Skip to main content
SpringerLink
Log in

Ocular motor measures of cognitive dysfunction in multiple sclerosis I: inhibitory control

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

Abstract

Our ability to control and inhibit behaviours that are inappropriate, unsafe, or no longer required is crucial for functioning successfully in complex environments. Here, we investigated whether a series of ocular motor (OM) inhibition tasks could dissociate deficits in patients with multiple sclerosis (MS), including patients with only a probable diagnosis (clinically isolated syndrome: CIS), from healthy individuals as well as a function of increasing disease duration. 25 patients with CIS, 25 early clinically definite MS patients (CDMS: ≤7 years of diagnosis), 24 late CDMS patients (>7 years from diagnosis), and 25 healthy controls participated. All participants completed a series of classic OM inhibition tasks [antisaccade (AS) task, memory-guided (MG) task, endogenous cue task], and a neuropsychological inhibition task [paced auditory serial addition test (PASAT)]. Clinical disability was characterised in CDMS patients using the Expanded Disability Severity Scale (EDSS). OM (latency and error) and PASAT performance were compared between patient groups and controls, as well as a function of disease duration. For CDMS patients only, results were correlated with EDSS score. All patient groups made more errors than controls on all OM tasks; error rate did not increase with increasing disease duration. In contrast, saccade latency (MG and endogenous cue tasks) was found to worsen with increasing disease duration. PASAT performance did not discriminate patient groups or disease duration. The EDSS did not correlate with any measure. These OM measures appear to dissociate deficit between patients at different disease durations. This suggests their utility as a measure of progression from the earliest inception of the disease.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Schippling S (2009) Differential Diagnosis and Therapy of CIS. Aktuelle Neurol 36:S239–S241. doi:10.1055/s-0029-1220408

    Article  Google Scholar 

  2. Kocak M (2010) Changes in the normal appearing white and grey matter and cognitive impairment in clinically isolated syndrome. Eur J Neurol 17:488

    Google Scholar 

  3. Fooladi M, Alam NR, Harirchyan MH, Firuznia K, Oghabian MA, Shakiba M, Rafie B, Bakhtiary M (2007) IEEE Prognostic value of brain tissue pathological changes in patients with clinically isolated syndromes (CIS) suggestive of multiple sclerosis using magnetization transfer ratio (MTR). In: the 29th Annual International Conference of the Engineering in Medicine and Biology Society, Buenos Aires, August 22–29. Proceedings of Annual International Conference of the Ieee Engineering in Medicine and Biology Society. pp 2031–2033. doi:10.1109/iembs.2007.4352718

  4. Caramia F, Pantano P, Di Legge S, Piattella MC, Lenzi D, Paolillo A, Nucciarelli W, Lenzi GL, Bozzao L, Pozzilli C (2002) A longitudinal study of MR diffusion changes in normal appearing white matter of patients with early multiple sclerosis. Magn Reson Imaging 20(5):383–388. doi:10.1016/s0730-725x(02)00519-2

    Article  PubMed  Google Scholar 

  5. Yu CS, Lin FC, Liu YU, Duan YY, Lei H, Li KC (2008) Histogram analysis of diffusion measures in clinically isolated syndromes and relapsing-remitting multiple sclerosis. Eur J Radiol 68(2):328–334. doi:10.1016/j.ejrad.2007.08.036

    Article  PubMed  Google Scholar 

  6. Calabrese M, Atzori M, Bernardi V, Morra A, Romualdi C, Rinaldi L, McAuliffe MJM, Barachino L, Perini P, Fischl B, Battistin L, Gallo P (2007) Cortical atrophy is relevant in multiple sclerosis at clinical onset. J Neurol 254(9):1212–1220. doi:10.1007/s00415-006-0503-6

    Article  PubMed  Google Scholar 

  7. Amato MP, Portaccio E, Goretti B, Zipoli V, Hakiki B, Giannini M, Pasto L, Razzolini L (2010) Cognitive impairment in early stages of multiple sclerosis. Neurol Sci 31:211–214. doi:10.1007/s10072-010-0376-4

    Article  Google Scholar 

  8. Simioni S, Ruffieux C, Bruggimann L, Annoni FM, Schluep M (2007) Cognition, mood and fatigue in patients in the early stage of multiple sclerosis. Swiss Med Wkly 137(35–36):496–501

    CAS  PubMed  Google Scholar 

  9. Summers M, Swanton J, Fernando K, Dalton C, Miller DH, Cipolotti L, Ron MA (2008) Cognitive impairment in multiple sclerosis can be predicted by imaging early in the disease. J Neurol Neurosurg Psychiatry 79(8):955–958. doi:10.1136/jnnp.2007.138685

    Article  CAS  PubMed  Google Scholar 

  10. Potagas C, Giogkaraki E, Koutsis G, Mandellos D, Tsirempolou E, Sfagos C, Vassilopoulos D (2008) Cognitive impairment in different MS subtypes and clinically isolated syndromes. J Neurol Sci 267(1–2):100–106. doi:10.1016/j.jns.2007.10.002

    Article  PubMed  Google Scholar 

  11. Achiron A, Barak Y (2003) Cognitive impairment in probable multiple sclerosis. J Neurol Neurosurg Psychiatry 74(4):443–446

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Feuillet L, Reuter F, Audoin B, Malikova I, Barrau K, Cherif AA, Pelletier J (2007) Early cognitive impairment in patients with clinically isolated syndrome suggestive of multiple sclerosis. Mult Scler 13(1):124–127. doi:10.1177/1352458506071196

    Article  CAS  PubMed  Google Scholar 

  13. Glanz BI, Holland CM, Gauthier SA, Amunwa EL, Liptak Z, Houtchens MK, Sperling RA, Khoury SJ, Guttmann CRG, Weiner HL (2007) Cognitive dysfunction in patients with clinically isolated syndromes or newly diagnosed multiple sclerosis. Mult Scler 13(8):1004–1010. doi:10.1177/1352458507077943

    Article  CAS  PubMed  Google Scholar 

  14. Anhoque CF, Domingues SCA, Teixeira AL, Domingues RB (2010) Cognitive impairment in clinically isolated syndrome: a systematic review. Dement Neuropsychol 4(2):86–90

    Google Scholar 

  15. Assouad R, Viret AC, Bensa C, Gueguen A, Lecanuet P, Moulignier A, Stankoff B, Arnaud C, Gout O (2010) Cognitive impairment in patients with clinically isolated syndrome: a reappraisal after 8 years. Neurology 74(9):A362–A362

    Google Scholar 

  16. Forn C, Bosca I, Bellonch V, Casanova B, Avila C (2009) Cognitive impairment in patients with clinically isolated syndrome: and fMRI study. Eur J Neurol 16:255

    Google Scholar 

  17. Henry RG, Shieh M, Amirbekian B, Chung SW, Okuda DT, Pelletier D (2009) Connecting white matter injury and thalamic atrophy in clinically isolated syndromes. J Neurol Sci 282(1–2):61–66. doi:10.1016/j.jns.2009.02.379

    Article  PubMed  Google Scholar 

  18. Henry RG, Shieh M, Okuda DT, Evangelista A, Gorno-Tempini ML, Pelletier D (2008) Regional grey matter atrophy in clinically isolated syndromes at presentation. J Neurol Neurosurg Psychiatry 79(11):1236–1244. doi:10.1136/jnnp.2007.134825

    Article  CAS  PubMed  Google Scholar 

  19. Hutton SB (2008) Cognitive control of eye movements. Brain Cogn 68(3):327–340

    Article  CAS  PubMed  Google Scholar 

  20. Ballanger B (2009) Top-down control of saccades as part of a generalized model of proactive inhibitory control. J Neurophysiol 102:2578–2580

    Article  PubMed  Google Scholar 

  21. Lo C-C, Boucher L, Pare M, Schall JD, Wang X-J (2009) Proactive inhibitory control and attractor dynamics in countermanding action: a spiking neural circuit model. J Neurosci 29(28):9059–9071

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Grosbras MN, Laird AR, Paus T (2005) Cortical regions involved in eye movements, shifts of attention, and gaze perception. Hum Brain Mapp 25(1):140–154

    Article  PubMed  Google Scholar 

  23. Fielding J, Kilpatrick T, Millist L, White O (2009) Antisaccade performance in patients with multiple sclerosis. Cortex 45(7):900–903

    Article  PubMed  Google Scholar 

  24. Fielding J, Kilpatrick T, Millist L, White O (2009) Control of visually guided saccades in multiple sclerosis: disruption to higher-order processes. Neuropsychologia 47(7):1647–1653

    Article  PubMed  Google Scholar 

  25. Fielding J, Kilpatrick T, Millist L, White O (2009) Multiple sclerosis: cognition and saccadic eye movements. J Neurol Sci 277(1–2):32–36

    Article  PubMed  Google Scholar 

  26. Nelson H, Willison J (1991) The revised national adult reading test–test manual. NFER-Nelson, Windsor

    Google Scholar 

  27. Beck AT, Steer RA (1987) Manual for the revised Beck Depression Inventory. Psychological Corporation, San Antonio

    Google Scholar 

  28. Gronwall DMA (1977) Paced Auditory Serial Addition Task (PASAT). Department of Psychology, University of Victoria, Victoria, Canada

  29. Reddi BAJ, Asrress KN, Carpenter RHS (2002) Accuracy, information, and response time in a saccadic decision task. J Neurophysiol 90:3538–3546

    Article  Google Scholar 

  30. Vitkovitch M, Bishop S, Dancey C, Richards A (2002) Stroop interference and negative priming in patients with multiple sclerosis. Neuropsychologia 40(9):1570–1576. doi:10.1016/S0028-3932(02)00022-2

    Article  PubMed  Google Scholar 

  31. Rao SM, Staubinfaubert P, Leo GJ (1989) Information-processing speed in patients with multiple-sclerosis. J Clin Exp Neuropsychol 11(4):471–477. doi:10.1080/01688638908400907

    Article  CAS  PubMed  Google Scholar 

  32. Bodling AM, Denney DR, Lynch SG (2012) Individual variability in speed of information processing: an index of cognitive impairment in multiple sclerosis. Neuropsychology 26(3):357–367. doi:10.1037/A0027972

    Article  PubMed  Google Scholar 

  33. Dong W, Yan B, Johnson BP, Millist L, Davis S, Fielding J, White OB (2013) Ischaemic stroke: the ocular motor system as a sensitive marker for motor and cognitive recovery. J Neurol Neurosurg Psychiatry 84(3):337–341. doi:10.1136/Jnnp-2012-303926

    Article  PubMed Central  PubMed  Google Scholar 

  34. Fielding J, Kilpatrick T, Millist L, Clough M, White O (2012) Longitudinal assessment of antisaccades in patients with multiple sclerosis. PLoS One 7(2):e30475. doi:10.1371/journal.pone.0030475

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank all the participants who gave up their time and conscientiously completed each task. We would also like to thank Bayer, Australia for providing the financial support for this study. This study was funded by Bayer, Australia. The authors are deeply grateful to Mr. Jason Thean Kit Ooi, for his patience, dedication, perseverance, and hard work on the creation of the medical illustrations contained within this two-part series on cognitive abnormalities in MS.

Conflicts of interest

Meaghan Clough, Nathaniel Lizak and Lynette Millist declare that they have no conflicts of interest. Dr. Owen White reports grants from Bayer, Australia, during the conduct of the study; personal fees from Bayer, Australia, grants from Biogen, grants and personal fees from Novartis, personal fees from Genzyme, outside the submitted work. Dr. Joanne Fielding reports grants from Bayer, Australia, during the conduct of the study; grants from Biogen, grants from Novartis, outside the submitted work. Teresa Frohman has received speaker and consulting fees from Novartis, Genzyme, and Acorda. Dr. Elliot Frohman has received speaker and consulting fees from Novartis, Genzyme, and Acorda.

Ethical standard

All human studies have been approved by the appropriate ethics committee and have, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons involved in this study gave their informed consent prior to their inclusion in the study.

Author information

Authors and Affiliations

  1. School of Psychological Sciences, Monash University, Clayton, Australia

    Meaghan Clough, Nathaniel Lizak & Joanne Fielding

  2. Department of Neurology, Royal Melbourne Hospital, Parkville, Australia

    Lynette Millist, Nathaniel Lizak & Owen B. White

  3. Department of Medicine, University of Melbourne, Parkville, Australia

    Lynette Millist, Owen B. White & Joanne Fielding

  4. Department of Neurology and Neurotherapeutics and Ophthalmology, University of Texas Southwestern School of Medicine, Dallas, USA

    Elliot M. Frohman

  5. Department of Neurology and Neurotherapeutics, University of Texas Southwestern School of Medicine, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA

    Shin Beh & Teresa C. Frohman

Authors
  1. Meaghan Clough
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lynette Millist
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nathaniel Lizak
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shin Beh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Teresa C. Frohman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elliot M. Frohman
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Owen B. White
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Joanne Fielding
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elliot M. Frohman.

Additional information

This study is part of a larger longitudinal study that is sponsored by Bayer.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Clough, M., Millist, L., Lizak, N. et al. Ocular motor measures of cognitive dysfunction in multiple sclerosis I: inhibitory control. J Neurol 262, 1130–1137 (2015). https://doi.org/10.1007/s00415-015-7645-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-015-7645-3

Keywords

Search

Navigation