TY - JOUR
T1 - Importance of reward and prefrontal circuitry in hunger and satiety
T2 - Prader-Willi syndrome vs simple obesity
AU - Holsen, L. M.
AU - Savage, C. R.
AU - Martin, L. E.
AU - Bruce, A. S.
AU - Lepping, R. J.
AU - Ko, E.
AU - Brooks, W. M.
AU - Butler, M. G.
AU - Zarcone, J. R.
AU - Goldstein, J. M.
N1 - Funding Information:
This study was supported by a K12-award grant to Dr Holsen from the Office for Research on Women’s Health and National Institute of Child Health and Human Development (K12 HD051959), the National Institute for Child Health and Human Development (HD041672), the Hall Family Foundation, and the Heartland Genetics and Newborn Screening Collaborative (HRSA U22MC03962-02). The Ho-glund Brain Imaging Center is supported by the generosity of Forrest and Sally Hoglund. The authors are grateful to Phil Lee, Allan Schmitt, Muriel Williams and Pat Weber for technical assistance and Stacey Ward, Jean Reeves, and Jean Guadagnino for help in project coordination.
PY - 2012/5
Y1 - 2012/5
N2 - Background: The majority of research on obesity (OB) has focused primarily on clinical features (eating behavior, adiposity measures) or peripheral appetite-regulatory peptides (leptin, ghrelin). However, recent functional neuroimaging studies have demonstrated that some reward circuitry regions that are associated with appetite-regulatory hormones are also involved in the development and maintenance of OB. Prader-Willi syndrome (PWS), characterized by hyperphagia and hyperghrelinemia reflecting multi-system dysfunction in inhibitory and satiety mechanisms, serves as an extreme model of genetic OB. Simple (non-PWS) OB represents an OB-control state. Objective: This study investigated subcortical food motivation circuitry and prefrontal inhibitory circuitry functioning in response to food stimuli before and after eating in individuals with PWS compared with OB. We hypothesized that groups would differ in limbic regions (that is, hypothalamus, amygdala) and prefrontal regions associated with cognitive control (that is, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC) after eating.Design and participants: A total of 14 individuals with PWS, 14 BMI-and age-matched individuals with OB, and 15 age-matched healthy-weight controls viewed food and non-food images while undergoing functional MRI before (pre-meal) and after (post-meal) eating. Using SPM8, group contrasts were tested for hypothesized regions: hypothalamus, nucleus accumbens (NAc), amygdala, hippocampus, OFC, medial PFC and DLPFC. Results: Compared with OB and HWC, PWS demonstrated higher activity in reward/limbic regions (NAc, amygdala) and lower activity in the hypothalamus and hippocampus in response to food (vs non-food) images pre-meal. Post meal, PWS exhibited higher subcortical activation (hypothalamus, amygdala, hippocampus) compared with OB and HWC. OB showed significantly higher activity versus PWS and HWC in cortical regions (DLPFC, OFC) associated with inhibitory control. Conclusion: In PWS, compared with OB per se, results suggest hyperactivations in subcortical reward circuitry and hypoactivations in cortical inhibitory regions after eating, which provides evidence of neural substrates associated with variable abnormal food motivation phenotypes in PWS and simple OB.
AB - Background: The majority of research on obesity (OB) has focused primarily on clinical features (eating behavior, adiposity measures) or peripheral appetite-regulatory peptides (leptin, ghrelin). However, recent functional neuroimaging studies have demonstrated that some reward circuitry regions that are associated with appetite-regulatory hormones are also involved in the development and maintenance of OB. Prader-Willi syndrome (PWS), characterized by hyperphagia and hyperghrelinemia reflecting multi-system dysfunction in inhibitory and satiety mechanisms, serves as an extreme model of genetic OB. Simple (non-PWS) OB represents an OB-control state. Objective: This study investigated subcortical food motivation circuitry and prefrontal inhibitory circuitry functioning in response to food stimuli before and after eating in individuals with PWS compared with OB. We hypothesized that groups would differ in limbic regions (that is, hypothalamus, amygdala) and prefrontal regions associated with cognitive control (that is, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC) after eating.Design and participants: A total of 14 individuals with PWS, 14 BMI-and age-matched individuals with OB, and 15 age-matched healthy-weight controls viewed food and non-food images while undergoing functional MRI before (pre-meal) and after (post-meal) eating. Using SPM8, group contrasts were tested for hypothesized regions: hypothalamus, nucleus accumbens (NAc), amygdala, hippocampus, OFC, medial PFC and DLPFC. Results: Compared with OB and HWC, PWS demonstrated higher activity in reward/limbic regions (NAc, amygdala) and lower activity in the hypothalamus and hippocampus in response to food (vs non-food) images pre-meal. Post meal, PWS exhibited higher subcortical activation (hypothalamus, amygdala, hippocampus) compared with OB and HWC. OB showed significantly higher activity versus PWS and HWC in cortical regions (DLPFC, OFC) associated with inhibitory control. Conclusion: In PWS, compared with OB per se, results suggest hyperactivations in subcortical reward circuitry and hypoactivations in cortical inhibitory regions after eating, which provides evidence of neural substrates associated with variable abnormal food motivation phenotypes in PWS and simple OB.
KW - DLPFC
KW - FMRI
KW - Inhibition
KW - Motivation
KW - Prader-Willi syndrome
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UR - http://www.scopus.com/inward/citedby.url?scp=84860766886&partnerID=8YFLogxK
U2 - 10.1038/ijo.2011.204
DO - 10.1038/ijo.2011.204
M3 - Article
C2 - 22024642
AN - SCOPUS:84860766886
SN - 0307-0565
VL - 36
SP - 638
EP - 647
JO - International Journal of Obesity
JF - International Journal of Obesity
IS - 5
ER -