Gene-Jack Wang, MD
2009 Summit video presentationChairman of the Brookhaven National Laboratory Medical
Department
BIOGRAPHY:
Dr. Gene-Jack Wang is a board certified Nuclear Medicine physician and began working at the Brookhaven National Laboratory (BNL) Medical Department in 1990. In addition to performing his own research, he is the Chairman of the BNL Medical Department and continues to hold a joint appointment as a Professor of Psychiatry at Mount Sinai School of Medicine. He also practices Nuclear Radiology at the Glen Cove Hospital. His research has focused on the application of Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (fMRI) techniques to the study of various brain disorders. He is interested in using PET to study the neuro-psychiatric mechanisms and manifestations of alcoholism, drug addiction, attention deficit/hyperactivity disorder (ADHD), obesity and eating disorder in humans and in animal models. He used PET to study the effects of drug expectation on the ability of psychostimulants to increase extracellular dopamine and the relationship to the reinforcing and addictive properties of stimulant drugs in cocaine addicted subjects. In methamphetamine abusers, he uses PET to assess the effect of long-term detoxification to the recovery of brain dopamine system. He is currently comparing the changes in brain dopamine activity in response to food stimulation for two subtypes of obese subjects, those with and those without binge eating disorders. He predicts that the two subtypes will differ in their brain dopamine activity. His other interests include the study of brain and gut interaction as well as the effect of diet control drug to brain satiety circuit using fMRI. He has published over 200 peer-reviewed papers on his imaging research. The National Institute of Health (NIMH, NIDA and NIAAA), the Department of Energy (DOE/OBER) and pharmaceutical companies fund his ongoing research.
PERSONAL STATEMENT:
To assess if low DA D2 receptors in obesity reflected the consequences of food over-consumption as opposed to a vulnerability that preceded obesity we assessed the effect of food intake on DA D2 receptor in a genetically leptin deficient rodent model of obesity using autoradiography. Results showed that the obese rats had lower D2 receptor levels than the lean rats and that food restriction increased D2 receptors both in the lean and the obese rats indicating that low D2 reflects in part the consequences of food over-consumption. In one study of normal-body-weight fasting human subjects, the presentation of food that could not be consumed was associated with increases in striatal extracellular DA. Since the research subjects experienced no reward or pleasure from eating the food, this finding provides evidence for the involvement of DA in the non-hedonic motivational properties of food.
Our imaging studies have also shown that metabolic activity in the orbitofrontal cortex (OFC), a part of the brain that is key to controlling and planning behavior, is in part regulated by DA activity. In drug-addicted subjects, lower striatal DA D2 receptor levels were associated with lower metabolism in the OFC. Lower activity in this region could indicate a reduced ability to plan or control behavior, which has been implicated in the compulsive behavioral characteristics of drug-addictive states. Additionally, in normal-body-weight fasting subjects, food presentation increased metabolism in OFC, which was significantly associated with the perception of hunger and the desire for food. Such changes in perception and desire could explain the deleterious effects of constant exposure to food stimuli (e.g., advertisements and food displays) in overeating.
In another study in obese subjects implanted with a gastric stimulator, which induces stomach expansion via electrical stimulation of the vagus nerve, we found the gastric stimulation increased metabolism in OFC, striatum, and hippocampus. The activation in the hippocampus during gastric stimulation is associated with a sensation of fullness. These regions are involved with self-control, motivation, and memory, respectively, and were previously shown to be involved in drug craving in addicted subjects. This finding suggests that similar brain circuits underlie the enhanced motivational drive for food (and for drugs) seen in obese (and drug-addicted) subjects.
Different from drug-addicted subjects, obese subjects have increased metabolism in the somatosensory cortex when compared with control subjects, making them more sensitive to the sensory properties of food. In the case of obesity the reduction in DA D2 receptors coupled with the enhanced sensitivity to food palatability makes food their most salient reinforcer, putting them at risk for food over-consumption.
The studies from our laboratory provide evidence that multiple but similar brain circuits (reward, motivation, learning, inhibitory control) are disrupted in drug addiction and obesity. The results implicate the need for a multimodal approach in the treatment of obesity.
PUBLICATIONS:
- Thanos P.K., Michaelides M., Piyis Y.K., Wang G.J. and Volkow N.D. Food restriction markedly increases dopamine D2 receptor (D2R) in a rat model of obesity as assessed with in-vivo muPET imaging ([11C] raclopride) and in-vitro ([3H] spiperone) autoradiography. Synapse, 62(1):50-61 (2008).
- Tomer R., Goldstein R.Z., Wang G.J., Wong C. and Volkow N.D. Incentive motivation is associated with striatal dopamine asymmetry. Biol. Psychol., 77(1):98-101 (2008).
- Volkow N.D., Wang G.J., Telang F., Fowler J.S., Logan J., Childress A.R., Jayne M., Ma Y. and Wong C. Dopamine increases in striatum do not elicit craving in cocaine abusers unless they are coupled with cocaine cues. Neuroimage, 39(3):1266-1273 (2008).
- Wang G.J., Tomasi D., Backus W., Wang R., Telang F., Geliebter A., Korner J., Bauman A., Fowler J.S., Thanos P.K. and Volkow N.D. Gastric distention activates satiety circuitry in the human brain. Neuroimage, 39(4):1824-1831 (2008).
- Alia-Klein N., Goldstein R.Z., Tomasi D., Zhang L., Fagin-Jones S., Telang F., Wang G.J., Fowler J.S. and Volkow N.D. What is in a word? No versus Yes differentially engage the lateral orbitofrontal cortex. Emotion, 7(3):649-659 (2007). Erratum in: Emotion. 2007 Nov;7(4):735.
- Alia-Klein N., Kriplani A., Logan J., Williams B., Zhu W., Craig I.W., Telang F., Goldstein R., Volkow N.D., Vaska P. and Wang G.J. Evidence that brain MAO A activity does not correspond to MAO A genotype in healthy male subjects. Biol. Psychiatry, 62(4):355-358 (2007). Epub 2006 Dec 4.
- Logan J., Wang G.J., Telang F., Fowler J.S., Alexoff D., Zabroski J., Jayne M., Hubbard B., King P., Carter P., Shea C., Xu Y., Muench L., Schlyer D., Learned-Coughlin S., Cosson V., Volkow N.D. and Ding Y.S. Imaging the norepinephrine transporter in humans with (S,S)-[11C]O-methyl reboxetine and PET: problems and progress. Nucl Med Biol., 34(6):667-679 (2007). Epub 2007 Jun 8.
- Thanos P.K., Michaelides M., Benveniste H., Wang G.J. and Volkow N.D. Effects of chronic oral methylphenidate on cocaine self-administration and striatal dopamine D2 receptors in rodents. Pharmacol. Biochem. Behav., 87(4):426-433 (2007).
- Volkow N.D., Fowler J.S., Wang G.J., Swanson J.M. and Telang F. Dopamine in drug abuse and addiction: results of imaging studies and treatment implications. Arch Neurol., 64(11):1575-1579 (2007).
- Volkow N.D., Wang G.J., Fowler J.S., Telang F., Jayne M. and Wong C. Stimulant-induced enhanced sexual desire as a potential contributing factor in HIV transmission. Am. J. Psychiatry, 164(1):157-160 (2007).
- Volkow N.D., Wang G.J., Newcorn J., Fowler J.S., Telang F., Solanto M.V., Logan J., Wong C., Ma Y., Swanson J.M., Schulz K. and Pradhan K. Brain dopamine transporter levels in treatment and drug naïve adults with ADHD. Neuroimage, 34(3):1182-1190 (2007). Epub 2006 Nov 27.
- Volkow N.D., Wang G.J., Newcorn J., Telang F., Solanto M.V., Fowler J.S., Logan J., Ma Y., Schulz K., Pradhan K., Wong C. and Swanson J.M. Depressed dopamine activity in caudate and preliminary evidence of limbic involvement in adults with attention-deficit/hyperactivity disorder. Arch.Gen. Psychiatry, 64(8):932-940 (2007).
- Volkow N.D., Wang G.J., Telang F., Fowler J.S., Logan J., Jayne M., Ma Y., Pradhan K. and Wong C. Profound decreases in dopamine release in striatum in detoxified alcoholics: possible orbitofrontal involvement. J. Neurosci., 27(46):12700-12706 (2007).
- Gastric distention activates satiety circuitry in the human brain
- Gastric stimulation in obese subjects activates the hippocampus and other regions involved in brain reward circuitry
- Inverse Association Between BMI and Prefrontal Metabolic Activity in Healthy Adults
- Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: Possible contributing factors
- Overlapping neuronal circuits in addiction and obesity: evidence of systems pathology
- Evidence of gender differences in the ability to inhibit brain activation elicited by food stimulation
- Imaging of Brain Dopamine Pathways - Implications for Understanding Obesity