Cognitive correlates of mathematical disabilities in children with velo-cardio-facial syndrome

Children with Velo-Cardio-Facial Syndrome (VCFS) consistently show mathematical disabilities (MD). At the neuropsychological level, it is important to know which general cognitive deficits underlie these MD. Therefore, we examined various mathematical abilities, working memory, rapid automatized naming and processing speed in 25 children with VCFS and 25 carefully selected matched controls. Children with VCFS showed a reduced ability to solve addition and subtraction problems and performed less accurately on multidigit arithmetic and word problem solving. There were no group differences on the general cognitive measures, except that children with VCFS performed higher than controls on the phonological loop tasks. To conclude, the administered general cognitive competencies could not give a satisfactory account of the MD in VCFS.     

Behavior problems and personality aspects of 40 children with velo-cardio-facial syndrome

Data are collected with the Child Behavior Check List (CBCL) as well as with the Teacher Report Form (TRF) of 40 VCFS children between 4 and 18 years of age. Half of the group shows very high problem scores in the "clinical" range. The average T-score of the VCFS children as a group are over 60 (one standard deviation above the mean) for the "total problem score" and the "internalising score". The highest scores with the subscales are found with "withdrawn" and "social problems". But also "thought problems" and "attention problems" score over 60. The VCFS children show more behavior problems and personality problems than the matched control children with a craniofacial anomaly. The differences are highly statistically significant.     

Effects of Mathematics Anxiety and Mathematical Metacognition on Word Problem Solving in Children with and without Mathematical Learning Difficulties

Mathematics is one of the most objective, logical, and practical academic disciplines. Yet, in addition to cognitive skills, mathematical problem solving also involves affective factors. In the current study, we first investigated effects of mathematics anxiety (MA) and mathematical metacognition on word problem solving (WPS). We tested 224 children (116 boys, M = 10.15 years old, SD = 0.56) with the Mathematics Anxiety Scale for Children, the Chinese Revised-edition Questionnaire of Pupil’s Metacognitive Ability in Mathematics, and WPS tasks. The results indicated that mathematical metacognition mediated the effect of MA on WPS after controlling for IQ. Second, we divided the children into four mathematics achievement groups including high achieving (HA), typical achieving (TA), low achieving (LA), and mathematical learning difficulty (MLD). Because mathematical metacognition and MA predicted mathematics achievement, we compared group differences in metacognition and MA with IQ partialled out. The results showed that children with MLD scored lower in self-image and higher in learning mathematics anxiety (LMA) than the TA and HA children, but not in mathematical evaluation anxiety (MEA). MLD children’s LMA was also higher than that of their LA counterparts. These results provide insight into factors that may mediate poor WPS performance which emerges under pressure in mathematics. These results also suggest that the anxiety during learning mathematics should be taken into account in mathematical learning difficulty interventions.     

Pre-academic and early academic achievement in children with velocardiofacial syndrome (del22q11.2) of borderline or normal intelligence

School-aged children with del22q11.2 tend to show a typical learning and neuropsychological profile, which is characterised by a VIQ-PIQ discrepancy (in favour of the VIQ) and significantly better scores for reading (decoding) and spelling compared to mathematics. To the best of our knowledge, there exists no systematic research on the pre-academic and early academic skills that might underpin these learning difficulties. The purpose of the current study was to investigate more systematically these pre-academic and early academic skills in borderline to normal intelligent (FSIQ > 70) children with del22q11.2 in the last year of kindergarten and first grade of primary school in Flanders. In the kindergarten group, meta-linguistic awareness and counting skills were examined. In the group of first graders, children were tested on reading, spelling and mathematics. Thirteen children (mean age: 6 years 4 months (SD = 0.84); 9 boys, 4 girls) participated in this study. In the present study, there were no differences in intelligence and academic outcomes between boys and girls, and no differences in IQ and academic achievement between children with cardiac defects or severe velopharyngeal insufficiency (VPI) and children without these deficits. With regard to pre-academic achievement in general, a characteristic profile with clearly better results for meta-linguistic awareness in comparison to counting skills was found, but this difference is not statistically significant. Concerning early academic achievement, children with del22q11.2, as a group, perform (despite their somewhat lower general intelligence) on average compared with their age-related peers. However, at an individual level--especially within the domain of counting skills and mathematics--there is a wide variability, with some children showing remarkable learning difficulties already at an early age.     

Molecular analysis of velo-cardio-facial syndrome patients with psychiatric disorders.

Velo-cardio-facial syndrome (VCFS) is characterized by conotruncal cardiac defects, cleft palate, learning disabilities, and characteristic facial appearance and is associated with hemizygous deletions within 22q11. A newly recognized clinical feature is the presence of psychiatric illness in children and adults with VCFS. To ascertain the relationship between psychiatric illness, VCFS, and chromosome 22 deletions, we evaluated 26 VCFS patients by clinical and molecular biological methods. The VCFS children and adolescents were found to share a set of psychiatric disorders, including bipolar spectrum disorders and attention-deficit disorder with hyperactivity. The adult patients, >18 years of age, were affected with bipolar spectrum disorders. Four of six adult patients had psychotic symptoms manifested as paranoid and grandiose delusions. Loss-of-heterozygosity analysis of all 26 patients revealed that all but 3 had a large 3-Mb common deletion. One patient had a nested distal deletion and two did not have a detectable deletion. Somatic cell hybrids were developed from the two patients who did not have a detectable deletion within 22q11 and were analyzed with a large number of sequence tagged sites. A deletion was not detected among the two patients at a resolution of 21 kb. There was no correlation between the phenotype and the presence of the deletion within 22q11. The remarkably high prevalence of bipolar spectrum disorders, in association with the congenital anomalies of VCFS and its occurrence among nondeleted VCFS patients, suggest a common genetic etiology.     

Personality profiles of youngsters with velo-cardio-facial syndrome

The personality profile of 48 youngsters (24 males and 24 females, mean age 8 years, 5 months) with Velo-Cardio-Facial Syndrome (VCFS) was compared with a group of 240 non VCFS control youngsters (matched on age and gender), and, in addition, with groups of youngsters with Prader-Willi (PWS), Fragile X (FXS), and Williams Syndromes (WS). Personality characteristics of each youngster were rated by both parents, using the California Child Q-set (CCQ). The scores on eight personality dimensions were compared, i.e., Extraversion, Agreeableness, Conscientiousness, Emotional Stability, Openness, Motor Activity, Irritability, and Dependency. Moreover, Individual differences in personality of VCFS youngsters were related to IQ level, presence or absence of cardiac defects, and de novo versus familial origin of VCFS. The personality profile of VCFS youngsters was markedly different from all non-VCFS groups. Compared to the 240 control children, they were equally extravert and agreeable, less conscientious and emotional stable and more Irritable and dependent. Some personality characteristics in youngsters with VCFS were related to IQ and Age, but not to cardiac defects or de novo versus familial genetic origin of the 22q11 deletion.     

Adolescents’ Functional Numeracy Is Predicted by Their School Entry Number System Knowledge

One in five adults in the United States is functionally innumerate; they do not possess the mathematical competencies needed for many modern jobs. We administered functional numeracy measures used in studies of young adults’ employability and wages to 180 thirteen-year-olds. The adolescents began the study in kindergarten and participated in multiple assessments of intelligence, working memory, mathematical cognition, achievement, and in-class attentive behavior. Their number system knowledge at the beginning of first grade was defined by measures that assessed knowledge of the systematic relations among Arabic numerals and skill at using this knowledge to solve arithmetic problems. Early number system knowledge predicted functional numeracy more than six years later (ß = 0.195, p = .0014) controlling for intelligence, working memory, in-class attentive behavior, mathematical achievement, demographic and other factors, but skill at using counting procedures to solve arithmetic problems did not. In all, we identified specific beginning of schooling numerical knowledge that contributes to individual differences in adolescents’ functional numeracy and demonstrated that performance on mathematical achievement tests underestimates the importance of this early knowledge.     

The velocardiofacial syndrome in older age: dementia and autistic features

Velocardiofacial syndrome (VCFS) is a syndrome with a known, but variable clinical and behavioural phenotype. Most reported cases are patients of a relatively young age. The development of the behavioural phenotype and psychopathology in older patients with VCFS is less known. We present a case of a 52 year old male patient with VCFS and a deletion in chromosome band 22q11.2. He presents with typical symptoms reported in the behavioural phenotype, autistic features and an overall deteriorating process, which fulfils the DSMIV criteria for dementia.     

Training early visuo-spatial abilities: A controlled classroom-based intervention study

Visuo-spatial training is considered a promising approach to provide young children with a sound foundation for later mathematical learning. We developed and implemented a tablet-based visuo-spatial intervention in kindergarten classrooms aiming to foster the development of children’s visuo-spatial and numerical abilities. A sample of N?=?125 children participated in the present study, 68 children were part of the intervention group and participated in 20 training sessions of 20?min over a 10-week period, 57 children formed a business as usual control group. Results show that, at this young age, visuo-spatial and early math skills are already strongly interlinked. However, the training effects were domain-specific as they only improved visuo-spatial skills, but did not transfer to early math performance in the present setting.     

When Problem Size Matters: Differential Effects of Brain Stimulation on Arithmetic Problem Solving and Neural Oscillations

The problem size effect is a well-established finding in arithmetic problem solving and is characterized by worse performance in problems with larger compared to smaller operand size. Solving small and large arithmetic problems has also been shown to involve different cognitive processes and distinct electroencephalography (EEG) oscillations over the left posterior parietal cortex (LPPC). In this study, we aimed to provide further evidence for these dissociations by using transcranial direct current stimulation (tDCS). Participants underwent anodal (30min, 1.5 mA, LPPC) and sham tDCS. After the stimulation, we recorded their neural activity using EEG while the participants solved small and large arithmetic problems. We found that the tDCS effects on performance and oscillatory activity critically depended on the problem size. While anodal tDCS improved response latencies in large arithmetic problems, it decreased solution rates in small arithmetic problems. Likewise, the lower-alpha desynchronization in large problems increased, whereas the theta synchronization in small problems decreased. These findings reveal that the LPPC is differentially involved in solving small and large arithmetic problems and demonstrate that the effects of brain stimulation strikingly differ depending on the involved neuro-cognitive processes.     

Children with a 22q11 deletion versus children with a speech-language impairment and learning disability: behavior during primary school age

Children with a 22q11 deletion versus children with a speech-language impairment and learning disability: behavior during primary school age: Common behavioral features described in children with the Velo-Cardio-Facial syndrome (VCFS) (del 22q11) are problems with attention and concentration, extremes in behavior and social problems, especially in relationship with peers. At present, it is unclear whether these behavioral manifestations are directly related to the chromosomal anomaly or related to other manifestations of the syndrome such as developmental delay and speech-language delay. This study describes for the first time the behavior of young primary school aged children with a del22q11 compared to a control group of children matched for age, sex and mental level, with similar developmental problems (speech-language impairment plus learning disability: SLI + LD) but without a del22q11 or any other known genetic condition. Parents and teachers evaluated the children's behavior with standardized questionnaires (CBCL; TRF). Results indicate that most of the behaviors are similar across both groups. The only differences found are in the field of and . Children with a del22q11 have a stronger tendency to withdraw from others, whereas children with a SLI+LD seem to be more aggressive.     

TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome

Velo-cardio-facial syndrome (VCFS)/DiGeorge syndrome (DGS) is a human disorder characterized by a number of phenotypic features including cardiovascular defects. Most VCFS/DGS patients are hemizygous for a 1.5-3.0 Mb region of 22q11. To investigate the etiology of this disorder, we used a cre-loxP strategy to generate mice that are hemizygous for a 1.5 Mb deletion corresponding to that on 22q11. These mice exhibit significant perinatal lethality and have conotruncal and parathyroid defects. The conotruncal defects can be partially rescued by a human BAC containing the TBX1 gene. Mice heterozygous for a null mutation in Tbx1 develop conotruncal defects. These results together with the expression patterns of Tbx1 suggest a major role for this gene in the molecular etiology of VCFS/DGS.     

High-density single nucleotide polymorphism array analysis in patients with germline deletions of 22q11.2 and malignant rhabdoid tumor

Malignant rhabdoid tumors are highly aggressive neoplasms found primarily in infants and young children. The majority of rhabdoid tumors arise as a result of homozygous inactivating deletions or mutations of the INI1 gene located in chromosome band 22q11.2. Germline mutations of INI1 predispose to the development of rhabdoid tumors of the brain, kidney and extra-renal tissues, consistent with its function as a tumor suppressor gene. We now describe five patients with germline deletions in chromosome band 22q11.2 that included the INI1 gene locus, leading to the development of rhabdoid tumors. Two patients had phenotypic findings that were suggestive but not diagnostic for DiGeorge/Velocardiofacial syndrome (DGS/VCFS). The other three infants had highly aggressive disease with multiple tumors at the time of presentation. The extent of the deletions was determined by fluorescence in situ hybridization and high-density oligonucleotide based single nucleotide polymorphism arrays. The deletions in the two patients with features of DGS/VCFS were distal to the region typically deleted in patients with this genetic disorder. The three infants with multiple primary tumors had smaller but overlapping deletions, primarily involving INI1. The data suggest that the mechanisms underlying the deletions in these patients may be similar to those that lead to DGS/VCFS, as they also appear to be mediated by related, low copy repeats (LCRs) in 22q11.2. These are the first reported cases in which an association has been established between recurrent, interstitial deletions mediated by LCRs in 22q11.2 and a predisposition to cancer. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Symbolic Numerical Magnitude Processing Is as Important to Arithmetic as Phonological Awareness Is to Reading

In this article, we tested, using a 1-year longitudinal design, whether symbolic numerical magnitude processing or children’s numerical representation of Arabic digits, is as important to arithmetic as phonological awareness is to reading. Children completed measures of symbolic comparison, phonological awareness, arithmetic, reading at the start of third grade and the latter two were retested at the start of fourth grade. Cross-sectional and longitudinal correlations indicated that symbolic comparison was a powerful domain-specific predictor of arithmetic and that phonological awareness was a unique predictor of reading. Crucially, the strength of these independent associations was not significantly different. This indicates that symbolic numerical magnitude processing is as important to arithmetic development as phonological awareness is to reading and suggests that symbolic numerical magnitude processing is a good candidate for screening children at risk for developing mathematical difficulties.     

On age distribution in population growth

The statistical problem of age distribution in population growth involves the well known difficulties in mathematical probability of defining the distribution of a discrete number of random points (individuals) in a continuous parametric space (age). The assumption of the possibility of multiple births makes the problem more complicated, and we are constrained to introduce the concept of multiple points. This leads to an extension of the method of product densities devised earlier for the treatment of population problems. The paper deals with such an extension and as an example of the application of this method the population problem with twins is discussed. This paper was written while on leave of absence from there.     

Specific features of the oscillatory brain activity during the final stage of creative problem solving in young and elderly subjects

The neurophysiological mechanisms underlying retention of creative potential during aging are still poorly studied. Previously, we have identified age-related changes in the temporal dynamics of brain activity and the speed of creative problem solving at its initial stage, suggesting that younger and older subjects used different strategies. These differences in strategies may also be observed at the final stage of problem solving. Therefore, we have studied the pattern of temporal changes in the EEG spectral characteristics (event-related spectral perturbation, ERSP) in younger (N = 89, 22.1 ± 3.2 years) and older (N = 90, 64.9 ± 6.7 years) age cohorts during 600 ms before the preparation to motor response, which indicates that solution is found. The general and ageand sex-related features of the oscillatory brain activity at the final stage of problem solving were revealed. All subjects displayed statistically significant EEG temporal dynamics associated with a reduction of power reactivity of rhythms prior to the response. The age-related differences included more pronounced ERSP frontal–parietal gradient in the θ frequency range and lower ERSP values in the β frequency range in elderly subjects as compared with the younger individuals. The most pronounced age-related differences in the β₁ rhythm were observed in the posterior cortex. The age-related differences in the α₃ frequency range were mediated by the sex factor: lateral differences were pronounced only in young men, and the coefficient of hemispheric asymmetry in this group differed significantly from that in older men and younger women. These data reflect the changes in EEG that were associated with the evaluation of creative idea, making a decision about completion of the search, and intention to make a motor response that indicates that solution is found.     

Incremental lines in root cementum of human teeth —A reliable age marker?

In root cementum of teeth, alternating dark and light lines become visible in cross-sections under the light microscope. These lines bear an apparent resemblance to the annual rings of trees. Numerous studies have been done to correlate the number of cementum lines with the dental age by examining a great number of teeth of known age. Our study used a different approach. If lines in root cementum develop in an annual rhythm and are thus comparable to annual rings of trees, the same or at least a very similar number of these structures should be found in all areas of the root cementum of the same tooth. We counted cementum lines in the buccal, lingual, distal and mesial region of different sections, all from the middle third of the same root. This was repeated in eight teeth. To our surprise, we had immense difficulty in counting reproducible line numbers in the same cementum area at repeated counts. Nevertheless, the same tooth was found to differ markedly in the number of lines in different sections as well as in different regions of the same sections. These differences cannot be ascribed to variations caused by difficulties with reproducible line counting. Therefore, we are more than skeptical about the reliability of counting lines in root cementum as a method for determining the age of human teeth.     

Early carotid atherosclerosis in overweight non-diabetic individuals is associated with subclinical chronic inflammation independent of underlying insulin resistance.

Overweight in children and young adults is an increasing problem in Western industrialized countries with potential impact on cardiovascular morbidity. Whether early arterial wall thickening in these subjects mainly results from the often associated insulin resistance syndrome or from increased subclinical chronic inflammation probably triggered by adipose tissue is still under discussion. We therefore determined insulin sensitivity index (ISI) by performing an euglycaemic hyperinsulinaemic glucose clamp (insulin infusion rate 1 mU/kg/min) and high-sensitivity C-reactive protein (hsCRP) levels in relation to the intima-media thickness (IMT) at the common carotid artery (high resolution ultrasound; 13 MHz) in 81 young (age 33 +/- 1 years), moderately overweight subjects. To reduce the number of confounding variables, subjects with disturbances in glucose metabolism (75 g oral glucose tolerance test) and hypertension were excluded. As expected, higher BMI was positively correlated with increased IMT (r = 0.358; p = 0.001). After multiple regression analysis, hsCRP levels independently correlated to IMT (r = 0.251; p = 0.03), even after adjusting for age, sex, BMI, ISI, LDL cholesterol and smoking as cofactors. However, taking all above listed factors into account, glucose-clamp assessed insulin sensitivity was not correlated with IMT. Thus, overweight might trigger inflammatory mechanisms leading to vascular wall hypertrophy independent of the insulin resistance syndrome already early in life.     

Acquired myopia in 11-year-old children.

Children who had acquired myopia by the age of 11 years were identified from a nationally representative sample. There were no overall sex differences in its occurrence but myopia was more common in children from non-manual families than in those from manual families. Short-sighted children were more likely to come from small families and to be of higher birth order than children with normal vision, and these associations held within each social class. At 11 years myopic children showed striking advantages in educational performance over their normal-sighted peers, as judged by tests of reading, arithmetic, and general ability. After adjustments had been made for social background, this age gain still amounted to over one year. Findings obtained at 7 years of age showed that superior educational attainments were already apparent before the onset of myopia. Children with myopia read in their leisure time more often than normally sighted children, but despite the visual impairment, they participated in outdoor sports as often as other children.     

What can functional brain imaging studies tell us about typical and atypical cognitive development in children?

Functional brain imaging has been largely reserved for adults. However, in recent years there have been increasing attempts to use functional brain imaging to inform our understanding of child development. These have taken three main forms: (1) Children with known or suspected neurological disorders may undergo brain imaging for medical diagnostic purposes and/or for the purpose of research into the nature of the disorders. (2) There have been a few studies where children, usually over the age of 8, have undergone functional brain imaging. (3) Results from brain imaging studies of adults have influenced theories about children's development. This chapter discusses the impact of brain imaging studies on our understanding of working memory; reading; and arithmetic. The different forms of brain imaging converge in demonstrating that different brain regions show differential activation for different domains and for different components within the domains: e.g. different reading strategies and different components of arithmetic. They show important similarities between children and adults, though it must be remembered that very few studies have involved young children. They also indicate that experience influences brain function, as well as the other way around.