Is the brain representation of hunger normal in the Prader-Willi syndrome?

We have read with profound interest the paper 'Neural representations of hunger and satiety in Prader–Willi syndrome' (PWS) by Hinton et al.1 Noting that the PWS patients had significantly increased blood flow in brain regions implicated in prior positron emission tomography (PET) studies of normal human hunger,2, 3 the authors suggest that an abnormality in the neural substrates of hunger does not account for hyperphagia in these individuals. We wish to suggest more caution in the interpretation of the interesting findings. First, direct comparisons between the state-dependent changes in blood flow in PSW patients and a control group are needed to determine whether the hunger and satiety-related blood flow responses differ in patients and controls. Second, a failure to detect a significant blood flow response to satiety could reflect a limitation in the statistical power of the study, (which involved 13 patients), after whole brain correction for multiple comparisons. Furthermore, fasting and satiety responses were measured on two separate days, which may have introduced important confounders in the contrast of conditions. Finally, exposure of most subjects to medications known to interfere with appetite regulation may have affected the observed brain responses. Despite these caveats, we share the authors' conviction that brain imaging studies promise to help understand how the brain conspires to produce hyperphagia in PWS and other obese populations.