Lesion-Based Disconnectome Explains Cognitive Outcomes in Multiple Sclerosis.

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.