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Importance of reward and prefrontal circuitry in hunger and satiety: Prader–Willi syndrome vs simple obesity

International Journal of Obesity volume 36, pages 638–647 (2012)Cite this article

Abstract

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.

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Acknowledgements

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 Hoglund 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.

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Authors and Affiliations

  1. Departments of Psychiatry and Medicine, Harvard Medical School, Boston, MA, USA

    L M Holsen & J M Goldstein

  2. Division of Women's Health, Connors Center for Women′s Health and Gender Biology, Brigham and Women's Hospital, Boston, MA, USA

    L M Holsen, E Ko & J M Goldstein

  3. Center for Health Behavior Neuroscience, University of Kansas Medical Center, Kansas City, KS, USA

    C R Savage

  4. Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, USA

    C R Savage, L E Martin, R J Lepping & W M Brooks

  5. Department of Psychiatry, University of Kansas Medical Center, Kansas City, KS, USA

    C R Savage & M G Butler

  6. Department of Preventive Medicine and Public Health, University of Kansas Medical Center, Kansas City, KS, USA

    L E Martin

  7. Department of Psychology, University of Missouri-Kansas City, Kansas City, MO, USA

    A S Bruce

  8. Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA

    W M Brooks

  9. Department of Pediatrics and Strong Center for Developmental Disabilities, University of Rochester Medical Center, Rochester, NY, USA

    J R Zarcone

  10. Massachusetts General Hospital & Massachusetts Institute of Technology Athinoula Martinos Center for Biomedical Imaging, Charlestown, MA, USA

    J M Goldstein

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  1. L M Holsen
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Correspondence to L M Holsen.

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Holsen, L., Savage, C., Martin, L. et al. Importance of reward and prefrontal circuitry in hunger and satiety: Prader–Willi syndrome vs simple obesity. Int J Obes 36, 638–647 (2012). https://doi.org/10.1038/ijo.2011.204

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