Advertisement

Functional MRI to Study Gait Impairment in Parkinson’s Disease: a Systematic Review and Exploratory ALE Meta-Analysis

  • Moran GilatEmail author
  • Bauke W. Dijkstra
  • Nicholas D’Cruz
  • Alice Nieuwboer
  • Simon J. G. Lewis
Neuroimaging (N. Pavese, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Neuroimaging

Abstract

Purpose of Review

Whilst gait impairment is a main cause for disability in Parkinson’s disease (PD), its neural control remains poorly understood. We performed a systematic review and meta-analysis of neuroimaging studies of surrogate features of gait in PD.

Findings

Assessing the results from PET or SPECT scans after a period of actual walking as well as fMRI during mental imagery or virtual reality (VR) gait paradigms, we found a varying pattern of gait-related brain activity. Overall, a decrease in activation of the SMA during gait was found in PD compared to elderly controls. In addition, the meta-analysis showed that the most consistent gait-related activation was situated in the cerebellar locomotor region (CLR) in PD.

Summary

Despite methodological heterogeneity, the combined neuroimaging studies of gait provide new insights into its neural control in PD, suggesting that CLR activation likely serves a compensatory role in locomotion.

Keywords

Parkinson’s disease Gait Neuroimaging Cerebellum Activation of likelihood estimation Meta-analysis 

Notes

Acknowledgements

The authors would like to thank Dr. Robert Hardwick for assisting with the ALE meta-analysis.

Funding

MG is supported by a Postdoctoral Mandate of the KU Leuven Internal Fund; AN and BWD are supported by Flanders Research Funds (G086715N), ND is supported by Jacques & Gloria Gossweiler Foundation, SJGL is supported by a NHMRC–Australia Research Council dementia fellowship (#1110414).

Compliance with Ethical Standards

Conflict of Interest

Moran Gilat, Bauke W. Dijkstra, Nicholas D’Cruz, Alice Nieuwboer and Simon JG Lewis each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Supplementary material

11910_2019_967_MOESM1_ESM.docx (23 kb)
ESM 1 (DOCX 23 kb)

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    • Allali G, Blumen HM, Devanne H, Pirondini E, Delval A, Van De Ville D. Brain imaging of locomotion in neurological conditions. Neurophysiol Clin. 2018;48:337–59 Review of the literature on brain imaging of locomotion in PD and other neurological conditions with pros and cons of different neuroimaging techniques highlighted. CrossRefGoogle Scholar
  2. 2.
    Allen NE, Schwarzel AK, Canning CG. Recurrent falls in Parkinson's disease: a systematic review. Parkinsons Dis. 2013;2013:906274–16.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Bekkers EMJ, Dijkstra BW, Heremans E, Verschueren SMP, Bloem BR, Nieuwboer A. Balancing between the two: are freezing of gait and postural instability in Parkinson's disease connected? Neurosci Biobehav Rev. 2018;94:113–25.CrossRefGoogle Scholar
  4. 4.
    Bloem BR, Hausdorff JM, Visser JE, Giladi N. Falls and freezing of gait in Parkinson's disease: a review of two interconnected, episodic phenomena. Mov Disord. 2004;19:871–84.CrossRefGoogle Scholar
  5. 5.
    • Bluett B, Bayram E, Litvan I. The virtual reality of Parkinson's disease freezing of gait: a systematic review. Parkinsonism Relat Disord. 2018. Systematic review on the different utilities of virtual reality to study freezing of gait in PD, including its ability to be combined with neuroimaging to study the neural underpinnings of freezing. Google Scholar
  6. 6.
    Bohnen NI, Jahn K. Imaging: what can it tell us about parkinsonian gait? Mov Disord. 2013;28:1492–500.CrossRefGoogle Scholar
  7. 7.
    • Bürki CN, Bridenbaugh SA, Reinhardt J, Stippich C, Kressig RW, Blatow M. Imaging gait analysis: An fMRI dual task study. Brain Behav. 2017;7:e00724 Healthy older participants in this study performed two cognitive dual-tasks while simultaneously tapping their feet inside the fMRI scanner. Such paradigms could be used to study the neural basis underlying gait automaticity impairments in PD. CrossRefGoogle Scholar
  8. 8.
    Crémers J, D'Ostilio K, Stamatakis J, Delvaux V, Garraux G. Brain activation pattern related to gait disturbances in Parkinson's disease. Mov Disord. 2012;27:1498–505.CrossRefGoogle Scholar
  9. 9.
    • de Lima-Pardini AC, de Azevedo Neto RM, Coelho DB, Boffino CC, Shergill SS, de Oliveira Souza C, et al. An fMRI-compatible force measurement system for the evaluation of the neural correlates of step initiation. Sci Rep. 2017;7:43088 The authors present a new apparatus that allows for the investigation of anticipatory postural adjustments during fMRI. CrossRefGoogle Scholar
  10. 10.
    Eickhoff SB, Laird AR, Grefkes C, Wang LE, Zilles K, Fox PT. Coordinate-based activation likelihood estimation meta-analysis of neuroimaging data: a random-effects approach based on empirical estimates of spatial uncertainty. Hum Brain Mapp. 2009;30:2907–26.CrossRefGoogle Scholar
  11. 11.
    Eickhoff SB, Bzdok D, Laird AR, Kurth F, Fox PT. Activation likelihood estimation meta-analysis revisited. Neuroimage. 2012;59:2349–61.CrossRefGoogle Scholar
  12. 12.
    •• Eickhoff SB, Nichols TE, Laird AR, Hoffstaedter F, Amunts K, Fox PT, et al. Behavior, sensitivity, and power of activation likelihood estimation characterized by massive empirical simulation. Neuroimage. 2016;137:70–85 Methodological paper by the developers of the ALE meta-analysis technique, presenting simulations on thresholding methods and sample-size requirements. CrossRefGoogle Scholar
  13. 13.
    •• Fasano A, Laganiere SE, Lam S, Fox MD. Lesions causing freezing of gait localize to a cerebellar functional network. Ann Neurol. 2017;81:129–41 This neuroanatomical study showed that the large majority of brain lesions that result in freezing of gait are located in areas that have strong functional connections with the cerebellar locomotor regions. CrossRefGoogle Scholar
  14. 14.
    Fling BW, Cohen RG, Mancini M, Carpenter SD, Fair DA, Nutt JG, et al. Functional reorganization of the locomotor network in Parkinson patients with freezing of gait. PLoS One. 2014;9:e100291.CrossRefGoogle Scholar
  15. 15.
    Gilat M, Shine JM, Walton CC, O'Callaghan C, Hall JM, Lewis SJG. Brain activation underlying turning in Parkinson's disease patients with and without freezing of gait: a virtual reality fMRI study. Nat Partner J Parkinsons Dis. 2015; 1. Available from: http://www.nature.com/articles/npjparkd201520. Accessed 12 Mar 2018
  16. 16.
    Gilat M, Bell PT, Ehgoetz Martens KA, Georgiades MJ, Hall JM, Walton CC, et al. Dopamine depletion impairs gait automaticity by altering cortico-striatal and cerebellar processing in Parkinson's disease. Neuroimage. 2017;152:207–20.CrossRefGoogle Scholar
  17. 17.
    Gilat M, Lígia Silva de Lima A, Bloem BR, Shine JM, Nonnekes J, Lewis SJG. Freezing of gait: promising avenues for future treatment. Parkinsonism Relat Disord. 2018;52:7–16.CrossRefGoogle Scholar
  18. 18.
    Hanakawa T, Fukuyama H, Katsumi Y, Honda M, Shibasaki H. Enhanced lateral premotor activity during paradoxical gait in Parkinson's disease. Ann Neurol. 1999a;45:329–36.CrossRefGoogle Scholar
  19. 19.
    Hanakawa T, Katsumi Y, Fukuyama H, Honda M, Hayashi T, Kimura J, et al. Mechanisms underlying gait disturbance in Parkinson's disease: a single photon emission computed tomography study. Brain. 1999b;122 (Pt 7:1271–82.CrossRefGoogle Scholar
  20. 20.
    •• Hardwick RM, Caspers S, Eickhoff SB, Swinnen SP. Neural correlates of action: Comparing meta-analyses of imagery, observation, and execution. Neurosci Biobehav Rev. 2018;94:31–44 Systematic review with ALE meta-analysis assessing the neural basis of motor imagery, action observation and motor execution in young healthy adults as derived from fMRI or PET, including locomotor tasks. CrossRefGoogle Scholar
  21. 21.
    Hausdorff JM, Lowenthal J, Herman T, Gruendlinger L, Peretz C, Giladi N. Rhythmic auditory stimulation modulates gait variability in Parkinson's disease. Eur J Neurosci. 2007;26:2369–75.CrossRefGoogle Scholar
  22. 22.
    Jacobs JV, Nutt JG, Carlson-Kuhta P, Stephens M, Horak FB. Knee trembling during freezing of gait represents multiple anticipatory postural adjustments. Exp Neurol. 2009;215:334–41.CrossRefGoogle Scholar
  23. 23.
    Kerr GK, Worringham CJ, Cole MH, Lacherez PF, Wood JM, Silburn PA. Predictors of future falls in Parkinson disease. Neurology. 2010;75:116–24.CrossRefGoogle Scholar
  24. 24.
    Lord S, Galna B, Yarnall AJ, Coleman S, Burn D, Rochester L. Predicting first fall in newly diagnosed Parkinson's disease: insights from a fall-naïve cohort. Mov Disord. 2016;31:1829–36.CrossRefGoogle Scholar
  25. 25.
    Maillet A, Pollak P, Debû B. Imaging gait disorders in parkinsonism: a review. J Neurol Neurosurg Psychiatry. 2012;83:986–93.CrossRefGoogle Scholar
  26. 26.
    Maillet A, Thobois S, Fraix V, Redouté J, Le Bars D, Lavenne F, et al. Neural substrates of levodopa-responsive gait disorders and freezing in advanced Parkinson's disease: a kinesthetic imagery approach. Hum Brain Mapp. 2015;36:959–80.CrossRefGoogle Scholar
  27. 27.
    Matar E, Shine JM, Gilat M, Ehgoetz Martens KA, Ward PB, Frank MJ, et al. Identifying the neural correlates of doorway freezing in Parkinson's disease. Hum Brain Mapp. 2019;40:2055–64.CrossRefGoogle Scholar
  28. 28.
    Michely J, Volz LJ, Barbe MT, Hoffstaedter F, Viswanathan S, Timmermann L, et al. Dopaminergic modulation of motor network dynamics in Parkinson's disease. Brain. 2015;138:664–78.CrossRefGoogle Scholar
  29. 29.
    Nieuwhof F, Bloem BR, Reelick MF, Aarts E, Maidan I, Mirelman A, et al. Impaired dual tasking in Parkinson's disease is associated with reduced focusing of cortico-striatal activity. Brain. 2017;140:1384–98.CrossRefGoogle Scholar
  30. 30.
    Nutt JG, Bloem BR, Giladi N, Hallett M, Horak FB, Nieuwboer A. Freezing of gait: moving forward on a mysterious clinical phenomenon. Lancet Neurol. 2011;10:734–44.CrossRefGoogle Scholar
  31. 31.
    Ouchi Y, Kanno T, Okada H, Yoshikawa E, Futatsubashi M, Nobezawa S, et al. Changes in dopamine availability in the nigrostriatal and mesocortical dopaminergic systems by gait in Parkinson's disease. Brain. 2001;124:784–92.CrossRefGoogle Scholar
  32. 32.
    Peterson DS, Horak FB. Neural control of walking in people with parkinsonism. Physiology (Bethesda). 2016;31:95–107.Google Scholar
  33. 33.
    Peterson DS, Pickett KA, Duncan R, Perlmutter J, Earhart GM. Gait-related brain activity in people with Parkinson disease with freezing of gait. PLoS One. 2014;9:e90634.CrossRefGoogle Scholar
  34. 34.
    Shine JM, Matar E, Ward PB, Bolitho SJ, Gilat M, Pearson M, et al. Exploring the cortical and subcortical functional magnetic resonance imaging changes associated with freezing in Parkinson's disease. Brain. 2013;136:1204–15.CrossRefGoogle Scholar
  35. 35.
    Shulman LM, Gruber-Baldini AL, Anderson KE, Vaughan CG, Reich SG, Fishman PS, et al. The evolution of disability in Parkinson disease. Mov Disord. 2008;23:790–6.CrossRefGoogle Scholar
  36. 36.
    Snijders AH, Leunissen I, Bakker M, Overeem S, Helmich RC, Bloem BR, et al. Gait-related cerebral alterations in patients with Parkinson's disease with freezing of gait. Brain. 2011;134:59–72.CrossRefGoogle Scholar
  37. 37.
    Tard C, Delval A, Devos D, Lopes R, Lenfant P, Dujardin K, et al. Brain metabolic abnormalities during gait with freezing in Parkinson's disease. Neuroscience. 2015;307:281–301.CrossRefGoogle Scholar
  38. 38.
    Turkeltaub PE, Eden GF, Jones KM, Zeffiro TA. Meta-analysis of the functional neuroanatomy of single-word reading: method and validation. Neuroimage. 2002;16:765–80.CrossRefGoogle Scholar
  39. 39.
    van der Hoorn A, Renken RJ, Leenders KL, de Jong BM. Parkinson-related changes of activation in visuomotor brain regions during perceived forward self-motion. PLoS One. 2014;9:e95861.CrossRefGoogle Scholar
  40. 40.
    Walton CC, Shine JM, Hall JM, O'Callaghan C, Mowszowski L, Gilat M, et al. The major impact of freezing of gait on quality of life in Parkinson's disease. J Neurol. 2015;262:108–15.CrossRefGoogle Scholar
  41. 41.
    Weiss PH, Herzog J, Pötter-Nerger M, Falk D, Herzog H, Deuschl G, et al. Subthalamic nucleus stimulation improves parkinsonian gait via brainstem locomotor centers. Mov Disord. 2015;30:1121–5.CrossRefGoogle Scholar
  42. 42.
    Wu T, Hallett M. The cerebellum in Parkinson’s disease. Brain. 2013;136(3):696–709.CrossRefGoogle Scholar
  43. 43.
    Wu T, Hallett M, Chan P. Motor automaticity in Parkinson's disease. Neurobiol. Dis. 2015;82:226–34.CrossRefGoogle Scholar
  44. 44.
    Gilman S, Koeppe RA, Nan B, Wang C-N, Wang X, Junck L, et al. Cerebral cortical and subcortical cholinergic deficits in parkinsoni an syndromes. Neurology. Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. 2010;74:1416–23.CrossRefGoogle Scholar
  45. 45.
    Morton SM, Bastian AJ. Cerebellar contributions to locomotor adaptations during splitbelt treadmill walking. J. Neurosci. Society for Neuroscience. 2006;26:9107–16.CrossRefGoogle Scholar
  46. 46.
    Janssen AM, Munneke MAM, Nonnekes J, van der Kraan T, Nieuwboer A, Toni I, et al. Cerebellar theta burst stimulation does not improve freezing of gait in patients with Parkinson's disease. J. Neurol. Springer Berlin Heidelberg. 2017;264:963–72.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Moran Gilat
    • 1
    Email author
  • Bauke W. Dijkstra
    • 1
  • Nicholas D’Cruz
    • 1
  • Alice Nieuwboer
    • 1
  • Simon J. G. Lewis
    • 2
  1. 1.Department of Rehabilitation SciencesKU LeuvenLeuvenBelgium
  2. 2.Brain and Mind CentreUniversity of SydneySydneyAustralia

Personalised recommendations