{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:06:12Z","timestamp":1791385572109,"version":"4.3.3"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":303,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Niemann\u2013Pick disease type C (NPC) is a rare genetic lysosomal storage disorder with a clinically heterogeneous phenotype that primarily affects the brain, liver and spleen. Most cases of NPC are diagnosed in childhood, but a subset of patients who are diagnosed in adulthood present with psychiatric symptoms and are initially diagnosed as schizophrenia or a mood disorder. Neuroimaging studies in NPC show a predilection for neurodegeneration in the subcortical nuclei, the cerebellum and subcortical white matter. We aimed to explore how adult NPC affects the connectivity of networks and hypothesized a state of widespread disconnectivity, particularly in subcortical areas. This cross-sectional neuroimaging study used diffusion-weighted magnetic resonance imaging to perform whole-brain tractography in 9 adult patients with NPC and 70 matched healthy controls. Connections between 84 unique brain regions were modelled with streamlines and weighted according to fibre bundle capacity. Statistical testing by each connection allowed the identification of significantly affected networks and regions in NPC. We observed diffusive disconnectivity in NPC primarily affecting left frontotemporal and subcortical networks. Globally and regionally, NPC showed reductions in the strength and number of affected connections, particularly in the thalamus and dorsal striatum. We show that left frontotemporal and subcortical networks are markedly affected in NPC. These findings may facilitate early diagnostic differentiation, monitoring and prognostication and may represent the neural correlates of neuropsychiatric symptoms in NPC.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf426","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T13:16:57Z","timestamp":1761830217000},"source":"Crossref","is-referenced-by-count":1,"title":["A whole-brain structural connectivity signature in adult Niemann\u2013Pick disease type C"],"prefix":"10.1093","volume":"7","author":[{"given":"Thomas C","family":"Reilly","sequence":"first","affiliation":[{"name":"Systems Lab, Department of Psychiatry, The University of Melbourne , Melbourne, VIC 3010 ,","place":["Australia"]},{"name":"The Neuropsychiatry Centre, The Royal Melbourne Hospital , Melbourne, VIC 3050 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A","family":"Di Biase","sequence":"additional","affiliation":[{"name":"Systems Lab, Department of Psychiatry, The University of Melbourne , Melbourne, VIC 3010 ,","place":["Australia"]},{"name":"Stem Cell Disease Modelling Lab, Department of Anatomy and Physiology, The University of Melbourne , Melbourne, VIC 3010 ,","place":["Australia"]},{"name":"Department of Psychiatry, Brigham and Women's Hospital and Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sina","family":"Mansour","sequence":"additional","affiliation":[{"name":"Systems Lab, Department of Psychiatry, The University of Melbourne , Melbourne, VIC 3010 ,","place":["Australia"]},{"name":"Centre for Sleep & Cognition and Centre for Translational Magnetic Resonance Research, Yong Loo Lin School of Medicine, National University of Singapore , Singapore 117597 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caio","family":"Seguin","sequence":"additional","affiliation":[{"name":"Systems Lab, 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