An Atypical Sulcal Pattern in Children with Disorders of the Corpus Callosum and Its Relation to Behavioral Outcomes.
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ABSTRACT:
SUBMITTER: Vasung L
PROVIDER: S-EPMC7391268 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Developmental dyslexia (DD) is highly heritable and previous studies observed reduced cortical volume, white matter integrity, and functional alterations in left posterior brain regions in individuals with DD. The primary sulcal pattern has been hypothesized to relate to optimal organization and connections of cortical functional areas. It is determined during prenatal development and may reflect early, genetically influenced, brain development. We characterize the sulcal pattern using graph-based pattern analysis and investigate whether sulcal patterns in parieto-temporal and occipito-temporal regions are atypical in elementary school-age children with DD and pre-readers/beginning readers (preschoolers/kindergarteners) with a familial risk (elementary school-age children: n [males/females], age range = 17/11, 84-155 months; preschoolers/kindergarteners: 16/15, 59-84 months). The pattern of sulcal basin area in left parieto-temporal and occipito-temporal regions was significantly atypical (more sulcal basins of smaller size) in children with DD and further correlated with reduced reading performance on single- and nonword reading measures. A significantly atypical sulcal area pattern was also confirmed in younger preschoolers/kindergarteners with a familial risk of DD. Our results provide further support for atypical early brain development in DD and suggest that DD may originate from altered organization or connections of cortical areas in the left posterior regions.
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Project description:Fetuses with isolated agenesis of the corpus callosum (ACC) are associated with a broad spectrum of neurodevelopmental disability that cannot be specifically predicted in prenatal neuroimaging. We hypothesized that ACC may be associated with aberrant cortical folding. In this study, we determined altered patterning of early primary sulci development in fetuses with isolated ACC using novel quantitative sulcal pattern analysis which measures deviations of regional sulcal features (position, depth, and area) and their intersulcal relationships in 7 fetuses with isolated ACC (27.1 ± 3.8 weeks of gestation, mean ± SD) and 17 typically developing (TD) fetuses (25.7 ± 2.0 weeks) from normal templates. Fetuses with ACC showed significant alterations in absolute sulcal positions and relative intersulcal positional relationship compared to TD fetuses, which were not detected by traditional gyrification index. Our results reveal altered sulcal positional development even in isolated ACC that is present as early as the second trimester and continues throughout the fetal period. It might originate from altered white matter connections and portend functional variances in later life.
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Project description:Neurodevelopmental disorders, such as attention-deficit/hyperactivity disorder (ADHD), are often accompanied by disrupted cortical folding. We applied a quantitative sulcal pattern analysis technique using graph structures to study the atypical cortical folding at the lobar level in ADHD brains in this study. A total of 183 ADHD patients and 167 typical developmental controls matched according to age and gender were enrolled. We first constructed sulcal graphs at the brain lobar level and then investigated their similarity to the typical sulcal patterns. The within-group variability and interhemispheric similarity in sulcal patterns were also compared between the ADHD and TDC groups. The results showed that, compared with controls, the left frontal, right parietal, and temporal lobes displayed altered similarities to the typical sulcal patterns in patients with ADHD. Moreover, the sulcal patterns in ADHD seem to be more heterogeneous than those in controls. The results also identified the disruption of the typical asymmetric sulcal patterns in the frontal lobe between the ADHD and control groups. Taken together, our results revealed the atypical sulcal pattern in boys with ADHD and provide new insights into the neuroanatomical mechanisms of ADHD.
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Project description:ObjectiveAir pollution (AP) may affect neurodevelopment, but studies about the effects of AP on the growing human brain are still scarce. We aimed to investigate the effects of prenatal exposure to AP on lateral ventricles (LV) and corpus callosum (CC) volumes in children and to determine whether the induced brain changes are associated with behavioral problems.MethodsAmong the children recruited through a set of representative schools of the city of Barcelona, (Spain) in the Brain Development and Air Pollution Ultrafine Particles in School Children (BREATHE) study, 186 typically developing participants aged 8-12 years underwent brain MRI on the same 1.5 T MR unit over a 1.5-year period (October 2012-April 2014). Brain volumes were derived from structural MRI scans using automated tissue segmentation. Behavioral problems were assessed using the Strengths and Difficulties Questionnaire (SDQ) and the criteria of the Attention Deficit Hyperactivity Disorder DSM-IV list. Prenatal fine particle (PM2.5) levels were retrospectively estimated at the mothers' residential addresses during pregnancy with land use regression (LUR) models. To determine whether brain structures might be affected by prenatal PM2.5 exposure, linear regression models were run and adjusted for age, sex, intracranial volume (ICV), maternal education, home socioeconomic vulnerability index, birthweight and mothers' smoking status during pregnancy. To test for associations between brain changes and behavioral outcomes, negative binomial regressions were performed and adjusted for age, sex, ICV.ResultsPrenatal PM2.5 levels ranged from 11.8 to 39.5 μg/m3 during the third trimester of pregnancy. An interquartile range increase in PM2.5 level (7 μg/m3) was significantly linked to a decrease in the body CC volume (mm3) (β = -53.7, 95%CI [-92.0, -15.5] corresponding to a 5% decrease of the mean body CC volume) independently of ICV, age, sex, maternal education, socioeconomic vulnerability index at home, birthweight and mothers' smoking status during the third trimester of pregnancy. A 50 mm3 decrease in the body CC was associated with a significant higher hyperactivity subscore (Rate Ratio (RR) = 1.09, 95%CI [1.01, 1.17) independently of age, sex and ICV. The statistical significance of these results did not survive to False Discovery Rate correction for multiple comparisons.ConclusionsPrenatal exposure to PM2.5 may be associated with CC volume decrease in children. The consequences might be an increase in behavioral problems.
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Project description:BackgroundThe corpus callosum (CC) is suggested as an indirect biomarker of white matter volume, which is often affected in preterm birth. However, diagnosing mild white matter injury is challenging.MethodsWe studied 124 children born preterm (mean age: 8.4 ± 1.1 years), using MRI to assess CC measurements and cognitive/motor outcomes based on the Wechsler Intelligence Scale for Children-V (WPPSI-V) and Movement Assessment Battery for Children-2 (MABC-2).ResultsChildren with normal outcomes exhibited greater height (10.2 ± 2.1 mm vs. 9.4 ± 2.3 mm; p = 0.01) and fractional anisotropy at splenium (895[680-1000] vs 860.5[342-1000]) and total CC length (69.1 ± 4.8 mm vs. 67.3 ± 5.1 mm; p = 0.02) compared to those with adverse outcomes. All measured CC areas were smaller in the adverse outcome group. Models incorporating posterior CC measurements demonstrated the highest specificity (83.3% Sp, AUC: 0.65) for predicting neurological outcomes. CC length and splenium height were the only linear measurements associated with manual dexterity and total MABC-2 score while both the latter and genu were related with Full-Scale Intelligence Quotient.ConclusionsCC biometry in children born very preterm at school-age is associated with outcomes and exhibits a specific subregion alteration pattern. The posterior CC may serve as an important neurodevelopmental biomarker in very preterm infants.ImpactThe corpus callosum has the potential to serve as a reliable and easily measurable biomarker of white matter integrity in very preterm children. Estimating diffuse white matter injury in preterm infants using conventional MRI sequences is not always conclusive. The biometry of the posterior part of the corpus callosum is associated with cognitive and certain motor outcomes at school age in children born very preterm. Length and splenium measurements seem to serve as reliable biomarkers for assessing neurological outcomes in this population.
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Project description:Autism spectrum disorder is associated with an altered early brain development. However, the specific cortical structure abnormalities underlying this disorder remain largely unknown. Nonetheless, atypical cortical folding provides lingering evidence of early disruptions in neurodevelopmental processes and identifying changes in the geometry of cortical sulci is of primary interest for characterizing these structural abnormalities in autism and their evolution over the first stages of brain development. Here, we applied state-of-the-art sulcus-based morphometry methods to a large highly-selective cohort of 73 young male children of age spanning from 18 to 108 months. Moreover, such large cohort was selected through extensive behavioral assessments and stringent inclusion criteria for the group of 59 children with autism. After manual labeling of 59 different sulci in each hemisphere, we computed multiple shape descriptors for each single sulcus element, hereby separating the folding measurement into distinct factors such as the length and depth of the sulcus. We demonstrated that the central, intraparietal and frontal medial sulci showed a significant and consistent pattern of abnormalities across our different geometrical indices. We also found that autistic and control children exhibited strikingly different relationships between age and structural changes in brain morphology. Lastly, the different measures of sulcus shapes were correlated with the CARS and ADOS scores that are specific to the autistic pathology and indices of symptom severity. Inherently, these structural abnormalities are confined to regions that are functionally relevant with respect to cognitive disorders in ASD. In contrast to those previously reported in adults, it is very unlikely that these abnormalities originate from general compensatory mechanisms unrelated to the primary pathology. Rather, they most probably reflect an early disruption on developmental trajectory that could be part of the primary pathology.
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Project description:The corpus callosum is the largest white matter pathway connecting homologous structures of the two cerebral hemispheres. Remarkably, children and adults with developmental absence of the corpus callosum (callosal dysgenesis, CD) show typical interhemispheric integration, which is classically impaired in adult split-brain patients, for whom the corpus callosum is surgically severed. Tovar-Moll and colleagues (2014) proposed alternative neural pathways involved in the preservation of interhemispheric transfer. In a sample of six adults with CD, they revealed two homotopic bundles crossing the midline via the anterior and posterior commissures and connecting parietal cortices, and the microstructural properties of these aberrant bundles were associated with functional connectivity of these regions. The aberrant bundles were specific to CD and not visualised in healthy brains. We extended this study in a developmental cohort of 20 children with CD and 29 typically developing controls (TDC). The two anomalous white-matter bundles were visualised using tractography. Associations between structural properties of these bundles and their regional functional connectivity were explored. The proposed atypical bundles were observed in 30% of our CD cohort crossing via the anterior commissure, and in 30% crossing via the posterior commissure (also observed in 6.9% of TDC). However, the structural property measures of these bundles were not associated with parietal functional connectivity, bringing into question their role and implication for interhemispheric functional connectivity in CD. It is possible that very early disruption of embryological callosal development enhances neuroplasticity and facilitates the formation of these proposed alternative neural pathways, but further evidence is needed.
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Project description:The corpus callosum is the main commissure connecting left and right cerebral hemispheres, and varies widely in size. Differences in the midsagittal area of the corpus callosum (MSACC) have been associated with a number of cognitive and behavioral phenotypes, including obsessive-compulsive disorders, psychopathy, suicidal tendencies, bipolar disorder, schizophrenia, autism, and attention deficit hyperactivity disorder. Although there is evidence to suggest that MSACC is heritable in normal human populations, there is surprisingly little evidence concerning the genetic modulation of this variation. Mice provide a potentially ideal tool to dissect the genetic modulation of MSACC. Here, we use a large genetic reference panel - the BXD recombinant inbred line - to dissect the natural variation of the MSACC. We estimated the MSACC in over 300 individuals from nearly 80 strains. We found a 4-fold difference in MSACC between individual mice, and a 2.5-fold difference among strains. MSACC is a highly heritable trait (h(2) = 0.60), and we mapped a suggestive QTL to the distal portion of Chr 14. Using sequence data and neocortical expression databases, we were able to identify eight positional and plausible biological candidate genes within this interval. Finally, we found that MSACC correlated with behavioral traits associated with anxiety and attention.
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Project description:Characterization of the human Anterior Temporal Lobe and Corpus Callosum: C-HPP
2014-06-05 | PXD000547 | Pride