Neural basis of genetically determined visuospatial construction deficit in Williams syndrome.
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.
Meyer-Lindenberg
Andreas
A
Unit on Integrative Neuroimaging, Clinical Brain Disorders Branch, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, 10-4C101, 9000 Rockville Pike, Bethesda, MD 20892, USA. andreasml@nih.gov
Kohn
Philip
P
Mervis
Carolyn B
CB
Kippenhan
J Shane
JS
Olsen
Rosanna K
RK
Morris
Colleen A
CA
Berman
Karen Faith
KF
D000328:Adult; D001288:Attention / Q000502:physiology; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D005260:Female; D007839:Functional Laterality / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D009154:Mutation / Q000235:genetics; D009421:Nervous System Malformations / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000002:abnormalities / Q000473:pathology / Q000503:physiopathology*; D010364:Pattern Recognition, Visual / Q000502:physiology; D013028:Space Perception / Q000502:physiology*; D014793:Visual Cortex / Q000002:abnormalities / Q000473:pathology / Q000503:physiopathology*; D014795:Visual Pathways / Q000002:abnormalities / Q000473:pathology / Q000503:physiopathology*; D018980:Williams Syndrome / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology