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Enhanced activation of reward mediating prefrontal regions in response to food stimuli in Prader–Willi syndrome
  1. Jennifer L Miller1,*,
  2. G Andrew James2,*,
  3. Anthony P Goldstone1,
  4. Jessica A Couch2,
  5. Guojun He2,
  6. Daniel J Driscoll1,
  7. Yijun Liu2
  1. 1Department of Pediatrics, University of Florida, College of Medicine, Gainesville, Florida, USA
  2. 2Department of Psychiatry, University of Florida, College of Medicine, Gainesville, Florida, USA
  1. Correspondence to:
 Dr Yijun Liu
 Department of Psychiatry, Box 100256, 100 Newell Dr L4-100, Gainesville, FL 32610, USA; yijunliu{at}


Background: Individuals with Prader–Willi syndrome (PWS) exhibit severe disturbances in appetite regulation, including delayed meal termination, early return of hunger after a meal, seeking and hoarding food and eating of non-food substances. Brain pathways involved in the control of appetite in humans are thought to include the hypothalamus, frontal cortex (including the orbitofrontal, ventromedial prefrontal, dorsolateral prefrontal and anterior cingulate areas), insula, and limbic and paralimbic areas. We hypothesised that the abnormal appetite in PWS results from aberrant reward processing of food stimuli in these neural pathways.

Methods: We compared functional MRI blood oxygen level dependent (BOLD) responses while viewing pictures of food in eight adults with PWS and eight normal weight adults after ingestion of an oral glucose load.

Results: Subjects with PWS demonstrated significantly greater BOLD activation in the ventromedial prefrontal cortex than controls when viewing food pictures. No significant differences were found in serum insulin, glucose or triglyceride levels between the groups at the time of the scan.

Conclusions: Individuals with PWS had an increased BOLD response in the ventromedial prefrontal cortex compared with normal weight controls when viewing pictures of food after an oral glucose load. These findings suggest that an increased reward value for food may underlie the excessive hunger in PWS, and support the significance of the frontal cortex in modulating the response to food in humans. Our findings in the extreme appetite phenotype of PWS support the importance of the neural pathways that guide reward related behaviour in modulating the response to food in humans.

  • BOLD, blood oxygen level dependent
  • fMRI, functional MRI
  • PET, positron emission tomography
  • PWS, Prader–Willi syndrome

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  • * Jennifer L Miller and G Andrew James contributed equally to the preparation of this manuscript.

  • Published Online First 8 December 2006

  • Competing interests: None.

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