Children with one of two genetic disorders (chromosome 22q11.2 deletion syndrome and Turner syndrome) as well typically developing controls, participated in three cognitive processing experiments. Two experiments were designed to test cognitive processes involved in basic aspects numerical cognition. The third was a test of simple manual motor reaction time. Despite significant differences in global intellectual abilities, as measured by IQ tests, performance on the two numerical cognition tasks differed little between the two groups of children with genetic disorders. However, both performed significantly more poorly than did controls. The pattern of results are consistent with the hypothesis that impairments were not due to global intellectual ability but arose in specific cognitive functions required by different conditions within the tasks. The fact that no group differences were found in the reaction time task, despite significant differences in the standardized processing speed measure, further supports the interpretation that specific cognitive processing impairments and not global intellectual or processing speed impairments explain the pattern of results. The similarity in performance on these tasks of children with unrelated genetic disorders counters the view that numerical cognition is under any direct genetic control. Instead, our findings are consistent with the view that disturbances in foundational spatiotemporal cognitive functions contribute to the development of atypical representations and processes in the domains of basic magnitude comparison and simple numerical enumeration.

The aim of the present research was to investigate the impact of abnormal fetal environment on explicit memory performance. Based on animal models, it was hypothesized that infants of diabetic mothers (IDMs) experience perturbations in memory performance due to exposure to multiple neurologic risk factors including: chronic hypoxia, hyperglycemia/reactive hypoglycemia, and iron deficiency. Memory performance, as measured by the elicited/deferred imitation paradigm, was compared between 13 IDMs (seven females, six males; mean age 365 days, SD 11) and 16 typically developing children (seven females, nine males; mean age 379 days, SD 9). The IDM group was characterized by shorter gestational age (mean 38w, SD 2), greater standardized birthweight scores (mean 3797g, SD 947), and lower iron stores (mean ferritin concentration 87C microg/L, SD 68) in comparison with the control group (mean gestational age: 40w, SD 1; mean birthweight: 3639g, SD 348; mean newborn ferritin concentration 140 microg/L, SD 46). After statistically controlling for both gestational age and global cognitive abilities, IDMs demonstrated a deficit in the ability to recall multi-step event sequences after a delay was imposed. These findings highlight the importance of the prenatal environment on subsequent mnemonic behavior and suggest a connection between metabolic abnormalities during the prenatal period, development of memory, circuitry, and behavioral mnemonic performance.

BackgroundPrevious investigations of individuals with chromosome 22q11.2 deletion syndrome (DS22q11.2) have reported alterations in both brain anatomy and cognitive function. Neuroanatomical studies have reported multiple abnormalities including changes in both gray and white matter in the temporal lobe, including the amygdala and hippocampus. Separate investigations of cognitive abilities have established the prevalence of general intellectual impairment, although the actual extent to which a single individual is affected varies greatly within the population. The present study was designed to examine structures within the temporal lobe and assess their functional significance in terms of cognition in children with DS22q11.2.MethodA total of 72 children (ages 7–14 years) participated in the investigation: 36 children (19 female, 17 male) tested FISH positive for chromosome 22q11.2 deletion (Mean age = 10 years 9 months, ± 2 yr 4 mo) and 36 were age-matched typically developing controls (13 female, 23 male; Mean age = 10 years 6 months, ± 1 yr 11 mo). For each subject, a three-dimensional high-resolution (1 mm isotropic) T1-weighted structural MRI was acquired. Neuroanatomical guidelines were used to define borders of the amygdala and hippocampus bilaterally and volumes were calculated based on manual tracings of the regions. The Wechsler Intelligence Scale for Children (WISC) was also administered.ResultsVolumetric reductions in total gray matter, white matter, and both the amygdala and hippocampus bilaterally were observed in children with DS22q11.2. Reductions in the left hippocampus were disproportionate to decreases in gray matter after statistically controlling for group differences in total gray matter, age, and data collection site. This specific reduction in hippocampal volume was significantly correlated with performance on standardized measures of intelligence, whereas the other neuroanatomical measures were not (gray/white matter, CSF, and amygdala).ConclusionResults from this study not only contribute to the understanding of the neuroanatomical variation in DS22q11.2, but also provide insight into the nature and source of the cognitive impairments associated with the syndrome. Specifically, we report that decreases in hippocampal volume may serve as an index of severity for cognitive impairments in children with DS22q11.2.

The aim of the present research was to investigate the impact of abnormal fetal environment on explicit memory performance. Based on animal models, it was hypothesized that infants of diabetic mothers (IDMs) experience perturbations in memory performance due to exposure to multiple neurologic risk factors including: chronic hypoxia, hyperglycemia/reactive hypoglycemia, and iron deficiency. Memory performance, as measured by the elicited/deferred imitation paradigm, was compared between 13 IDMs (7 female, 6 male; mean age 365 days, SD 11) and 16 typically developing children (7 female, 9 male; mean age 379 days, SD 9). The IDM group was characterized by shorter gestational age (mean 38 weeks, SD 2), greater standardized birth weight scores (mean 3797 grams, SD 947), and lower iron stores (mean ferritin concentration 87 μg/L, SD 68) in comparison with the control group (mean gestational age: 40 weeks, SD 1; mean birth weight: 3639 grams, SD 348; mean newborn ferritin concentration 140 μg/L, SD 46). After statistically controlling for both gestational age and global cognitive abilities, IDMs demonstrated a deficit in the ability to recall multi-step event sequences when a delay was imposed. These findings underscore the importance of the prenatal environment on subsequent mnemonic behavior and suggest a connection between metabolic abnormalities during the prenatal period, development of memory circuitry, and behavioral mnemonic performance.Infants of diabetic mothers (IDMs) comprise a compelling group in which to examine associations between fetal risk factors and subsequent memory performance. The adverse environment associated with the diabetic pregnancy consists of multiple neurologic risk factors including: 1) chronic hypoxia (Widness et al., 1981), 2) hyperglycemia/reactive hypoglycemia, and 3) iron deficiency (Petry et al., 1992), which, on the basis of animal models, have been shown to act selectively on regions of the fetal brain that are involved in explicit memory (e.g., the hippocampus, Barks et al., 1995;de Ungria, et al., 2000). Based on the known Several studies have demonstrated that neurobehavioral outcomes in human children who were born to diabetic mothers are inversely correlated with the quality of metabolic regulation during pregnancy (e.g., Rizzo et al., 1997). However, these investigations have typically examined global cognitive development in children well downstream from the proposed insult, and are not necessarily related to specific risk factors or areas of injury. The purpose of the present research was to further characterize outcomes related to development in an abnormal prenatal environment by examining the relation between IDM's abnormal prenatal environment and behavioral explicit memory performance using the elicited imitation paradigm. Risk FactorsPrenatal hypoxia and hyperglycemia/reactive hypoglycemia have been associated with both poor behavioral and neurologic outcomes. Specifically, prenatal hypoxia is linked with motor and cognitive deficits in humans (e.g., Low et...

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