Obesity-Related Differences between Women and Men in Brain Structure and Goal-Directed Behavior

Annette Horstmann, Franziska P Busse, David Mathar, Karsten Müller, Jöran Lepsien, Haiko Schlögl, Stefan Kabisch, Jürgen Kratzsch, Jane Neumann, Michael Stumvoll, Arno Villringer, Burkhard Pleger, Annette Horstmann, Franziska P Busse, David Mathar, Karsten Müller, Jöran Lepsien, Haiko Schlögl, Stefan Kabisch, Jürgen Kratzsch, Jane Neumann, Michael Stumvoll, Arno Villringer, Burkhard Pleger

Abstract

Gender differences in the regulation of body-weight are well documented. Here, we assessed obesity-related influences of gender on brain structure as well as performance in the Iowa Gambling Task. This task requires evaluation of both immediate rewards and long-term outcomes and thus mirrors the trade-off between immediate reward from eating and the long-term effect of overeating on body-weight. In women, but not in men, we show that the preference for salient immediate rewards in the face of negative long-term consequences is higher in obese than in lean subjects. In addition, we report structural differences in the left dorsal striatum (i.e., putamen) and right dorsolateral prefrontal cortex for women only. Functionally, both regions are known to play complimentary roles in habitual and goal-directed control of behavior in motivational contexts. For women as well as men, gray matter volume correlates positively with measures of obesity in regions coding the value and saliency of food (i.e., nucleus accumbens, orbitofrontal cortex) as well as in the hypothalamus (i.e., the brain's central homeostatic center). These differences between lean and obese subjects in hedonic and homeostatic control systems may reflect a bias in eating behavior toward energy-intake exceeding the actual homeostatic demand. Although we cannot infer from our results the etiology of the observed structural differences, our results resemble neural and behavioral differences well known from other forms of addiction, however, with marked differences between women and men. These findings are important for designing gender-appropriate treatments of obesity and possibly its recognition as a form of addiction.

Keywords: Iowa gambling task; brain structure; gender difference; obesity; reward system; voxel-based morphometry.

Figures

Figure 1
Figure 1
Distribution of body mass index [in kg/m2 (A)] and age [in years (B)] for female and male participants.
Figure 2
Figure 2
Obesity is associated with structural alterations of the brain's gray matter structure. Results are shown in detail for the whole group (n = 122), including both men and women. Top row: coronal slices, numbers indicate slice location in MNI coordinates. The position of the slices in relation to the whole brain is indicated visually on the right (blue lines). Middle row: sagittal slices, conventions as above. Bottom row: axial slices, conventions as above.
Figure 3
Figure 3
The association of obesity with profound, gender-dependent structural alterations within brain regions involved in reward processing, cognitive, and homeostatic control. The volume of posterior medial orbitofrontal cortex (OFC), nucleus accumbens (NAcc), and hypothalamus increases significantly with BMI (first panel, warm colors) in both genders. For women, an additional association between gray matter volume and BMI can be observed in the left putamen (second panel: warm colors and scatterplot). Leptin, a more direct measure of the degree of obesity, is also associated with gender-dependent changes in brain structure. The association between BMI and GMV in the left putamen overlaps with the association between the concentration of central leptin and GMV in the putamen, an effect, which we only find in women (third panel: red). Women show additional alterations in the NAcc bilaterally and the fornix (third panel, red); men show alterations of brain structure in the NAcc bilaterally and the hypothalamus (third panel, blue). We found a significant negative association between central leptin and GMV restricted to women in the right lateral prefrontal cortex (lower panel). All GMV values are mean standardized and corrected for age, total gray and white matter.
Figure 4
Figure 4
Differences in lean and obese women in their ability to adjust choice behavior to match long-term goals. (A) Preference for deck B over all trials correlates with BMI within the group of women. Gray line: linear regression. (B) Difference between lean and obese women in choice behavior during learning. Lean women learn to gradually select fewer cards from deck B. In contrast, obese women continue to select cards from deck B. Each block consists of five trials. (C) No difference between lean and obese men in choice behavior is observable during learning. Each block consists of five trials.

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