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Antisaccade errors reveal cognitive control deficits in Parkinson’s disease with freezing of gait

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Abstract

Freezing of gait is a poorly understood symptom of Parkinson’s disease (PD) that is commonly accompanied by executive dysfunction. This study employed an antisaccade task to measure deficits in inhibitory control in patients with freezing, and to determine if these are associated with a specific pattern of grey matter loss using voxel-based morphometry. PD patients with (n = 15) and without (n = 11) freezing along with 10 age-matched controls were included. A simple prosaccade task was administered, followed by a second antisaccade task that required subjects to either look towards or away from a peripheral target. Behavioral results from the antisaccade task were entered as covariates in the voxel-based morphometry analysis. Patient and control groups performed equally well on the first task. However, patients with freezing were significantly worse on the second, which was driven by a specific impairment in suppressing their responses toward the target on the antisaccade trials. Impaired antisaccade performance was associated with grey matter loss across bilateral visual and fronto-parietal regions. These results suggest that patients with freezing have a significant deficit of inhibitory control that is associated with volume reductions in regions crucial for orchestrating both complex motor behaviors and cognitive control. These findings highlight the inter-relationship between freezing of gait and cognition and confirm that dysfunction along common neural pathways is likely to mediate the widespread cognitive dysfunction that emerges with this symptom.

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Acknowledgments

We thank the patients and their families who contribute to our research at the Parkinson’s Disease Research Clinic. We also thank Mr. David Foxe for his help collecting some of the data used in the study.

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Authors and Affiliations

  1. Parkinson’s Disease Research Clinic, Brain and Mind Centre, University of Sydney, 94 Mallett Street, Camperdown, NSW, Australia

    Courtney C. Walton, Claire O’Callaghan, Julie M. Hall, Moran Gilat, Loren Mowszowski, Sharon L. Naismith & Simon J. G. Lewis

  2. Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK

    Claire O’Callaghan

  3. School of Social Sciences and Psychology, Western Sydney University, Parramatta, NSW, Australia

    Julie M. Hall

  4. Healthy Brain Ageing Program, School of Psychology; Brain and Mind Centre & The Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia

    Loren Mowszowski & Sharon L. Naismith

  5. Neuroscience Research Australia, University of New South Wales, Sydney, NSW, Australia

    James R. Burrell & James M. Shine

  6. School of Psychology, Stanford University, Stanford, CA, USA

    James M. Shine

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  1. Courtney C. Walton
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  2. Claire O’Callaghan
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Correspondence to Simon J. G. Lewis.

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Conflicts of interest

CC Walton is supported by an Australian Postgraduate Award at the University of Sydney. C. O’Callaghan is supported by a National Health and Medical Research Council of Australia (NHMRC) Neil Hamilton Fairley Postdoctoral Fellowship (GNT1091310) at the University of Cambridge. J.M. Hall is supported by an International Postgraduate Research Scholarship at the University of Western Sydney. M. Gilat is supported by an International Postgraduate Research Scholarship at the University of Sydney. L. Mowszowski is supported by an Alzheimer’s Australia Dementia Research Foundation Postdoctoral Research Fellowship at the University of Sydney. S.L. Naismith is supported by an NHMRC Career Development Award No. 1008117. J.R. Burrell was supported in part by funding to Forefront, a collaborative research group dedicated to the study of frontotemporal dementia and motor neuron disease, from the NHMRC program Grant (APP1037746) and the Australian Research Council Centre of Excellence in Cognition and its Disorders Memory Node (CE110001021). J.R. Burrell is also supported by an NHMRC Early Career Fellowship (APP1072451). J.M. Shine is supported by a NHMRC CJ Martin Postdoctoral Fellowship (GNT1072403) at Stanford University. S.J.G. Lewis is supported by an NHMRC Practitioner Fellowship No. 1003007.

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Walton, C.C., O’Callaghan, C., Hall, J.M. et al. Antisaccade errors reveal cognitive control deficits in Parkinson’s disease with freezing of gait. J Neurol 262, 2745–2754 (2015). https://doi.org/10.1007/s00415-015-7910-5

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