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The association between alterations of eye movement control and cerebral intrinsic functional connectivity in Parkinson’s disease

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Abstract

Patients with Parkinson’s disease (PD) present with eye movement disturbances that accompany the cardinal motor symptoms. Previous studies have consistently found evidence that large-scale functional networks are critically involved in eye movement control. We challenged the hypothesis that altered eye movement control in patients with PD is closely related to alterations of whole-brain functional connectivity in association with the neurodegenerative process. Saccadic and pursuit eye movements by video-oculography and ‘resting-state’ functional MRI (3 Tesla) were recorded from 53 subjects, i.e. 31 patients with PD and 22 matched healthy controls. Video-oculographically, a broad spectrum of eye movement impairments was demonstrated in PD patients vs. controls, including interrupted smooth pursuit, hypometric saccades, and a high distractibility in anti-saccades. Significant correlations between altered oculomotor parameters and functional connectivity measures were observed, i.e. the worse the oculomotor performance was, the more the regional functional connectivity in cortical, limbic, thalamic, cerebellar, and brainstem areas was decreased. Remarkably, decreased connectivity between major nodes of the default mode network was tightly correlated with the prevalence of saccadic intrusions as a measure for distractability. In conclusion, dysfunctional eye movement control in PD seems to be primarily associated with (cortical) executive deficits, rather than being related to the ponto-cerebellar circuits or the oculomotor brainstem nuclei. Worsened eye movement performance together with the potential pathophysiological substrate of decreased intrinsic functional connectivity in predominantly oculomotor-associated cerebral functional networks may constitute a behavioral marker in PD.

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Acknowledgments

Data were generated within the LANDSCAPE study (Representatives: Prof. Dr. R. Dodel, Prof. Dr. D. Berg, Prof. Dr. R. Hilker-Roggendorf, Prof. Dr. E. Kalbe, Prof. Dr. J. Kassubek, Prof. Dr. B. Mollenhauer, Prof. Dr. J. Schulz, Dr. A. Spottke, Prof. Dr. A. Storch, Prof. Dr. H.-U. Wittchen). The LANDSCAPE study is part of the Competence Network Degenerative Dementias (KNDD) which was funded by the German Federal Ministry of Education and Research (project number 01GI1008C). The authors thank Prof. Dr. W. Becker and Dr. R. Jürgens for their helpful support in video-oculographic data analysis. We also thank S. Fuchs for the MRI data acquisition, R. Kühne for his technical support in the oculomotor measurements as well as D. Hueske and S. Schüle for their administration assistance.

Disclosures

Martin Gorges, Hans-Peter Müller, Dorothée Lulé, Elmar H. Pinkhardt, Albert C. Ludolph, and Jan Kassubek declare no conflicts of interest. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients for being included in the study. Additional informed consent was obtained from all patients for which identifying information is included in this article.

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  1. Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany

    Martin Gorges, Hans-Peter Müller, Dorothée Lulé, Elmar H. Pinkhardt, Albert C. Ludolph & Jan Kassubek

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  1. Martin Gorges
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Gorges, M., Müller, HP., Lulé, D. et al. The association between alterations of eye movement control and cerebral intrinsic functional connectivity in Parkinson’s disease. Brain Imaging and Behavior 10, 79–91 (2016). https://doi.org/10.1007/s11682-015-9367-7

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