Brain and Cognition

Ursula Bellugi and Paul P. Wang
Laboratory for Cognitive Neuroscience
The Salk Institute for Biological Studies
La Jolla, CA

Encyclopedia of Neuroscience
Elsevier Science Publishers
Amsterdam, The Netherlands
(1996)

Genetic syndromes of retardation provide a unique opportunity to explore the fractionation of higher cortical functions on multiple neuroscientific levels. Down syndrome is the most common one (1 in 600) involving mental retardation whose cytogenetic etiology is established. Williams syndrome is a second, more rare genetic disorder (1 in 25,000) that also involves mental retardation. Both syndromes manifest distinctive patterns of pathology in many organ systems, these results being well known for three decades in Williams syndrome and longer still in Down syndrome. In Williams syndrome individuals, these include a characteristic facial appearance, cardiovascular problems, especially supravalvular aortic stenosis, hyperacusis.

The genetic basis for Williams syndrome has recently been illuminated as a hemizygous deletion of the gene for elastin (and surrounds) on chromosome 7. The genetic basis for Down syndrome has long been known. The cognitive profiles of the two populations, on the other hand, were considered essentially similar until recently, a result of standardized testing instruments designed mainly to probe only broad interconnected aspects of cognition. Investigations over the past decade have focused on examining the validity of this perception through coordinated application of a focused set of experimental probes using paradigms of neuropsychology, neurophysiology, and neuromorphology. The results of these continuing studies show dramatic differences between Williams and Down syndrome. Most remarkable neuropsychologically is the preservation of linguistic skills in Williams, relative to Down syndrome and relative to the level of general cognitive impairment of the two age- and IQ-matched experimental cohorts. Probes of visual-based cognition present a contrasting picture: although impairment is evident in both groups, the deficit is significantly more severe in Williams and is characterized by fractionated attention to detail at the expense of the whole. We describe studies of Williams and Down subjects, matched on age, IQ and educational background, which may highlight the different profiles of cognitive function in these two groups of subjects.

Marked Dissociations Within and Across Domains of Cognitive Functions:

Language and Spatial Cognition

Recent investigations seek to forge links between specific genetically based neurodevelopmental disorders, unusual neuropsychological profiles, and abnormal brain organization. Comparison of two well-defined populations of children who are mentally retarded but show opposite patterns of decoupling of language capacities can be revealing. In adolescent subjects with Williams Syndrome, there is an unusual fractionation of higher cognitive functioning, with relatively intact linguistic functioning in the face of severe deficits in other cognitive capacities. Williams subjects are contrasted with age-matched Down subjects, a better known and more common disorder, where linguistic functions are selectively impaired even when compared to other cognitive functions. The figure below one of the hallmarks of Williams syndrome: the marked contrast between remarkably spared language and impaired spatial abilities. A Williams individual age 15 with an IQ of 49 was asked to draw an elephant and tell what she knows about an elephant.

Decoupling of Language from Cognition. Age and IQ matched Williams and Down adolescents show equally depressed abilities across cognitive tasks including those of conservation. However, on linguistic performance, studies are finding that the two groups show opposite dissociations. Williams subjects exhibit spontaneous language that is not only syntactically impeccable, but also grammatically complex across a wide range of structures. In contrast, language performance in Down syndrome shows marked impairment relative to other cognitive abilities. These results present a challenge to important theoretical models of cognitive abilities. Even within language, there may be a cleavage among major components in Williams subjects. The results suggest that there is disproportionate preservation of the most autonomous aspects of linguistic processing (syntax). However, in the domain which interacts most directly with other cognitive capacities (semantics), the organization appears to be rich but perhaps aberrant.

Differential Processing in Spatial Cognition. Studies investigate spatial cognition, specifically because this aspect of cognition is the polar opposite of language, both in terms of processing operations that are brought into play and in terms of the basic functional organization of the brain. Both Williams and Down subjects show depressed performance on spatial cognitive tasks, but with striking qualitative differences. On a task of Block Design, both Williams and Down subjects are markedly impaired; however, the process by which they arrive at their depressed scores is very different. Down subjects typically fail on internal detail of the block design task, while Williams subjects fail to achieve the overall configuration of the blocks. Similarly, on a drawing task, Williams subjects show specific attention to parts of an object, but parts may be placed on a page with no integration into coherent wholes. In contrast, the Down subjects’ drawings depicted the overall gestalt of objects, with little internal detail. On an experimental task which differentiates processing of parts versus wholes, the same striking dissociation between the two groups may be found. Williams performance is characterized by selective attention to details of a configuration at the expense of the whole, while Down subjects show the opposite pattern.

Developmental Trajectories of Language and Cognitive Function in

Two Syndromes: Opposite Patterns of Decoupling

A series of studies on of the origins of language development in young children with Williams and Down syndrome is underway. Studies of adolescents point to unique behavioral profiles in which there are fractionations of higher cortical function in opposite directions: in Williams, linguistic functions are remarkably and selectively preserved in the face of severe general cognitive deficits, while in Down subjects, there is selective impairment of language relative to other cognitive functions. Examination of the developmental trajectories of language and cognition in these groups have important implications for the understanding of the neural substrate for language and cognition in normal development. The results from a cross-sectional group of 30 Williams and 30 Down children ranging in age from 12 – 55 months were compared. Language abilities were assessed through the Infant version of the MacArthur Communicative Development Inventory, a parental report rating scale which includes language comprehension and production measures as well as communicative gesture production. This measure provides a powerful tool for examining milestones in early language development in both normal and language-delayed children. Results show surprisingly similar language trajectories in Williams and Down children under five years of age, with marked delay in the onset of vocabulary comprehension and production in both groups, falling far below the 10th percentile for normally-developing infants. The results displayed by young Williams and Down children stand in marked contrast to the phenotypes found in adolescents.

Cerebral Morphological Distinctions Between Williams and Down Syndromes

In vivo magnetic resonance imaging in subjects with Williams and Down subjects is revealing that each syndrome appears to leave a distinctive morphological stamp on brain development, as well as distinct profiles of cognitive strengths and weaknesses. Several gross brain morphologic distinctions have been described between these two developmental disorders. While the observed cerebral hypoplasia is of equal degree in the two groups, cerebellar size is entirely normal in the Williams subjects but dramatically reduced in Down subjects. In addition, in Williams, while paleocerebellar vermal lobules subtend a smaller area on midsagittal sections, neocerebellar lobules are actually larger. These results suggest important distinctions between Williams and Down in terms of the action and anatomical targets of factors that alter brain development in these syndromes. We extend the earlier findings by focusing in detail on the morphologic features of the cerebral hemispheres, particularly cerebral gray matter. Morphometric analysis was used to estimate the volumes of cortical and subcortical gray matter structures. Comparisons of Williams, Down and control subjects yield many significant differences. The results suggest that some frontal and temporal limbic structures are relatively preserved in Williams, while some basal ganglia and diencephalic structures are relatively preserved in Down individuals. It is likely that these differences reflect different neurodevelopmental courses in the two genetically based disorders.

These studies provide an unusual opportunity to explore some of the central issues of developmental cognitive neuroscience. Since individuals with Williams and Down are often in the same classrooms for the educable mentally retarded, understanding the cognitive differences should lead to more tailored outcomes for treatment and education.