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Prader-Willi syndrome is a rare neurodevelopmental genetic disorder characterized by various endocrine, cognitive and behavioural problems. The symptoms include an obsession for food and reduced satiety, which leads to hyperphagia and morbid obesity. Neuropsychological studies have reported that Prader-Willi patients display altered social interactions with a specific weakness in interpreting social information and responding to them, a symptom close to that observed in autism spectrum disorders. In the present case-control study, we hypothesized that brain regions associated with compulsive eating behaviour would be abnormally activated by food-related odours in Prader-Willi syndrome, as these can stimulate the appetite and induce hunger-related behaviour. We conducted a brain imaging study using the olfactory modality because odours have a high-hedonic valence and can cause stronger emotional reactions than other modalities. Further, the olfactory system is also intimately associated with the endocrine regulation of energy balance and is the most appropriate modality for studies of Prader-Willi syndrome. A total of 16 Prader-Willi participants were recruited for this study, which is a significant achievement given the low incidence rate of this rare disease. The second group of 11 control age-matched subjects also participated in the brain imaging study. In the MRI scanner, using an MRI-compatible olfactometer during 56 block sessions, we randomly presented two odours (tulip and caramel), which have different hedonic valence and a different capacity to arouse hunger-related behaviour. Our results demonstrate that Prader-Willi participants have abnormal activity in the brain reward system that regulates eating behaviour. Indeed, we found that these patients had right amygdala activity up to five times higher in response to a food odour (caramel) compared with the tulip odour. In contrast, age-matched control participants had similar activity levels in response to both odours. The amygdala activity levels were found to be associated with the severity of the hyperphagia in Prader-Willi patients. Our results provide evidence for functional alteration of the right amygdala in Prader-Willi syndrome, which is part of the brain network involved in food addiction modulated by the ghrelin and oxytocin systems, which may drive the hyperphagia. Our study provides important new insights into the functioning of emotion-related brain circuits and pathology, and it is one of the few to explore the dysfunction of the neural circuits involved in emotion and addiction in Prader-Willi syndrome. It suggests new directions for the exploration and remediation of addictive behaviours., Competing Interests: The authors report no conflicts of interest., (© Crown copyright 2023.)

Background: Prader-Willi syndrome (PWS) is a rare and complex neurodevelopmental disorder of genetic origin. It manifests itself in endocrine and cognitive problems, including highly pronounced hyperphagia and severe obesity. In many cases, impaired acquisition of social and communication skills leads to autism spectrum features, and individuals with this syndrome are occasionally diagnosed with autism spectrum disorder (ASD) using specific scales. Given that communicational skills are largely based on vocal communication, it is important to study human voice processing in PWS. We were able to examine a large number of participants with PWS (N = 61) recruited from France's national reference center for PWS and other hospitals. We tested their voice and nonvoice recognition abilities, as well as their ability to distinguish between voices and nonvoices in a free choice task. We applied the hierarchical drift diffusion model (HDDM) with Bayesian estimation to compare decision-making in participants with PWS and controls., Results: We found that PWS participants were impaired on both voice and nonvoice processing, but displayed a compensatory ability to perceive voices. Participants with uniparental disomy had poorer voice and nonvoice perception than participants with a deletion on chromosome 15. The HDDM allowed us to demonstrate that participants with PWS need to accumulate more information in order to make a decision, are slower at decision-making, and are predisposed to voice perception, albeit to a lesser extent than controls., Conclusions: The categorization of voices and nonvoices is generally preserved in participants with PWS, though this may not be the case for the lowest IQ.

Background: Faces are critical social cues that must be perfectly processed in order to engage appropriately in everyday social interactions. In Prader-Willi Syndrome (PWS), a rare genetic disorder characterized by cognitive and behavioural difficulties including autism spectrum disorder, the literature referring to face processing is sparse. Given reports of poor social interactions in individuals with PWS, we sought to assess their face and emotion recognition skills during eyetracking recordings., Results: Compared with controls, patients with PWS performed more poorly on face/emotion recognition. We observed atypical facial exploration by patients with maternal disomy. These patients looked preferentially at the mouth region, whereas patients with a deletion and controls were more attracted to the eye region. During social scenes, the exploration became more atypical as the social content increased., Conclusions: Our comprehensive study brings new insights into the face processing of patients with PWS. Atypical facial exploration was only displayed by patients with the maternal disomy subtype, corresponding to their higher rate of autism spectrum disorder. This finding strongly argues in favor of early identification of this genetic subgroup in order to optimize care by implementing tailored interventions for each patient as soon as possible.