Multiple white matter tract abnormalities underlie cognitive impairment in RRMS

Hui Jing Yu, Christopher Christodoulou, Vikram Bhise, Daniel Greenblatt, Yashma Patel, Dana Serafin, Mirjana Maletic-Savatic, Lauren B. Krupp, Mark E. Wagshul

Research output: Contribution to journalArticle

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Abstract

Diffusion tensor imaging (DTI) is a sensitive tool for detecting microstructural tissue damage . in vivo. In this study, we investigated DTI abnormalities in individuals with relapsing remitting multiple sclerosis (RRMS) and examined the relations between imaging-based measures of white matter injury and cognitive impairment. DTI-derived metrics using tract-based spatial statistics (TBSS) were compared between 37 individuals with RRMS and 20 healthy controls. Cognitive impairment was assessed with three standard tests: the Symbol Digit Modalities Test (SDMT), which measures cognitive processing speed and visual working memory, the Rey Auditory Verbal Learning Test (RAVLT), which examines verbal memory, and the Paced Auditory Serial Addition Test (PASAT), which assesses sustained attention and working memory. Correlations between DTI-metrics and cognition were explored in regions demonstrating significant differences between the RRMS patients and the control group. Lower fractional anisotropy (FA) was found in RRMS participants compared to controls across the tract skeleton (0.40. ±. 0.03 . vs. 0.43. ±. 0.01, p. <. 0.01). In areas of reduced FA, mean diffusivity was increased and was dominated by increased radial diffusivity with no significant change in axial diffusivity, an indication of the role of damage to CNS myelin in MS pathology. In the RRMS group, voxelwise correlations were found between FA reduction and cognitive impairment in cognitively-relevant tracts, predominantly in the posterior thalamic radiation, the sagittal stratum, and the corpus callosum; the strongest correlations were with SDMT measures, with contributions to these associations from both lesion and normal-appearing white matter. Moreover, results using threshold-free cluster enhancement (TFCE) showed more widespread white matter involvement compared to cluster-based thresholding. These findings indicate the important role for DTI in delineating mechanisms underlying MS-associated cognitive impairment and suggest that DTI could play a critical role in monitoring the clinical and cognitive effects of the disease.

Original languageEnglish (US)
Pages (from-to)3713-3722
Number of pages10
JournalNeuroImage
Volume59
Issue number4
DOIs
StatePublished - Feb 15 2012

Fingerprint

Relapsing-Remitting Multiple Sclerosis
Diffusion Tensor Imaging
Anisotropy
Short-Term Memory
Verbal Learning
Corpus Callosum
Myelin Sheath
Skeleton
Cognition
Cognitive Dysfunction
White Matter
Radiation
Pathology
Control Groups
Wounds and Injuries

Keywords

  • Cognitive impairment
  • Diffusion tensor imaging
  • Relapsing remitting multiple sclerosis
  • Threshold-free cluster enhancement
  • Tract-based spatial statistics

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Neurology

Cite this

Yu, H. J., Christodoulou, C., Bhise, V., Greenblatt, D., Patel, Y., Serafin, D., ... Wagshul, M. E. (2012). Multiple white matter tract abnormalities underlie cognitive impairment in RRMS. NeuroImage, 59(4), 3713-3722. https://doi.org/10.1016/j.neuroimage.2011.10.053

Multiple white matter tract abnormalities underlie cognitive impairment in RRMS. / Yu, Hui Jing; Christodoulou, Christopher; Bhise, Vikram; Greenblatt, Daniel; Patel, Yashma; Serafin, Dana; Maletic-Savatic, Mirjana; Krupp, Lauren B.; Wagshul, Mark E.

In: NeuroImage, Vol. 59, No. 4, 15.02.2012, p. 3713-3722.

Research output: Contribution to journalArticle

Yu, HJ, Christodoulou, C, Bhise, V, Greenblatt, D, Patel, Y, Serafin, D, Maletic-Savatic, M, Krupp, LB & Wagshul, ME 2012, 'Multiple white matter tract abnormalities underlie cognitive impairment in RRMS', NeuroImage, vol. 59, no. 4, pp. 3713-3722. https://doi.org/10.1016/j.neuroimage.2011.10.053
Yu HJ, Christodoulou C, Bhise V, Greenblatt D, Patel Y, Serafin D et al. Multiple white matter tract abnormalities underlie cognitive impairment in RRMS. NeuroImage. 2012 Feb 15;59(4):3713-3722. https://doi.org/10.1016/j.neuroimage.2011.10.053
Yu, Hui Jing ; Christodoulou, Christopher ; Bhise, Vikram ; Greenblatt, Daniel ; Patel, Yashma ; Serafin, Dana ; Maletic-Savatic, Mirjana ; Krupp, Lauren B. ; Wagshul, Mark E. / Multiple white matter tract abnormalities underlie cognitive impairment in RRMS. In: NeuroImage. 2012 ; Vol. 59, No. 4. pp. 3713-3722.
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