title: Reduced cortical complexity in children with Prader-Willi Syndrome and its association with cognitive impairment and developmental delay.
abstract: BACKGROUND
  Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder with symptoms involving not only hypothalamic, but also a global, central nervous system dysfunction. Previously, qualitative studies reported polymicrogyria in adults with PWS. However, there have been no quantitative neuroimaging studies of cortical morphology in PWS and no studies to date in children with PWS. Thus, our aim was to investigate and quantify cortical complexity in children with PWS compared to healthy controls. In addition, we investigated differences between genetic subtypes of PWS and the relationship between cortical complexity and intelligence within the PWS group.
  
  
  METHODS
  High-resolution structural magnetic resonance images were acquired in 24 children with genetically confirmed PWS (12 carrying a deletion (DEL), 12 with maternal uniparental disomy (mUPD)) and 11 age- and sex-matched typically developing siblings as healthy controls. Local gyrification index (lGI) was obtained using the FreeSurfer software suite.
  
  
  RESULTS
  Four large clusters, two in each hemisphere, comprising frontal, parietal and temporal lobes, had lower lGI in children with PWS, compared to healthy controls. Clusters with lower lGI also had significantly lower cortical surface area in children with PWS. No differences in cortical thickness of the clusters were found between the PWS and healthy controls. lGI correlated significantly with cortical surface area, but not with cortical thickness. Within the PWS group, lGI in both hemispheres correlated with Total IQ and Verbal IQ, but not with Performance IQ. Children with mUPD, compared to children with DEL, had two small clusters with lower lGI in the right hemisphere. lGI of these clusters correlated with cortical surface area, but not with cortical thickness or IQ.
  
  
  CONCLUSIONS
  These results suggest that lower cortical complexity in children with PWS partially underlies cognitive impairment and developmental delay, probably due to alterations in gene networks that play a prominent role in early brain development.
authors.affiliation: Dutch Growth Research Foundation, Rotterdam, The Netherlands; Department of Pediatrics, Erasmus Medical Centre Rotterdam/Sophia Children's Hospital Rotterdam Rotterdam, The Netherlands.
authors.forename: Akvile
authors.initials: A
authors.lastname: Lukoshe
authors.affiliation: Dutch Growth Research Foundation, Rotterdam, The Netherlands; Department of Pediatrics, Erasmus Medical Centre Rotterdam/Sophia Children's Hospital Rotterdam Rotterdam, The Netherlands.
authors.forename: Anita C
authors.initials: AC
authors.lastname: Hokken-Koelega
authors.affiliation: Department of Radiology, Erasmus Medical Centre Rotterdam, Rotterdam, The Netherlands.
authors.forename: Aad
authors.initials: A
authors.lastname: van der Lugt
authors.affiliation: Department of Child and Adolescent Psychiatry, Erasmus Medical Centre Rotterdam - Sophia Children's Hospital, Rotterdam, The Netherlands; Department of Radiology, Erasmus Medical Centre Rotterdam, Rotterdam, The Netherlands.
authors.forename: Tonya
authors.initials: T
authors.lastname: White
mesh_terms: D000293:Adolescent; D001931:Brain Mapping; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000473:pathology*; D002648:Child; D003072:Cognition Disorders / Q000150:complications*; D002658:Developmental Disabilities / Q000150:complications*; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007360:Intelligence; D008279:Magnetic Resonance Imaging; D008297:Male; D011218:Prader-Willi Syndrome / Q000150:complications / Q000473:pathology* / Q000523:psychology*