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The onset of hyperphagia in childhood and developmental, physical and neuropsychiatric characteristics indicate atypical brain development and specifically hypothalamic dysfunction. Whether the latter is a consequence of disruption of hypothalamic pathways for genetic reasons or due to a failure of hypothalamic development remains uncertain. Twenty participants with Prader\u2013Willi syndrome, 40 age-matched controls and 42 obese participants underwent structural MRI scanning. The whole hypothalamus and its subnuclei were segmented from structural acquisitions. The Food-Related Problem Questionnaire was used to provide information relating to eating behaviour. All hypothalamic nuclei were significantly smaller in the Prader\u2013Willi group, compared with age and gender matched controls (P\u2009&amp;lt;\u20090.01) with the exception of the right anterior\u2013inferior nucleus (P\u2009=\u20090.07). Lower whole hypothalamus volume was significantly associated with higher body mass index in Prader\u2013Willi syndrome (P\u2009&amp;lt;\u20090.05). Increased preoccupation with food was associated with lower volumes of the bilateral posterior nuclei and left tubular superior nucleus. The whole hypothalamus and all constituent nuclei were also smaller in Prader\u2013Willi syndrome compared with obese participants (P\u2009&amp;lt;\u20090.001). Connectivity profiles of the hypothalamus revealed that fractional anisotropy was associated with impaired satiety in Prader\u2013Willi syndrome (P\u2009&amp;lt;\u20090.05). We establish that hypothalamic structure is significantly altered in Prader\u2013Willi syndrome, demonstrating that hypothalamic dysfunction linked to eating behaviour is likely neurodevelopmental in nature and furthermore, distinctive compared with obesity in the general population.<\/jats:p>","DOI":"10.1093\/braincomms\/fcac229","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T16:33:02Z","timestamp":1662741182000},"source":"Crossref","is-referenced-by-count":37,"title":["<i>In vivo<\/i> neuroimaging evidence of hypothalamic alteration in Prader\u2013Willi syndrome"],"prefix":"10.1093","volume":"4","author":[{"given":"Stephanie S G","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Cambridge , Addenbrookes Hospital, Cambridge CB2 0QQ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine E","family":"Manning","sequence":"additional","affiliation":[{"name":"Department of 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