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Clearly, much more work needs to be done to establish firmly the neural substrates of quantification processing in visuospatial circuitry, but it already looks like a promising enterprise. Dehaene et al. have presented data that provide strong new evidence for the dichotomy between perceptually and conceptually based quantitative competence. However, the findings pose new questions about which common cultural experiences are necessary to stimulate our brains to organize themselves in such a way as to add these, initially unspecified, functional capabilities. The fact that societies still exist without requirements to go beyond a number system of three items19xYanomamo: The Last Days of Eden. Chagnon, N.A. See all References19, indicates that Dehaene et al.’s findings characterize a pattern of ontogenetic brain organization that has responded to ecological demands. Questions of how environmental stimulation transforms cognitive competence from one level to another are central to the field of developmental cognitive science. Unfortunately, these are not the kinds of investigations that many of us are experienced at tackling. With the powerful new tools of brain imaging to add to our experimental methods we have reached the point where we should be able to discover how mathematical thinking arises from a brain without numbers. These new findings of Dehaene et al. and Sathian et al. should stimulate us to do so with renewed zeal.

In this article, I present an updated account that attempts to explain, in cognitive processing and neural terms, the nonverbal intellectual impairments experienced by most children with deletions of chromosome 22q11.2. Specifically, I propose that this genetic syndrome leads to early developmental changes in the structure and function of clearly delineated neural circuits for basic spatiotemporal cognition. This dysfunction then cascades into impairments in basic magnitude and then numerical processes, because of the central role that representations of space and time play in their construction. I propose that this takes the form of "spatiotemporal hypergranularity"; the increase in grain size and thus reduced resolution of mental representations of spatial and temporal information. The result is that spatiotemporal processes develop atypically and thereby produce the characteristic impairments in nonverbal cognitive domains that are a hallmark feature of chromosome 22q11.2 deletion syndrome. If this hypothesis driven account is supported by future research, the results will create a neurocognitive explanation of spatiotemporal and numerical impairments in the syndrome that is specific enough to be directly translated into the development of targeted therapeutic interventions.

This paper proposes a method to improve brain-tissue segmentation, especially in subcortical region, by fusing the information in structural magnetic resonance (MR) images and diffusion tensor (DT) images in a sound statistical framework. The proposed method incorporates the information in DT images by parameterizing the space of diffusion tensors, in a principled and efficient manner, based on a set of independent orthogonal invariants. The proposed method couples the Markov tissue statistics of the structural-MR intensities with the tissue statistics of the DT invariants to define multivarite/joint probability density functions (PDFs) that differentiate brain tissues. The paper shows that while the information in DT images can allow improved differentiation between tissues in the subcortical region, which comprises anatomical structures having smooth (blob-like) shapes, it can produce unreliable results in the cortical regions that depict convoluted sulci/gyri. The proposed method exploits these characteristics of the images by introducing an appropriate anisotropic distance metric in the multivariate feature space.

In this paper, we describe a novel technique for modeling sheet-like white matter (WM) fasciculi using continuous medial representation (cm-rep). In the cm-rep framework, the skeleton of a fasciculus is described by a parametric surface patch. This modeling scheme is particularly appropriate for sheet-like structures, because the shapes of such objects can be effectively captured by their skeletons. We show that dimensionality reduction can be achieved without much loss of spatial specificity by projecting data along the "less interesting" thickness direction onto the skeletons. We demonstrate that local fiber orientation of the modeled fasciculi can be encoded in our framework and show how this information can be leveraged for deriving and analyzing brain connectivity patterns on the skeleton themselves.

Recently, concerns have been raised that the correspondences computed by volumetric registration within homogeneous structures are primarily driven by regularization priors that differ among algorithms. This paper explores the correspondence based on geometric models for one of those structures, midsagittal section of the corpus callosum (MSCC), and compared the result with registration paradigms. We use geometric model called continuous medial representation (cm-rep) to normalize anatomical structures on the basis of medial geometry, and use features derived from diffusion tensor tractography for validation. We show that shape-based normalization aligns subregions of the MSCC, defined by connectivity, more accurately than normalization based on volumetric registration. Furthermore, shape-based normalization helps increase the statistical power of group analysis in an experiment where features derived from diffusion tensor tractography are compared between two cohorts. These results suggest that cm-rep is an appropriate tool for normalizing the MSCC in white matter studies.

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 cognitive profile of several different populations of children, each with a distinct neurogenetic disorder that has been described as fitting the pattern of a “nonverbal learning disorder”, is examined. In particular, this paper presents the view that a cognitive endophenotype, specified in terms of specific cognitive processes involving the spatial, temporal and attentional domains, can be used to generate an explanation of the neurocognitive foundation of the common impairments found in these disorders. Methods for evaluating cognitive impairments are first compared and contrasted and the concept of “nonverbal learning disorders” is described. The paper then examines data from experimental tests of spatiotemporal and executive cognitive function acquired from children with one of several disorders to determine whether such a cognitive endophenotype holds promise for moving from descriptions of to explanations for the impairments observed and whether prescriptions for therapeutic interventions might flow from such an account.

Children with chromosome 22q11.2 deletion syndrome commonly are found to have morphological brain changes, cognitive impairments, and elevated rates of psychopathology. One of the most commonly and consistently reported brain changes is reduced cerebellar volume. Here, we demonstrate that, in addition to the global cerebellum reductions previously reported, volumetric reductions of the anterior lobule and the vermal region of the neo-cerebellum in the mid-sagittal plane best differentiate children with the deletion from typically developing children. These results suggest that the morphological changes of specific portions of the cerebellum may be an important underlying substrate of cognitive impairments and increased incidence of psychopathology in this group.

In recent years, a great deal has been learned about a disorder that is one of the most common genetic causes of developmental disability, mental retardation, and psychopathology. Resulting from a 1.5- to 3-Mb microdeletion on the long (q) arm of chromosome 22 (Driscoll, Budarf, & Emanuel, 1992; Driscoll et al., 1992), this disorder is most accurately characterized as the “chromosome 22q11.2 deletion syndrome” (DS22q11.2). Thus defined, the disorder encompasses previously described phenotypes including DiGeorge (1965), velocardiofacial (Shprintzen, Goldberg, Lewin, Sidoti, Berkman, Argamaso, & Young, 1978), and conotruncal anomaly face (Burn, Takao, Wilson, Cross, Momma, Wadey, Scambler, & Goodship, 1993) syndromes, and some cases of Cayler cardiofacial syndrome (Giannotti, Digilio, Marino, Mingarelli, & Dallapiccola, 1994) and Opitz G/BBB syndrome (McDonald–McGinn, Driscoll, Bason, Christensen, Lynch, Sullivan, Canning, Zavod, Quinn, & Rome, 1995). A molecular fluorescence in situ hybridization probe for the deletion set the prevalence at 1 in 4,000 live births (Burn & Goodship, 1996), an estimate currently thought to be quite conservative (e.g., Shashi, Muddasani, Santos, Berry, Kwapil, Lewandowski, & Keshavan, 2004). Furthermore, several factors point to a significant growth in the identified population of individuals with DS22q11.2 in the near future. One is that the major cause for mortality in the syndrome, congenital heart defects, is now routinely resolved surgically. Another is that, because this is a contiguous gene deletion syndrome with no effect on reproductive fitness, adults with this deletion will have a 50% chance of having an affected child. A third is that growing knowledge of the disorder is increasing rates of early identification and diagnosis. Given that DS22q11.2 typically produces developmental disability and frequently results in serious psychopathology it is essential to develop a deep understanding of the cognitive and behavioral phenotype. That should improve clinical management of the disorder and may provide important clues into gene–brain–behavior relationships. Investigation of this syndrome from a cognitive neuroscience perspective can provide valuable information for basic research scientists and for clinicians. For example, studies of DS22q11.2 are likely to help explicate the neural bases of basic cognitive processes that are disturbed in other developmental disorders that produce characteristic impairments in visuospatial and numerical cognition (e.g., fragile X, Turner, and Williams–Beuren syndromes). Such studies involving children with DS22q11.2 are also likely to shed light on developing brain structure/function relationships and to what extent these can account for the observable impairments. Furthermore, investigations of disorders like DS22q11.2 can complement research into the role of genetic variation in individual differences in cognitive function (for review, see Parasuraman & Greenwood, 2004), as well as the genetic etiology of complex neuropsychiatric disorders. In contrast to traditional psychiatric genetics studies, in which one begins with a complex cluster of symptoms (i.e., psychiatric diagnosis) and attempts to map these traits to specific genetic loci, here we are investigating the phenotypic manifestations of a disorder with a known, homogeneous genetic etiology. The effects of a known alteration in a system with an identified function (e.g., the ability to produce the catechol-O-methyltransferase [COMT] enzyme, which affects regulation of synaptic dopamine particularly in the prefrontal cortex), can thus be studied in terms of its effect on a theoretically motivated research question (i.e., the genetic mediation of dysfunction in executive cognition). As we shall make clear below, a multiple levels approach to such investigations is likely to prove fruitful as a way to integrate the findings of investigations of the neurocognitive basis of developmental disability and psychopathology. Most of the early progress in understanding the effects of the deletion was related to its physical manifestations (see Figure 1 for an image of a child with the deletion). These typically involve cleft palate and/or velopharyngeal insufficiency, immune deficiencies, neonatal hypocalcemia, the aforementioned congenital heart defects, and facial dysmorphisms (Emanuel, McDonald–McGinn, Saitta, & Zackai, 2001; McDonald–McGinn et al, 1999). Although many of these symptoms are at present well understood and can be effectively treated and managed, far less is known about the apparent changes in brain structure and function, and their relation to the range of cognitive impairments and psychiatric disorders that have been reported. The first reports of these behavioral aspects of the phenotype came from standardized tests of intellectual function, academic achievement, and behavioral parent-report measures. For example, a study of 33 children and adults with DS22q11.2 reported a mean full-scale IQ in the borderline range of intellectual functioning (71.2 ± 12.8), with a mean Verbal IQ of 77.5 (±14.9), and a mean performance IQ of 69.1 (±12.0; Moss, Batshaw, Solot, Gerdes, McDonald–McGinn, Driscoll, Emmanuel, Zackai, & Wang, 1999). Similar results were reported in a Belgian sample that extended the age range from infancy to older adults (Swillen, Devriendt, Legius, Prinzie, Vogels, Ghesquiere, & Fryns, 1999). With regard to academic achievement, Moss et al. also reported that math composite scores (from the Wechsler Achievement Scales) were significantly lower than spelling and reading composite scores (80.1 ± 15.2 vs. 88.3 ± 16.4 and 86.7 ± 18.2, respectively). Analyses on enlarged samples of this same study population generally replicated and extended this pattern (e.g., Woodin, Wang, Aleman, McDonald–McGinn, Zackai, & Moss, 2001). In addition, within-subject comparisons of memory function indicated that rote verbal memory scores were significantly higher than those for visuospatial memory (Bearden, Woodin, Wang, Moss, McDonald–McGinn, Zackai, Emannuel, & Cannon, 2001). This was consistent with the findings of Wang, Woodin, Kreps–Falk, and Moss (2000) who, in a study of the basis of arithmetical cognitive impairments in this syndrome, found poorer performance on a test of visuospatial short-term memory than a test of auditory number recall. Figure 1 A 4-year-old girl with DS22q11.2. With regard to psychosocial and behavioral functioning, Swillen, Devriendt, Legius, Eyskens, Dumoulin, Gewillig, and Fryns (1997) reported results from the Child Behavior Checklist, indicating significantly elevated scores for the “social problems,” “attention problems,” and “withdrawn” sub-scales. A study focusing on younger children (13 to 63 months) with DS22q11.2 (Gerdes et al., 1999) not only reported the typical findings of delayed language, speech, and motor development, but also found that 75% of the toddlers studied exhibited behaviors during testing judged to be “highly active, emotional and disorganized,” as measured by the Bayley Scale of Infant Development (Bayley, 1969), whereas one-quarter of the toddlers in the sample were judged to be “behaviorally inhibited.” It is possible that early childhood behavioral problems in DS22q11.2 do develop into more chronic, severe mental illnesses in adolescence and early adulthood. Indeed, this syndrome is one of the highest known risk factors to date for schizophrenia, with prevalence rates on the order of 25–30% in adult patients (Bassett & Chow, 1999; Bassett, Hodgkinson, Chow, Correia, Scutt, & Weksberg, 1998; Murphy, Jones, & Owen, 1999). However, it is not known at present whether these cases are related to the childhood behavioral disorders that have been observed in DS22q11.2. In addition, elevated rates of bipolar disorder (Papolos, Faedda, Veit, Goldberg, Morrow, Kucherlapati, & Shprintzen, 1996), anxiety disorders and attention-deficit/hyperactivity disorder (ADHD; Niklasson, Rasmussen, Oskarsdottir, & Gillberg, 2001; Swillen, Devriendt, Legius, Prinzie, Vogels, Ghesquiere, & Fryns, 1999) are frequently reported. ADHD (particularly the inattentive or combined type, rather than the hyperactive type) appears to be the most common psychiatric morbidity in children and adolescents with DS22q11.2, found in 35–55% of patients. There are estimates that the prevalence of autistic spectrum disorders is between 14 and 31% (Fine, Weissman, Gerdes, Pinto–Martin, Zackai, McDonald–McGinn, & Emannuel, in press; Niklasson, Rasmussen, Oskarsdottir, & Gillberg, 2001). Oppositional defiant disorder is reported in 8–43% of children with the syndrome (Arnold, Siegel–Bartelt, Cytrynbaum, Teshima, & Schachar, 2001; Feinstein, Eliez, Blasey, & Reiss, 2002; Niklasson, Rasmussen, Oskarsdottir, & Gillberg, 2001, 2002; Papolos et al., 1996), and one study found that about one-third meet criteria for obsessive–compulsive disorder (OCD; Gothelf et al., 2004). The reason for these elevated rates of psychopathology is not known at present.

This article presents some of the earliest evidence of visuospatial and numerical cognitive deficits in children with the chromosome 22q11.2 deletion syndrome; a common but ill-understood genetic disorder resulting in medical complications, cognitive impairment, and brain morphologic changes. Relative to a group of typically developing controls, deleted children performed more poorly on tests of visual attentional orienting, visual enumeration and relative numerical magnitude judgment. Results showed that performance deficits in children with the deletion could not be explained by a global deficit in psychomotor speed. Instead, our findings are supportive of the hypothesis that visuospatial and numerical deficits in children with the chromosome 22q11.2 deletion are due, at least in part, to posterior parietal dysfunction.

Children with 22q11.2 microdeletions (Velocardiofacial Syndrome; VCFS) have previously been shown to exhibit learning deficits and elevated rates of psychopathology. The aim of this study was to assess regional brain abnormalities in children with 22q11DS, and to determine the relationship of these measures to neurocognitive and behavioral function. Thirteen children with confirmed deletions and 9 demographically matched comparison subjects were assessed with a neurocognitive battery, behavioral measures, and high-resolution MRI. Twenty-two qllDS children showed a nonsignificant 4.3% global decrease in total brain volume as compared to healthy controls,with differential reduction in white matter, and significantly increased sulcal cerebrospinal fluid (CSF) in temporal and posterior brain regions. In 22q11 DS subjects, but not controls, bilateral temporal gray and white matter volumes were significant predictors of overall cognitive performance. Further, reduced temporal gray matter was associated with elevated Thought Problems score on the CBCL. Results indicate that global alterations in brain volume are common in children with 22q deletions, particularly those with low IQ and/or behavioral disturbance. Although preliminary,these findings suggest a possible underlying pathophysiology of the cognitive deficits seen in this syndrome,and provide insight into complex gene-brain-behavior relationships.

We investigated the neurobiologies! basis of visual processes involved in object enumeration. Subitizing, the ability to rapidly and accurately enumerate four or fewer objects, is thought to depend on preattentive processing of visual stimuli, whereas counting of more numerous objects is thought to require serial shifts of attention. We attempted to distinguish between the hypothesis that the magnocellular (M) visual pathway is the preferential route for subitizing, and the alternative hypothesis that there is no selectivity for the M pathway or its counterpart, the parvocellular (P) visual pathway, in visual object enumeration. Green rectangles were presented on an equiluminant red background to impair M pathway processing. This slowed enumeration performance relative to a control condition in which object/background luminance differed, especially when the rectangles were relatively large and widely spaced and had constant retinal eccentricity. When low luminance contrast was used to impair processing along the P pathway, enumeration performance was slowed relative to a high-contrast control condition, especially when the rectangles were small and closely spaced. Overall, our manipulations affected enumeration performance without selectivity for subitizing or counting ranges and without altering the slope of the functions relating reaction time to numerosity. Thus, our results favor the hypothesis that visual enumeration does not depend preferentially on either the M or the P pathway.

Two experiments showed that, when selective eye movements were disabled by the presentation of stimuli in the form of afterimages, increased inspection time and facilitative stimulus configurations failed to increase the subitizing limit of 4 objects. Afterimages of two to eight dots induced by a photographic flashgun were shown to 3 adult subjects. For more than 4 objects, enumeration errors occurred at a rate of 20%–30%. Enumeration was effectively perfect for 2–4 linearly configured dots, with occasional errors surprisingly occurring in that range when dots appeared in groups of up to 3 items. No errors occurred in nonafterimage control conditions. Enumeration errors were attributed to failures of individuating dots to be counted due to the deactivation of selective eye movements in afterimages. A third experiment supported this interpretation by disabling eye movements with briefly presented stimuli and producing results much like those of the afterimage conditions.

Autism is a neurodevelopmental disorder characterized by impairments in social behavior and communication and by the presence of repetitive or restricted interests.1 Although much remains to be determined regarding the biological features of autism, one prominent theme is the altered trajectory of brain development, both globally as reflected in total brain volume2-4 and in specific structures, such as the amygdala.5 Substantial evidence of precocious amygdala and brain enlargement in young children with autism exists,6-8 but their relative growth patterns remain unclear. Longitudinal studies of brain development could identify critical periods of abnormal brain enlargement as a first step toward establishing neurobiological factors responsible for the abnormal growth. Previous cross-sectional magnetic resonance imaging (MRI) studies have demonstrated that the time course of development for the total brain and the amygdala is altered in autism, but the overall patterns may be different. Courchesne and colleagues3 demonstrated that total brain enlargement is present in children aged 2 to 4 years but not in older children and adolescents. This has led to the proposal that the maturational process is more rapid in children with autism but that the end result, in terms of overall volume, is similar to that of children with typical development (TD). A similar abnormal growth trajectory occurs within the amygdala, although the time frame appears to be quite different. In TD, the amygdala undergoes a preadolescent growth phase that is disproportionate to the change in total brain size.9 It is not clear if, or when, the amygdala of children with autism undergoes a comparable growth phase. It is clear that the amygdala is larger in children with autism into middle childhood (7-12 years).5 Previous studies6-8 of the amygdala in young children with autism report volumetric enlargements in age-matched control subjects as young as 2.5 years. In the only longitudinal study of amygdala development in autism, Mosconi et al6 reported that the amygdala was larger in children with an average age of 2.6 years but that the rate of growth of the amygdala during a 2-year interval was no different than the rate in their control group, which consisted of TD children and children with developmental delays. In an earlier cross-sectional study from our group, we found that the amygdala in boys with autism reached adult size by approximately 8 years of age, whereas the amygdala of TD children did not reach adult size until several years later.5 Thus, accelerated growth of the amygdala must occur at some point during early childhood. The early trajectory of amygdala growth from infancy through middle childhood remains unclear. In the present longitudinal study, we endeavored to extend previous work by evaluating the rate of amygdala growth relative to total brain growth during a 1-year interval in a large sample of children with autism spectrum disorders (ASDs). We hoped to shed light on the following questions: (1) What is the early developmental trajectory of amygdala growth? (2) What are the relative growth rates of amygdala and total brain volume? and (3) How consistent is abnormal amygdala growth across a large population of children with autism?

Background Chromosome 22q11.2 deletion syndrome is one of the most common genetic causes of cognitive impairment and developmental disability yet little is known about the neural bases of those challenges. Here we expand upon our previous neurocognitive studies by specifically investigating the hypothesis that changes in neural connectivity relate to cognitive impairment in children with the disorder. Methods Whole brain analyses of multiple measures computed from diffusion tensor image data acquired from the brains of children with the disorder and typically developing controls. We also correlated diffusion tensor data with performance on a visuospatial cognitive task that taps spatial attention. Results Analyses revealed four common clusters, in the parietal and frontal lobes, that showed complementary patterns of connectivity in children with the deletion and typical controls. We interpreted these results as indicating differences in connective complexity to adjoining cortical regions that are critical to the cognitive functions in which affected children show impairments. Strong, and similarly opposing patterns of correlations between diffusion values in those clusters and spatial attention performance measures considerably strengthened that interpretation. Conclusion Our results suggest that atypical development of connective patterns in the brains of children with chromosome 22q11.2 deletion syndrome indicate a neuropathology that is related to the visuospatial cognitive impairments that are commonly found in affected individuals.

Background Previous 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. Method A 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. Results Volumetric 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). Conclusion Results 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.

Several studies have suggested that, so far as lure-retrieval tasks are concerned, previous ‘play’ and ‘training’ experiences are roughly comparable in facilitating subsequent problem-solving performance. In certain circumstances, ‘play’ experience has proved superior. However, Cheyne (1982) has criticized all these studies for poor or absent controls for possible experimenter bias. The present study carried out a close replication of the Smith & Dutton (1979) experiment, but incorporated manipulations of and controls for experimenter bias. Even when the experimenter giving the problem task was unaware of the previous experience of the child, and when scoring was done blindly, it was found that the effects of the ‘play’ experience were equivalent to those of a ‘training’ experience directly related to the problem to be given. This replicated previous results but excludes experimenter bias as a possible explanation. However, the second finding of the Smith & Dutton (1979) study, that ‘play’ experience was markedly superior to the ‘raining’ experience for a problem task more innovative with respect to the training, was not replicated. It is hypothesized that a combination of procedural differences and possible experimenter bias as suggested by Cheyne (1982) was responsible for this latter result.

(1985). Play and learning with computers. Early Child Development and Care: Vol. 19, CHILDREN'S PLAY, pp. 69-78.

This study investigated the effects of structured training at two informational levels on children's performance on a problem-solving computer program. An informed-training group (strategy training with detailed explanations) performed at a superior level to a blind-training group (strategy training with no explanations) and a control group. This superiority was maintained 3 weeks later on retest. The results are discussed in relation to the processes that mediate and facilitate training.

Background Chromosome 22q11.2 deletion syndrome (22q11.2DS) results from a 1.5- to 3-megabase deletion on the long arm of chromosome 22 and occurs in approximately 1 in 4000 live births. Previous studies indicate that children with 22q11.2DS are impaired on tasks involving spatial attention. However, the degree to which these impairments are due to volitionally generated (endogenous) or reflexive (exogenous) orienting of attention is unclear. Additionally, the efficacy of these component attention processes throughout child development in 22q11.2DS has yet to be examined. Methods Here we compared the performance of a wide age range (7 to 14 years) of children with 22q11.2DS to typically developing (TD) children on a comprehensive visual cueing paradigm to dissociate the contributions of endogenous and exogenous attentional impairments. Paired and two-sample t-tests were used to compare outcome measures within a group or between groups. Additionally, repeated measures regression models were fit to the data in order to examine effects of age on performance. Results We found that children with 22q11.2DS were impaired on a cueing task with an endogenous cue, but not on the same task with an exogenous cue. Additionally, it was younger children exclusively who were impaired on endogenous cueing when compared to age-matched TD children. Older children with 22q11.2DS performed comparably to age-matched TD peers on the endogenous cueing task. Conclusions These results suggest that endogenous but not exogenous orienting of attention is selectively impaired in children with 22q11.2DS. Additionally, the age effect on cueing in children with 22q11.2DS suggests a possible altered developmental trajectory of endogenous cueing.

© 2014 Hwang et al. Background: Chromosome 22q11.2 deletion syndrome (22q11DS) is the most common human microdeletion syndrome and is associated with many cognitive, neurological and psychiatric disorders. The majority of individuals have a 3 Mb deletion while others have a nested 1.5 Mb deletion, but rare atypical deletions have also been described. To date, a study using droplet digital PCR (ddPCR) has not been conducted to systematically map the chromosomal breakpoints in individuals with 22q11DS, which would provide important genotypic insight into the various phenotypes observed in this syndrome. Methods: This study uses ddPCR to assess copy number (CN) changes within the chromosome 22q11 deletion region and allows the mapping of the deletion endpoints. We used eight TaqMan assays interspersed throughout the deleted region of 22q11.2 to characterize the deleted region of chromosome 22 in 80 individuals known to have 22q11DS by FISH. Ten EvaGreen assays were used for finer mapping of the six identified individuals with 22q11DS atypical deletions and covering different regions of chromosome 22. Results: ddPCR provided non-ambiguous CN measurements across the region, confirmed the presence of the deletion in the individuals screened, and led to the identification of five differently sized and located deletions. The majority of the participants (n = 74) had the large 3 Mb deletions, whereas three had the smaller 1.5 Mb deletions, and the remaining three had an interstitial deletion of different size. Conclusions: The lower cost, rapid execution and high reliability and specificity provided by ddPCR for CN measurements in the 22q11 region constitutes a significant improvement over the variable CN values generated by other technologies. The ability of the ddPCR approach, to provide a high resolution mapping of deletion endpoints may result in the identification of genes that are haplo-insufficient and play a role in the pathogenesis of 22q11DS. Finally, this methodology can be applied to the characterization of other microdeletions throughout the genome.

© 2014 Wong et al.; licensee BioMed Central. Background: Fragile X premutation carriers (fXPCs) have an expansion of 55-200 CGG repeats in the FMR1 gene. Male fXPCs are at risk for developing a neurodegenerative motor disorder (fragile X-associated tremor/ataxia syndrome (FXTAS)) often accompanied by cognitive decline. Several broad domains are implicated as core systems of dysfunction in fXPCs, including perceptual processing of spatial information, orienting of attention to space, and inhibiting attention to irrelevant distractors. We tested whether orienting of spatial attention is impaired in fXPCs. Methods: Participants were fXPCs or healthy controls (HCs) asymptomatic for FXTAS. In experiment 1, they were male and female children and adults (aged 7-45 years). They oriented attention in response to volitional (endogenous) and reflexive (exogenous) cues. In experiment 2, the participants were men (aged 18-48 years). They oriented attention in an endogenous cueing task that manipulated the amount of information in the cue. Results: In women, fXPCs exhibited slower reaction times than HCs in both the endogenous and exogenous conditions. In men, fXPCs exhibited slower reaction times than HCs in the exogenous condition and in the challenging endogenous cueing task with probabilistic cues. In children, fXPCs did not differ from HCs. Conclusions: Because adult fXPCs were slower even when controlling for psychomotor speed, results support the interpretation that a core dysfunction in fXPCs is the allocation of spatial attention, while perceptual processing and attention orienting are intact. These findings indicate the importance of considering age and sex when interpreting and generalizing studies of fXPCs.