title: Multiple sclerosis-related white matter microstructural change alters the BOLD hemodynamic response.
abstract: Multiple sclerosis (MS) results in inflammatory damage to white matter microstructure. Prior research using blood-oxygen-level dependent (BOLD) imaging indicates MS-related alterations to brain function. What is currently unknown is the extent to which white matter microstructural damage influences BOLD signal in MS. Here we assessed changes in parameters of the BOLD hemodynamic response function (HRF) in patients with relapsing-remitting MS compared to healthy controls. We also used diffusion tensor imaging to assess whether MS-related changes to the BOLD-HRF were affected by changes in white matter microstructural integrity. Our results showed MS-related reductions in BOLD-HRF peak amplitude. These MS-related amplitude decreases were influenced by individual differences in white matter microstructural integrity. Other MS-related factors including altered reaction time, limited spatial extent of BOLD activity, elevated lesion burden, or lesion proximity to regions of interest were not mediators of group differences in BOLD-HRF amplitude. Results are discussed in terms of functional hyperemic mechanisms and implications for analysis of BOLD signal differences.
authors.affiliation: School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Hubbard
authors.affiliation: School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, USA.
authors.forename: Monroe
authors.initials: M
authors.lastname: Turner
authors.affiliation: School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, USA.|Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Hutchison
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.|Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Austin
authors.initials: A
authors.lastname: Ouyang
authors.affiliation: School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Strain
authors.affiliation: School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, USA.
authors.forename: Larry
authors.initials: L
authors.lastname: Oasay
authors.affiliation: School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, USA.
authors.forename: Saranya
authors.initials: S
authors.lastname: Sundaram
authors.affiliation: Department of Applied Physiology and Wellness, Southern Methodist University, Dallas, TX, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Davis
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.|Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Gina
authors.initials: G
authors.lastname: Remington
authors.affiliation: School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Brigante
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.|Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Huang
authors.affiliation: School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, USA.|Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.|Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: John
authors.initials: J
authors.lastname: Hart
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Frohman
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.|Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Elliot
authors.initials: E
authors.lastname: Frohman
authors.affiliation: Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, USA.
authors.forename: Bharat B
authors.initials: BB
authors.lastname: Biswal
authors.affiliation: School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, USA bart.rypma@utdallas.edu.|Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Bart
authors.initials: B
authors.lastname: Rypma
mesh_terms: D000328:Adult; D002560:Cerebrovascular Circulation / Q000502:physiology*; D005260:Female; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D011930:Reaction Time / Q000502:physiology; D012680:Sensitivity and Specificity; D066127:White Matter / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000648:ultrastructure*
chemical_list: D010100:Oxygen
keywords: Bold contrast; brain imaging; cerebral hemodynamics; multiple sclerosis; white matter disease