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  • Review Article
  • Published:

Ocular motor signatures of cognitive dysfunction in multiple sclerosis

This article has been updated

Key Points

  • Cognitive dysfunction is a common concomitant of multiple sclerosis (MS), representing the most frequent cause of a patient's loss of gainful employment

  • Ramifying and interactive networks that form the scaffolding for cognition are potential targets of the pathobiological mechanisms that produce injury and disorganization in brain tissue architecture in MS

  • Selected measures of ocular motor function can be used to elucidate the integrity of networks that form the scaffolding for cognition

  • The value of ocular motor assessment lies in the sensitive detection of the often subtle cognitive changes that occur early in disease, longitudinally with disease progression, and in response to treatment

  • The ease of use of the examination methodologies is a further advantage of ocular motor assessment

Abstract

The anatomical and functional overlap between ocular motor command circuitry and the higher-order networks that form the scaffolding for cognition makes for a compelling hypothesis that measures of ocular motility could provide a means to sensitively interrogate cognitive dysfunction in people with multiple sclerosis (MS). Such an approach may ultimately provide objective and reproducible measures of cognitive dysfunction that offer an innovative capability to refine diagnosis, improve prognostication, and more accurately codify disease burden. A further dividend may be the validation and application of biomarkers that can be used in studies aimed at identifying and monitoring preventative, protective and even restorative properties of novel neurotherapeutics in MS. This Review discusses the utility of ocular motor measures in patients with MS to characterize disruption to wide-ranging networks that support cognitive function.

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Figure 1: Primary cortical and subcortical networks responsible for eliciting prosaccades and antisaccades.
Figure 2: Procedure for eliciting prosaccades and antisaccades.

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Change history

  • 29 September 2015

    In the version of this article initially published online, the first sentence of the section 'Ocular motility and cognitive control' was incorrect. The error has been corrected for the print and online versions of the article.

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Acknowledgements

The authors thank Mr Jason Ooi, our medical illustrator, for his dedication, patience, and persistence in working with our team to formulate and render the figures herein. R.L.R. has received research support from the NIH. E.M.F. has received grants from the National Multiple Sclerosis Society (RG 3780A3/3 to E.M.F., PP1485 to E.M.F., RG 4091A3/1 to Robert Fox subcontracted to E.M.F., RG 4212-A-4 to Laura J. Balcer subcontracted to E.M.F.), the National Eye Institute (R01 EY 014993 and R01 EY 019473 to Laura J. Balcer subcontracted to E.M.F.), the Dale Energy Corporation (to E.M.F.), Braxton Debbie Angela Dillon and Skip (DADS) Donor Advisor Fund (to E.M.F.), and Cain Denius MS Research Fund (to E.M.F.).

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O.B.W. and E.M.F. are joint senior authors of this article. J.F., M.C., D.S., A.N.F., N.L., S.K., T.C.F., O.B.W. and E.M.F. researched data for the article. All authors made substantial contributions to discussions of the content. J.F., M.C., S.B., L.M., N.L., J.L., S.K., R.L.R., T.C.F., O.B.W. and E.M.F. wrote the article. J.F., M.C., S.B., D.S., A.N.F., N.L., J.L., S.K., R.L.R., T.C.F., O.B.W. and E.M.F. reviewed and/or edited the manuscript before submission.

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Correspondence to Owen B. White or Elliot M. Frohman.

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J. F., S.K. and O.B.W. have received research support from Bayer, Biogen Idec and Novartis. The other authors declare no competing interests.

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Fielding, J., Clough, M., Beh, S. et al. Ocular motor signatures of cognitive dysfunction in multiple sclerosis. Nat Rev Neurol 11, 637–645 (2015). https://doi.org/10.1038/nrneurol.2015.174

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