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Food-related Neural Circuitry in Prader-Willi Syndrome: Response to High- Versus Low-calorie Foods

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Abstract

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by hyperphagia and food preoccupations. Although dysfunction of the hypothalamus likely has a critical role in hyperphagia, it is only one of several regions involved in the regulation of eating. The purpose of this research was to examine food-related neural circuitry using functional magnetic resonance imaging in individuals with PWS and matched controls. Individuals with PWS showed increased activation in neural circuitry known to mediate hunger and motivation (hypothalamus, OFC) in response to high- versus low-calorie foods and in comparison to controls. This suggests neural circuitry for PWS is abnormally activated during hunger, particularly for high-calorie foods, and may mediate abnormally strong hunger states, therefore playing a significant role in PWS-induced hyperphagia.

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Notes

  1. This research was approved by the Human Investigations Committee of the Yale University School of Medicine. In order to prepare our participants for the MRI procedure, we conducted a mock scanning session using a replica of the actual MRI scanner, equipped with audio equipment to simulate the MRI noise level.

  2. Prior to scanning this sample, a pilot study of six healthy-weight adults was conducted to solidify the study design and replicate previous findings with healthy-weight participants. No attempt was made to match the pilot sample to the PWS sample. Pilot data indicated food-related activation in areas consistent with previous research in normal-weight individuals, including the insula, thalamus, FG, and OFC (Dimitropoulos and Schultz 2004).

  3. In PWS: (1) paroxetine, (2) paroxetine, risperidone, (3) fluoxetine. In MR/DD: (1) escitalopram, topiramate, (2) methylphenidate hydrochloride, (3) risperidone, (4) atomoxetine, zonisamide, sertraline, (5) methylphenidate hydrochloride , (6) divalproex sodium, olanzapine, (7) divalproex sodium, risperidone, (8) bupropion.

  4. Our first three PWS participants received these stimuli presented over three runs instead of two (Stimulus duration = 3,000 ms, ISI = 1,500 ms) but short response times and high accuracy on the task led us to shorten the protocol to two runs. A direct comparison between data from those who received three runs versus two runs did not reveal any differences in activation level in our primary ROIs (p > .20).

References

  • Anand, B. K., & Brobeck, J. R. (1951). Localization of a feeding center in he hypothalamus of the rat. Proceedings of the Society for Experimental Biology and Medicine, 77, 323–324.

    PubMed  Google Scholar 

  • Araujo, I. E., & Rolls, E. T. (2004). Representation in the human brain of food texture and oral fat. The Journal of Neuroscience, 24(12), 3086–3093.

    Article  PubMed  Google Scholar 

  • Baylis, L. L., Rolls, E. T., & Baylis, G. C. (1995). Afferent connections of the caudolateral orbitofrontal cortex taste area of the primate. Neuroscience, 64, 801–812.

    Article  PubMed  Google Scholar 

  • Burton, M. J., Rolls, E. T., & Mora, F. (1976). Effects of hunger on the responses of neurons in the lateral hypothalamus to the sight and taste of food. Experimental Neurology, 51, 668–677.

    Article  PubMed  Google Scholar 

  • Cahill, L., Babinsky, R., Markowitsch, H. J., & McCaugh, J. L. (1995). The amygdala and emotional memory. Nature, 377, 295–296.

    Article  PubMed  Google Scholar 

  • Carpenter, M. B. (1985). Core text of neuroanatomy (3rd ed.). Baltimore: Williams & Wilkins.

    Google Scholar 

  • Clark, J. M., Clark, A. J. M., Bartle, A., & Winn, P. (1991). The regulation of feeding and drinking in rats with lesions of the lateral hypothalamus made by N-methyl-D-aspartate. Neuroscience, 4, 631–640.

    Article  Google Scholar 

  • Coons, E. E., Levak, M., & Miller, N. E. (1965). Lateral hypothalamus: Learning of food-seeking response motivated by electrical stimulation. Science, 150, 1320–1321.

    Article  PubMed  Google Scholar 

  • Critchley, H. D., & Rolls, E. T. (1996). Hunger and satiety modify the responses of olfactory and visual neurons in the primate orbitofrontal cortex. Journal of Neurophysiology, 75, 1673–1686.

    PubMed  Google Scholar 

  • DeFalco, J., Tomishima, M., Liu, H., Zhao, C., Cai, X., Marth, J. D., et al. (2001). Virus-assisted mapping of neural inputs to a feeding center in the hypothalamus. Science, 291, 2608–2613.

    Article  PubMed  Google Scholar 

  • Del Parigi, A., Tschop, M., Heiman, M., Salbe, A., Vozarova, B., Sell, S., et al. (2002). High circulating ghrelin: A potential cause for hyperphagia and obesity in PWS. Journal of Clinical Endocrinology & Metabolism, 87(12), 5461–5464.

    Article  Google Scholar 

  • Dimitropoulos, A., Feurer, I., Butler, M., & Thompson, T. (2001). Emergence of compulsive behavior and tantrums in children with Prader-Willi syndrome. American Journal on Mental Retardation, 106(1), 39–51.

    Article  PubMed  Google Scholar 

  • Dimitropoulos, A., & Schultz, R. (2004, March). Hyperphagia in Prader-Willi syndrome: Using fMRI to explore brain mechanisms in response to food stimuli. Paper presented at the 37th Annual Gatlinburg Conference on Research and Theory in Mental Retardation and Developmental Disabilities, San Diego, California.

  • Doyle, P., Rohner-Jeanrenaud, F., & Jeanrenaud, B. (1993). Local cerebral glucose utilization in brains of lean and genetically obese (fa/fa) rats. American Journal of Physiology, 264(1), E29–E36.

    PubMed  Google Scholar 

  • Duvernoy, H. M. (1991). The human brain: Structure, three-dimensional sectional anatomy and MRI. New York: Springer-Verlag.

    Google Scholar 

  • Fieldstone, A., Zipf, W. B., Schwartz, H. C., & Berntson, G. G. (1997). Food preferences in Prader-Willi syndrome, normal weight and obese controls. International Journal of Obesity, 21, 1046–1052.

    Article  PubMed  Google Scholar 

  • Gauthier, I., Skudlarski, P., Gore, J. C., & Anderson, A. W. (2000). Expertise for cars and birds recruits areas involved in face recognition. Nature Neuroscience, 3(2), 191–197.

    Article  PubMed  Google Scholar 

  • Glover, D., Maltzman, I., & Williams, C. (1996). Food preferences among individuals with and without Prader-Willi syndrome. American Journal on Mental Retardation, 101(2), 195–205.

    PubMed  Google Scholar 

  • Grelotti, D. J., Klin, A. J., Gauthier, I., Skudlarski, P., Cohen, D. J., Gore, J. C., et al. (2005). fMRI activation of the fusiform gyrus and amygdala to cartoon characters but not to faces in a boy with autism. Neuropsychologia, 43(3), 373–385.

    Article  PubMed  Google Scholar 

  • Grossman, S. P. (1975). Role of the hypothalamus in the regulation of food and water intake. Psychological Review, 82(3), 200–224.

    Article  PubMed  Google Scholar 

  • Haqq, A., Farooqi, I., O’Rahilly, S., Stadler, D., Rosenfeld, R., Pratt, K., et al. (2003). Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in PWS. Journal of Clinical Endocrinology and Metabolism, 88(1), 174–178.

    Article  PubMed  Google Scholar 

  • Hinton E. C., Holland A. J., Gellatly M. S., Soni S., & Owen A. M. (2006a). An investigation into food preferences and the neural basis of food-related incentive motivation in Prader-Willi syndrome. Journal of Intellectual Disability Research, 50(Pt 9), 633–642.

    Article  PubMed  Google Scholar 

  • Hinton E. C., Holland A. J., Gellatly M. S., Soni S., Patterson M., Ghatei M. A., & Owen A. M. (2006b). Neural representations of hunger and satiety in Prader-Willi syndrome. International Journal of Obesity, 30(2), 313–321.

    Article  PubMed  Google Scholar 

  • Holland, A. J. (1998). Understanding the eating disorder affecting people with Prader-Willi syndrome. Journal of Applied Research in Intellectual Disabilities, 11(3), 192–206.

    Article  Google Scholar 

  • Holland, A., Whittington, J., & Hinton, E. (2003). The paradox of Prader-Willi syndrome: a genetic model of starvation. The Lancet, 362, 989–991.

    Article  Google Scholar 

  • Holm, V. A., Cassidy, S. B., Butler, M. G., Hanchett, J. M., Greenswag, L. R., Whitman, B. Y., et al. (1993). Prader-Willi syndrome: Consensus Diagnostic Criteria. Pediatrics, 91, 398–402.

    PubMed  Google Scholar 

  • Holsen L. M., Zarcone J. R., Brooks W. M., Butler M. G., Thompson T. I., Ahluwalia J. S., Nollen N. L., & Savage C. R. (2006). Neural mechanisms underlying hyperphagia in Prader-Willi syndrome. Obesity, 14(6), 1028–1037.

    Article  PubMed  Google Scholar 

  • Joseph, B., Egli, M., Koppekin, A., & Thompson, T. (2002). Food choice in people with Prader-Willi syndrome: Quantity and relative preference. American Journal on Mental Retardation, 107(2), 128–135.

    Article  PubMed  Google Scholar 

  • Kanwisher, N., McDermott, J., & Chun, M. M. (1997). The fusiform face area: A module in human extrastriate cortex specialized for face perception. The Journal of Neuroscience, 17(11), 4302–4311.

    PubMed  Google Scholar 

  • Killgore, W. D. S., Young, A. D., Femia, L. A., Bogorodzki, P., Rogowska, J., & Yurgelun-Todd, D. A. (2003). Cortical and limbic activation during viewing of high- versus low-calorie foods. Neuroimage, 1381–1394.

  • Kringelbach, M. L., Doherty, J. O., Rolls, E. T., & Andrews, C. (2003). Activation of the human orbitofrontal cortex to a liquid food stimulus is correlated with its subjective pleasantness. Cerebral Cortex, 13, 1064–1071.

    Article  PubMed  Google Scholar 

  • LaBar, K. S., Gitelman, D. R., Parrish, T. B., Kim, Y., Nobre, A. C., Mesulam, M. (2001). Hunger selectively modulates corticolimbic activation to food stimuli in humans. Behavioral Neuroscience, 115(2), 493–500.

    Article  PubMed  Google Scholar 

  • Ledbetter, D. H., Riccardi, V. M., Youngbloom, S. A., Strobel, R. J., Keenan, B. S., Crawford, J. D., & Louro, J. M. (1980). Deletion (15q) as a cause of the Prader-Willi syndrome (PWS). American Journal of Human Genetics, 32, 77A.

    Google Scholar 

  • Martin, A., State, M., Anderson, G. M., Kaye, W. M., Hanchett, J. M., McConahay, C. W., et al. (1998). Cerebrospinal fluid levels of oxytocin in Prader-Willi syndrome: A preliminary report. Biological Psychiatry, 44, 1349–1352.

    Article  PubMed  Google Scholar 

  • Miller, L., Angula, M., Price, D., & Taneja, S. (1996). MR of the pituitary in patients with Prader-Willi syndrome: size determination and imaging findings. Pediatric Radiology, 26, 43–47.

    Article  PubMed  Google Scholar 

  • Mora, F., Rolls, E. T., & Burton, M. J. (1976). Modulation during learning of the responses of neurons in the hypothalamus to the sight of food. Experimental Neurology, 53, 508–519.

    Article  PubMed  Google Scholar 

  • Morris, J. S., Friston, K. J., Buchel, C., Frith, C. D., Young, A. W., Calder, A. J., Dolan, R.J. (1998). A neuromodulatory role for the human amygdala in processing emotional facial expressions. Brain, 121, 47–57.

    Article  PubMed  Google Scholar 

  • Nicholls, R. D., Knoll, J. H. M., Butler, M. G., Karam, S., & Lalande, M. (1989). Genetic imprinting suggested by maternal heterodisomy in non-deletion Prader-Willi syndrome. Nature, 342, 281–285.

    Article  PubMed  Google Scholar 

  • Ongur, D., & Price, J. L. (2000). The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys, and humans. Cerebral Cortex, 10, 206–219.

    Article  PubMed  Google Scholar 

  • Oomura, Y. (1973). Central mechanism of feeding. Advances in Biophysics, 5, 65–142.

    PubMed  Google Scholar 

  • Pritchard, T. C., Macaluso, D. A., & Eslinger, P. J. (1999). Taste perception in patients with insular cortex lesions. Behavior Neuroscience, 113(4), 663–71.

    Article  Google Scholar 

  • Reilly, S. (1998). The role of the gustatory thalamus in taste-guided behavior. Neuroscience and Biobehavioral Reviews, 22(6), 883–901.

    Article  PubMed  Google Scholar 

  • Rolls, E. T. (1999). The brain and emotion. New York: Oxford University Press.

    Google Scholar 

  • Rolls, E. T., Sienkiewicz, Z. J., & Yaxley, S. (1989). Hunger modulates the responses to gustatory stimuli of single neurons in the caudolateral orbitofrontal cortex of the macaque monkey. European Journal of Neuroscience, 1, 53–60.

    Article  PubMed  Google Scholar 

  • Schneider, F., Grodd, W., Weiss, U., Klose, U., Mayer, K. R., Nagele, T., et al. (1997). Functional MRI reveals left amygdala activation during emotion. Psychiatry Research: Neuroimaging, 76, 75–82.

    Article  PubMed  Google Scholar 

  • Shapira, N. A., Lessig, M. C., He, A. G., James, G. A., Driscoll, D. J., Liu, Y. (2005). Satiety dysfunction in Prader-Willi syndrome demonstrated by fMRI. Journal of Neurology, Neurosurgery, and Psychiatry, 76, 260–262.

    Article  PubMed  Google Scholar 

  • Simmons, W. K., Martin, A., & Barsalou, L. W. (2005). Pictures of appetizing foods activate gustatory cortices for taste and reward. Cerebral Cortex, 15(10), 1602–1608.

    Article  PubMed  Google Scholar 

  • Swaab, D. F., Purba, J. S., & Hofman, M. A. (1995). Alterations in the hypothalamic paraventricular nucleus and its oxytocin neurons (putative satiety cells) in Prader-Willi syndrome: A study of five cases. Journal of Clinical Endocrinology and Metabolism, 80, 573–579.

    Article  PubMed  Google Scholar 

  • Talairach, J., & Tournoux, P. (1988). Co-planar steriotaxic atlas of the human brain. New York: Thieme.

    Google Scholar 

  • Tataranni, P. A., Gautier, J., Chen, K., Uecker, A., Bandy, D., Salbe, A. D., et al. (1999). Neuroanatomical correlates of hunger and satiation in humans using positron emission tomography. Proceedings of the National Academy of Sciences, 96, 4569–4574.

    Article  Google Scholar 

  • Taylor, R. L., & Caldwell, M. L. (1985). Type and strength of food preference of individuals with Prader-Willi syndrome. Journal of Mental Deficiency Research, 29, 109–112.

    PubMed  Google Scholar 

  • Thompson, T., Butler, M. G., MacLean, Jr., W. E., Joseph, B., & Delaney, D. (1999). Cognition, behavior, neurochemistry, and genetics in Prader-Willi syndrome. In H. Tager-Flusberg (Ed.), Neurodevelopmental disorders (pp. 155–178). Cambridge: The MIT Press.

  • Vuilleumier, P. (2000). Faces call for attention: Evidence from patients with visual extinction. Neuropsychologia, 38, 693–700.

    Article  PubMed  Google Scholar 

  • Yaxley, S., Rolls, E. T., & Sienkiewicz. (1988). The responsiveness of neurons in the insular gustatory cortex of the macaque monkey is independent of hunger. Physiology & Behavior, 42, 223–229.

  • Zald, D. H. (2003). The human amygdala and the emotional evaluation of sensory stimuli. Brain Research Reviews, 41, 88–123.

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grant PO1 HD 03008 from the National Institute of Child Health and Human Development and T32 MH 18268 from the National Institute of Mental Health. We thank the individuals and their families for their participation in this study. We would also like to thank Carley Piatt, Elinora Hunyadi, Jennifer Hetzke, Cheryl Klaiman, and the technicians of the Yale MR Imaging Center for their assistance with this research.

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Correspondence to Anastasia Dimitropoulos.

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Dimitropoulos, A., Schultz, R.T. Food-related Neural Circuitry in Prader-Willi Syndrome: Response to High- Versus Low-calorie Foods. J Autism Dev Disord 38, 1642–1653 (2008). https://doi.org/10.1007/s10803-008-0546-x

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  • DOI: https://doi.org/10.1007/s10803-008-0546-x

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