SpringerLink
Log in

Structural and functional magnetic resonance imaging correlates of fatigue and dual-task performance in progressive multiple sclerosis

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Background

Frontal cortico-subcortical dysfunction may contribute to fatigue and dual-task impairment of walking and cognition in progressive multiple sclerosis (PMS).

Purpose

To explore the associations among fatigue, dual-task performance and structural and functional abnormalities of frontal cortico-subcortical network in PMS.

Methods

Brain 3 T structural and functional MRI sequences, Modified Fatigue Impact Scale (MFIS), dual-task motor and cognitive performances were obtained from 57 PMS patients and 10 healthy controls (HC). The associations of thalamic, caudate nucleus and dorsolateral prefrontal cortex (DLPFC) atrophy, microstructural abnormalities of their connections and their resting state effective connectivity (RS-EC) with fatigue and dual-task performance were investigated using random forest.

Results

Thirty-seven PMS patients were fatigued (F) (MFIS ≥ 38). Compared to HC, non-fatigued (nF) and F-PMS patients had significantly worse dual-task performance (p ≤ 0.002). Predictors of fatigue (out-of-bag [OOB]-accuracy = 0.754) and its severity (OOB-R2 = 0.247) were higher Expanded Disability Status scale (EDSS) score, lower RS-EC from left-caudate nucleus to left-DLPFC, lower fractional anisotropy between left-caudate nucleus and left-thalamus, higher mean diffusivity between right-caudate nucleus and right-thalamus, and longer disease duration. Microstructural abnormalities in connections among thalami, caudate nuclei and DLPFC, mainly left-lateralized in nF-PMS and more bilateral in F-PMS, higher RS-EC from left-DLPFC to right-DLPFC in nF-PMS and lower RS-EC from left-caudate nucleus to left-DLPFC in F-PMS, higher EDSS score, higher WM lesion volume, and lower cortical volume predicted worse dual-task performances (OOB-R2 from 0.426 to 0.530).

Conclusions

In PMS, structural and functional frontal cortico-subcortical abnormalities contribute to fatigue and worse dual-task performance, with different patterns according to the presence of fatigue.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The dataset used and analyzed during the current study is available from the corresponding author on reasonable request.

References

  1. Marchesi O, Vizzino C, Filippi M, Rocca MA (2022) Current perspectives on the diagnosis and management of fatigue in multiple sclerosis. Expert Rev Neurother 22(8):681–693

    Article  CAS  PubMed  Google Scholar 

  2. Arm J, Ribbons K, Lechner-Scott J, Ramadan S (2019) Evaluation of MS related central fatigue using MR neuroimaging methods: sco** review. J Neurol Sci 400:52–71

    Article  PubMed  Google Scholar 

  3. Bertoli M, Tecchio F (2020) Fatigue in multiple sclerosis: does the functional or structural damage prevail? Mult Scler 26(14):1809–1815

    Article  PubMed  Google Scholar 

  4. Filippi M, Preziosa P, Rocca MA (2019) Brain map** in multiple sclerosis: lessons learned about the human brain. Neuroimage 190:32–45

    Article  PubMed  Google Scholar 

  5. Leone C, Feys P, Moumdjian L, D’Amico E, Zappia M, Patti F (2017) Cognitive-motor dual-task interference: a systematic review of neural correlates. Neurosci Biobehav Rev 75:348–360

    Article  PubMed  Google Scholar 

  6. Postigo-Alonso B, Galvao-Carmona A, Benitez I, Conde-Gavilan C, Jover A, Molina S et al (2018) Cognitive-motor interference during gait in patients with multiple sclerosis: a mixed methods systematic review. Neurosci Biobehav Rev 94:126–148

    Article  CAS  PubMed  Google Scholar 

  7. Wajda DA, Sosnoff JJ (2015) Cognitive-motor interference in multiple sclerosis: a systematic review of evidence, correlates, and consequences. Biomed Res Int 2015:720856

    Article  PubMed  PubMed Central  Google Scholar 

  8. Learmonth YC, Ensari I, Motl RW (2017) Cognitive motor interference in multiple sclerosis: insights from a systematic quantitative review. Arch Phys Med Rehabil 98(6):1229–1240

    Article  PubMed  Google Scholar 

  9. Veldkamp R, Goetschalckx M, Hulst HE, Nieuwboer A, Grieten K, Baert I et al (2021) Cognitive-motor interference in individuals with a neurologic disorder: a systematic review of neural correlates. Cogn Behav Neurol 34(2):79–95

    Article  PubMed  Google Scholar 

  10. Hernandez ME, Holtzer R, Chaparro G, Jean K, Balto JM, Sandroff BM et al (2016) Brain activation changes during locomotion in middle-aged to older adults with multiple sclerosis. J Neurol Sci 370:277–283

    Article  PubMed  Google Scholar 

  11. Chaparro G, Balto JM, Sandroff BM, Holtzer R, Izzetoglu M, Motl RW et al (2017) Frontal brain activation changes due to dual-tasking under partial body weight support conditions in older adults with multiple sclerosis. J Neuroeng Rehabil 14(1):65

    Article  PubMed  PubMed Central  Google Scholar 

  12. Saleh S, Sandroff BM, Vitiello T, Owoeye O, Hoxha A, Hake P et al (2018) The Role of premotor areas in dual tasking in healthy controls and persons with multiple sclerosis: an fNIRS imaging study. Front Behav Neurosci 12:296

    Article  PubMed  PubMed Central  Google Scholar 

  13. Wolkorte R, Heersema DJ, Zijdewind I (2015) Reduced dual-task performance in MS patients is further decreased by muscle fatigue. Neurorehabil Neural Repair 29(5):424–435

    Article  PubMed  Google Scholar 

  14. Feinstein A, Amato MP, Brichetto G, Chataway J, Chiaravalloti N, Dalgas U et al (2020) Study protocol: improving cognition in people with progressive multiple sclerosis: a multi-arm, randomized, blinded, sham-controlled trial of cognitive rehabilitation and aerobic exercise (COGEx). BMC Neurol 20(1):204

    Article  PubMed  PubMed Central  Google Scholar 

  15. Lublin FD, Reingold SC, Cohen JA, Cutter GR, Sorensen PS, Thompson AJ et al (2014) Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology 83(3):278–286

    Article  PubMed  PubMed Central  Google Scholar 

  16. Sacco R, Santangelo G, Stamenova S, Bisecco A, Bonavita S, Lavorgna L et al (2016) Psychometric properties and validity of Beck Depression Inventory II in multiple sclerosis. Eur J Neurol 23(4):744–750

    Article  CAS  PubMed  Google Scholar 

  17. Strober L, DeLuca J, Benedict RH, Jacobs A, Cohen JA, Chiaravalloti N et al (2019) Symbol Digit Modalities Test: a valid clinical trial endpoint for measuring cognition in multiple sclerosis. Mult Scler 25(13):1781–1790

    Article  PubMed  Google Scholar 

  18. Fisk JD, Ritvo PG, Ross L, Haase DA, Marrie TJ, Schlech WF (1994) Measuring the functional impact of fatigue: initial validation of the fatigue impact scale. Clin Infect Dis 18(Suppl 1):S79-83

    Article  PubMed  Google Scholar 

  19. Flachenecker P, Kumpfel T, Kallmann B, Gottschalk M, Grauer O, Rieckmann P et al (2002) Fatigue in multiple sclerosis: a comparison of different rating scales and correlation to clinical parameters. Mult Scler 8(6):523–526

    Article  CAS  PubMed  Google Scholar 

  20. Learmonth YC, Sandroff BM, Pilutti LA, Klaren RE, Ensari I, Riskin BJ et al (2014) Cognitive motor interference during walking in multiple sclerosis using an alternate-letter alphabet task. Arch Phys Med Rehabil 95(8):1498–1503

    Article  PubMed  Google Scholar 

  21. Valverde S, Cabezas M, Roura E, Gonzalez-Villa S, Pareto D, Vilanova JC et al (2017) Improving automated multiple sclerosis lesion segmentation with a cascaded 3D convolutional neural network approach. Neuroimage 155:159–168

    Article  PubMed  Google Scholar 

  22. Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H et al (2004) Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 23(Suppl 1):S208–S219

    Article  PubMed  Google Scholar 

  23. Zhang H, Avants BB, Yushkevich PA, Woo JH, Wang S, McCluskey LF et al (2007) High-dimensional spatial normalization of diffusion tensor images improves the detection of white matter differences: an example study using amyotrophic lateral sclerosis. IEEE Trans Med Imaging 26(11):1585–1597

    Article  CAS  PubMed  Google Scholar 

  24. Zhang H, Yushkevich PA, Rueckert D, Gee JC (2007) Unbiased white matter atlas construction using diffusion tensor images. Med Image Comput Comput Assist Interv 10(Pt 2):211–218

    PubMed  Google Scholar 

  25. Jeurissen B, Tournier JD, Dhollander T, Connelly A, Sijbers J (2014) Multi-tissue constrained spherical deconvolution for improved analysis of multi-shell diffusion MRI data. Neuroimage 103:411–426

    Article  PubMed  Google Scholar 

  26. Pravata E, Zecca C, Sestieri C, Caulo M, Riccitelli GC, Rocca MA et al (2016) Hyperconnectivity of the dorsolateral prefrontal cortex following mental effort in multiple sclerosis patients with cognitive fatigue. Mult Scler 22(13):1665–1675

    Article  PubMed  Google Scholar 

  27. Jaeger S, Paul F, Scheel M, Brandt A, Heine J, Pach D et al (2019) Multiple sclerosis-related fatigue: Altered resting-state functional connectivity of the ventral striatum and dorsolateral prefrontal cortex. Mult Scler 25(4):554–564

    Article  PubMed  Google Scholar 

  28. Friston KJ, Harrison L, Penny W (2003) Dynamic causal modelling. Neuroimage 19(4):1273–1302

    Article  CAS  PubMed  Google Scholar 

  29. Friston KJ, Kahan J, Biswal B, Razi A (2014) A DCM for resting state fMRI. Neuroimage 94:396–407

    Article  PubMed  Google Scholar 

  30. Zeidman P, Jafarian A, Corbin N, Seghier ML, Razi A, Price CJ et al (2019) A guide to group effective connectivity analysis, part 1: first level analysis with DCM for fMRI. Neuroimage 200:174–190

    Article  PubMed  Google Scholar 

  31. Kursa MB, Rudnicki WR (2010) Feature selection with the Boruta Package. J Stat Softw 36(11):1–13

    Article  Google Scholar 

  32. Marchesi O, Vizzino C, Meani A, Conti L, Riccitelli GC, Preziosa P et al (2020) Fatigue in multiple sclerosis patients with different clinical phenotypes: a clinical and magnetic resonance imaging study. Eur J Neurol 27(12):2549–2560

    Article  CAS  PubMed  Google Scholar 

  33. Filippi M, Rocca MA, Colombo B, Falini A, Codella M, Scotti G et al (2002) Functional magnetic resonance imaging correlates of fatigue in multiple sclerosis. Neuroimage 15(3):559–567

    Article  CAS  PubMed  Google Scholar 

  34. DeLuca J, Genova HM, Hillary FG, Wylie G (2008) Neural correlates of cognitive fatigue in multiple sclerosis using functional MRI. J Neurol Sci 270(1–2):28–39

    Article  PubMed  Google Scholar 

  35. Rocca MA, Gatti R, Agosta F, Broglia P, Rossi P, Riboldi E et al (2009) Influence of task complexity during coordinated hand and foot movements in MS patients with and without fatigue. A kinematic and functional MRI study. J Neurol 256(3):470–482

    Article  PubMed  Google Scholar 

  36. Engstrom M, Flensner G, Landtblom AM, Ek AC, Karlsson T (2013) Thalamo-striato-cortical determinants to fatigue in multiple sclerosis. Brain Behav 3(6):715–728

    Article  PubMed  PubMed Central  Google Scholar 

  37. Damasceno A, Damasceno BP, Cendes F (2016) Atrophy of reward-related striatal structures in fatigued MS patients is independent of physical disability. Mult Scler 22(6):822–829

    Article  PubMed  Google Scholar 

  38. Hidalgo de la Cruz M, d’Ambrosio A, Valsasina P, Pagani E, Colombo B, Rodegher M et al (2018) Abnormal functional connectivity of thalamic sub-regions contributes to fatigue in multiple sclerosis. Mult Scler 24(9):1183–1195

    Article  PubMed  Google Scholar 

  39. Genova HM, Rajagopalan V, Deluca J, Das A, Binder A, Arjunan A et al (2013) Examination of cognitive fatigue in multiple sclerosis using functional magnetic resonance imaging and diffusion tensor imaging. PLoS ONE 8(11):e78811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Finke C, Schlichting J, Papazoglou S, Scheel M, Freing A, Soemmer C et al (2015) Altered basal ganglia functional connectivity in multiple sclerosis patients with fatigue. Mult Scler 21(7):925–934

    Article  CAS  PubMed  Google Scholar 

  41. Pardini M, Bonzano L, Bergamino M, Bommarito G, Feraco P, Murugavel A et al (2015) Cingulum bundle alterations underlie subjective fatigue in multiple sclerosis. Mult Scler 21(4):442–447

    Article  PubMed  Google Scholar 

  42. Roelcke U, Kappos L, Lechner-Scott J, Brunnschweiler H, Huber S, Ammann W et al (1997) Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue: a 18F-fluorodeoxyglucose positron emission tomography study. Neurology 48(6):1566–1571

    Article  CAS  PubMed  Google Scholar 

  43. Rocca MA, Meani A, Riccitelli GC, Colombo B, Rodegher M, Falini A et al (2016) Abnormal adaptation over time of motor network recruitment in multiple sclerosis patients with fatigue. Mult Scler 22(9):1144–1153

    Article  PubMed  Google Scholar 

  44. Stephan KE, Friston KJ (2010) Analyzing effective connectivity with functional magnetic resonance imaging. Wiley Interdiscip Rev Cogn Sci 1(3):446–459

    Article  PubMed  PubMed Central  Google Scholar 

  45. Rocca MA, Valsasina P, Colombo B, Martinelli V, Filippi M (2021) Cortico-subcortical functional connectivity modifications in fatigued multiple sclerosis patients treated with fampridine and amantadine. Eur J Neurol 28(7):2249–2258

    Article  PubMed  Google Scholar 

  46. Ruggieri S, Fanelli F, Castelli L, Petsas N, De Giglio L, Prosperini L (2018) Lesion symptom map of cognitive-postural interference in multiple sclerosis. Mult Scler 24(5):653–662

    Article  PubMed  Google Scholar 

  47. Tartaglia MC, Narayanan S, Arnold DL (2008) Mental fatigue alters the pattern and increases the volume of cerebral activation required for a motor task in multiple sclerosis patients with fatigue. Eur J Neurol 15(4):413–419

    Article  CAS  PubMed  Google Scholar 

  48. Chen MH, DeLuca J, Genova HM, Yao B, Wylie GR (2020) Cognitive fatigue is associated with altered functional connectivity in interoceptive and reward pathways in multiple sclerosis. Diagnostics (Basel). 10(11):930

    Article  PubMed  PubMed Central  Google Scholar 

  49. Chen MH, Wylie GR, Sandroff BM, Dacosta-Aguayo R, DeLuca J, Genova HM (2020) Neural mechanisms underlying state mental fatigue in multiple sclerosis: a pilot study. J Neurol 267(8):2372–2382

    Article  PubMed  Google Scholar 

  50. Au Duong MV, Boulanouar K, Audoin B, Treseras S, Ibarrola D, Malikova I et al (2005) Modulation of effective connectivity inside the working memory network in patients at the earliest stage of multiple sclerosis. Neuroimage 24(2):533–538

    Article  CAS  PubMed  Google Scholar 

  51. Dobryakova E, Rocca MA, Valsasina P, Ghezzi A, Colombo B, Martinelli V et al (2016) Abnormalities of the executive control network in multiple sclerosis phenotypes: an fMRI effective connectivity study. Hum Brain Mapp 37(6):2293–2304

    Article  PubMed  PubMed Central  Google Scholar 

  52. Dobryakova E, Rocca MA, Valsasina P, DeLuca J, Filippi M (2017) Altered neural mechanisms of cognitive control in patients with primary progressive multiple sclerosis: an effective connectivity study. Hum Brain Mapp 38(5):2580–2588

    Article  PubMed  PubMed Central  Google Scholar 

  53. Meng D, Welton T, Elsarraj A, Morgan PS, das Nair R, Constantinescu CS et al (2021) Dorsolateral prefrontal circuit effective connectivity mediates the relationship between white matter structure and PASAT-3 performance in multiple sclerosis. Hum Brain Mapp 42(2):495–509

    Article  PubMed  Google Scholar 

  54. Cordani C, Preziosa P, Valsasina P, Meani A, Pagani E, Morozumi T et al (2022) MRI of transcallosal white matter helps to predict motor impairment in multiple sclerosis. Radiology 302(3):639–649

    Article  PubMed  Google Scholar 

Download references

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: this study was funded by a grant from the Multiple Sclerosis Society of Canada (Grant No. #EGID3185) and the National MS Society.

Author information

Author notes

  1. Anthony Feinstein and Massimo Filippi have contributed equally to this work.

Authors and Affiliations

  1. Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Paolo Preziosa, Maria A. Rocca, Elisabetta Pagani, Paola Valsasina, Alessandro Meani & Massimo Filippi

  2. Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Paolo Preziosa, Maria A. Rocca & Massimo Filippi

  3. Vita-Salute San Raffaele University, Milan, Italy

    Paolo Preziosa, Maria A. Rocca & Massimo Filippi

  4. Department NEUROFARBA, Section Neurosciences, University of Florence, Florence, Italy

    Maria Pia Amato

  5. IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy

    Maria Pia Amato

  6. Scientific Research Area, Italian Multiple Sclerosis Foundation (FISM), Genoa, Italy

    Giampaolo Brichetto

  7. AISM Rehabilitation Service, Italian Multiple Sclerosis Society, Genoa, Italy

    Giampaolo Brichetto

  8. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy

    Nicolò Bruschi & Matilde Inglese

  9. Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK

    Jeremy Chataway & Rachel Farrell

  10. National Institute for Health Research, Biomedical Research Centre, University College London Hospitals, London, UK

    Jeremy Chataway & Rachel Farrell

  11. Kessler Foundation, West Orange, NJ, USA

    Nancy D. Chiaravalloti, John DeLuca & Brian M. Sandroff

  12. Department of Physical Medicine and Rehabilitation, Rutgers NJ Medical School, Newark, NJ, USA

    Nancy D. Chiaravalloti, John DeLuca & Brian M. Sandroff

  13. Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA

    Gary Cutter

  14. Exercise Biology, Department of Public Health, Aarhus University, Aarhus, Denmark

    Ulrik Dalgas

  15. REVAL, Faculty of Rehabilitation Sciences, Hasselt University, Diepenbeek, Belgium

    Peter Feys

  16. Faculty of Health, School of Health Professions, University of Plymouth, Plymouth, UK

    Jennifer Freeman

  17. IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Matilde Inglese

  18. Department of Psychiatry, University of Toronto and Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Cecilia Meza & Anthony Feinstein

  19. Department of Kinesiology and Nutrition, University of Illinois Chicago, Chicago, IL, USA

    Robert W. Motl

  20. Department of Neurology, Section on Statistical Planning and Analysis, UT Southwestern Medical Center, Dallas, TX, USA

    Amber Salter

Authors
  1. Paolo Preziosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria A. Rocca
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elisabetta Pagani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paola Valsasina
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria Pia Amato
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Giampaolo Brichetto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nicolò Bruschi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jeremy Chataway
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nancy D. Chiaravalloti
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Gary Cutter
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ulrik Dalgas
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. John DeLuca
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Rachel Farrell
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Peter Feys
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Jennifer Freeman
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Matilde Inglese
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Alessandro Meani
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Cecilia Meza
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Robert W. Motl
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Amber Salter
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Brian M. Sandroff
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Anthony Feinstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Massimo Filippi
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

the CogEx Research Team

Corresponding author

Correspondence to Massimo Filippi.

Ethics declarations

Conflicts of interest

Paolo Preziosa received speaker honoraria from Roche, Biogen, Novartis, Merck Serono, Bristol Myers Squibb and Genzyme. He has received research support from Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla. Maria Assunta Rocca received speaker honoraria from Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva, and receives research support from the MS Society of Canada and Fondazione Italiana Sclerosi Multipla. Elisabetta Pagani, Paola Valsasina, Nicolò Bruschi, Alessandro Meani, Cecilia Meza, Robert W. Motl and Brian Sandroff have nothing to disclose. Maria Pia Amato received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Roche, Pharmaceutical Industries and Fondazione Italiana Sclerosi Multipla. Giampaolo Brichetto has been awarded and receives research support from Roche, Fondazione Italiana Sclerosi Multipla, ARSEP, H2020 EU Call. Jeremy Chataway has received support from the Efficacy and Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership and the Health Technology Assessment (HTA) Programme (NIHR), the UK MS Society, the US National MS Society and the Rosetrees Trust. He is supported in part by the NIHR University College London Hospitals (UCLH) Biomedical Research Centre, London, UK. He has been a local principal investigator for a trial in MS funded by the Canadian MS society. A local principal investigator for commercial trials funded by: Actelion, Novartis and Roche; and has taken part in advisory boards/consultancy for Azadyne, Janssen, Merck, NervGen, Novartis and Roche. Nancy D. Chiaravalloti is on an Advisory Board for Akili Interactive and is a member of the Editorial Boards of Multiple Sclerosis Journal and Frontiers in NeuroTrauma. Gary Cutter is a member of Data and Safety Monitoring Boards for Astra-Zeneca, Avexis Pharmaceuticals, Biolinerx, Brainstorm Cell Therapeutics, Bristol Meyers Squibb/Celgene, CSL Behring, Galmed Pharmaceuticals, Horizon Pharmaceuticals,Hisun Pharmaceuticals, Mapi Pharmaceuticals LTD, Merck, Merck/Pfizer, Opko Biologics, OncoImmune, Neurim, Novartis, Ophazyme, Sanofi Aventis, Reata Pharmaceuticals, Teva pharmaceuticals, VielaBio Inc, Vivus, NHLBI (Protocol Review Committee), NICHD (OPRU oversight committee). He is on Consulting or Advisory Boards for Biodelivery Sciences International, Biogen, Click Therapeutics, Genzyme, Genentech, GW Pharmaceuticals, Klein-Buendel Incorporated, Medimmune, Medday, Neurogenesis LTD, Novartis, Osmotica Pharmaceuticals, Perception Neurosciences, Recursion/Cerexis Pharmaceuticals, Roche, TG Therapeutics. Dr. Cutter is employed by the University of Alabama at Birmingham and President of Pythagoras, Inc. a private consulting company located in Birmingham AL. Ulrik Dalgas has received research support, travel grants, and/or teaching honorary from Biogen Idec, Merck-Serono, Novartis, Bayer Schering, and Sanofi Aventis as well as honoraria from serving on scientific advisory boards of Biogen Idec and Genzyme. John DeLuca is an Associate Editor of the Archives of Physical Medicine and Rehabilitation, and Neuropsychology Review; received compensation for consulting services and/or speaking activities from Biogen Idec, Celgene, MedRhythms, and Novartis; and receives research support from Biogen Idec, National Multiple Sclerosis Society, Consortium of Multiple Sclerosis Centers, and National Institutes of Health. Rachel Farrell has received honoraria and served on advisory panels for Merck, TEVA, Novartis, Genzyme, GW pharma (Jazz pharmaceuticals), Allergan, Merz, Ipsen and Biogen. She is supported in part by the National Institute for Health Research, University College London Hospitals, Biomedical Research Centre, London, UK. Peter Feys is editorial board member of NNR and MSJ, provides consultancy to NeuroCompass and was board of advisory board meetings for BIOGEN. Jennifer Freeman has been awarded research grants from the NIHR, UK. Matilde Inglese is Co-Editor for Controversies for Multiple Sclerosis Journal; received compensation for consulting services and/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme; and received research support from NIH, NMSS, the MS Society of Canada, the Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, H2020 EU Call. Amber Salter receives research funding from Multiple Sclerosis Society of Canada, National Multiple Sclerosis Society, CMSC and the US Department of Defense and is a member of editorial board for Neurology. Anthony Feinstein is on Advisory Boards for Akili Interactive and Roche, and reports grants from the MS Society of Canada, book royalties from Johns Hopkins University Press, Cambridge University Press, Amadeus Press and Glitterati Editions, and speaker’s honoraria from Novartis, Biogen, Roche and Sanofi Genzyme. Massimo Filippi is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Map**, Associate Editor of Radiology, and Associate Editor of Neurological Sciences; received compensation for consulting services and/or speaking activities from Alexion, Almirall, Bayer, Biogen, Celgene, Eli Lilly, Genzyme, Merck-Serono, Novartis, Roche, Sanofi, Takeda, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Ethical approval

Approval was received from the local institutional ethical standards committees on human experimentation for any experiments using human subjects. Written informed consent was obtained from all subjects prior to study participation according to the Declaration of Helsinki.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 35 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Preziosa, P., Rocca, M.A., Pagani, E. et al. Structural and functional magnetic resonance imaging correlates of fatigue and dual-task performance in progressive multiple sclerosis. J Neurol 270, 1543–1563 (2023). https://doi.org/10.1007/s00415-022-11486-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-022-11486-0

Keywords

Search

Navigation