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Multi-scale resting state functional reorganization in response to multiple sclerosis damage.

Silvia Tommasin1, Laura De Giglio2, Serena Ruggieri1

  • 1Department of Human Neuroscience, Sapienza - University of Rome, Viale dell'Università 30, 00185, Rome, Italy.

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Multiple sclerosis (MS) patients show altered brain functional connectivity (FC). Increased within-network FC may be compensatory, while decreased network integration reflects disability progression.

Keywords:
Functional connectivityGraph theoryMultiple sclerosisPlasticityResting state networks

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Area of Science:

  • Neuroscience
  • Medical Imaging
  • Clinical Neurology

Background:

  • The relationship between brain functional changes and clinical conditions in multiple sclerosis (MS) remains incompletely understood.
  • Investigating functional connectivity (FC) at multiple scales is crucial for understanding MS pathophysiology.

Purpose of the Study:

  • To examine how functional connectivity (FC) reorganization across local, network, and whole-brain scales relates to tissue damage and clinical disability in MS.
  • To differentiate between adaptive and maladaptive functional changes in MS patients compared to healthy controls.

Main Methods:

  • Clinical evaluation of 119 MS patients using the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC).
  • Multimodal 3T MRI, including resting-state functional MRI (rs-fMRI), acquired from MS patients and 42 healthy controls.
  • Independent component analysis (ICA) to identify 16 resting-state networks and measure within-network, between-network, and whole-brain FC.

Main Results:

  • MS patients exhibited higher within-network FC in default mode, frontoparietal, and executive-control networks, correlating with lower clinical impairment.
  • Reduced between-network and whole-brain FC (global efficiency, degree centrality) were observed in MS patients, correlating with higher disability.
  • Combined functional indices derived from altered FC measures showed linear relationships with disease duration, cognitive performance, and lesion load, and non-linear relationships with EDSS.

Conclusions:

  • Combined assessment of multi-scale functional alterations provides a comprehensive view of neuroplasticity in MS.
  • Increased within-network FC likely represents adaptive compensatory mechanisms in MS.
  • Decreased between-network and whole-brain FC suggest impaired functional network integration due to structural damage in MS.