The corpus callosum as anatomical marker of intelligence? A critical examination in a large-scale developmental study.

Intellectual abilities are supported by a large-scale fronto-parietal brain network distributed across both cerebral hemispheres. This bihemispheric network suggests a functional relevance of inter-hemispheric coordination, a notion which is supported by a series of recent structural magnetic resonance imaging (MRI) studies demonstrating correlations between intelligence scores (IQ) and corpus-callosum anatomy. However, these studies also reveal an age-related dissociation: mostly positive associations are reported in adult samples, while negative associations are found in developing samples. In the present study, we re-examine the association between corpus callosum and intelligence measures in a large (734 datasets from 495 participants) developmental mixed cross-sectional and longitudinal sample (6.4-21.9 years) using raw test scores rather than deviation IQ measures to account for the ongoing cognitive development in this age period. Analyzing mid-sagittal measures of regional callosal thickness, a positive association in the splenium of the corpus callosum was found for both verbal and performance raw test scores. This association was not present when the participants' age was considered in the analysis. Thus, we did not reveal any association that cannot be explained by a temporal co-occurrence of overall developmental trends in intellectual abilities and corpus callosum maturation in the present developing sample.

Selective increase in posterior corpus callosum thickness between the age of 4 and 11years.

Establishing an efficient functional and structural connectivity between the two cerebral hemispheres is an important developmental task during childhood, and alterations in this development have accordingly been linked to a series of neurodevelopmental and pediatric disorders. The corpus callosum, the major white-matter structure connecting the hemispheres, has been shown to increase in size throughout the three first decades of life. However, behavioral studies indicate that adult-like performance levels of functional hemispheric interaction are already reached during middle and late childhood. Thus, here we specifically examine the structural development of the corpus callosum during the functionally relevant time period by for the first time (a) selectively addressing prospective childhood development and (b) analyzing a sample in which also younger children are well represented. Corpus callosum anatomy was assessed from 732 T1-weighted MRI datasets acquired from 428 children (213 boys, 215 girls) aged of 4.1 and 10.9years, of which 304 were scanned at two time points. Regional callosal thickness was determined from an outline-based segmentation of the mid-sagittal cross-sectional surface area. Linear-mixed model analyses revealed a significant increase in thickness with age (effect size: up to 15% explained variance) equivalent to a growth in callosal thickness of up to 0.19mm per year in the posterior corpus callosum. The age effect was found to be stronger in posterior segments (i.e., splenium) than in other callosal subregions. Also, the age effect was found to be comparable between boys and girls, and was detected irrespective of whether developmental or individual differences in overall brain size where accounted for or not. Our results demonstrate a selective increase in posterior corpus-callosum thickness during middle and late childhood. Since axons crossing the midline in the splenium mainly connect occipital and parietal cortices, the accentuated posterior growth might reflect the onset of a posterior-to-anterior moving maturation wave in cortical development known to take place in the same time period.

Genes determining the severity of cerebral palsy: the role of single nucleotide polymorphisms on the amount and structure of apolipoprotein E.

AIM: Apolipoprotein E (apoE) influences repair and other processes in the brain, and the apoE4 variant is a risk factor for Alzheimer's disease and for prolonged recovery following traumatic brain injury. We previously reported that specific single nucleotide polymorphisms in the APOE or TOMM40 genes affecting the structure and production of apoE were associated with epilepsy, more impaired hand function and gastrostomy tube feeding in children with cerebral palsy (CP). This study explored how various combinations of the same polymorphisms may affect these clinical manifestations. METHODS: Successful DNA analyses of APOE and TOMM40 were carried out on 227 children. The CP Register of Norway provided details of gross and fine motor function, epilepsy and gastrostomy tube feeding. Possible associations between these clinical manifestations and various combinations of the APOEε2, ε3 or ε4 alleles and of the rs59007384 polymorphism in the TOMM40 gene were explored. RESULTS: Epilepsy, impaired fine motor function and gastrostomy tube feeding were less common in children carrying the combination of rs59007384 GG and APOEε2 or ε3 than in children with other combinations. CONCLUSION: Our findings suggest that specific combinations of genes influence the structure and production of apoE differently and affect the clinical manifestations of CP.

Apolipoprotein E polymorphisms and severity of cerebral palsy: a cross-sectional study in 255 children in Norway.

AIM: The aim of this study was to examine whether the presence of the apolipoprotein E (ApoE) allele APOEε4 is associated with less severe manifestations of cerebral palsy (CP), consistent with the suggested beneficial effect of this allele on neurodevelopment in children. METHOD: ApoE genotyping was performed on buccal epithelial cells from 255 children (141 males 114 females; mean age 12y, SD 2y 3mo, range 9-17y) recorded in the Cerebral Palsy Register of Norway. The main outcome measure of CP severity was the Gross Motor Function Classification System (GMFCS). Secondary outcome measures were fine motor function, epilepsy, and the need for gastrostomy tube feeding (GTF). RESULTS: There was no association between the APOEε4 genotype and GMFCS levels (odds ratio [OR] 1.15; 95% confidence interval [CI] 0.66-1.99). However, the APOEε4 genotype was more often present among children with epilepsy (OR 2.2; 95% CI 1.1-4.2) and/or receiving GTF (OR 2.7; 95% CI 1.1-6.6). Among children with unilateral CP, the presence of APOEε4 was associated with more severe fine motor impairment (OR 2.6; 95% CI 1.3-6.9). INTERPRETATION: Our main hypothesis that APOEε4 would have a protective effect on neurodevelopment was not supported. Instead, subgroup analyses suggested an adverse effect of the APOEε4 genotype on the developing brain after injury.

Cerebral palsy in Norway: prevalence, subtypes and severity.

BACKGROUND/AIM: To describe prevalence, subtypes and severity of cerebral palsy (CP) in Norway using criteria proposed by the Surveillance of Cerebral Palsy in Europe (SCPE) network. MATERIAL: All children in Norway with CP born in January 1996-December 1998 were registered in the Cerebral Palsy Registry of Norway. The Medical Birth Registry of Norway provided the perinatal data. RESULTS: A total of 374 children with CP were identified with a prevalence of 2.1 per 1000 live births. Detailed information was obtained from 294 (79%) children. Median age at clinical assessment was 6.9 years (range: 1.9-10.2 years). Thirty-three percent of the children had spastic unilateral CP, 49% spastic bilateral, 6% dyskinetic, 5% ataxic CP and 7% were not classified. Severely impaired vision and hearing were present in 5% and 4% of the children, respectively. Active epilepsy was present in 28%, mental retardation in 31% and severely impaired or no speech in 28% children. The most severe impairments in gross motor function were observed in children with low Apgar scores, and the most severe impairments in fine motor function in children born at term, with normal birth weight and low Apgar scores. CONCLUSION: Compared with other populations, the prevalence of CP as well as the proportions of subtypes and gross motor impairments were similar, whereas fine motor impairments and associated impairments were more common. The classification of children with mixed forms of CP is still a challenge. Children were more severely affected if Apgar scores were low, and if they were born at term.

Differentiating prospective control information for catching in at-risk and control adolescents.

This paper investigated the use of prospective control in catching and how the results can be used as a sensitive tool to detect diffuse signs of brain dysfunction. A detailed analysis of 286 catching movements of eight adolescents (two males, six females [four very-low-birth weight {VLBW}, one small for gestational age {SGA}, and three appropriate for gestational age]; mean age 14 y 5 mo [SD 6 mo]; range 14-15 y) was performed blind for this purpose. The moving target approached the participants from the side at three different, non-constant accelerations. The results showed that three adolescents used less advanced timing strategies that involved the lower-order variables of distance or velocity to govern movement initiation of at least one of their hands. Two of these were preterm VLBW and one was term SGA. The remaining adolescents, on the other hand, all relied on the higher-order variable of time-to-contact to initiate their hand movements, and were, therefore, considered low-risk. These results were compared with the cerebral magnetic resonance imaging results of the adolescents. The findings show that timing strategy pinpoints successfully those adolescents at risk of neurological problems. It was, therefore, concluded that the skill of using prospective information for catching can be used as a tool to detect diffuse signs of motor dysfunction, which are not readily detected by standard behavioural tests alone.

Low-birth-weight adolescents: psychiatric symptoms and cerebral MRI abnormalities.

To explore associations between psychiatric symptoms and cerebral magnetic resonance imaging abnormalities in low-birth-weight adolescents, 55 very low-birth-weight (or=10th centile) were assessed at 14-15 years of age. Outcome measures were Schedule for Affective Disorders and Schizophrenia for School-Age Children, Attention-Deficit/Hyperactivity Disorder Rating Scale IV, Autism Spectrum Screening Questionnaire, and qualitatively assessed cerebral magnetic resonance images. The very low-birth-weight group manifested increased prevalence of psychiatric symptoms and disorders compared with controls (P < 0.001), especially symptoms of attention-deficit/hyperactivity disorder, and high frequency of ventricular dilatation, white matter reduction, thinning of corpus callosum, and gliosis (P < 0.01 vs controls). The Attention-Deficit/Hyperactivity Disorder Rating Scale score was significantly associated with white matter reduction and thinning of corpus callosum in this group. The term small for gestational age group had increased prevalence of psychiatric symptoms compared with control subjects, but not more frequent abnormalities on cerebral magnetic resonance imaging. In conclusion, attention-deficit/hyperactivity disorder symptoms were significantly associated with white matter reduction and thinning of corpus callosum in very low-birth-weight adolescents. No associations were found for other psychiatric symptoms and brain abnormalities in any of the groups.

Cerebral MRI findings in very-low-birth-weight and small-for-gestational-age children at 15 years of age.

BACKGROUND: A high prevalence of abnormal cerebral MRI findings has been reported in low-birth-weight children. OBJECTIVE: To compare MRI findings in very-low-birth-weight (VLBW) and term small-for-gestational-age (SGA) children with controls in early adolescence. MATERIALS AND METHODS: Cerebral MRI was used to examine 55 VLBW, 54 SGA and 66 controls at 15 years of age. The MR images were qualitatively assessed, and size of ventricles, white-matter and grey-matter abnormalities were reported. RESULTS: The VLBW teenagers had a higher prevalence of various MRI abnormalities than SGA children and controls. Dilation of the ventricular system, especially of the occipital horns, was found in 82% of the VLBW group, in 19% of the SGA group and in 21% of controls. White-matter reduction was found in 53% of the VLBW, in 6% of the SGA and in 2% of controls. Corpus callosum thinning was found in 47% of the VLBW, in 2% of the SGA and in 6% of controls. Periventricular gliosis was found in 29% of the VLBW, in 4% of the SGA and in 8% of controls. CONCLUSIONS: Cerebral MRI pathology in white matter is a common finding in VLBW teenagers. The findings may indicate minor perinatal PVL with resulting loss of white-matter tissue and ventricular dilation.