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Multiple sclerosis lesions that impair memory map to a connected memory circuit.

Isaiah Kletenik1,2,3,4, Alexander L Cohen5,6,7,8, Bonnie I Glanz9

  • 1Division of Cognitive and Behavioral Neurology, Brigham and Women's Hospital, 60 Fenwood Road, 9016H, Boston, MA, 02115, USA. ikletenik@bwh.harvard.edu.

Journal of Neurology
|August 2, 2023
PubMed
Summary
This summary is machine-generated.

Memory dysfunction in multiple sclerosis (MS) is linked to white matter lesions in a specific brain circuit, not just overall lesion burden. Damage to this memory circuit fully explains the relationship between lesion volume and memory impairment.

Keywords:
Lesion network mappingMemoryMultiple sclerosisWhite matter lesionfMRI

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Area of Science:

  • Neuroscience
  • Neurology
  • Medical Imaging

Background:

  • Multiple sclerosis (MS) affects nearly 1 million Americans, with 30-50% experiencing memory dysfunction.
  • The neuroanatomical basis of MS-related memory dysfunction remains unclear, with debate on whether it stems from overall white matter lesion load or specific structural damage.

Purpose of the Study:

  • To investigate the association between white matter lesions in specific neuroanatomical circuits and memory dysfunction in patients with MS.
  • To determine if MS memory dysfunction is linked to a particular brain circuit rather than diffuse white matter damage.

Main Methods:

  • Cross-sectional analysis of structural MRI and verbal memory scores from 431 MS patients.
  • Mapping white matter lesion locations using a validated algorithm.
  • Testing associations between memory dysfunction and total lesion volume, and lesion intersection with a predefined memory circuit.
  • Utilizing mediation analyses and data-driven analyses with functional and structural connectomes to identify MS memory circuits.

Main Results:

  • Both total lesion volume and lesion damage within a predefined memory circuit correlated with memory dysfunction.
  • Damage to the memory circuit fully mediated the relationship between total lesion volume and memory performance.
  • Data-driven analysis identified key brain regions, including the hippocampus, parahippocampus, fornix, and cingulate, associated with memory dysfunction, aligning with the predefined circuit.

Conclusions:

  • MS-related memory dysfunction is associated with white matter lesions within a specific brain circuit centered on the hippocampus.
  • Damage to this hippocampal-centered circuit fully explains the impact of overall lesion volume on memory.
  • A circuit-based approach using standard MRI may aid in localizing and predicting higher-order cognitive deficits in MS.