Widespread reward-system activation in obese women in response to pictures of high-calorie foods Luke E. Stoeckel, a, ⁎ Rosalyn E. Weller, a Edwin W. Cook III, a Donald B. Twieg, b Robert C. Knowlton, c and James E. Cox a a Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA b Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USA c Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA Received 24 July 2007; revised 16 January 2008; accepted 13 February 2008 Available online 4 March 2008 Behavioral studies have suggested that exaggerated reactivity to food cues, especially those associated with high-calorie foods, may be a factor underlying obesity. This increased motivational potency of foods in obese individuals appears to be mediated in part by a hyperactive reward system. We used a Philips 3T magnet and fMRI to investigate activation of reward-system and associated brain structures in response to pictures of high-calorie and low-calorie foods in 12 obese compared to 12 normal-weight women. A regions of interest (ROI) analysis revealed that pictures of high-calorie foods produced significantly greater activation in the obese group compared to controls in medial and lateral orbitofrontal cortex, amygdala, nucleus accumbens/ventral striatum, medial prefrontal cortex, insula, anterior cingulate cortex, ventral pallidum, caudate, putamen, and hippocampus. For the contrast of high-calorie vs. low-calorie foods, the obese group also exhibited a larger difference than the controls did in all of the same regions of interest except for the putamen. Within-group contrasts revealed that pictures of high-calorie foods uniformly stimulated more activation than low-calorie foods did in the obese group. By contrast, in the control group, greater activation by high-calorie foods was seen only in dorsal caudate, whereas low-calorie foods were more effective than high- calorie foods in the lateral orbitofrontal cortex, medial prefrontal cor- tex, and anterior cingulate cortex. In summary, compared to normal- weight controls, obese women exhibited greater activation in response to pictures of high-calorie foods in a large number of regions hypothesized to mediate motivational effects of food cues. Published by Elsevier Inc. Keywords: Food cues; High-calorie food; Obesity; Reward system Recently, there has been increased interest in potential parallels between drug addiction and obesity (Del Parigi et al., 2003; Pelchat, 2002; Volkow and Wise, 2005). It is well established that rewarding effects of addictive drugs and natural reinforcers such as foods are mediated by a common neural substrate (Kelley and Berridge, 2002; Volkow and Wise, 2005; Wang et al., 2001; Wang et al., 2004b). Stimuli associated with primary rewards can acquire motivational potency such that they trigger “wanting” of the reward by virtue of their acquired ability to activate the reward system (Berridge, 2004). Current neural models of addiction have proposed that drug-related cues may trigger drug-seeking behavior by eliciting hyperactivity in a brain network of reward areas, such as the ventral tegmental area (VTA), nucleus accumbens/ventral striatum (NAc), amygdala (AMYG), orbitofrontal cortex (OFC), and ventral pallidum (Jentsch and Taylor, 1999; Kalivas and Volkow, 2005; Kolb, 1999; Robinson and Berridge, 2003; Simansky, 2005; Volkow et al., 2003, 2004). Food cues may play a similar role in the development and main- tenance of obesity (Del Parigi et al., 2003; James et al., 2004; Pelchat, 2002; Volkow and Wise, 2005; Wang et al., 2004b). In obese individuals, stimuli associated with high-incentive foods, such as those high in fat and energy density, may possess greater than normal potency for activating the reward system and, as a result, triggering excessive motivation for non-homeostatic eating of such foods (Berthoud, 2004; Mela, 2006). Preliminary neuroimaging studies have found differences in responses to food or food cues in obese subjects compared to con- trols (e.g., Del Parigi et al., 2004; Gautier et al., 2000; Matsuda et al., 1999). For example, PET studies have found that consumption of a small (2 ml) quantity of liquid food produced greater increases in blood flow in several areas, such as insula and ventral midbrain, and greater decreases in medial orbitofrontal cortex (OFC) in obese subjects (Del Parigi et al., 2005; Karhunen et al., 1997). Most rele- vant to the present research, a recent functional magnetic resonance imaging (fMRI) study by Rothemund et al. (2007) compared ac- tivation in obese and normal-weight individuals in response to www.elsevier.com/locate/ynimg NeuroImage 41 (2008) 636 – 647 ⁎ Corresponding author. Department of Psychology, 415 Campbell Hall, 1530 3rd Avenue South, University of Alabama at Birmingham, Birming- ham, AL 35294-1170, USA. Fax: +1 205 975 6110. E-mail address: stoeckel@uab.edu (L.E. Stoeckel). Available online on ScienceDirect (www.sciencedirect.com). 1053-8119/$ - see front matter. Published by Elsevier Inc. doi:10.1016/j.neuroimage.2008.02.031