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Alternative Neuropsychological and Magnetic Resonance Imaging Measures in Multiple Sclerosis: Exploring the relation between brain lesion measured by diffusion tensor magnetic resonance imaging and interhemispheric communication and processing speed in multiple sclerosis

Nele Warlop UGent (2009)
abstract
Multiple sclerosis (MS) is a chronic neurological disease of the central nerve system that affects young adults with a higher prevalence in women (ratio 3:2). The neuropathology of the disease is characterised by demyelination of the white matter in the brain and central cord. MS may involve degeneration of white matter throughout the nervous system, with a predilection for specific target zones that includes the corpus callosum. The pathologic process may lead to motor problems, but halve of the patients has cognitive problems associated with MS. In this thesis, we focus on the cognitive problems and the relation with neuropathological brain damage. One of the brain areas preferentially involved in MS, is the corpus callosum. This brain structure is the largest white matter tract connecting both hemispheres. Research in callosotomy patients, acallosal patients and callosal section patients indicates that robust callosal damage may lead to interhemispheric transfer dysfunctions. In the first part of this thesis callosal problems in MS are explored. Damage to the corpus callosum in this patient group is subtler than in callosotomy patients. Moreover, the callosal damage strongly varies from patient to patient. In this thesis the redundancy gain paradigm, a behavioural measure to investigate interhemispheric communication is used. In this task, flashes of light are presented to the left, right or bilateral (left and right simultaneously) visual hemifield while the subject fixates to the middle of the screen. As soon as the subject detects a flash, he presses the response button with the left or right hand (detection task). An effect that is typically observed in healthy subjects is that reaction times to bilateral stimuli are faster than to unilateral stimuli. This effect is referred to as the redundancy gain effect. Previous research shows that the redundancy gain effect is enlarged in patients with callosal problems (acallosal patients or patients with callosal section). The results in this thesis show, in analogy with the results in patients with robust callosal damage, an enlarged redundancy gain effect for MS patients. These results demonstrate the sensitiveness of the redundancy gain paradigm to investigate callosal problems in MS. To explore the effect of the amount of callosal brain damage on the redundancy gain effect, the callosal damage needs to be quantified. For this purpose diffusion tensor imaging was used. With this technique, water diffusion in the white matter can be investigated. Water in the brain spreads preferentially along the direction of the axonal fibers. Intact myelin sheets are effective barriers for the water. Demyelination, an important pathological aspect of MS, leads to decreased delineation of the tracts along which the water spreads. This results in changed diffusion derived measures. Fractional anisotropy is an important diffusion derived measure for inter- and intravoxel fiber coherence. Previous research shows that fractional anisotropy is decreased in MS patients compared to healthy controls. To calculate the fractional anisotropy, diffusion measures along three directions are defined, more specific along the principal direction, along the direction of minimal diffusion and along a third Alternative Neuropsychological and MRI Measures in MS 89 Summary direction that is orthogonal to the previous two. With this information, the longitudinal and transverse diffusivity can be calculated. Longitudinal diffusivity is the diffusion eigenvalue along the principal direction, whereas the transverse diffusivity is the mean of the eigenvalues along the other two directions. Recent research shows that demyelination and axonal loss, specific for MS pathology, is characterised by increased transverse diffusivity. Hence, transverse diffusivity is a unique marker for MS. The results of this thesis confirm this and show that transverse diffusivity is significantly more increased than longitudinal diffusivity in MS patients compared to healthy matched controls. Thirdly, a correlation between the behavioural results, the redundancy gain effect, and the brain imaging measures, the diffusion derived measures, was found: the larger the transverse diffusivity, or in other words, the MS related callosal damage, the larger the redundancy gain effect in MS patients. Moreover, neither longitudinal diffusivity, nor callosal lesion load as defined on conventional T2 images were additional factors in explaining this correlation. The results of the first part of this thesis show a) that the redundancy gain paradigm is a sensitive measure to investigate callosal brain damage in MS, b) that diffusion derived parameters are subtle measures to indicate MS related brain damage and c) that a significant correlation between callosal brain damage and the redundancy gain effect could be found in MS patients. In the second part of this thesis the focus was on the relation between cerebral brain damage as defined by diffusion derived measures and information processing speed in MS. Information processing speed is a cognitive measure tested by the Paced Serial Addition Test (PASAT) and the Symbol Digit Modalities Test (SDMT), two commonly used neuropsychological tests in MS. A significant correlation between the performance on the SDMT and transverse diffusivity in the whole brain was found in MS patients, indicating that demyelination and axonal damage, characteristic for MS pathology, are important factors for explaining the slowed information processing speed in MS. No correlation was found with the performance on the PASAT, which can be explained by the weaker psychometric qualities of the PASAT compared to the SDMT. First of all, the results of this thesis corroborate the heterogeneous pathological condition in MS. Research on callosal problems in MS can not be done without considering these individual differences. Based on our results, diffusion weighted imaging seems to offer a promising technique to determine cerebral damage in MS. Transverse diffusivity, considered to be a unique benchmark of white matter demyelination as seen in MS, is of special interest. Moreover, this diffusion derived measures correlate with cognitive (dys)function in MS, a correlation not consistently found for conventional imaging (lesion load on T2 of T1 images).
Please use this url to cite or link to this publication:
author
promoter
UGent and UGent
organization
year
type
dissertation (monograph)
subject
keyword
Magnetic resonance imaging, Multiple Sclerosis, interhemispheric communication, Diffusion Tensor Imaging
pages
103 pages
place of publication
Gent
defense date
2009-01-26 00:00
language
English
UGent publication?
yes
classification
D1
copyright statement
I don't know the status of the copyright for this publication
id
706403
handle
http://hdl.handle.net/1854/LU-706403
alternative location
http://lib.ugent.be/fulltxt/RUG01/001/308/052/RUG01-001308052_2010_0001_AC.pdf
date created
2009-06-22 22:13:27
date last changed
2009-06-23 10:50:19
@phdthesis{706403,
  abstract     = {Multiple sclerosis (MS) is a chronic neurological disease of the central nerve system that affects young  adults with a higher prevalence in women (ratio 3:2). The neuropathology of the disease is  characterised by demyelination of the white matter in the brain and central cord. MS may involve  degeneration of white matter throughout the nervous system, with a predilection for specific target  zones that includes the corpus callosum. The pathologic process may lead to motor problems, but  halve of the patients has cognitive problems associated with MS. In this thesis, we focus on the  cognitive problems and the relation with neuropathological brain damage.  One of the brain areas preferentially involved in MS, is the corpus callosum. This brain structure is the  largest white matter tract connecting both hemispheres. Research in callosotomy patients, acallosal  patients and callosal section patients indicates that robust callosal damage may lead to  interhemispheric transfer dysfunctions. In the first part of this thesis callosal problems in MS are  explored. Damage to the corpus callosum in this patient group is subtler than in callosotomy patients.  Moreover, the callosal damage strongly varies from patient to patient.  In this thesis the redundancy gain paradigm, a behavioural measure to investigate interhemispheric  communication is used. In this task, flashes of light are presented to the left, right or bilateral (left and  right simultaneously) visual hemifield while the subject fixates to the middle of the screen. As soon as  the subject detects a flash, he presses the response button with the left or right hand (detection task).  An effect that is typically observed in healthy subjects is that reaction times to bilateral stimuli are  faster than to unilateral stimuli. This effect is referred to as the redundancy gain effect. Previous  research shows that the redundancy gain effect is enlarged in patients with callosal problems (acallosal  patients or patients with callosal section). The results in this thesis show, in analogy with the results in  patients with robust callosal damage, an enlarged redundancy gain effect for MS patients. These  results demonstrate the sensitiveness of the redundancy gain paradigm to investigate callosal problems  in MS.  To explore the effect of the amount of callosal brain damage on the redundancy gain effect, the  callosal damage needs to be quantified. For this purpose diffusion tensor imaging was used. With this  technique, water diffusion in the white matter can be investigated. Water in the brain spreads  preferentially along the direction of the axonal fibers. Intact myelin sheets are effective barriers for the  water. Demyelination, an important pathological aspect of MS, leads to decreased delineation of the  tracts along which the water spreads. This results in changed diffusion derived measures. Fractional  anisotropy is an important diffusion derived measure for inter- and intravoxel fiber coherence.  Previous research shows that fractional anisotropy is decreased in MS patients compared to healthy  controls. To calculate the fractional anisotropy, diffusion measures along three directions are defined,  more specific along the principal direction, along the direction of minimal diffusion and along a third  Alternative Neuropsychological and MRI Measures in MS 89  Summary  direction that is orthogonal to the previous two. With this information, the longitudinal and transverse  diffusivity can be calculated. Longitudinal diffusivity is the diffusion eigenvalue along the principal  direction, whereas the transverse diffusivity is the mean of the eigenvalues along the other two  directions. Recent research shows that demyelination and axonal loss, specific for MS pathology, is  characterised by increased transverse diffusivity. Hence, transverse diffusivity is a unique marker for  MS. The results of this thesis confirm this and show that transverse diffusivity is significantly more  increased than longitudinal diffusivity in MS patients compared to healthy matched controls.  Thirdly, a correlation between the behavioural results, the redundancy gain effect, and the brain  imaging measures, the diffusion derived measures, was found: the larger the transverse diffusivity, or  in other words, the MS related callosal damage, the larger the redundancy gain effect in MS patients.  Moreover, neither longitudinal diffusivity, nor callosal lesion load as defined on conventional T2  images were additional factors in explaining this correlation.  The results of the first part of this thesis show a) that the redundancy gain paradigm is a sensitive  measure to investigate callosal brain damage in MS, b) that diffusion derived parameters are subtle  measures to indicate MS related brain damage and c) that a significant correlation between callosal  brain damage and the redundancy gain effect could be found in MS patients.  In the second part of this thesis the focus was on the relation between cerebral brain damage as defined  by diffusion derived measures and information processing speed in MS. Information processing speed  is a cognitive measure tested by the Paced Serial Addition Test (PASAT) and the Symbol Digit  Modalities Test (SDMT), two commonly used neuropsychological tests in MS. A significant  correlation between the performance on the SDMT and transverse diffusivity in the whole brain was  found in MS patients, indicating that demyelination and axonal damage, characteristic for MS  pathology, are important factors for explaining the slowed information processing speed in MS. No  correlation was found with the performance on the PASAT, which can be explained by the weaker  psychometric qualities of the PASAT compared to the SDMT.  First of all, the results of this thesis corroborate the heterogeneous pathological condition in MS.  Research on callosal problems in MS can not be done without considering these individual  differences. Based on our results, diffusion weighted imaging seems to offer a promising technique to  determine cerebral damage in MS. Transverse diffusivity, considered to be a unique benchmark of  white matter demyelination as seen in MS, is of special interest. Moreover, this diffusion derived  measures correlate with cognitive (dys)function in MS, a correlation not consistently found for  conventional imaging (lesion load on T2 of T1 images).},
  author       = {Warlop, Nele},
  keyword      = {Magnetic resonance imaging,Multiple Sclerosis,interhemispheric communication,Diffusion Tensor Imaging},
  language     = {eng},
  pages        = {103},
  school       = {Ghent University},
  title        = {Alternative Neuropsychological and Magnetic Resonance Imaging Measures in Multiple Sclerosis: Exploring the relation between brain lesion measured by diffusion tensor magnetic resonance imaging and interhemispheric communication and processing speed in multiple sclerosis},
  url          = {http://lib.ugent.be/fulltxt/RUG01/001/308/052/RUG01-001308052\_2010\_0001\_AC.pdf},
  year         = {2009},
}

Chicago
Warlop, Nele. 2009. “Alternative Neuropsychological and Magnetic Resonance Imaging Measures in Multiple Sclerosis: Exploring the Relation Between Brain Lesion Measured by Diffusion Tensor Magnetic Resonance Imaging and Interhemispheric Communication and Processing Speed in Multiple Sclerosis”. Gent.
APA
Warlop, N. (2009). Alternative Neuropsychological and Magnetic Resonance Imaging Measures in Multiple Sclerosis: Exploring the relation between brain lesion measured by diffusion tensor magnetic resonance imaging and interhemispheric communication and processing speed in multiple sclerosis. Gent.
Vancouver
1.
Warlop N. Alternative Neuropsychological and Magnetic Resonance Imaging Measures in Multiple Sclerosis: Exploring the relation between brain lesion measured by diffusion tensor magnetic resonance imaging and interhemispheric communication and processing speed in multiple sclerosis. [Gent]; 2009.
MLA
Warlop, Nele. “Alternative Neuropsychological and Magnetic Resonance Imaging Measures in Multiple Sclerosis: Exploring the Relation Between Brain Lesion Measured by Diffusion Tensor Magnetic Resonance Imaging and Interhemispheric Communication and Processing Speed in Multiple Sclerosis.” 2009 : n. pag. Print.