose. Metrics of the brain network architecture derived from resting-state fMRI have been shown to provide physiologically meaningful markers of IQ in children with epilepsy. However, traditional measures of functional connectivity (FC), specifically the Pearson correlation, assume a dominant linear relationship between BOLD time courses; this assumption may not be valid. Mutual information is an alternative measure of FC which has shown promise in the study of complex networks due to its ability to flexibly capture association of diverse forms. We aimed to compare network metrics derived from mutual information-defined FC to those derived from traditional correlation in terms of their capacity to predict patient-level IQ. Materials and Methods. Patients were retrospectively identified with the following: (1) focal epilepsy; (2) resting-state fMRI; and (3) full-scale IQ by a neuropsychologist. Brain network nodes were defined by anatomic parcellation. Parcellation was performed at the size threshold of 350 mm2, resulting in networks containing 780 nodes. Whole-brain, weighted graphs were then constructed according to the pairwise connectivity between nodes. In the traditional condition, edges (connections) between each pair of nodes were defined as the absolute value of the Pearson correlation coefficient between their BOLD time courses. In the mutual information condition, edges were defined as the mutual information between time courses. The following metrics were then calculated for each weighted graph: clustering coefficient, modularity, characteristic path length, and global efficiency. A machine learning algorithm was used to predict the IQ of each individual based on their network metrics. Prediction accuracy was assessed as the fractional variation explained for each condition. Results. Twenty-four patients met the inclusion criteria (age: 8–18 years). All brain networks demonstrated expected small-world properties. Network metrics derived from mutual information-defined FC significantly outperformed the use of the Pearson correlation. Specifically, fractional variation explained was 49% (95% CI: 46%, 51%) for the mutual information method; the Pearson correlation demonstrated a variation of 17% (95% CI: 13%, 19%). Conclusion. Mutual information-defined functional connectivity captures physiologically relevant features of the brain network better than correlation. Clinical Relevance. Optimizing the capacity to predict cognitive phenotypes at the patient level is a necessary step toward the clinical utility of network-based biomarkers