Neurophysiological dysconnectivity across multiple resting state brain networks and cognitive impairment in children with Prader-Willi Syndrome

Prader-Willi Syndrome (PWS) is a rare genetic condition with multifaceted physical, behavioural and cognitive difficulties that is characterized by hyperphagia and low executive functioning. Food-seeking behaviours may be moderated by hormonal, cognitive, and psychological factors, and are thought to be mediated in part by functional brain abnormalities. Here, we used an experimental protocol integrating eyes opens resting state magnetoencephalography (MEG) - a high-resolution neurophysiological imaging technique - and neuropsychological profiling to understand the relationship between executive functioning, and intrinsic brain activity & functional connectivity in a prospective, cross-sectional cohort with PWS, and a sex-, age- and BMI-matched control group. We observed lower executive functioning in PWS as well as functional dysconnectivity across multiple channels of brain synchrony - in other words, across multiple frequency bands that mediate communication within and between brain networks - in the visual, attentional, and the default mode networks. Moreover, we found ‘brain-wide’ changes in the topological structure of brain networks in those with PWS, with increased ‘hubness’ of functional networks, but decreased centrality. However, none of these measures survived multiple comparison correction after correlating with neuropsychological outcomes, although there were moderate effect sizes (degree of association). This is the first study to combine neuropsychology and neurophysiological imaging to show that functional synchrony in multiple brain networks is dysregulated in PWS.