Figure 4: Modulation of the rewarding aspects of food. In this highly simplified schematic, the orbitofrontal cortex (OFC) is highlighted as the most important hub in the reward encoding network. External food cues, via the visual cortex (VC), modulate the OFC response, with increased activity seen in fasted and obese patients and in response to high- versus low-calorie foods. OFC activity is also thought to be modulated by inputs from the hypothalamus, which senses internal information about nutritional status in the form of adiposity signals (such as leptin, which gives information about longer-term energy stores) and gut hormones (which are meal dependent and therefore give information about shorter-term nutrient availability). Anorectic (postprandial) gut hormones, such as PYY and GLP-1, attenuate OFC activity and, in fasted individuals induce, an OFC response to visual food cues more similar to that measured when fed. Conversely, the orexigenic hormone ghrelin upregulates reward centre activity.