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Objective:Neuroimaging studies have demonstrated alterations in brain activity in obese (OB) subjects that might be causally linked to their disorder. Roux-en Y gastric bypass (RYGB) surgery induces a marked and sustained weight loss and may affect brain activity. The aim of this study was to compare brain activity pattern between severely OB women (n=11), normal-weight women (NW, n=11) and previously severely OB women who had undergone RYGB surgery (RYGB, n=9) on average 3.4±0.8 years (all >1 year) before the experiment.Design:Brain activity was assessed by functional magnetic resonance imaging during a one-back task containing food- and non-food-related pictures and during resting state. Hunger and satiety were repeatedly rated on a visual analog scale during the experiment.Results:As compared with NW and also with RYGB women, OB women showed (1) a higher cerebellar and a lower fusiform gyrus activity during the visual stimulation independently of the picture category, (2) a higher hypothalamic activation during the presentation of low- vs high-caloric food pictures, (3) a higher hippocampal and cerebellar activity during the working memory task and (4) a stronger functional connectivity in frontal regions of the default mode network during resting state. There were no differences in brain activity between the NW and RYGB women, both during picture presentation and during resting state. RYGB women generally rated lower on hunger and higher on satiety, whereas there were no differences in these ratings between the OB and NW women.Conclusion:Data provide evidence for an altered brain activity pattern in severely OB women and suggest that RYGB surgery and/or the surgically induced weight loss reverses the obesity-associated alterations.International Journal of Obesity advance online publication, 28 May 2013; doi:10.1038/ijo.2013.60.