Deactivation of the left dorsolateral prefrontal cortex in Prader-Willi syndrome after meal consumption.
Prader-Willi syndrome (PWS) is a type of human genetic obesity that may give us information regarding the physiology of non-syndromic obesity. The objective of this study was to investigate the functional correlates of hunger and satiety in individuals with PWS in comparison with healthy controls with obesity, hypothesizing that we would see significant differences in activation in the left dorsolateral prefrontal cortex (DLPFC) based on prior findings.



This study compared the central effects of food consumption in nine individuals with PWS (7 men, 2 women; body fat 35.3±10.0%) and seven controls (7 men; body fat 28.8±7.6%), matched for percentage body fat. H2(15)O-PET (positron emission tomography) scans were performed before and after consumption of a standardized liquid meal to obtain quantitative measures of regional cerebral blood flow (rCBF), a marker of neuronal activity.



Compared with obese controls, PWS showed altered (P<0.05 family-wise error cluster-level corrected; voxelwise P<0.001) rCBF before and after meal consumption in multiple brain regions. There was a significant differential rCBF response within the left DLPFC after meal ingestion with decreases in DLPFC rCBF in PWS; in controls, DLPFC rCBF tended to remain unchanged. In more liberal analyses (P<0.05 family-wise error cluster-level corrected; voxelwise P<0.005), rCBF of the right orbitofrontal cortex (OFC) increased in PWS and decreased in controls. In PWS, ΔrCBF of the right OFC was associated with changes in appetite ratings.



The pathophysiology of eating behavior in PWS is characterized by a paradoxical meal-induced deactivation of the left DLPFC and activation in the right OFC, brain regions implicated in the central regulation of eating behavior.
Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Phoenix, AZ, USA.|Department of Diagnostic and Interventional Radiology, University of Leipzig, Leipzig, Germany.
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M
Reinhardt
Department of Nutrition Sciences, Drexel University, Philadelphia, PA, USA.|Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA.
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Parigi
Banner Alzheimer's Institute, Phoenix, AZ, USA.
K
K
Chen
Banner Alzheimer's Institute, Phoenix, AZ, USA.|Neurogenomics Division, Translational Genomics Research Institute, University of Arizona, and Arizona State University, Phoenix, AZ, USA.
E M
EM
Reiman
Banner Alzheimer's Institute, Phoenix, AZ, USA.
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Thiyyagura
Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Phoenix, AZ, USA.
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J
Krakoff
Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Phoenix, AZ, USA.
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MG
Hohenadel
Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Phoenix, AZ, USA.
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DS
Le
Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Phoenix, AZ, USA.|Department of Neurology, University of Leipzig, Leipzig, Germany.
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Weise
D000328:Adult; D001931:Brain Mapping; D002560:Cerebrovascular Circulation; D005247:Feeding Behavior; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D062407:Meals; D019518:Postprandial Period; D011218:Prader-Willi Syndrome / Q000453:epidemiology / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012201:Reward; D012527:Satiation; D012528:Satiety Response