Understanding Number Line Estimation in Williams Syndrome and Down Syndrome.

Previous studies suggest that tasks dependent on the mental number line may be difficult for Williams Syndrome (WS) and Down Syndrome (DS) groups. However, few have directly assessed number line estimation in these groups. The current study assessed 28 WS, 25 DS and 25 typically developing (TD) participants in non-verbal intelligence, number familiarity, visuo-spatial skills and number line estimation. Group comparisons indicated no differences in number line estimation. However, the WS group displayed difficulties with visuo-spatial skills and the DS group displayed difficulties with number familiarity. Differential relationships between number line estimation and visuo-spatial/number familiarity skills were observed across groups. Data is discussed in the context of assessment of skills in neurodevelopmental disorders.

Atypical development of configural face recognition in children with autism, Down syndrome and Williams syndrome.

BACKGROUND: Configural processing in face recognition is a sensitivity to the spacing between facial features. It has been argued both that its presence represents a high level of expertise in face recognition, and also that it is a developmentally vulnerable process. METHOD: We report a cross-syndrome investigation of the development of configural face recognition in school-aged children with autism, Down syndrome and Williams syndrome compared with a typically developing comparison group. Cross-sectional trajectory analyses were used to compare configural and featural face recognition utilising the 'Jane faces' task. Trajectories were constructed linking featural and configural performance either to chronological age or to different measures of mental age (receptive vocabulary, visuospatial construction), as well as the Benton face recognition task. RESULTS: An emergent inversion effect across age for detecting configural but not featural changes in faces was established as the marker of typical development. Children from clinical groups displayed atypical profiles that differed across all groups. CONCLUSION: We discuss the implications for the nature of face processing within the respective developmental disorders, and how the cross-sectional syndrome comparison informs the constraints that shape the typical development of face recognition.

Attention deficits predict phenotypic outcomes in syndrome-specific and domain-specific ways.

Attentional difficulties, both at home and in the classroom, are reported across a number of neurodevelopmental disorders. However, exactly how attention influences early socio-cognitive learning remains unclear. We addressed this question both concurrently and longitudinally in a cross-syndrome design, with respect to the communicative domain of vocabulary and to the cognitive domain of early literacy, and then extended the analysis to social behavior. Participants were young children (aged 4-9 years at Time 1) with either Williams syndrome (WS, N = 26) or Down syndrome (DS, N = 26) and typically developing controls (N = 103). Children with WS displayed significantly greater attentional deficits (as indexed by teacher report of behavior typical of attention deficit hyperactivity disorder (ADHD) than children with DS, but both groups had greater attentional problems than the controls. Despite their attention differences, children with DS and those with WS were equivalent in their cognitive abilities of reading single words, both at Time 1 and 12 months later, at Time 2, although they differed in their early communicative abilities in terms of vocabulary. Greater ADHD-like behaviors predicted poorer subsequent literacy for children with DS, but not for children with WS, pointing to syndrome-specific attentional constraints on specific aspects of early development. Overall, our findings highlight the need to investigate more precisely whether and, if so, how, syndrome-specific profiles of behavioral difficulties constrain learning and socio-cognitive outcomes across different domains.

Severity of hyperacusis predicts individual differences in speech perception in Williams Syndrome.

BACKGROUND: Williams Syndrome (WS) is a neurodevelopmental disorder of genetic origin, characterised by relative proficiency in language in the face of serious impairment in several other domains. Individuals with WS display an unusual sensitivity to noise, known as hyperacusis. METHODS: In this study, we examined the extent to which hyperacusis interferes with the perception of speech in children and adults with WS. Participants were required to discriminate words which differed in one consonant of a cluster when these contrasts were embedded in a background of noise. RESULTS: Although the introduction of noise interfered with performance on a consonant cluster discrimination task equally in the WS and control groups, the severity of hyperacusis significantly predicted individual variability in speech perception within the WS group. CONCLUSIONS: These results suggest that alterations in sensitivity to input mediate atypical pathways for language development in WS, where hyperacusis exerts an important influence together with other non-auditory factors.

Audiovisual speech perception in Williams syndrome.

People with the genetic disorder of Williams syndrome (WS) show an anomalous cognitive profile, wherein some purely verbal and social communicative abilities are relatively proficient, while visuo-spatial skills can be extremely impaired. Face processing, while apparently relatively spared among visuo-spatial skills, can show deficits suggesting developmental immaturity. In this context, the exploration of visual and audiovisual speech perception in WS is of interest. A new test based on tokens from a single natural English speaker of the form /(inverted v)ba:/, /(inverted v) va:/, /(inverted v)(theta)a:/, /(inverted v)da:/ and /(inverted v)ga:/, digitally manipulated and presented in unimodal (vision alone, audition alone) and audiovisual conditions, was presented for participants to identify each token. Compared with age-matched controls, WS participants were impaired at visual but not auditory identification, and in audiovisual testing showed correspondingly reduced effects of vision on report of auditory token identity. Audiovisual integration was nevertheless demonstrable in WS. Speech-reading may require skills which do not reach age-appropriate levels in WS, despite their age-appropriate (auditory) phonological abilities.

Learning to read in Williams syndrome: looking beneath the surface of atypical reading development.

In this paper, we make a fundamental distinction between literacy attainment scores and the actual process of learning to read, and examine these two aspects of reading in atypical development. Reading skills in a group of children and adults with the genetic disorder Williams syndrome (WS) were compared to a group of typically developing children matched for reading age and receptive vocabulary scores. Study 1 focused on the product of reading and explored the relationship between reading, general cognition, and phonological skills. Phonological skills were shown to be related to individual differences in reading attainment in both groups, although more weakly in the WS group. Experiment 2 examined the process of learning to read. The two groups were taught to associate abbreviated spellings (cues) with spoken words. The cues differed in their phonetic closeness to the target words, whereas the target words differed on the semantic variable of imageability. Compared to controls, the WS group showed slower learning, less sensitivity to the phonetic quality of the cue, and reduced influence from the imageability of words. The results support the hypothesis that although reading levels in WS depend on phonological skills, the full development of their reading is compromised by weak semantics. The studies highlight the importance in atypical populations of examining both reading levels and the actual process of learning to read.

Disordered visual processing and oscillatory brain activity in autism and Williams syndrome.

Two developmental disorders, autism and Williams syndrome, are both commonly described as having difficulties in integrating perceptual features, i.e. binding spatially separate elements into a whole. It is already known that healthy adults and infants display electroencephalographic (EEG) gamma-band bursts (around 40 Hz) when the brain is required to achieve such binding. Here we explore gamma-band EEG in autism and Williams Syndrome and demonstrate differential abnormalities in the two phenotypes. We show that despite putative processing similarities at the cognitive level, binding in Williams syndrome and autism can be dissociated at the neurophysiological level by different abnormalities in underlying brain oscillatory activity. Our study is the first to identify that binding-related gamma EEG can be disordered in humans.

Electrophysiological correlates of category goodness.

We report the results obtained from a behavioural and electrophysiological study. A synthesised continuum going from labial /ba/ to retroflex /da/ through dental /da/ was tested for category goodness. Native English speakers rated different tokens from each category as good, bad or ambiguous. The results showed that not all of the representatives of each category were ideal and that the categories tested have an internal structure. The electrophysiological study evaluated whether event related potentials (ERPs) mirrored the goodness judgements. During a passive oddball task, the same participants were exposed to native /ba/-/da/, Hindi dental /da/-retroflex /da/ and within-category /ba/-/ba/ contrasts. Results showed that participants pre-attentively perceive the differences in all cases, as shown by mis-match negativities (MMN), late positive deflections (LPD) or greater N1 and/or P2 components for deviant stimuli. Acoustic sensitivities, categorical perception and category goodness all contributed to the waveforms obtained. We attribute the ERP effects to a combination of (1) prototypes built from initial sensitivities, (2) reinforcement with exposure to one's native language and (3) no permanent loss of the initial boundaries explains the effects observed.

Electrophysiological correlates of cross-linguistic speech perception in native English speakers.

The present study examined the electrophysiological responses that Native English speakers display during a passive oddball task when they are presented with different types of syllabic contrasts, namely a labial /ba/-dental /d a/, a Hindi dental /d a/-retroflex /da/ and a within-category (two /ba/ tokens) contrasts. The analyses of the event-related potentials obtained showed that subjects pre-attentively perceive the differences in all experimental conditions, despite not showing such detection behaviourally in the Hindi and within-category conditions. These results support the notion that there is no permanent loss of the initial perceptual abilities that humans have as infants, but that there is an important neural reorganisation which allows the system to overcome the differences detected and only be aware of contrasts that are relevant in the language which will become the subjects native tongue. We also report order asymmetries in the ERP responses and suggest that the percepts and not only the physical attributes of the stimuli have to be considered for the evaluation of the responses obtained.

Williams syndrome: from genotype through to the cognitive phenotype.

Williams syndrome, due to a contiguous gene deletion at 7q11.23, is associated with a distinctive facial appearance, cardiac abnormalities, infantile hypercalcemia, and growth and developmental retardation. The deletion is approximately 1.5Mb and includes approximately 17 genes. Large repeats containing genes and pseudogenes flank the deletion breakpoints, and the mutation mechanism commonly appears to be unequal meiotic recombination. Elastin hemizygosity is associated with supravalvular aortic stenosis and other vascular stenoses. LIM Kinase 1 hemizygosity may contribute to the characteristic cognitive profile. The relationship of the other deleted genes to phenotypic features is not known. People with Williams syndrome tend to be over friendly-though anxious-and lack social judgement skills. They exhibit an uneven cognitive-linguistic profile together with mild to severe mental retardation. Analysis of the cognitive phenotype based on analyses of the mental processes underlying overt behavior demonstrates major differences between normal and WS subjects although for some areas, such as face processing, WS subjects can achieve near normal scores. Cognitive analysis of patients with small deletions in 7q11.23 which include elastin and LIM Kinase 1 have revealed varying results and it is premature to draw genotype-phenotype correlations.

Cognitive modularity and genetic disorders.

This study challenges the use of adult neuropsychological models for explaining developmental disorders of genetic origin. When uneven cognitive profiles are found in childhood or adulthood, it is assumed that such phenotypic outcomes characterize infant starting states, and it has been claimed that modules subserving these abilities start out either intact or impaired. Findings from two experiments with infants with Williams syndrome (a phenotype selected to bolster innate modularity claims) indicate a within-syndrome double dissociation: For numerosity judgments, they do well in infancy but poorly in adulthood, whereas for language, they perform poorly in infancy but well in adulthood. The theoretical and clinical implications of these results could lead to a shift in focus for studies of genetic disorders.

Williams syndrome: use of chromosomal microdeletions as a tool to dissect cognitive and physical phenotypes.

In Williams syndrome (WS), a deletion of approximately 1.5 Mb on one copy of chromosome 7 causes specific physical, cognitive, and behavioral abnormalities. Molecular dissection of the phenotype may be a route to identification of genes important in human cognition and behavior. Among the genes known to be deleted in WS are ELN (which encodes elastin), LIMK1 (which encodes a protein tyrosine kinase expressed in the developing brain), STX1A (which encodes a component of the synaptic apparatus), and FZD3. Study of patients with deletions or mutations confined to ELN showed that hemizygosity for elastin is responsible for the cardiological features of WS. LIMK1 and STX1A are good candidates for cognitive or behavioral aspects of WS. Here we describe genetic and psychometric testing of patients who have small deletions within the WS critical region. Our results suggest that neither LIMK1 hemizygosity (contrary to a previous report) nor STX1A hemizygosity is likely to contribute to any part of the WS phenotype, and they emphasize the importance of such patients for dissecting subtle but highly penetrant phenotypes.

Brain biochemistry in Williams syndrome: evidence for a role of the cerebellum in cognition?

OBJECTIVE: To determine what biochemical changes may occur in the brain in Williams syndrome (WS) and whether these changes may be related to the cognitive deficits. BACKGROUND: WS is a rare, congenital disorder with a characteristic physical, linguistic, and behavioral phenotype with known cognitive deficits. METHODS: We obtained 31P magnetic resonance spectra (MRS) from a region consisting of mostly frontal and parietal lobe of 14 patients with WS (age, 8 to 37 years) and 48 similarly-aged controls. 1H MRS (27 cm3) localized to the left cerebellum obtained from the WS cohort were compared with those from 16 chronological age- and sex-matched normal controls. A battery of cognitive tests were administered to all subjects undergoing 1H MRS. RESULTS: WS brains exhibited significant biochemical abnormalities. All 31P MRS ratios containing the phosphomonoester (PME) peak were significantly altered in WS, suggesting that PME is significantly decreased. Ratios of choline-containing compounds and creatine-containing compounds to N-acetylaspartate (Cho/NA and Cre/NA) were significantly elevated in the cerebellum in WS cf. controls, whereas the ratio of Cho/Cre was not altered. This suggests a decrease in the neuronal marker N-acetylaspartate in the cerebellum. Significant correlations were found between the cerebellar ratios Cho/NA and Cre/NA and the ability of all subjects at various neuropsychological tests, including Verbal and Performance IQ, British Picture Vocabulary Scale, Ravens Progressive Matrices, and Inspection Time. CONCLUSIONS: The correlations can be interpreted in two ways: 1) Our sampling of cerebellar biochemistry reflects a measure of "global" cerebral biochemistry and is unrelated to cerebellar function, or 2) The relations indicate that cerebellar neuronal integrity is a requirement (on a developmental time scale or in real-time) for ability on a variety of cognitive tests.

Linguistic dissociations in Williams syndrome: evaluating receptive syntax in on-line and off-line tasks.

Williams syndrome (WS) is a neurodevelopmental disorder of genetic origin which results in relatively spared language in the face of serious non-verbal deficits. There is controversy, however, about how intact WS language abilities are. The discussion has focused on impairments of lexico-semantics and of morphological feature analysis, with the presumption that WS syntax is intact. We challenged this view and assessed WS receptive syntax by using two tasks testing various syntactic structures: an on-line word monitoring task and an off-line picture-pointing task. WS performance on the off-line task was generally poor. By contrast, their performance on the on-line task was far better and allowed us to ascertain precisely which aspects of WS receptive syntax are preserved and which are impaired. WS participants were sensitive to the violation of auxiliary markers and phrase structure rules but, unlike both the normal young and elderly controls, they did not show sensitivity to violations of subcategory constraints. The present study suggests that there exist dissociations within WS language which are not restricted to lexico-semantics or to morphological feature analysis, but which also invade their processing of certain syntactic structures. We conclude by arguing that WS syntax is not intact and that their language might turn out to be more like second language learning than normal acquisition.

Development itself is the key to understanding developmental disorders.

It is a truism that development involves contributions from both genes and environment, but theories differ with respect to the roles they attribute to each, which deeply affects the ways in which developmental disorders are researched. The strict nativist approach to abnormal phenotypes, inspired by adult neuropsychology and evolutionary psychology, seeks to identify impairments to domain-specific cognitive modules and studies the purported juxtaposition of impaired and intact abilities. The neuroconstructivist approach differs in several respects: (i) it seeks more indirect, lower-level causes of abnormality than impaired cognitive modules; (ii)modules are thought to emerge from a developmental process of modularization; (iii) unlike empiricism, neuroconstructivism accepts some form of innately specified starting points, but unlike nativism, these are considered to be initially `domain-relevant', only becoming domain-specific with the process of development and specific environmental interactions; and (iv) different cognitive disorders are considered to lie on a continuum rather than to be truly specific. These alternative theoretical positions are briefly considered as they apply to Specific Language Impairment, and followed by a more detailed case study of a well-defined neurodevelopmental disorder, Williams syndrome. It is argued that development itself plays a crucial role in phenotypical outcomes.

Do individuals with Williams syndrome have bizarre semantics? Evidence for lexical organization using an on-line task.

Williams syndrome, a neurodevelopmental disorder, has attracted a great deal of debate concerning the purported intactness of language in the face of other serious cognitive deficits. As more in-depth studies of specific aspects of WS language have emerged, the notion of a preserved language module has been seriously challenged. Although WS vocabulary scores are often impressive, several investigators have claimed the WS semantics are aberrant. All studies hitherto have been based on off-line experiments which necessarily involve metalinguistic processes. This clearly affects the performance of individuals with cognitive deficits. We report here an on-line study probing the semantic structure of the WS lexicon, using a task-semantic priming-which minimises metalinguistic demands. We show that WS subjects display the same taxonomic/category and thematic/functional priming effects as normal controls. The results are discussed in terms of the differences between receptive and expressive language, as well as the fact that although semantic memory and the automatic access to semantic information for individual words is normal in WS, the integration of semantic information into sentence comprehension may be abnormal. The importance of online tasks to highlight such differences is stressed.

Language and Williams syndrome: how intact is "intact"?

It has been claimed that Williams syndrome (WS), a rare neurodevelopmental disorder, is characterized by serious cognitive deficits alongside intact language. The syndrome is often used as a prime example of the modularity of an innate faculty for morphosyntactic rules. We challenge this claim and hypothesize that morphosyntax, although surprisingly good given WS level of mental retardation, is by no means intact. We make an initial test of this hypothesis through an analysis of the receptive language of a group of English-speaking WS individuals on a standardized morphosyntactic test. We then present an experimental study of expressive language that examines grammatical gender assignment in French-speaking WS patients. Despite a Verbal Mental Age selected to be higher than the chronological age of the young control group, these people with WS continue even in adulthood to show clear-cut deficits in their production of an aspect of morphosyntax that normal children acquire effortlessly very early. The results of the 2 studies, one focusing on receptive language and the other on expressive language, challenge the notion that comprehension and use of morphosyntactic rules in WS individuals are intact. The Within-domain dissociations regarding the use of grammatical gender assignment across several sentence clements and their difficulties in understanding embedded sentences-two quintessentially linguistic skills-suggest that we must rethink the notion of spared, modular, language capacities in Williams syndrome. We conclude that WS language follows a different path to normal acquisition and may turn out to be more like second language learning.

Connectionism and developmental psychology.

What features of brain processing and neural development support linguistic and cognitive development in young children? To what extent are the profile and timing of development in young children determined by a preordained genetic programme? Does the environment play a crucial role in determining the patterns of change observed in children growing up? These questions have been of central concern to developmental psychologists for well over a century. Yet none of them have received answers that are generally accepted by the profession. This article reviews some recent computational modelling of developmental change in children that promises to contribute to a deeper understanding of the issues behind these questions. The modelling work exploits artificial neural networks that mimic some of the basic properties of neural processing in the brain. These networks involve densely connected webs of simple processing units that propagate and transform complex patterns of activity. When exposed to a training environment, they undergo a process of self-organisation, yielding information processing systems that support new forms of behaviour. The study of the dynamics of these systems and their learning capabilities promises to provide us with important clues as to the nature of the mechanisms underlying development in infants and young children.

Phonological Short-term Memory and its Relationship to Language in Williams Syndrome.

Williams syndrome (WS), a rare neurodevelopmental disorder of genetic origin, is characterised by a relative advantage of language over more serious deficits in other cognitive domains. In this study the relationship of phonological short-term memory to WS language, in particular vocabulary, was explored. Using Gathercole and Baddeley's Children's Test of Nonword Repetition (CNRep) (Gathercole & Baddeley, 1996), we examined the pattern of performance by WS participants on that task and compared it to performance on measures of receptive language, visuospatial ability, and digit span. In addition, a comparison was made of WS nonword repetition score with those of two groups of individually matched normally developing 5-year-olds, one on the basis of nonverbal test age and the other on the basis of verbal test age. As expected WS repetition scores showed an effect of nonword length but not of phonological complexity. Nonwords that were relatively wordlike were better repeated than nonwords that were less wordlike. CNRep scores were correlated with test ages on TROG, Ravens, and digit span but not with chronological age. Test age on the CNRep was at a similar level to that on TROG, Ravens, and digit span but significantly lower than on BPVS. The results lend support to the view that phonology in WS is a relative strength. In contrast, despite relatively good productive and receptive vocabulary, certain aspects of the processes of word learning in WS do not seem to develop beyond that of normal 4year-olds. The good vocabulary scores of older children and adults with WS may be simply due to their relatively good phonological short-term memory.