| | 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.
REFERENCES
Bellugi, U. & Morris, C.A. (Eds.) "Williams Syndrome: From
Cognition to Gene." Williams Syndrome Association
Professional Conference. Special Issue, Genetic Counseling,
6(1), 1995, pp. 131-192.
Bellugi, U., Bihrle, A., Jernigan, T., Trauner, D., &
Doherty, S. "Neuropsychological, Neurological, &
Neuroanatomical Profile of Williams Syndrome." Amer.
Journal Medical Genetics, 1990, 6, 115-125.
Bellugi, U., Bihrle, A., Neville, H., Jernigan, T., &
Doherty, S., "Language, Cognition, and Brain Organization
in a Neurodevelopmental Disorder." In M. Gunnar & C. Nelson
(Eds.), Developmental Behavioral Neuroscience. Hillsdale,
NJ: Erlbaum Press, 1992, 201-232.
Bellugi, U., Klima, E.S., & Wang, P.P. "Cognitive and
Neural Development: Clues from Genetically Based
Syndromes." In D. Magnussen (Ed.), Nobel Symposium:
Life-Span Development of Individuals New York: Cambridge
University Press, in press.
Bellugi, U., Wang, P., & Jernigan, T.L. "Williams Syndrome:
An Unusual Neuropsychological Profile." In S. Broman & J.
Grafman (Eds.), Atypical Cognitive Deficits in
Developmental Disorders: Implications for Brain Function.
Hillsdale, NJ: Lawrence Erlbaum Associates, 1994, 23-56.
Galaburda, A., Wang, P.P., Bellugi, U., & Rossen, M.
"Cytoarchitectonic Findings in a Genetically Based
Disorder: Williams Syndrome." NeuroReport, 1994, 5, pp.
758-787.
Jernigan, T.L., Bellugi, U., Sowell, E., Doherty, S., &
Hesselink, J.R. "Cerebral Morphological Distinctions
between Williams and Down Syndromes." Archives of
Neurology, 1993, 50, 186-191.
Wang, P.P., Hesselink, J.R., Jernigan, T.L., Doherty, S., &
Bellugi, U. "Specific Neurobehavioral Profile of Williams
Syndrome is Associated with Neocerebellar Hemispheric
Preservation." Neurology, 1992, 42, 1999-2002.
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