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Lesion-Based Disconnectome Explains Cognitive Outcomes in Multiple Sclerosis

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    Lesion-Based Disconnectome Explains Cognitive Outcomes in Multiple Sclerosis

    ABSTRACT


    Background and Purpose

    Cognitive impairment is common and disabling in multiple sclerosis (MS), yet poorly explained by lesion burden. This study aimed to determine whether the indirect impact of lesions, quantified through disconnectomes, explains multidomain cognitive deficits more effectively than lesion load, and to identify specific white matter tracts underlying these deficits.
    Methods

    Thirty adults with MS completed the Brief International Cognitive Assessment for MS, covering 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 using 3 Tesla fluid-attenuated inversion recovery images and used to estimate tract-specific disconnections and generate voxel-wise disconnectome maps. Tract-specific and voxel-wise analyses were used to identify disconnection patterns associated with cognitive performance.
    Results

    Cognition was impaired across all domains (all p < 0.001). Disconnectome volume was a significant independent determinant of cognitive performance (β = –0.41, p = 0.004), whereas lesion volume was not. Tract-specific analyses revealed distinct disconnection patterns: slower SDMT was associated with left cingulum posterior (β = −0.310, 95% confidence interval [CI] [−0.599, −0.021]); poorer CVLT-II with left arcuate fasciculus (β = −0.232, 95% CI [−0.435, −0.030]); and lower BVMT-R with right cingulum posterior (β = −0.218, 95% CI [−0.383, −0.054]). Voxel-wise analyses identified where the strongest associations between disconnectomes and cognitive performance were located.

    Conclusion


    Lesion-driven disconnection is a more robust determinant of cognitive impairment in MS than lesion burden alone, and disconnectome mapping may help understand the indirect network-level mechanisms underlying cognitive deficits in MS.

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    Yet inside there is this perpetual nagging doubt;
    the feeling we are possessed by a 'subtle lack of togetherness''.

    #2
    Thank you for finding and posting this, Tim.

    I looked up "disconnectome" and here is what AI is saying:

    Only registered and activated users can see links., Click Here To Register...

    Apparently they're saying that "lesion burden" hasn't been a very good way of charting cognitive impairment in MS. I believe that "lesion burden" doesn't just mean the number of white matter lesions found on the MRI. I've noticed how vague those descriptions can be on the MRI reports--it's as if they're not sure how to count them or maybe the exact number just doesn't matter much. You get reports saying "...numerous lesions" or "at least 12 lesions." "Lesion burden" seems to mean, not just how many lesions are found, but where they are located and what type of lesion they are.

    So here we're being told that there are certain connections in the brain that can be mapped, and there are ways of mapping where those connections are broken. Seems to be a new way of looking at those brain lesions.
    Last edited by agate; 09-04-2025, 10:25 AM.
    SPMS diagnosed 1980. Avonex 2001-2004. Copaxone 2006-2009. Glatopa (glatiramer acetate = Copaxone) 12/20 - 3/19/24.

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