Occipital Visual Dysfunction and Its Consequences in Hungarian Williams Syndrome Children

Williams Syndrome (WMS) is a genetic condition in which a relatively consistent neurobehavioral phenotype is produced by a genetic deletion. The syndrome has high potentials in bridging genes and behavior because of the genetic specificity and the consistent cognitive features in WMS. The crucial link between the genetic and behavioral levels is likely to be provided by cortical neuroanatomy. Recent neuroanatomical studies indicate that the most severe volumetric reductions in WMS are in the occipital lobe involving especially the primary visual cortex (V1). Furthermore, V1 is the only cortical area where anatomical observations have shown signs of abnormal neural connectivity. These anatomical findings call for studies addressing early levels of visual processing in WMS. The current study, in response to the NSF Children's Research Initiative, will be the first systematic behavioral investigation of low-level visual processing in WMS.

The primary visual cortex not only carries out a local analysis of the retinal image along the main feature dimensions (such as color, texture, depth), it also participates in the integration of local information, primitive figure-ground segmentation, and visual contextual integration. V1 also remains plastic and dynamically changing even in adult life, and takes part in visual short-term memory. How are these functions affected by the anatomically indicated abnormal connectivity in V1? The first objective of the study is to assess the development of local and integrative visual functions, and their plasticity related to occipital cortical areas in WMS. The assessment involves psychophysical measurements to estimate (1) orientation discrimination abilities, (2) contour integration abilities, (3) contextual sensitivity, and (4) perceptual learning in WMS subjects. All these procedures are based on the PI's previous work in visual spatial integration, visual plasticity and development. The PI's previous work also provides normal developmental trends in the studied visual functions, enabling the research group to evaluate developmental dispositions in WMS from the perspective of normal development.

How does occipital visual dysfunction affect the development of higher-level cognitive functions, such as language? The cortical areas mediating language are not as severely involved anatomically as the low-level visual areas, and language seems to be preserved in WMS. However, abnormal visual processing might interfere with the normal development of some linguistic functions, such as visuo-spatial language. It has recently been indicated that the link between low-level vision and language might be visual memory. The second objective of the study is to assess the consequences of occipital dysfunction on the development of higher-level cognitive functions. The assessment involves behavioral studies on (1) visuo-spatial working memory and (2) visuo-spatial long-term memory, and (3) visuo-spatial language. Correlations between memory and language related task performances are evaluated. The conjecture is that abnormal connectivity in the visual cortex leads to memory limitations, and language impairments.

The research is novel in that it offers a systematic investigation of (a) the development of occipital functions, and (b) consequential memory limitations, and language impairments in WMS. It also offers to test the whole population of Hungarian WMS children and young adults, therefore the whole range of patients with a genetic disorder within an isolated population. Experiments are designed to ensure age-matched (normal), mental-age matched (normal), and IQ matched (Down Syndrome) controls. In addition to its potential to reveal neurobehavioral developmental rules in WMS, the research is significant in terms of a better understanding of both psychological functions (e.g., contextual integration, working memory, visuo-spatial language), and the neural circuits underlying these.