In this pilot study, we will use functional magnetic resonance imaging (fMRI) to determine the effects of high calorie visual food cues \[i.e. images of foods that are high in both sugar and fat (HS/HF), such as ice cream\] on activation of taste, appetite, and reward pathways in the brain following the separate ingestion of (1) an artificial sweetened solution (2) a sucrose solution and (3) a tasteless solution in obese individuals. Obesity rates are high among US adults with 33.8% of adults having a BMI of 30 or greater (1). The prevailing belief is that homeostatic systems are in place to monitor energy homeostasis. Sugar sweetened beverages appear to alter the homeostatic systems so that (1) metabolic feedback signals do not function correctly or as intended (2), as little or no dietary compensation is seen with energy from beverages (3), or (2) sweet and savory foods (sugar sweetened beverages) override the system (i.e. hedonics) (2). Epidemiological data suggest Americans are consuming 20-25% of their energy in beverage form which equates to \~430-535 kcal/day (3, 4). In most studies, sugar sweetened beverage intake has been shown to increase weight (5, 6). While limited data are available, a meta-analysis in humans demonstrates that the inclusion of aspartame compared to sugar reduces energy intake (7). A prospective study found that weight loss maintainers utilize artificial sweeteners more than normal weight individuals (8). This suggests artificial sweeteners may be a method to promote weight loss in obese individuals. Public policy on sugar sweetened beverages is starting to be reexamined, however, it is currently unknown what effect sugar sweetened beverage intake and artificial sweetened solutions have on (1) taste, appetite, and reward regions of the brain and (2) food cravings and related brain activation, among obese vs. normal weight individuals. The aim of this study is to provide important data on why obese individuals continue to consume sugar-sweetened beverages despite the associated negative health outcomes. We hypothesize that this consumption is due to sugar sweetened beverages, but not artificial sweeteners, activating reward pathways of the brain (hedonics).

Sucrose and artificial sweetners Previously it has been found that there is an altered hypothalamic response to glucose ingestion in obese humans (9). In obese humans, brain activation seems impaired; i.e., it was lower and delayed compared to lean subjects. This study lacked a functional contrast and had higher noise and less accuracy than current fMRI blood-oxygen-level-dependent (BOLD) technology and only the hypothalamus was analyzed (9). The current study and future studies from this pilot and feasibility work will further determine if dietary sugar responses are differentially regulated in obese individuals possibility contributing to the over consumption of sugar sweetened beverages in obese adults.

Frank et al. concluded that taste pathways are activated with sucralose and sucrose taste in younger normal weight women (10). Only sucrose recruited reward pathways but appetite pathways were not documented due to either lack of significance or examination (10). This study will confirm beverage ingestion opposed to tasting evokes a similar reward response and also examines appetite and reward pathways in obese individuals.

The effects of caloric vs. non caloric sweetener on taste activation were previously examined in normal weight men (11). During the non-caloric solution tasting, 2 caloric tastants were also consumed. These caloric tastants could invoke differential cephalic phase responses altering the results (12). Consumption of the artificial sweetener or the caloric solution increased activation of the insula, middle OFC, lateral OFC and amygdala. With the artificial sweetener, there was greater activation of the OFC (11). Next, the effects of sweet taste (2.4 mL) in younger male and female diet soda drinkers was examined (13). Water was utilized as the rinse and baseline for the comparison between diet and regular soda. In these persons, higher right orbitalfrontal cortex brain activation response in non-caloric compared to caloric solution was observed (13). These previous studies utilized only normal weight participants and taste to examine for the effects of artificial sweeteners on brain response. The current study examines obese individuals and solution ingestion to observe differences in brain activation. Overall there are differential brain responses to caloric vs. non-caloric sweetener in normal weight individuals thus previously authors suggested that more research needs to be performed as to the effectiveness of artificial sweeteners at decreasing energy intake.

Obesity Women were shown food picture cues of high energy foods. The high energy foods produced significantly greater activation in the brain reward regions in obese compared to normal weight control women (14). Differences between groups included ACC, VTA, nucleus accumbens (NAc), amygdala, ventral pallidum (Vent Pall), Caudate, and Putamen (14). Postmeal, obese individuals, but not normal weight individuals, increase activation of the putamen (part of striatum) and amygdala suggesting these regions may play a role in overeating (15) which is why these regions are incorporated into the current study hypothesis. These cross-sectional studies are important as previously Murdaugh et. al (16) found that obese individuals that were not successful at short term weight loss or longer term weight loss maintenance had greater activation of reward pathway brain regions. While speculative, artificial sweeteners may reduce cravings by not activating reward pathways especially in obese persons. This grant will help provide pilot data to further elucidate this important question.