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Obesity & Addiction: Neuroimaging Studies

Obesity & Addiction: Neuroimaging Studies. Gene-Jack Wang, M.D. Brookhaven Center for Translational Neuroimaging. Obesity. Newsday / Walt Handelsman Oct 10, 2002. Factors Contributing to Obesity. Culture, Genetics, High energy intake, Lowered energy expenditure,

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Obesity & Addiction: Neuroimaging Studies

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  1. Obesity & Addiction: Neuroimaging Studies Gene-Jack Wang, M.D. Brookhaven Center for Translational Neuroimaging

  2. Obesity Newsday / Walt Handelsman Oct 10, 2002

  3. Factors Contributing to Obesity • Culture, • Genetics, • High energy intake, • Lowered energy expenditure, • Abnormal eating behavior.

  4. Signals that Control Food Intake Emotional factors Stress, boredom Intrinsic factors Leptin, Insulin,Ghrelin, PYY, Dopamine Extrinsic factors food-related cue & availability Hypothalamus

  5. Eating Habits Many obesity researchers focus on how the body's fuel and fat levels control appetite. But as comfort eaters know, habits and desires often override metabolic need.

  6. Body Weight & Drug Treatment • Drugs (stimulants: e.g. amphetamine, cocaine, methylphenidate) that increase brain dopamine concentration are anorexigenic. • Drugs (antipsychotic: e.g. Haloperidol,.. ) that block dopamine D2 receptors increase appetite and result in significant weight gain.

  7. Dopamine D2 images of Drug Addiction Alcohol Heroin Control Abuser Control Abuser Control Abuser Cocaine [11C]raclopride

  8. Low Dopamine (DA) State in Addiction DA DA DA DA DA DA Dopamine DA DA DA DA DA DA DA DA DA DA DA Reward Circuits Reward Circuits Dopamine Non Drug Abuser Addicted Subject

  9. Obesity • Compulsive overeating shares many of the same characteristics as drug addiction. • Do obese subjects have abnormal dopamine receptors?

  10. Dopamine Receptors Obese Subjects [11C]raclopride 2 0 ml/gm Control Subjects Wang et al, Lancet 2001

  11. Dopamine Receptor and BMI • Obese subjects p < 0.002 • Control subjects BMI p = 0.3 Dopamine Receptor Concentration Wang et al, Lancet 2001

  12. Implication • Dopamine modulates motivation and reward circuits and hence dopamine deficiency in obese subjects may perpetuate pathologic eating as a means to compensate for the decreased activation of reward circuits.

  13. Dopamine movement motivation Reward& well-being addiction

  14. Food • Eating is highly reinforcing behavior, just like taking drugs and as for drugs it can elicit powerful conditioned responses. • Are the conditioned responses associated with DA release? That is would DA be released by viewing food without eating it?

  15. Food Stimulation 1) Subjects were asked to describe their favorite foods and how they like to eat them while they were presented with foods that they had reported as among their favorite ones. Food was warmed to enhance the smell and the subjects were presented with it so that they could view it and smell it and a cotton swab impregnated with the food was placed in their tongues so they could taste it. A given food item was presented for 4 minutes and then it was exchanged for a new one.

  16. Neutral Stimulation Subjects viewed neutral images and/or were asked to describe in as much detail as possible their family genealogy.

  17. Methylphenidate ( MP) block the Dopamine Transporter ( ) MP DA DA DA DA DA DA DA DA DA DA DA DA DA DA DA DA DA DA DA DA DA DA DA DA DA DA DA signal signal MP enhances weak signals

  18. Study Design Study 1 Ritalin (20mg, po) Placebo [11C]raclopride [11C]raclopride PET scan PET scan 60 min. A B Neutral Food Ritalin (20mg, po) Study 2 Placebo [11C]raclopride [11C]raclopride PET scan PET scan C D Food Neutral Subjects were scanned 4 times with [11C]racloprideover a two day period. Six subjects participated study 1 on the first day and four subjects participated study 2 on the first day of the studies

  19. Brain Dopamine Response to Food Stimulation 4 3.5 3 2.5 Sum images of 10 normal weight subjects ([11C]raclopride) 1.5 DA D2 Receptor Availability 0 ml/g p < 0.11 p < 0.02 p < 0.005 (Bmax/Kd) Placebo/Neutral Placebo/Food MP/Neutral MP/Food Volkow, Wang, et al, Synapse 2002

  20. Extracellular DA vs Self-report of Hunger & Desire for Food + Ritalin 10 10 8 8 6 6 4 4 2 2 0 0 -2 -2 0 5 10 15 20 25 30 0 5 10 15 20 25 30 r = 0.76 p < 0.01 Desire for Food Hunger % Change Bmax/kd Volkow, Wang, et al, Synapse 2002

  21. Implication These results support the role of DA neurotransmission in dorsal striatum in mediating food motivation in human brain.

  22. Brain Metabolic Response to Food Stimulation 85 Food Presentation 0 µmol/100g/min 18FDG Neutral Presentation Right Wang et al, Neuroimage 2004

  23. Statistical Parameter Map of Metabolic Changes between Food and Neutral stimulation R • Twelve normal weight subjects. • Insula is a brain region modulating emotional responses to appetitive stimuli. • Orbitofrontal cortex is a brain region involved with salience attribution. Wang et al, Neuroimage 2004

  24. Metabolism in orbitofrontal cortex during food stimulation r = 0.84, p = 0.001 % Changes of feeling of hunger • Orbitofrontal cortex is a brain region involved with salience attribution and drive, may underlie the motivation to procure food, which may be subjectively experienced as “desire for food” and “hunger”. Wang et al, Neuroimage 2004

  25. Implication • The enhanced orbitofrontal cortex activation by food stimulation may reflect downstream effects from dopamine stimulation. • Dopaminergic involvement in the drive for food consumption in humans is in part mediated by its effects in orbitofrontal cortex. • The results could explain the deleterious effects of constant exposure to food stimuli (e.g. advertisements, candy machines, food channels, stores) in overeating.

  26. Brain Activation during Cocaine Theme Interview 85 Neutral Theme Interview Orbitofrontal Activation Cocaine Theme Interview 0 µmole/100g/min 18FDG Wang et al, Life Science 1999

  27. Cocaine Craving & Insular Metabolism p < 0.0002 • - Right Insula, p < 0.01 O - Left Insula, p < 0.008 Wang et al, Life Science 1999

  28. Prospective Activation of the temporal insula, a brain region involved with autonomic control, and of the orbitofrontal cortex, a brain region involved with expectancy and salience attribution, during the cocaine theme support their involvement with craving in cocaine addicted subjects.

  29. Obesity VS Drug Abuse • What makes obese subjects different from drug abusers?

  30. Obesity • Would obese subjects have an enhanced sensitivity in the brain regions involved with sensory processing of the food?

  31. Averaged FDG images Control subjects Obese subjects 55 0 µmol/100g/min L R What brain regions differ? Wang et al, NeuroReport 2002

  32. Enhanced Somatosensory Cortex Metabolism in Obese Subjects • Ten obese subjects (n = 10, BMI > 40) and 25 lean subjects (BMI < 25). • At baseline condition after fasting for 14-16 hours. • Obese subjects had higher metabolism than lean subjects in the somatosensory areas where the mouth, lips and tongue are represented. FDG Wang et al, NeuroReport 2002

  33. Implication • The enhanced activation in somatic parietal areas for mouth, tongue and lips in obese subjects suggests that enhanced sensitivity in regions involved in the sensory processing of food may make food more rewarding and may be one of the variables contributing to their excess food consumption.

  34. Addiction Biology Genes Drug or Behavior Addiction Environment

  35. Brookhaven PET Group Scientists Joanna Fowler (organic chemist) David Alexoff (engineer) Helene Benveniste (anesthesiologist) Anat Biegon (pharmacologist) Stephen Dewey (anatomist) Yu-Shin Ding (organic chemist) Richard Ferrieri (physical chemist) S. John Gatley (pharmacologist) Rita Goldstein (psychologist) Kuo-Shan Lin (organic chemist) Jean Logan (theoretical chemist) Yeming Ma (physical chemist) David Schlyer (inorganic chemist) Michael Schueller (biomedical physicist) Frank Telang (neurologist) Peter Thanos (neuroscientist) Paul Vaska (physicist) Nora Volkow (psychiatrist) Gene-Jack Wang (nuclear med physician) Support Staff Karen Apelskog (protocol coordinator) Pauline Carter (nurse) Victor Garza (chemist) Barbara Hubbard (nurse) Millard Jayne (nurse) Payton King (Lab Technician) Hai-Dee Lee (Lab Technician) Noel Netusil (nurse) Colleen Shea (chemist) Azael Villanueva (biomedical engineering) Donald Warner (electronics) Youwen Xu (chemist) Lisa Zimmerman (study coordinator) Post Doctoral/Fellow Nelly Klein (psychologist) Kim Lindsey (pharmacologist) Igor Izrailtyan (anesthesiologist) Daryn Moeller (anesthesiologist) Alex Morgan (physician) Lisa Cotton (psychologist)

  36. Support Department of Energy (Office of Biology & Environmental Research) National Institute on Drug Abuse Office of National Drug Control Policy

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