Abnormal functional connectivity and cortical integrity influence dominant hand motor disability in multiple sclerosis - a multimodal analysis

Background

Previous functional MRI (fMRI) studies involving dominant hand motor tasks suggest functional reorganization occurs in the brains of people with multiple sclerosis (MS) throughout the disease course, potentially explaining the low correlation between structural degeneration and disability [1-4]. However, the relationship between resting state functional connectivity (rsFC) reorganization in the sensorimotor network and motor disability in MS is not clear yet. Such information would improve our understanding of the mechanisms underlying motor impairment and may guide future treatments to preserve functional ability.

Aim

This study investigated changes in rsFC of the left hemisphere hand motor (LM1) region between MS participants with and without right hand dysfunction, compared to healthy controls (HC). Structural abnormalities of grey matter volume and magnetization transfer ratio (MTR) values measured at the global level and within regions with rsFC abnormalities in people with MS, were also investigated.

Data Collection

  • Right-handed participants underwent T1-weighted MRI,T2-weighted MRI, magnetization transfer (MT) images and resting-state functional MRI with their eyes closed.
  • The 9-hole peg test (9HPT) was performed as a measure of hand motor performance outside of the scanner.
  • MS participants were considered as motor preserved (MP) if they scored within two standard deviations (SDs) of published norms [5] with the right hand on the 9HPT and as motor impaired (MI) if they scored two SDs or more.
  • 26 MP, 17 MI, and 20 HCs (age and sex matched)

Statistical Analyses

  • Seed-based correlation [6] for each subject, with the LM1 used as the seed
  • One-way ANCOVA analysis to examine within-group and between-group (MP, MI, HC) comparisons of FC, with age, sex and normalized volume of whole brain grey matter controlled for
  • Normalized volume and MTR values within ROIs calculated and compared between groups
  • Logistic regression analysis

The figure above shows the end-to-end image processing, statistical analysis (hypothesis testing).

Results

The figure below shows the functional network of the LM1 for the HC, MP, and MI groups.

  • Motor preserved MS participants had stronger FC in structurally intact visual information processing regions relative to motor impaired MS participants.
  • Motor impaired MS participants showed weaker FC in the sensorimotor and somatosensory association cortices and more severe structural damage throughout the brain compared with the other groups.
  • Logistic regression analysis showed that regional MTR predicted motor disability beyond the impact of global atrophy whereas regional grey matter volume did not.
  • More importantly, as the first multimodal analysis combining resting-state fMRI,T1-weighted, T2-weighted and MTR images in MS, we demonstrate how a combination of structural and functional changes may contribute to motor impairment or preservation in MS.

For more details of the results please refer to the information section below.

References

  1. Ceccarelli et al., Eur J Neurosci. 2010 (31): 1273-80.
  2. Reddy et al., Brain: a journal of neurology 2002 (125): 2646-57.
  3. Valsasina et al., Eur J Neurosci. 2011 (33): 1256-63.
  4. Rocca et al., Neurology 2002 (58): 866-72.
  5. Oxford et al., Am J Occup Ther. 2003 (57): 570-3.
  6. Fox M.D. et al., Nature reviews Neuroscience 2007 (8): 700-11.

Information

This study is publshed in Human Brain Mapping 37:4262–4275, 2016. For more information please head over to the paper.

Written on June 22, 2016