Large portions promote intake of energy dense foods (i.e., the portion size effect–PSE), but the neurobiological drivers of this effect are not known. We tested the association between blood oxygen level dependent (BOLD) brain response to food images varied by portion size (PS) and energy density (ED) and children's intake at test-meals of high- and low-ED foods served at varying portions. Children (N = 47; age 7–10 years) participated in a within-subjects, crossover study consisting of 4 meals of increasing PS of high- and low-ED foods and 1 fMRI to evaluate food images at 2 levels of PS (Large, Small) and 2 levels of ED (High, Low). Contrast values between PS conditions (e.g., Large PS - Small PS) were calculated from BOLD signal in brain regions implicated in cognitive control and reward and input as covariates in mixed models to determine if they moderated the PSE curve. Results showed a significant effect of PS on intake. Responses to Large relative to Small PS in brain regions implicated in salience (e.g., ventromedial prefrontal cortex and orbitofrontal cortex) were positively associated with the linear slope (i.e., increase in intake from baseline) of the PSE curve, but negatively associated with the quadratic coefficient for the total meal. Responses to Large PS High ED relative to Small PS High ED cues in regions associated with cognitive control (e.g., dorsolateral prefrontal cortex) were negatively associated with the linear slope of the PSE curve for high-ED foods. Brain responses to PS cues were associated with individual differences in children's susceptibility to overeating from large portions. Responses in food salience regions positively associated with PSE susceptibility while activation in control regions negatively associated with PSE susceptibility.
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