Article Figures & Data
Figures
- Figure 1.
Schematic of study design.
- Figure 2.
Brain activations in response to high-calorie food images, and modulations by sibutramine and satiety. Coronal (at y = −14 mm, −4 mm, +2 mm, and +6 mm relative to the anterior commissure) and sagittal (at x = +6 mm, +8 mm, +22 mm, and +8 mm to the right of the midline) sections from the group average structural image are shown. Superimposed on these in red are significant activations from the comparison between high- and low-calorie food images (all surviving p < 0.05, familywise error correction for multiple comparisons). Key regions showing this effect were insula, striatum [including putamen and globus pallidus (Put/Pall)], midbrain, amygdala, and hypothalamus. Superimposed in yellow is the region of ventral striatum (VS) showing a significantly greater response in the fasted state. In green are those regions—hypothalamus (Hy) and amygdala (Amyg)—that showed a stimulus-type-by-drug interaction, i.e., significant reduction in high-calorie stimulus-related activation following treatment with sibutramine (compared to placebo). The interactions threshold is p < 0.01, uncorrected, for display.
- Figure 3.
Right ventral striatal response showing attenuation of calorie-specific response by satiety. Top left, A coronal section of the group average structural MRI at 6 mm anterior to the anterior commissure. Superimposed in red are the local regions showing a calorie-specific (high-calorie vs low-calorie images) effect (p < 0.05, corrected), and in yellow is the region of ventral striatum (p < 0.01 uncorrected) in which this calorie-specific response is significantly greater in the fasted than the fed state. Top right, The plots show estimates of stimulus-related brain activation for each of the eight key conditions, divided by image type (high calorie/low calorie), satiety state (fasted/fed), and treatment (sibutramine/placebo). The y-axis show the effect sizes in the ventral striatal region as parameter estimates derived from the general linear model (units are arbitrary). As can be seen there is a strong effect of image type and of fasted state but no drug effect. Bottom, Scatter plot showing the association between the fasted versus fed effect for high-calorie compared to low-calorie images in ventral striatum and the subsequent weight of popcorn consumed in the ad libitum snack test. As can be seen, the greater the striatal response to high-calorie images under fasting conditions, the greater the subsequent consumption.
- Figure 4.
a, Hypothalamic responses to experimental manipulations (image type and sibutramine status). Top left, A coronal section of the group average structural MRI at 4 mm posterior to the anterior commissure. Superimposed in red are the local regions showing a calorie-specific (high-calorie vs low-calorie images) effect (p < 0.05, corrected), and in green (p < 0.01, uncorrected) are the hypothalamic regions in which this calorie-specific response is significantly attenuated by sibutramine. Top right, The plots show estimates of stimulus-related brain activation for each of the eight key conditions, divided by image type (high calorie/low calorie), satiety state (fasted/fed), and treatment (sibutramine/placebo). The y-axes show the effect sizes in the ventral striatal region shown or parameter estimates derived from the general linear model (units are arbitrary). As can be seen there is a strong effect of image type and of sibutramine but not of fasted/fed state. Bottom, Scatter plots showing the associations between the effect of sibutramine on suppression of hypothalamic activation by high-calorie food images (x-axis) and its effects on the proportion of ad libitum popcorn consumed on sibutramine compared to placebo (left) and on body weight in kilograms (right). In both graphs, a value of greater than zero on the x-axis indicates a suppression of activation on sibutramine compared to placebo; a value of less than zero on the y-axis indicates that there was a greater reduction in snacking or weight for sibutramine compared with for placebo. The graphs show that participants who demonstrated greater suppression of hypothalamic activation by sibutramine also showed greater treatment-related reduction in popcorn snacking and body weight. b, Amygdala responses to experimental manipulations (image type and sibutramine status). Left, A coronal section of the group average structural MRI at 2 mm anterior to the anterior commissure. Superimposed in red are the local regions showing a calorie-specific (high-calorie vs low-calorie images) response (p < 0.05, corrected), and in green (at crosshairs) is the amygdala region in which this calorie-specific response is significantly attenuated by sibutramine (p < 0.01, uncorrected). Right, The plots show estimates of stimulus-related brain activation for each of the eight key conditions, divided by image type (high calorie/low calorie), satiety state (fasted/fed), and treatment (sibutramine/placebo). The y-axis show the effect sizes in the ventral striatal region shown or parameter estimates derived from the general linear model (units are arbitrary). As can be seen, there is a strong effect of image type and of sibutramine but not of fasted/fed state.
Tables
Subjects undergoing fMRI (24) Age (years) Mean (SD) 34.9 (6.89) Range 22–44 Sex Male 19 (79%) Female 5 (21%) Ethnicity Black 0 (0%) Caucasian 22 (92%) Other 2 (8%) Weight (kg) Mean (SD) 85.2 (7.54) Range 71.3–102.5 BMI (kg/m2) Mean (SD) 27.06 (1.40) Range 25.3–30.6 Fat mass (kg) Mean (SD) 21.1 (6.63) Range 9.7–39.4 Barratt Impulsiveness Scale Mean (SD) 62.1 (7.58) Range 47–79 Sibutramine Placebo Difference 95% CI t df p value Mean SD Mean SD Change in fat mass (kg) −0.76 0.55 0.04 0.62 −0.79 (−1.14, −0.44) 4.6 41 <0.0001 Change in weight (kg) −1.85 1.19 −0.31 1.07 −1.56 (−2.27, −0.86) 4.5 39 <0.0001 Eating rate (g/min) 27.5 8.9 29.2 10.4 −2.6 (−6.5, 1.3) 1.4 18.5 0.1742 HCFQ total score 18.0 2.6 20.8 2.7 −2.9 (−4.2, −1.6) 4.7 21.6 0.0001 Ad libitum eating (g) 53.3 43.8 71.7 44.7 −15.7 (−30.8, −0.5) 2.2 20.9 0.0430 - Table 3.
Greater brain responses to high-calorie than to low-calorie images (across all fasted/fed and drug/placebo conditions)
Region Coordinates (x, y, z) Z score Ventral pallidum/putamen Left −12, 2, 4 7.3 −24, −18, 4 6.1 Right 12, 2, 2 7 Hypothalamus Left −10, −2, −4 6.2 Right 8, −4, −3 6 Ventral striatum Right 10, 4, 2 7 Left −10, 2, 0 6.9 Midbrain (substantia nigra/red nucleus) Right 6, −14, −3 5.5 Left −8, −20, −10 5.3 Amygdala Left −26, −3, −15 5.9 −18, −12, −9 4.1 Right 22, 1, −17 5.7 20, −12, −10 3.6 Insula Right 32, 11, −6 5 42, 17, −1 5 36, 23, 1 4.5 Left −42, 17, −3 4.8 −32, 10, 02 4.3 -
All regions survived small volume correction for multiple comparisons.
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Supplemental Material
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