Orbitofrontal cortex connectivity is associated with food reward and body weight in humans.

The aim was to investigate with very large-scale analyses whether there are underlying functional connectivity differences between humans that relate to food reward and whether these in turn are associated with being overweight. In 37 286 humans from the UK Biobank, resting-state functional connectivities of the orbitofrontal cortex (OFC), especially with the anterior cingulate cortex, were positively correlated with the liking for sweet foods (False Discovery Rate (FDR) P < 0.05). They were also positively correlated with the body mass index (BMI) (FDR P < 0.05). Moreover, in a sample of 502 492 people, the 'liking for sweet foods' was correlated with their BMI (r = 0.06, P < 10-125). In a cross-validation with 545 participants from the Human Connectome Project, a higher functional connectivity involving the OFC relative to other brain areas was associated with a high BMI (≥30) compared to a mid-BMI group (22-25; P = 6 × 10-5), and low OFC functional connectivity was associated with a low BMI (≤20.5; P < 0.024). It is proposed that a high BMI relates to increased efficacy of OFC food reward systems and a low BMI to decreased efficacy. This was found with no stimulation by food, so may be an underlying individual difference in brain connectivity that is related to food reward and BMI.