{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T13:18:19Z","timestamp":1783084699663,"version":"3.54.6"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["192706"],"award-info":[{"award-number":["192706"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>In early\u2010treated adults with phenylketonuria (PKU), the effects of elevated phenylalanine (Phe) on functional brain networks remain poorly understood. While subacute structural brain changes have been reported, their functional significance remains unclear. Executive and attentional functions have been shown to be particularly sensitive to metabolic control in PKU. In this double\u2010blind, randomized, placebo\u2010controlled crossover trial, we investigated the effects of a 4\u2010week high\u2010Phe period on resting\u2010state functional connectivity using seed\u2010based analyses of the dorsal attention and frontoparietal networks, which are critically involved in executive and attentional functions. Twenty\u2010three adults with PKU (median age 35.3\u2009years [IQR 12.0]; 43% female) were included. When baseline connectivity was considered, no significant differences in functional connectivity were observed between the Phe and placebo periods. Without baseline adjustment, exploratory analyses revealed increased functional connectivity of the right frontal eye field within the dorsal attention network with frontal regions. Changes in functional connectivity were neither associated with changes in metabolite concentrations nor in working memory, attention, or executive function. These findings suggest that subacute increases in Phe may induce subtle and potentially transient changes in functional brain networks, although their functional relevance and persistence over longer exposure periods remain unclear.<\/jats:p>","DOI":"10.1002\/jmd2.70108","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T12:21:11Z","timestamp":1783081271000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Are Functional Brain Networks Sensitive to High Phenylalanine in Adults With Phenylketonuria?"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6372-4901","authenticated-orcid":false,"given":"Vanessa","family":"Vallesi","sequence":"first","affiliation":[{"name":"Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital Bern University Hospital and University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Morishima","sequence":"additional","affiliation":[{"name":"Translational Research Center, University Hospital of Psychiatry and Psychotherapy University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9904-9102","authenticated-orcid":false,"given":"Laura","family":"Winiger","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital Bern University Hospital and University of Bern  Bern Switzerland"},{"name":"Graduate School for Health Sciences University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Trepp","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital Bern University Hospital and University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regula","family":"Everts","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital Bern University Hospital and University of Bern  Bern Switzerland"},{"name":"Translational Imaging Center (TIC) Swiss Institute for Translational and Entrepreneurial Medicine  Bern Switzerland"},{"name":"Division of Neuropaediatrics, Development and Rehabilitation, Department of Paediatrics, Inselspital Bern University Hospital and University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6911-1313","authenticated-orcid":false,"given":"Raphaela","family":"Muri","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital Bern University Hospital and University of Bern  Bern Switzerland"},{"name":"Translational Imaging Center (TIC) Swiss Institute for Translational and Entrepreneurial Medicine  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(10)60961\u20100"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2009.01.001"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022\u20103476(95)70303\u20109"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo15030197"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689\u2010024\u201009553\u2010w"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689\u2010025\u201009622\u20108"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae139"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12823"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13063\u2010019\u20104022\u2010z"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajcnut.2023.11.007"},{"key":"e_1_2_12_12_1","doi-asserted-by":"crossref","DOI":"10.56441\/hilbertpress.2246.5840","volume-title":"CONN Functional Connectivity Toolbox: RRID SCR_009550, Release 22","author":"Nieto\u2010Castanon A.","year":"2022"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/brain.2012.0073"},{"key":"e_1_2_12_14_1","volume-title":"Statistical Parametric Mapping: The Analysis of Functional Brain Images","author":"Penny W. 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