title: White matter lesions relate to tract-specific reductions in functional connectivity.
abstract: White matter lesions play a role in cognitive decline and dementia. One presumed pathway is through disconnection of functional networks. Little is known about location-specific effects of lesions on functional connectivity. This study examined location-specific effects within anatomically-defined white matter tracts in 1584 participants of the Rotterdam Study, aged 50-95. Tracts were delineated from diffusion magnetic resonance images using probabilistic tractography. Lesions were segmented on fluid-attenuated inversion recovery images. Functional connectivity was defined across each tract on resting-state functional magnetic resonance images by using gray matter parcellations corresponding to the tract ends and calculating the correlation of the mean functional activity between the gray matter regions. A significant relationship between both local and brain-wide lesion load and tract-specific functional connectivity was found in several tracts using linear regressions, also after Bonferroni correction. Indirect connectivity analyses revealed that tract-specific functional connectivity is affected by lesions in several tracts simultaneously. These results suggest that local white matter lesions can decrease tract-specific functional connectivity, both in direct and indirect connections.
authors.affiliation: Department of Radiology and Nuclear Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Medical Informatics, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Carolyn D
authors.initials: CD
authors.lastname: Langen
authors.affiliation: Department of Radiology and Nuclear Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Hazel I
authors.initials: HI
authors.lastname: Zonneveld
authors.affiliation: Department of Radiology and Nuclear Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Child and Adolescent Psychiatry, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Tonya
authors.initials: T
authors.lastname: White
authors.affiliation: Department of Radiology and Nuclear Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Medical Informatics, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Wyke
authors.initials: W
authors.lastname: Huizinga
authors.affiliation: Department of Radiology and Nuclear Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Lotte G M
authors.initials: LGM
authors.lastname: Cremers
authors.affiliation: Department of Radiology and Nuclear Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Medical Informatics, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Marius
authors.initials: M
authors.lastname: de Groot
authors.affiliation: Department of Radiology and Nuclear Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Mohammad Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: Department of Radiology and Nuclear Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Medical Informatics, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Imaging Physics, Faculty of Applied Sciences, Delft University of Technology, Delft, the Netherlands.
authors.forename: Wiro J
authors.initials: WJ
authors.lastname: Niessen
authors.affiliation: Department of Radiology and Nuclear Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands. Electronic address: m.vernooij@erasmusmc.nl.
authors.forename: Meike W
authors.initials: MW
authors.lastname: Vernooij
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003072:Cognition Disorders / Q000209:etiology*; D003704:Dementia / Q000209:etiology*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D066128:Gray Matter; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D066127:White Matter / Q000000981:diagnostic imaging* / Q000503:physiopathology*
keywords: Brain; Connectivity; Function; Lesions; Location-specific