Journal of Neurology

, Volume 264, Issue 1, pp 88–101 | Cite as

Brain plasticity in Parkinson’s disease with freezing of gait induced by action observation training

  • Federica Agosta
  • Roberto Gatti
  • Elisabetta Sarasso
  • Maria Antonietta Volonté
  • Elisa Canu
  • Alessandro Meani
  • Lidia Sarro
  • Massimiliano Copetti
  • Erik Cattrysse
  • Eric Kerckhofs
  • Giancarlo Comi
  • Andrea Falini
  • Massimo FilippiEmail author
Original Communication


Gait disorders represent a therapeutic challenge in Parkinson’s disease (PD). This study investigated the efficacy of 4-week action observation training (AOT) on disease severity, freezing of gait and motor abilities in PD, and evaluated treatment-related brain functional changes. 25 PD patients with freezing of gait were randomized into two groups: AOT (action observation combined with practicing the observed actions) and “Landscape” (same physical training combined with landscape-videos observation). At baseline and 4-week, patients underwent clinical evaluation and fMRI. Clinical assessment was repeated at 8-week. At 4-week, both groups showed reduced freezing of gait severity, improved walking speed and quality of life. Moreover, AOT was associated with reduced motor disability and improved balance. AOT group showed a sustained positive effect on motor disability, walking speed, balance and quality of life at 8-week, with a trend toward a persisting reduced freezing of gait severity. At 4-week vs. baseline, AOT group showed increased recruitment of fronto-parietal areas during fMRI tasks, while the Landscape group showed a reduced fMRI activity of the left postcentral and inferior parietal gyri and right rolandic operculum and supramarginal gyrus. In AOT group, functional brain changes were associated with clinical improvements at 4-week and predicted clinical evolution at 8-week. AOT has a more lasting effect in improving motor function, gait and quality of life in PD patients relative to physical therapy alone. AOT-related performance gains are associated with an increased recruitment of motor regions and fronto-parietal mirror neuron and attentional control areas.


Parkinson’s disease Action observation Gait disorders Freezing of gait Functional MRI 



We thank Dr. Elisa Pelosin for providing us with the video clips used during the training sessions. This study was partially supported by a grant from the Jacques and Gloria Gossweiler Foundation.

Compliance with ethical standards

Conflicts of interest

F Agosta serves on the editorial board of the Journal of Neurology; has received speaker honoraria from EXCEMED– Excellence in Medical Education; and receives research supports from the Italian Ministry of Health, AriSLA (Fondazione Italiana di Ricerca per la SLA), and the European Research Council. R. Gatti, E. Sarasso, M.A. Volonté, E. Canu, A. Meani, L. Sarro, M. Copetti, E. Cattrysse, E. Kerckhofs, and A. Falini report no disclosures. G. Comi has received compensation for consulting services and/or speaking activities from Novartis, Teva Pharmaceutical Ind., Sanofi, Genzyme, Merck Serono, Biogen, Bayer, Actelion, Serono Symposia International Foundation, Almirall, Chugai and Receptos. M. Filippi is Editor-in-Chief of Journal of Neurology; serves on the scientific advisory board of Teva Pharmaceutical Industries; has received compensation for consulting services and/or speaking activities from Biogen Idec, Excemed, Novartis, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Teva Pharmaceutical Industries, Novartis, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, Cure PSP, Alzheimer’s Drug Discovery Foundation (ADDF), the Jacques and Gloria Gossweiler Foundation (Switzerland), and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Supplementary material

415_2016_8309_MOESM1_ESM.pdf (165 kb)
Supplementary material 1 (PDF 165 kb)


  1. 1.
    Nieuwboer A, Giladi N (2013) Characterizing freezing of gait in Parkinson’s disease: models of an episodic phenomenon. Mov Disord 28:1509–1519CrossRefPubMedGoogle Scholar
  2. 2.
    Vandenbossche J, Deroost N, Soetens E, Coomans D, Spildooren J, Vercruysse S, Nieuwboer A, Kerckhofs E (2012) Freezing of gait in Parkinson’s disease: disturbances in automaticity and control. Front Hum Neurosci 6:356PubMedGoogle Scholar
  3. 3.
    Nonnekes J, Snijders AH, Nutt JG, Deuschl G, Giladi N, Bloem BR (2015) Freezing of gait: a practical approach to management. Lancet Neurol 14:768–778CrossRefPubMedGoogle Scholar
  4. 4.
    Buccino G (2014) Action observation treatment: a novel tool in neurorehabilitation. Philos Trans R Soc Lond B Biol Sci 369:20130185CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Rizzolatti G, Craighero L (2004) The mirror-neuron system. Annu Rev Neurosci 27:169–192CrossRefPubMedGoogle Scholar
  6. 6.
    Stefan K, Cohen LG, Duque J, Mazzocchio R, Celnik P, Sawaki L, Ungerleider L, Classen J (2005) Formation of a motor memory by action observation. J Neurosci 25:9339–9346CrossRefPubMedGoogle Scholar
  7. 7.
    Buccino G, Gatti R, Giusti MC, Negrotti A, Rossi A, Calzetti S, Cappa SF (2011) Action observation treatment improves autonomy in daily activities in Parkinson’s disease patients: results from a pilot study. Mov Disord 26:1963–1964CrossRefPubMedGoogle Scholar
  8. 8.
    Pelosin E, Bove M, Ruggeri P, Avanzino L, Abbruzzese G (2013) Reduction of bradykinesia of finger movements by a single session of action observation in Parkinson disease. Neurorehabil Neural Repair 27:552–560CrossRefPubMedGoogle Scholar
  9. 9.
    Pelosin E, Avanzino L, Bove M, Stramesi P, Nieuwboer A, Abbruzzese G (2010) Action observation improves freezing of gait in patients with Parkinson’s disease. Neurorehabil Neural Repair 24:746–752CrossRefPubMedGoogle Scholar
  10. 10.
    Giladi N, Shabtai H, Simon ES, Biran S, Tal J, Korczyn AD (2000) Construction of freezing of gait questionnaire for patients with Parkinsonism. Parkinsonism Relat Disord 6:165–170CrossRefPubMedGoogle Scholar
  11. 11.
    Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17:427–442CrossRefPubMedGoogle Scholar
  12. 12.
    Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198CrossRefPubMedGoogle Scholar
  13. 13.
    Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571CrossRefPubMedGoogle Scholar
  14. 14.
    Orsini A, Grossi D, Capitani E, Laiacona M, Papagno C, Vallar G (1987) Verbal and spatial immediate memory span: normative data from 1355 adults and 1112 children. Ital J Neurol Sci 8:539–548CrossRefPubMedGoogle Scholar
  15. 15.
    Carlesimo GA, Caltagirone C, Gainotti G (1996) The Mental Deterioration Battery: normative data, diagnostic reliability and qualitative analyses of cognitive impairment. The Group for the Standardization of the Mental Deterioration Battery. Eur Neurol 36:378–384CrossRefPubMedGoogle Scholar
  16. 16.
    Caffarra P, Vezzadini G, Dieci F, Zonato F, Venneri A (2002) Rey-Osterrieth complex figure: normative values in an Italian population sample. Neurol Sci 22:443–447CrossRefPubMedGoogle Scholar
  17. 17.
    Novelli G, Papagno C, Capitani E, Laiacona N, Vallar G, Cappa SF (1986) Tre test clinici di ricerca e produzione lessicale. Taratura su soggetti normali. Arch Psicol Neurol Psichiatr 47:477–506Google Scholar
  18. 18.
    Abrahams S, Leigh PN, Harvey A, Vythelingum GN, Grise D, Goldstein LH (2000) Verbal fluency and executive dysfunction in amyotrophic lateral sclerosis (ALS). Neuropsychologia 38:734–747CrossRefPubMedGoogle Scholar
  19. 19.
    Manos PJ (1999) Ten-point clock test sensitivity for Alzheimer’s disease in patients with MMSE scores greater than 23. Int J Geriatr Psychiatry 14:454–458CrossRefPubMedGoogle Scholar
  20. 20.
    Caffarra P, Vezzadini G, Dieci F, Zonato F, Venneri A (2004) Modified card sorting test: normative data. J Clin Exp Neuropsychol 26:246–250CrossRefPubMedGoogle Scholar
  21. 21.
    Monaco M, Costa A, Caltagirone C, Carlesimo GA (2013) Forward and backward span for verbal and visuo-spatial data: standardization and normative data from an Italian adult population. Neurol Sci 34:749–754CrossRefPubMedGoogle Scholar
  22. 22.
    Spinnler H, Tognoni G (1987) Standardizzazione e taratura italiana di test neuropsicologici. Ital J Neurol Sci 6:1–120Google Scholar
  23. 23.
    Giovagnoli AR, Del Pesce M, Mascheroni S, Simoncelli M, Laiacona M, Capitani E (1996) Trail making test: normative values from 287 normal adult controls. Ital J Neurol Sci 17:305–309CrossRefPubMedGoogle Scholar
  24. 24.
    Miceli G, Laudanna A, Burani C, Capasso R (1994) Batteria per l’Analisi del Deficit Afasico. B.A.D.A. [B.A.D.A. A battery for the assessment of aphasic disorders]. CEPSAG, RomaGoogle Scholar
  25. 25.
    De Renzi E, Faglioni P (1978) Normative data and screening power of a shortened version of the Token Test. Cortex 14:41–49CrossRefPubMedGoogle Scholar
  26. 26.
    Mioshi E, Dawson K, Mitchell J, Arnold R, Hodges JR (2006) The Addenbrooke’s Cognitive Examination Revised (ACE-R): a brief cognitive test battery for dementia screening. Int J Geriatr Psychiatry 21:1078–1085CrossRefPubMedGoogle Scholar
  27. 27.
    Fahn S, Elton RL, Committee motUD (1987) Unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Goldstein M, Calne DB (eds) Recent developments in Parkinson’s disease II. MacMillan, New York, pp 153–163Google Scholar
  28. 28.
    Peto V, Jenkinson C, Fitzpatrick R, Greenhall R (1995) The development and validation of a short measure of functioning and well being for individuals with Parkinson’s disease. Qual Life Res 4:241–248CrossRefPubMedGoogle Scholar
  29. 29.
    Franchignoni F, Velozo CA (2005) Use of the Berg Balance Scale in rehabilitation evaluation of patients with Parkinson’s disease. Arch Phys Med Rehabil 86:2225–2226 (author reply 2226) CrossRefPubMedGoogle Scholar
  30. 30.
    Johnston M, de Morton N, Harding K, Taylor N (2013) Measuring mobility in patients living in the community with Parkinson disease. NeuroRehabilitation 32:957–966PubMedGoogle Scholar
  31. 31.
    Worsley KJ, Friston KJ (1995) Analysis of fMRI time-series revisited–again. Neuroimage 2:173–181CrossRefPubMedGoogle Scholar
  32. 32.
    Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, Mazoyer B, Joliot M (2002) Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 15:273–289CrossRefPubMedGoogle Scholar
  33. 33.
    Maldjian JA, Laurienti PJ, Kraft RA, Burdette JH (2003) An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage 19:1233–1239CrossRefPubMedGoogle Scholar
  34. 34.
    Litvan I, Goldman JG, Troster AI, Schmand BA, Weintraub D, Petersen RC, Mollenhauer B, Adler CH, Marder K, Williams-Gray CH, Aarsland D, Kulisevsky J, Rodriguez-Oroz MC, Burn DJ, Barker RA, Emre M (2012) Diagnostic criteria for mild cognitive impairment in Parkinson’s disease: Movement Disorder Society Task Force guidelines. Mov Disord 27:349–356CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Herz DM, Eickhoff SB, Lokkegaard A, Siebner HR (2014) Functional neuroimaging of motor control in Parkinson’s disease: a meta-analysis. Hum Brain Mapp 35:3227–3237CrossRefPubMedGoogle Scholar
  36. 36.
    Snijders AH, Leunissen I, Bakker M, Overeem S, Helmich RC, Bloem BR, Toni I (2011) Gait-related cerebral alterations in patients with Parkinson’s disease with freezing of gait. Brain 134:59–72CrossRefPubMedGoogle Scholar
  37. 37.
    Ertelt D, Small S, Solodkin A, Dettmers C, McNamara A, Binkofski F, Buccino G (2007) Action observation has a positive impact on rehabilitation of motor deficits after stroke. Neuroimage 36(Suppl 2):T164–173CrossRefPubMedGoogle Scholar
  38. 38.
    Buccino G, Vogt S, Ritzl A, Fink GR, Zilles K, Freund HJ, Rizzolatti G (2004) Neural circuits underlying imitation learning of hand actions: an event-related fMRI study. Neuron 42:323–334CrossRefPubMedGoogle Scholar
  39. 39.
    Gatti R, Tettamanti A, Gough PM, Riboldi E, Marinoni L, Buccino G (2013) Action observation versus motor imagery in learning a complex motor task: a short review of literature and a kinematics study. Neurosci Lett 540:37–42CrossRefPubMedGoogle Scholar
  40. 40.
    Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME (2005) The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci USA 102:9673–9678CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Rowe J, Stephan KE, Friston K, Frackowiak R, Lees A, Passingham R (2002) Attention to action in Parkinson’s disease: impaired effective connectivity among frontal cortical regions. Brain 125:276–289CrossRefPubMedGoogle Scholar
  42. 42.
    Vercruysse S, Gilat M, Shine JM, Heremans E, Lewis S, Nieuwboer A (2014) Freezing beyond gait in Parkinson’s disease: a review of current neurobehavioral evidence. Neurosci Biobehav Rev 43:213–227CrossRefPubMedGoogle Scholar
  43. 43.
    Fasano A, Herman T, Tessitore A, Strafella AP, Bohnen NI (2015) Neuroimaging of Freezing of Gait. J Parkinsons Dis 5:241–254CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    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 136:3671–3681CrossRefPubMedGoogle Scholar
  45. 45.
    Tessitore A, Amboni M, Esposito F, Russo A, Picillo M, Marcuccio L, Pellecchia MT, Vitale C, Cirillo M, Tedeschi G, Barone P (2012) Resting-state brain connectivity in patients with Parkinson’s disease and freezing of gait. Parkinsonism Relat Disord 18:781–787CrossRefPubMedGoogle Scholar
  46. 46.
    Fling BW, Cohen RG, Mancini M, Carpenter SD, Fair DA, Nutt JG, Horak FB (2014) Functional reorganization of the locomotor network in Parkinson patients with freezing of gait. PLoS One 9:e100291CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Wu T, Hallett M (2005) A functional MRI study of automatic movements in patients with Parkinson’s disease. Brain 128:2250–2259CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Federica Agosta
    • 1
  • Roberto Gatti
    • 3
    • 7
  • Elisabetta Sarasso
    • 1
    • 3
  • Maria Antonietta Volonté
    • 2
  • Elisa Canu
    • 1
  • Alessandro Meani
    • 1
  • Lidia Sarro
    • 1
    • 2
  • Massimiliano Copetti
    • 5
  • Erik Cattrysse
    • 6
  • Eric Kerckhofs
    • 6
  • Giancarlo Comi
    • 2
  • Andrea Falini
    • 4
  • Massimo Filippi
    • 1
    • 2
    Email author
  1. 1.Neuroimaging Research Unit, Institute of Experimental Neurology, Division of NeuroscienceSan Raffaele Scientific Institute, Vita-Salute San Raffaele UniversityMilanItaly
  2. 2.Department of Neurology, Institute of Experimental Neurology, Division of NeuroscienceSan Raffaele Scientific Institute, Vita-Salute San Raffaele UniversityMilanItaly
  3. 3.Laboratory of Movement AnalysisSan Raffaele Scientific Institute, Vita-Salute San Raffaele UniversityMilanItaly
  4. 4.Department of NeuroradiologySan Raffaele Scientific Institute, Vita-Salute San Raffaele UniversityMilanItaly
  5. 5.Biostatistics UnitIRCCS-Ospedale Casa Sollievo Della SofferenzaSan Giovanni RotondoItaly
  6. 6.Faculty of Physical Education and PhysiotherapyVrije Universiteit BrusselBruxellesBelgium
  7. 7.Physiotherapy UnitHumanitas University and Humanitas Clinical and Research CenterRozzanoItaly

Personalised recommendations