Cognitive rehabilitation effects on grey matter volume and Go-NoGo activity in progressive multiple sclerosis: results from the CogEx trial

Maria A. Rocca, Paola Valsasina, Francesco Romanò, Nicolò Tedone, Maria Pia Amato, Giampaolo Brichetto, Vincenzo Daniele Boccia, Jeremy Chataway, Nancy D. Chiaravalloti, Gary Cutter, Ulrik Dalgas, John Deluca, Rachel A. Farrell, Peter Feys, Jennifer Freeman, Matilde Inglese, Cecilia Meza, Robert W. Motl, Amber Salter, Brian M. SandroffAnthony Feinstein, Massimo Filippi

Research output: Contribution to journalArticlepeer-review


Background: Research on cognitive rehabilitation (CR) and aerobic exercise (EX) to improve cognition in progressive multiple sclerosis (PMS) remains limited. CogEx trial investigated the effectiveness of CR and EX in PMS: here, we present MRI substudy volumetric and task-related functional MRI (fMRI) findings. Methods: Participants were randomised to: 'CR plus EX', ' CR plus sham EX (EX-S)', ' EX plus sham CR (CR-S)' and ' CR-S plus EX-S"and attended 12-week intervention. All subjects performed physical/cognitive assessments at baseline, week 12 and 6 months post intervention (month 9). All MRI substudy participants underwent volumetric MRI and fMRI (Go-NoGo task). Results: 104 PMS enrolled at four sites participated in the CogEx MRI substudy; 84 (81%) had valid volumetric MRI and valid fMRI. Week 12/month 9 cognitive performances did not differ among interventions; however, 25-62% of the patients showed Symbol Digit Modalities Test improvements. Normalised cortical grey matter volume (NcGMV) changes at week 12 versus baseline were heterogeneous among interventions (p=0.05); this was mainly driven by increased NcGMV in ' CR plus EX-S' (p=0.02). Groups performing CR (ie, ' CR plus EX' and ' CR plus EX-S') exhibited increased NcGMV over time, especially in the frontal (p=0.01), parietal (p=0.04) and temporal (p=0.04) lobes, while those performing CR-S exhibited NcGMV decrease (p=0.008). In CR groups, increased NcGMV (r=0.36, p=0.01) at week 12 versus baseline correlated with increased California Verbal Learning Test (CVLT)-II scores. ' CR plus EX-S' patients exhibited Go-NoGo activity increase (p<0.05, corrected) at week 12 versus baseline in bilateral insula. Conclusions: In PMS, CR modulated grey matter (GM) volume and insular activity. The association of GM and CVLT-II changes suggests GM plasticity contributes to cognitive improvements. Trial registration number: NCT03679468.

Original languageEnglish (US)
Article numberjnnp-2024-333460
JournalJournal of Neurology, Neurosurgery and psychiatry
StateAccepted/In press - 2024


  • MRI

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology
  • Psychiatry and Mental health


Dive into the research topics of 'Cognitive rehabilitation effects on grey matter volume and Go-NoGo activity in progressive multiple sclerosis: results from the CogEx trial'. Together they form a unique fingerprint.

Cite this