Neural basis of genetically determined visuospatial construction deficit in Williams syndrome

Neuron. 2004 Sep 2;43(5):623-31. doi: 10.1016/j.neuron.2004.08.014.


A unique opportunity to understand genetic determinants of cognition is offered by Williams syndrome (WS), a well-characterized hemideletion on chromosome 7q11.23 that causes extreme, specific weakness in visuospatial construction (the ability to visualize an object as a set of parts or construct a replica). Using multimodal neuroimaging, we identified a neural mechanism underlying the WS visuoconstructive deficit. Hierarchical assessment of visual processing with fMRI showed isolated hypoactivation in WS in the parietal portion of the dorsal stream. In the immediately adjacent parietooccipital/intraparietal sulcus, structural neuroimaging showed a gray matter volume reduction in participants with WS. Path analysis demonstrated that the functional abnormalities could be attributed to impaired input from this structurally altered region. Our observations confirm a longstanding hypothesis about dorsal stream dysfunction in WS, demonstrate effects of a localized abnormality on visual information processing in humans, and define a systems-level phenotype for mapping genetic determinants of visuoconstructive function.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Attention / physiology
  • Chromosomes, Human, Pair 7 / genetics
  • Female
  • Functional Laterality / genetics
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Models, Neurological
  • Mutation / genetics
  • Nervous System Malformations / genetics
  • Nervous System Malformations / pathology
  • Nervous System Malformations / physiopathology
  • Neuropsychological Tests
  • Parietal Lobe / abnormalities
  • Parietal Lobe / pathology
  • Parietal Lobe / physiopathology*
  • Pattern Recognition, Visual / physiology
  • Space Perception / physiology*
  • Visual Cortex / abnormalities
  • Visual Cortex / pathology
  • Visual Cortex / physiopathology*
  • Visual Pathways / abnormalities
  • Visual Pathways / pathology
  • Visual Pathways / physiopathology*
  • Williams Syndrome / pathology
  • Williams Syndrome / physiopathology*
  • Williams Syndrome / psychology