Antisaccade errors reveal cognitive control deficits in Parkinson’s disease with freezing of gait
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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.
KeywordsAntisaccades Cognitive control Freezing of gait Parkinson’s disease
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.
Compliance with ethical standards
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.
- 8.Terao Y, Fukuda H, Yugeta A, Hikosaka O, Nomura Y, Segawa M, Hanajima R, Tsuji S, Ugawa Y (2011) Initiation and inhibitory control of saccades with the progression of Parkinson’s disease: changes in three major drives converging on the superior colliculus. Neuropsychologia 49(7):1794–1806. doi: 10.1016/j.neuropsychologia.2011.03.002 CrossRefPubMedGoogle Scholar
- 20.Walton CC, Shine JM, Mowszowski L, Gilat M, Hall JM, O’Callaghan C, Naismith SL, Lewis SJ (2015) Impaired cognitive control in Parkinson’s disease patients with freezing of gait in response to cognitive load. J Neural Transm 122(5):653–660. doi: 10.1007/s00702-014-1271-6 CrossRefPubMedGoogle Scholar
- 23.Tessitore A, Amboni M, Cirillo G, Corbo D, Picillo M, Russo A, Vitale C, Santangelo G, Erro R, Cirillo M, Esposito F, Barone P, Tedeschi G (2012) Regional gray matter atrophy in patients with Parkinson disease and freezing of gait. AJNR Am J Neuroradiol 33(9):1804–1809. doi: 10.3174/ajnr.A3066 CrossRefPubMedGoogle Scholar
- 26.Sunwoo MK, Cho KH, Hong JY, Lee JE, Sohn YH, Lee PH (2013) Thalamic volume and related visual recognition are associated with freezing of gait in non-demented patients with Parkinson’s disease. Parkinsonism Relat Disord 19(12):1106–1109. doi: 10.1016/j.parkreldis.2013.07.023 CrossRefPubMedGoogle Scholar
- 28.Emre M, Aarsland D, Brown R, Burn DJ, Duyckaerts C, Mizuno Y, Broe GA, Cummings J, Dickson DW, Gauthier S, Goldman J, Goetz C, Korczyn A, Lees A, Levy R, Litvan I, McKeith I, Olanow W, Poewe W, Quinn N, Sampaio C, Tolosa E, Dubois B (2007) Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord 22(12):1689–1707. doi: 10.1002/mds.21507 (quiz 1837) CrossRefPubMedGoogle Scholar
- 29.Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N, Movement Disorder Society URTF (2008) Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord 23(15):2129–2170. doi: 10.1002/mds.22340 CrossRefPubMedGoogle Scholar
- 34.Ober JK, Przedpelska-Ober E, Gryncewicz W, Dylak J, Carpenter RHS, Ober JJ (2003) Hand-held system for ambulatory measurement of saccadic durations of neurological patients. In: Gajda J (ed) Modelling and Measurement in Medicine Komitet Biocybernityki i Inzyneierii Biomedycznej PAN, Warsaw, pp 187–198Google Scholar
- 38.Beck A, Steer R, Brown G (1996) Manual for the BDI-II. Psychological Corporation, San AntonioGoogle Scholar
- 40.Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H (2005) The Montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53(4):695–699. doi: 10.1111/j.1532-5415.2005.53221.x CrossRefPubMedGoogle Scholar
- 41.Reitan RM (1979) Manual for administration of neuropsychological test batteries for adults and children. Neuropsychology Laboratory, Indiana University medical CenterGoogle Scholar
- 45.Andersson JL, Jenkinson M, Smith S (2007) Non-linear optimisation. FMRIB technical report TR07JA1. Practice 2007a JunGoogle Scholar
- 49.Matsuda T, Matsuura M, Ohkubo T, Ohkubo H, Matsushima E, Inoue K, Taira M, Kojima T (2004) Functional MRI mapping of brain activation during visually guided saccades and antisaccades: cortical and subcortical networks. Psychiatry Res 131(2):147–155. doi: 10.1016/j.pscychresns.2003.12.007 CrossRefPubMedGoogle Scholar
- 51.Shine JM, Matar E, Ward PB, Frank MJ, Moustafa AA, Pearson M, Naismith SL, Lewis SJ (2013) Freezing of gait in Parkinson’s disease is associated with functional decoupling between the cognitive control network and the basal ganglia. Brain 136(Pt 12):3671–3681. doi: 10.1093/brain/awt272 CrossRefPubMedGoogle Scholar
- 54.Leung IHK, Walton CC, Hallock H, Lewis SJG, Valenzuela M, Lampit A (2015) Cognitive training in Parkinson’s disease: a systematic review and meta-analysis. Neurology. doi: 10.1212/WNL.0000000000002145