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Annette Karmiloff-Smith

Publications and source records attributed to Annette Karmiloff-Smith.

At least 19 recordsLinked to original sources
PubMed2007

Atypical epigenesis.

It is becoming increasingly clear that little in development is predetermined or permanently fixed. Rather, gene expression is activity dependent, and epigenesis is probabilistic. So, the study of genetic disorders needs to change from the still widely held view that developmental disorders can be accounted for in terms of intact versus impaired modules, to one which takes serious account of the fact that the infant cortex passes from an initial state of high regional interconnectivity to a subsequent state of increasing specialization and localization of function. With such early interconnectivity in mind, developmental neuroscientists must consider the possibility that an early deficit in one part of the brain may have subtle effects on other parts of the developing brain, even when scores fall 'in the normal range'. In studying developmental disorders, it is thus crucial to examine not only domains of clear-cut deficit, but also domains of behavioural proficiency. Atypical epigenesis may often involve a lack of specialization and localization of brain function over developmental time, even in cases of behavioural proficiency.

Brain↗
PubMed2006

High functioning children with autism spectrum disorder: a novel test of multitasking.

High functioning children with a diagnosis of autism or Asperger's syndrome (HF-ASD) often experience difficulties organising goal-directed actions in their day-to-day lives, requiring support to schedule daily activities. This study aimed to capture these everyday difficulties experimentally using multitasking, a methodology that taps into the cognitive processes necessary for successful goal-directed activities in everyday life. We investigated multitasking in children with HF-ASD using a novel multitask test, the Battersea Multitask Paradigm. Thirty boys participated in the study, 14 with HF-ASD and 16 typically developing controls, matched for age and IQ. Group differences in multitasking were observed. Participants with HF-ASD were less efficient at planning, attempted fewer tasks, switched inflexibly between tasks and broke performance rules more frequently than controls.

Autistic Disorder↗
PubMed2006

Are numerical impairments syndrome specific? Evidence from Williams syndrome and Down's syndrome.

BACKGROUND: Several theorists maintain that exact number abilities rely on language-relevant processes whereas approximate number calls on visuo-spatial skills. We chose two genetic disorders, Williams syndrome and Down's syndrome, which differ in their relative abilities in verbal versus spatial skills, to examine this hypothesis. Five experiments assessed number skills in these two genetic syndromes and in their mental age (MA) and chronological age (CA) matched controls. METHODS: Experiment 1 used a preferential looking paradigm with infants and toddlers to measure sensitivity to changes in numerosity. Experiment 2 measured reaction times in older children and adults in a numerosity comparison task with dots in a random pattern. Experiment 3 comprised a number battery that measured various forms of counting and simple arithmetic. RESULTS: The WS infants displayed a level of performance equal to that of their CA-controls, whereas the DS infants failed to reach even the level of their MA-controls. By contrast, the older DS children and adults outstripped the older WS group in their numerosity abilities, with different patterns of errors in the two clinical groups. CONCLUSIONS: Differences in the infant and adult number phenotypes between these two genetic disorders are discussed with reference to the processing styles used by each group and how these might impact on their developmental trajectories. Theoretically, we highlight our contention that one cannot infer the infant starting state from the adult end state. Rather, the development process itself must be taken into account.

Adolescent↗
PubMed2006

The tortuous route from genes to behavior: A neuroconstructivist approach.

In their excitement at using the human genome project to uncover the functions of specific genes, researchers have often ignored one fundamental factor: the gradual process of ontogenetic development. The view that there might be a gene for spatial cognition or language has emanated from a focus on the structure of the adult brain in neuropsychological patients whose brains were fully and normally developed until their brain insult. The developing brain is very different. It starts out highly interconnected across regions and is neither localized nor specialized at birth, allowing interaction with the environment to play an important role in gene expression and the ultimate cognitive phenotype. This article takes a neuroconstructivist perspective, arguing that domain-specific end states can stem from more domain-general start states, that associations may turn out to be as informative as dissociations, and that genetic mutations that alter the trajectory of ontogenetic development can inform nature/nurture debates.

Animals↗
PubMed2005

GTF2IRD1 in craniofacial development of humans and mice.

Craniofacial abnormalities account for about one-third of all human congenital defects, but our understanding of the genetic mechanisms governing craniofacial development is incomplete. We show that GTF2IRD1 is a genetic determinant of mammalian craniofacial and cognitive development, and we implicate another member of the TFII-I transcription factor family, GTF2I, in both aspects. Gtf2ird1-null mice exhibit phenotypic abnormalities reminiscent of the human microdeletion disorder Williams-Beuren syndrome (WBS); craniofacial imaging reveals abnormalities in both skull and jaws that may arise through misregulation of goosecoid, a downstream target of Gtf2ird1. In humans, a rare WBS individual with an atypical deletion, including GTF2IRD1, shows facial dysmorphism and cognitive deficits that differ from those of classic WBS cases. We propose a mechanism of cumulative dosage effects of duplicated and diverged genes applicable to other human chromosomal disorders.

Adolescent↗
PubMed2005

Discriminating power of localized three-dimensional facial morphology.

Many genetic syndromes involve a facial gestalt that suggests a preliminary diagnosis to an experienced clinical geneticist even before a clinical examination and genotyping are undertaken. Previously, using visualization and pattern recognition, we showed that dense surface models (DSMs) of full face shape characterize facial dysmorphology in Noonan and in 22q11 deletion syndromes. In this much larger study of 696 individuals, we extend the use of DSMs of the full face to establish accurate discrimination between controls and individuals with Williams, Smith-Magenis, 22q11 deletion, or Noonan syndromes and between individuals with different syndromes in these groups. However, the full power of the DSM approach is demonstrated by the comparable discriminating abilities of localized facial features, such as periorbital, perinasal, and perioral patches, and the correlation of DSM-based predictions and molecular findings. This study demonstrates the potential of face shape models to assist clinical training through visualization, to support clinical diagnosis of affected individuals through pattern recognition, and to enable the objective comparison of individuals sharing other phenotypic or genotypic properties.

Adult↗
PubMed2005

In-depth analysis of spatial cognition in Williams syndrome: A critical assessment of the role of the LIMK1 gene.

The LIM kinase1 protein (LIMK1) is thought to be involved in neuronal development and brain function. However, its role in spatial cognition in individuals with Williams syndrome (WS) is currently ambiguous, with conflicting reports on the cognitive phenotypes of individuals who do not have classic WS but harbour partial deletions including LIMK1. Two families with partial WS deletions have been described with deficits in visuospatial cognition (Frangiskakis, J. M., Ewart, A. K., Morris, C. A., Mervis, C. B., Bertrand, & J., Robinson, et al. (1996). LIM-kinase 1 hemizygosity implicated in impaired visuospatial constructive cognition. Cell, 86, 59-69), in contrast to others with similar partial deletions who did not display spatial impairments (Tassabehji, M., Metcalfe, K., Karmiloff-Smith, A., Carette, M. J., Grant, J., & Dennis, N., et al. (1999). Williams syndrome: Use of chromosomal microdeletions as a tool to dissect cognitive and physical phenotypes. American Journal of Human Genetics, 64, 118-125). To determine the role of LIMK1 in the highly penetrant visuospatial deficits associated with classic WS, it is essential to investigate the discrepancies between the two studies. Previous research used a standardised task to measure spatial cognition, which may not pick up subtle impairments. We therefore undertook more extensive testing of the spatial cognition of two adults with partial genetic deletions in the WS critical region (LIMK1 and ELN only), who had not displayed spatial impairments in the previous study, and compared them to two high-functioning adults with WS matched on verbal ability. All participants completed a broad battery of 16 perceptual and constructive spatial tests, and the clear-cut spatial difficulties observed in the WS group were not found in the partial deletion group. These findings rule out the claim that the deletion of one copy of LIMK1 is alone sufficient to result in spatial impairment, but leave open the possibility that LIMK1 contributes to the WS cognitive deficits if deleted in combination with other genes within the WS deletion. We conclude that a deeper assessment of WS at the genetic level is required before the contribution of specific genes to phenotypic outcomes can be fully understood.

Adult↗
PubMed2005

The dawn of cognitive genetics? Crucial developmental caveats.

Attempts to bridge genetics and cognition are rapidly coming to the forefront of cognitive neuroscience. It is therefore crucial to evaluate the current state of knowledge about disorders of known genetic origin as a way of assessing whether, and if so how, links between genotype and cognitive phenotype can be drawn, however indirect these links might be. We review recent empirical findings from research on genetic disorders at three levels of description--cognitive, neural systems, and cellular--that caution against simple genotype-phenotype mappings at all levels. Most importantly, interdisciplinary efforts to integrate human genetics and cognition will need to operationalize the mechanisms driving both typical and atypical developmental processes over time.

Brain↗
PubMed2005

Love is... an abstract word: the influence of lexical semantics on verbal short-term memory in Williams syndrome.

It has been claimed that verbal short-term memory in Williams syndrome is characterised by an over-use of phonological coding alongside a reduced contribution of lexical semantics. We critically examine this hypothesis and present results from a memory span task comparing performance on concrete and abstract words, together with a replication of a span task using phonologically similar and phonologically dissimilar words. Fourteen participants with Williams syndrome were individually matched to two groups of typically developing children. The first control group was matched on digit span and the second on vocabulary level. Significant effects were found for both the semantic and the phonological variables in the WS group as well as in the control groups, with no interaction between experimental variable and group in either experiment. The results demonstrate that, despite claims to the contrary, children and adults with WS are able to access and make use of lexical semantics in a verbal short-term memory task in a manner comparable to typically developing individuals.

Adolescent↗
PubMed2005

Asynchrony in the cognitive and lexical development of young children with Williams syndrome.

The present study investigates whether five-to-six-year-old children with Williams syndrome (N = 8) can form new object categories based on naming information alone, and compares them with five groups of typically developing children aged 2;0 to 6;0 (N = 34 children). Children were presented with triads of dissimilar objects; all objects in a triad were labelled, two of them with the same pseudoname. Name-based categorization was evaluated through object selection. Performance was above chance level for all groups. Performance reached a ceiling at about 4;0 for the typically developing children. For the children with Williams Syndrome, performance remained below chronological age level. The present results are discussed in light of previous findings of a failure to perform name-based categorization in younger children with Williams syndrome and the persistent asynchrony between cognitive and lexical development in this disorder.

Child↗
PubMed2005

To look or not to look? Typical and atypical development of oculomotor control.

The ability to inhibit saccades toward suddenly appearing peripheral stimuli (prosaccades) and direct them to contralateral locations instead (antisaccades) is a crucial marker of eye movement control. Typically developing infants as young as 4-month-olds can learn to inhibit reflexive saccades to peripheral stimuli, but they do not produce antisaccades, whose development later in infancy and its underlying neural computations remain unexplored. Here we tested oculomotor control in typically developing toddlers and toddlers with fragile X syndrome (FXS), a disorder of known genetic origin that allows the investigation of the neuro-computational properties contributing to the development of saccadic control. Typically developing toddlers decreased looking toward peripheral cues that predicted contralateral rewards, whose appearance they anticipated. Furthermore, this correlated with age, indicating a gradual development of saccadic control. In contrast with the typical case, toddlers with FXS did not decrease their looks to peripheral onsets that predicted contralateral events. Importantly, the atypical pattern of performance was also evident in the elimination of the correlation with mental or chronological age found in controls. Taken together, the findings suggest that control of saccades and its developmental trajectory is atypical in toddlers with FXS, consistent with inhibitory deficits previously shown at later ages in this condition. Potential implications for the neural mechanisms underlying the typical and atypical development of oculomotor control are discussed.

Age Factors↗
PubMed2004

Comprehension of spatial language terms in Williams syndrome: evidence for an interaction between domains of strength and weakness.

Individuals with Williams syndrome show an unusual neuropsychological profile, with relatively strong language abilities and impoverished visual and spatial abilities. Two studies are reported that examine the interaction between these two domains in Williams syndrome by assessing individuals' comprehension of spoken language with a spatial component. In a first study, the Test for Reception of Grammar (Bishop, 1983) was given to 32 individuals with Williams syndrome and to controls matched individually for total number of errors on the task. Individuals with Williams syndrome had particular problems when asked to comprehend sentences containing spatial prepositions, making significantly more errors on these items than control groups. A second study examined in more detail comprehension of sentences with spatial and non-spatial components, comparing the performance of 15 individuals with Williams syndrome and control groups matched for vocabulary ability. Individuals with Williams syndrome again showed impaired comprehension of spoken spatial terms. In contrast, they were unimpaired in comprehending utterances without a spatial component, with the exception of descriptions testing comprehension of non-spatial comparatives (lighter than and darker than). These results suggest that the spatial difficulties experienced by individuals with Williams syndrome may constrain language comprehension in certain circumstances. They also shed light on the ways in which spatial cognition may interact with language comprehension more generally.

Adolescent↗
PubMed2004

Visual search in typically developing toddlers and toddlers with Fragile X or Williams syndrome.

Visual selective attention is the ability to attend to relevant visual information and ignore irrelevant stimuli. Little is known about its typical and atypical development in early childhood Experiment 1 investigates typically developing toddlers' visual search for multiple targets on a touch-screen. Time to hit a target, distance between successively touched items, accuracy and error types revealed changes in 2- and 3-year-olds' vulnerability to manipulations of the search display. Experiment 2 examined search performance by toddlers with Fragile X syndrome (FXS) or Williams syndrome (WS). Both of these groups produced equivalent mean time and distance per touch as typically developing toddlers matched by chronological or mental age; but both produced a larger number of errors. Toddlers with WS confused distractors with targets more than the other groups; while toddlers with FXS perseverated on previously found targets. These findings provide information on how visual search typically develops in toddlers, and reveal distinct search deficits for atypically developing toddlers.

Attention↗
PubMed2004

Exploring the Williams syndrome face-processing debate: the importance of building developmental trajectories.

BACKGROUND: Face processing in Williams syndrome (WS) has been a topic of heated debate over the past decade. Initial claims about a normally developing ('intact') face-processing module were challenged by data suggesting that individuals with WS used a different balance of cognitive processes from controls, even when their behavioural scores fell within the normal range. Measurement of evoked brain potentials also point to atypical processes. However, two recent studies have claimed that people with WS process faces exactly like normal controls. METHOD: In this paper, we examine the details of this continuing debate on the basis of three new face-processing experiments. In particular, for two of our experiments we built task-specific full developmental trajectories from childhood to adolescence/adulthood and plotted the WS data on these trajectories. RESULTS: The first experiment used photos of real faces. While it revealed broadly equivalent accuracy across groups, the WS participants were worse at configural processing when faces were upright and less sensitive than controls to face inversion. In Experiment 2, measuring face processing in a storybook context, the face inversion effect emerged clearly in controls but only weakly in the WS developmental trajectory. Unlike the controls, the Benton Face Recognition Test and the Pattern Construction results were not correlated in WS, highlighting the different developmental patterns in the two groups. Again in contrast to the controls, Experiment 3 with schematic faces and non-face stimuli revealed a configural-processing deficit in WS both with respect to their chronological age (CA) and to their level of performance on the Benton. CONCLUSION: These findings point to both delay and deviance in WS face processing and illustrate how vital it is to build developmental trajectories for each specific task.

Adolescent↗
PubMed2003

ERP abnormalities of illusory contour perception in Williams syndrome.

Williams syndrome is a genetic disorder in which visuo-spatial performance is poor. Theorists have claimed that the deficit lies in high-level processing, leaving low-level visual processes intact. We investigated this claim by examining an aspect of low-level processing, perceptual completion, i.e. the ability of this clinical group to perceive illusory Kanizsa squares. We then used event-related potentials to examine neural correlates of perceptual completion. While participants were able to perceive illusory contours, the neural correlates of this apparently normal perception were different from controls. Such differences in low-level visual processes may significantly impact on the development of higher-level visual processes. We conclude that, contrary to earlier claims, there is atypical neural processing during low-level visual perception in Williams syndrome.

Adolescent↗
PubMed2003

What makes counting count? Verbal and visuo-spatial contributions to typical and atypical number development.

Williams Syndrome (WS) is marked by a relative strength in verbal cognition coupled with a serious impairment in non-verbal cognition. A strong deficit in numerical cognition has been anecdotally reported in this disorder; however, its nature has not been systematically investigated. Here, we tested 14 children with WS (mean age=7 years 2 months), 14 typically developing controls individually matched on visuo-spatial ability (mean age=3 years 5 months) as well as a larger group of typically developing controls (mean age=3 years 4 months) on two tasks to assess their understanding that counting determines the exact quantity of sets (cardinality principle). The understanding of the cardinality principle in children with WS is extremely delayed and only at the level predicted by their visuo-spatial MA. In this clinical group, only language accounted for a significant amount of the variance in cardinality understanding, whereas in the normal comparison group only visuo-spatial competence predicted the variance. The present findings suggest that visuo-spatial ability plays a greater role than language ability in the actual development of cardinality understanding in typically developing children, whereas the opposite obtains for the clinical group.

Child↗
PubMed2003

Spatial representation and attention in toddlers with Williams syndrome and Down syndrome.

The nature of the spatial representations that underlie simple visually guided actions early in life was investigated in toddlers with Williams syndrome (WS), Down syndrome (DS), and healthy chronological age- and mental age-matched controls, through the use of a "double-step" saccade paradigm. The experiment tested the hypothesis that, compared to typically developing infants and toddlers, and toddlers with DS, those with WS display a deficit in using spatial representations to guide actions. Levels of sustained attention were also measured within these groups, to establish whether differences in levels of engagement influenced performance on the double-step saccade task. The results showed that toddlers with WS were unable to combine extra-retinal information with retinal information to the same extent as the other groups, and displayed evidence of other deficits in saccade planning, suggesting a greater reliance on sub-cortical mechanisms than the other populations. Results also indicated that their exploration of the visual environment is less developed. The sustained attention task revealed shorter and fewer periods of sustained attention in toddlers with DS, but not those with WS, suggesting that WS performance on the double-step saccade task is not explained by poorer engagement. The findings are also discussed in relation to a possible attention disengagement deficit in WS toddlers. Our study highlights the importance of studying genetic disorders early in development.

Attention↗