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Background <p>Functional neuroplasticity likely occurs following cognitive rehabilitation (CR) and aerobic exercise (EX) in progressive multiple sclerosis (PMS). We explored network resting state (RS) functional connectivity (FC) changes and associations with cognitive measure modifications in CogEx study participants.</p> Methods <p>Patients with PMS were randomly assigned to four groups and underwent 12&#xa0;weeks of treatment with a combination of CR and EX or sham therapies. Cognitive and fMRI assessments were performed at baseline, immediately post-intervention (week-12) and 6&#xa0;months post-intervention (month-9). RS FC within the main cognitive brain networks was extracted and compared between groups at whole-network and voxel-wise levels and correlated with cognitive changes.</p> Results <p>We included 87 PMS patients with moderate-to-severe disability (Expanded Disability Status Scale score 4.0–6.5). There were no differences in whole-network RS FC between the four groups. When comparing patients performing CR <i>vs</i> CR-S, we found increased salience (<i>p</i> = 0.01) and default-mode network (<i>p</i> = 0.02) RS FC at week-12, and increased left (<i>p</i> = 0.05) and right frontoparietal network (<i>p</i> = 0.04) RS FC at month-9 in CR compared with CR-S groups. Increased default-mode network RS FC correlated weakly with increased verbal memory in CR (rho = 0.27, <i>p</i> = 0.06). At voxel-wise level, we found increased RS FC in most analyzed networks in CR groups (<i>p</i> &lt; 0.001, uncorrected) and decreased RS FC in CR-S groups at week-12 (<i>p</i> &lt; 0.05, family-wise error corrected).</p> Conclusions <p>CR modulated RS FC in cognitive networks of patients with PMS, suggesting treatment-related functional plasticity of large-scale networks even in late, disabling MS phases. These network-level changes may reflect neural processes that support cognitive improvement following CR.</p>

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Increased functional network connectivity following cognitive rehabilitation in progressive multiple sclerosis with moderate to severe disabilty: findings from the CogEx study

  • 期刊论文

  • 发表日期：

    2026年5月21日

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  • Francesco Romanò,
  • Paola Valsasina,
  • Matteo Albergoni,
  • Maria Pia Amato,
  • Giampaolo Brichetto,
  • Jeremy Chataway,
  • Nancy D. Chiaravalloti,
  • Gary Cutter,
  • Ulrik Dalgas,
  • John DeLuca,
  • Rachel Farrell,
  • Peter Feys,
  • Jennifer Freeman,
  • Matilde Inglese,
  • Emilio Cipriano,
  • Cecilia Meza,
  • Robert W. Motl,
  • Amber Salter,
  • Brian M. Sandroff,
  • Anthony Feinstein,
  • Maria A. Rocca,
  • Massimo Filippi,
  • Anne Sophie Michelsen,
  • Laurits Emil Taul Madsen,
  • Marie-Louise Kjeldgaard Jørgensen,
  • Mette Dahl Diedmann,
  • Charly Keytsman,
  • Ellen Vanzeir,
  • Joke Lenaerts,
  • Leen Knevels,
  • Mieke D’Hooge,
  • Natasja De Weerdt,
  • Renee Veldkamp,
  • Rudi Donnee,
  • Séline Vandecasteele,
  • Veerle Vandael,
  • Claudio Cordani,
  • Paola Valsasina,
  • Carmen Vizzino,
  • Nicolò Tedone,
  • Paolo Preziosa,
  • Jessica Podda,
  • Ludovico Pedullà,
  • Andrea Tacchino,
  • Angela Smith,
  • Blake Bichler,
  • Jimmy Morecraft,
  • Michael DiBenedetto,
  • Nancy Moore,
  • Catherine Holme,
  • Chris Cole,
  • Kimberley Algie,
  • Sara Chatfield,
  • Juliana Puopolo,
  • Laura Kenton,
  • Laura Toll,
  • Ashlie Kristin Ithurburn,
  • Brendon Truax,
  • Catherine Danielle Jones,
  • Jessica Baird,
  • Petra Silic,
  • Michelle Koch,
  • Patrizia Pajak,
  • Alexsandra Pietrusz,
  • Catherine Smith,
  • Holly Wilkinson,
  • James Braisher,
  • Marie Braisher,
  • Rebecca Bex Walters,
  • Claudia Niccolai,
  • Guido Pasquini,
  • Irene Mosca,
  • Sara Della Bella,
  • Fedrica Vannetti,
  • Filippo Gerli,
  • Chiara Pollio,
  • Eleonora Colombo,
  • Elisa Pelosin,
  • Maria Cellerino,
  • Matteo Pardini,
  • Roberto Hernandez,
  • Michele Curran

摘要

Background

Functional neuroplasticity likely occurs following cognitive rehabilitation (CR) and aerobic exercise (EX) in progressive multiple sclerosis (PMS). We explored network resting state (RS) functional connectivity (FC) changes and associations with cognitive measure modifications in CogEx study participants.

Methods

Patients with PMS were randomly assigned to four groups and underwent 12 weeks of treatment with a combination of CR and EX or sham therapies. Cognitive and fMRI assessments were performed at baseline, immediately post-intervention (week-12) and 6 months post-intervention (month-9). RS FC within the main cognitive brain networks was extracted and compared between groups at whole-network and voxel-wise levels and correlated with cognitive changes.

Results

We included 87 PMS patients with moderate-to-severe disability (Expanded Disability Status Scale score 4.0–6.5). There were no differences in whole-network RS FC between the four groups. When comparing patients performing CR vs CR-S, we found increased salience (p = 0.01) and default-mode network (p = 0.02) RS FC at week-12, and increased left (p = 0.05) and right frontoparietal network (p = 0.04) RS FC at month-9 in CR compared with CR-S groups. Increased default-mode network RS FC correlated weakly with increased verbal memory in CR (rho = 0.27, p = 0.06). At voxel-wise level, we found increased RS FC in most analyzed networks in CR groups (p < 0.001, uncorrected) and decreased RS FC in CR-S groups at week-12 (p < 0.05, family-wise error corrected).

Conclusions

CR modulated RS FC in cognitive networks of patients with PMS, suggesting treatment-related functional plasticity of large-scale networks even in late, disabling MS phases. These network-level changes may reflect neural processes that support cognitive improvement following CR.