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Lesion-Based Disconnectome Explains Cognitive Outcomes in Multiple Sclerosis.

Jonadab Dos Santos Silva1,2,3, Claudia C F Vasconcelos4, Carina T Spedo5

  • 1Postgraduate Program in Neurology, Universidade Federal Fluminense, Niterói, Brazil.

Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging
|September 3, 2025
PubMed
Summary

Brain lesion disconnections, not just lesion load, significantly impact cognitive function in multiple sclerosis (MS). Disconnectome mapping reveals specific white matter tracts linked to processing speed, verbal, and visuospatial memory deficits in MS patients.

Keywords:
cognitive impairmentconnectomicsdisconnectomemultiple sclerosisneuroimagingwhite matter

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Area of Science:

  • Neuroscience
  • Neurology
  • Medical Imaging

Background:

  • Cognitive impairment is a significant and disabling symptom in multiple sclerosis (MS).
  • Traditional measures of lesion burden do not fully explain the extent of cognitive deficits observed in MS patients.

Purpose of the Study:

  • To investigate if disconnectomes, representing indirect effects of lesions, better explain multidomain cognitive deficits in MS compared to lesion load.
  • To identify specific white matter tracts associated with cognitive impairments in MS.

Main Methods:

  • Thirty adults with MS underwent cognitive assessments including processing speed (Symbol Digit Modalities Test; SDMT), verbal memory (California Verbal Learning Test-II; CVLT-II), and visuospatial memory (Brief Visuospatial Memory Test-Revised; BVMT-R).
  • Lesions were segmented from 3 Tesla fluid-attenuated inversion recovery MRI scans.
  • Tract-specific disconnections and voxel-wise disconnectome maps were generated to analyze associations with cognitive performance.

Main Results:

  • Cognitive functions were impaired across all assessed domains in the MS cohort (p < 0.001).
  • Disconnectome volume significantly predicted cognitive performance (β = -0.41, p = 0.004), outperforming lesion volume as a determinant.
  • Specific white matter tracts were linked to distinct cognitive deficits: left cingulum posterior for SDMT, left arcuate fasciculus for CVLT-II, and right cingulum posterior for BVMT-R.

Conclusions:

  • Lesion-driven disconnection is a more significant factor in MS-related cognitive impairment than lesion burden alone.
  • Disconnectome mapping offers a valuable approach to understanding the network-level mechanisms underlying cognitive deficits in MS.