Alterations in White Matter Microstructure in Neurofibromatosis-1

Neurofibromatosis (NF1) represents the most common single gene cause of learning disabilities. NF1 patients have impairments in frontal lobe based cognitive functions such as attention, working memory, and inhibition. Due to its well–characterized genetic etiology, investigations of NF1 may shed lig...

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Main Authors:	Karlsgodt, Katherine H., Rosser, Tena, Lutkenhoff, Evan S., Cannon, Tyrone D., Silva, Alcino, Bearden, Carrie E.
Format:	Online
Language:	English
Published:	Public Library of Science 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477133/

id	pubmed-3477133
recordtype	oai_dc
spelling	pubmed-34771332012-10-23 Alterations in White Matter Microstructure in Neurofibromatosis-1 Karlsgodt, Katherine H. Rosser, Tena Lutkenhoff, Evan S. Cannon, Tyrone D. Silva, Alcino Bearden, Carrie E. Research Article Neurofibromatosis (NF1) represents the most common single gene cause of learning disabilities. NF1 patients have impairments in frontal lobe based cognitive functions such as attention, working memory, and inhibition. Due to its well–characterized genetic etiology, investigations of NF1 may shed light on neural mechanisms underlying such difficulties in the general population or other patient groups. Prior neuroimaging findings indicate global brain volume increases, consistent with neural over-proliferation. However, little is known about alterations in white matter microstructure in NF1. We performed diffusion tensor imaging (DTI) analyses using tract-based spatial statistics (TBSS) in 14 young adult NF1 patients and 12 healthy controls. We also examined brain volumetric measures in the same subjects. Consistent with prior studies, we found significantly increased overall gray and white matter volume in NF1 patients. Relative to healthy controls, NF1 patients showed widespread reductions in white matter integrity across the entire brain as reflected by decreased fractional anisotropy (FA) and significantly increased absolute diffusion (ADC). When radial and axial diffusion were examined we found pronounced differences in radial diffusion in NF1 patients, indicative of either decreased myelination or increased space between axons. Secondary analyses revealed that FA and radial diffusion effects were of greatest magnitude in the frontal lobe. Such alterations of white matter tracts connecting frontal regions could contribute to the observed cognitive deficits. Furthermore, although the cellular basis of these white matter microstructural alterations remains to be determined, our findings of disproportionately increased radial diffusion against a background of increased white matter volume suggest the novel hypothesis that one potential alteration contributing to increased cortical white matter in NF1 may be looser packing of axons, with or without myelination changes. Further, this indicates that axial and radial diffusivity can uniquely contribute as markers of NF1-associated brain pathology in conjunction with the typically investigated measures. Public Library of Science 2012-10-19 /pmc/articles/PMC3477133/ /pubmed/23094098 http://dx.doi.org/10.1371/journal.pone.0047854 Text en © 2012 Karlsgodt et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Karlsgodt, Katherine H. Rosser, Tena Lutkenhoff, Evan S. Cannon, Tyrone D. Silva, Alcino Bearden, Carrie E.
spellingShingle	Karlsgodt, Katherine H. Rosser, Tena Lutkenhoff, Evan S. Cannon, Tyrone D. Silva, Alcino Bearden, Carrie E. Alterations in White Matter Microstructure in Neurofibromatosis-1
author_facet	Karlsgodt, Katherine H. Rosser, Tena Lutkenhoff, Evan S. Cannon, Tyrone D. Silva, Alcino Bearden, Carrie E.
author_sort	Karlsgodt, Katherine H.
title	Alterations in White Matter Microstructure in Neurofibromatosis-1
title_short	Alterations in White Matter Microstructure in Neurofibromatosis-1
title_full	Alterations in White Matter Microstructure in Neurofibromatosis-1
title_fullStr	Alterations in White Matter Microstructure in Neurofibromatosis-1
title_full_unstemmed	Alterations in White Matter Microstructure in Neurofibromatosis-1
title_sort	alterations in white matter microstructure in neurofibromatosis-1
description	Neurofibromatosis (NF1) represents the most common single gene cause of learning disabilities. NF1 patients have impairments in frontal lobe based cognitive functions such as attention, working memory, and inhibition. Due to its well–characterized genetic etiology, investigations of NF1 may shed light on neural mechanisms underlying such difficulties in the general population or other patient groups. Prior neuroimaging findings indicate global brain volume increases, consistent with neural over-proliferation. However, little is known about alterations in white matter microstructure in NF1. We performed diffusion tensor imaging (DTI) analyses using tract-based spatial statistics (TBSS) in 14 young adult NF1 patients and 12 healthy controls. We also examined brain volumetric measures in the same subjects. Consistent with prior studies, we found significantly increased overall gray and white matter volume in NF1 patients. Relative to healthy controls, NF1 patients showed widespread reductions in white matter integrity across the entire brain as reflected by decreased fractional anisotropy (FA) and significantly increased absolute diffusion (ADC). When radial and axial diffusion were examined we found pronounced differences in radial diffusion in NF1 patients, indicative of either decreased myelination or increased space between axons. Secondary analyses revealed that FA and radial diffusion effects were of greatest magnitude in the frontal lobe. Such alterations of white matter tracts connecting frontal regions could contribute to the observed cognitive deficits. Furthermore, although the cellular basis of these white matter microstructural alterations remains to be determined, our findings of disproportionately increased radial diffusion against a background of increased white matter volume suggest the novel hypothesis that one potential alteration contributing to increased cortical white matter in NF1 may be looser packing of axons, with or without myelination changes. Further, this indicates that axial and radial diffusivity can uniquely contribute as markers of NF1-associated brain pathology in conjunction with the typically investigated measures.
publisher	Public Library of Science
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477133/
_version_	1611917812941455360

Alterations in White Matter Microstructure in Neurofibromatosis-1

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