Gastric stimulation in obese subjects activates the hippocampus and other regions involved in brain reward circuitry

doi:10.1073/pnas.0601977103

Gastric stimulation in obese subjects activates the hippocampus and other regions involved in brain reward circuitry

*Medical Department, Brookhaven National Laboratory, Upton, NY 11973;
^†Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029;
^§National Institute on Alcohol Abuse and Alcoholism/National Institute on Drug Abuse, Rockville, MD 20857; and
^¶Department of Applied Mathematics and Statistics, State University of New York, Stony Brook, NY 11794

Edited by Michael I. Posner, University of Oregon, Eugene, OR, and approved August 21, 2006 (received for review March 10, 2006)

Abstract

The neurobiological mechanisms underlying overeating in obesity are not understood. Here, we assessed the neurobiological responses to an Implantable Gastric Stimulator (IGS), which induces stomach expansion via electrical stimulation of the vagus nerve to identify the brain circuits responsible for its effects in decreasing food intake. Brain metabolism was measured with positron emission tomography and 2-deoxy-2[¹⁸F]fluoro-d-glucose in seven obese subjects who had the IGS implanted for 1–2 years. Brain metabolism was evaluated twice during activation (on) and during deactivation (off) of the IGS. The Three-Factor Eating Questionnaire was obtained to measure the behavioral components of eating (cognitive restraint, uncontrolled eating, and emotional eating). The largest difference was in the right hippocampus, where metabolism was 18% higher (P < 0.01) during the “on” than “off” condition, and these changes were associated with scores on “emotional eating,” which was lower during the on than off condition and with “uncontrolled eating,” which did not differ between conditions. Metabolism also was significantly higher in right anterior cerebellum, orbitofrontal cortex, and striatum during the on condition. These findings corroborate the role of the vagus nerve in regulating hippocampal activity and the importance of the hippocampus in modulating eating behaviors linked to emotional eating and lack of control. IGS-induced activation of regions previously shown to be involved in drug craving in addicted subjects (orbitofrontal cortex, hippocampus, cerebellum, and striatum) suggests that similar brain circuits underlie the enhanced motivational drive for food and drugs seen in obese and drug-addicted subjects, respectively.

Footnotes

^‡To whom correspondence should be addressed. E-mail: gjwang{at}bnl.gov
Author contributions: G.-J.W., J.Y., N.D.V., P.K.T., and J.S.F. designed research; F.T. performed research; G.-J.W., N.D.V., Y.M., W.Z., C.T.W., D.T., and P.K.T. analyzed data; G.-J.W. wrote the paper; and N.D.V. and J.S.F. revised the manuscript.
Conflict of interest statement: J.Y. was an employee of Transneuronix, Inc. (Mt. Arlington, NJ) at the time of the experiment; however, the company did not provide funding for the study.
This article is a PNAS direct submission.
Abbreviations:

DA,

dopamine;

FDG,

2-deoxy-2[18F]fluoro-d-glucose;

IGS,

Implantable Gastric Stimulator;

OFC,

orbitofrontal cortex;

PET,

positron emission tomography;

ROI,

region of interest;

SPM,

statistical parametric mapping.
Freely available online through the PNAS open access option.