Journal of Neurology

, Volume 262, Issue 4, pp 899–908 | Cite as

Changes in oxygenated hemoglobin link freezing of gait to frontal activation in patients with Parkinson disease: an fNIRS study of transient motor-cognitive failures

  • Inbal Maidan
  • Hagar Bernad-Elazari
  • Eran Gazit
  • Nir Giladi
  • Jeffery M. Hausdorff
  • Anat Mirelman
Original Communication


Recent studies have suggested that deficits in executive function contribute to freezing of gait (FOG), an episodic disturbance common among patients with Parkinson’s disease (PD). To date, most findings provide only indirect evidence of this relationship. Here, we evaluated a more direct link between FOG and frontal lobe dysfunction. Functional, near infrared spectroscopy measured frontal activation, i.e., oxygenated hemoglobin (HbO2) levels in Brodmann area 10 before and during FOG. Eleven patients with PD and eleven healthy older adults were studied. Changes in frontal lobe activation before and during FOG that occurred during turns were determined. Altogether, 49 FOG episodes were observed—28 occurred during turns that were anticipated (i.e., the patient knew in advance that the turn was coming), 21 during unanticipated turns that were performed “abruptly”, according to the examiner’s request. During anticipated turns, HbO2 increased by 0.22 ± 0.08 µM (p = 0.004) before FOG and by an additional 0.19 ± 0.13 µM (p = 0.072) during FOG. In contrast, during unanticipated turns, HbO2 did not increase before or during FOG. HbO2 decreased by 0.32 ± 0.08 µM (p = 0.004) during turns without FOG; in healthy controls HbO2 did not change during turns. These findings support the existence of an association between FOG episodes and changes in frontal lobe HbO2. Increased activation in Brodmann area 10 before FOG, specifically during anticipated turns, highlights the connections between motor planning, information processing, and FOG. These results support the idea that alterations in executive control play a role in this debilitating motor disturbance.


Parkinson’s disease Freezing of gait Frontal lobe fNIRS Executive function 



This study was supported in part by European Union—Seventh Framework Programme (FP7-HEALTH-2011) under Grant agreement n. 278169 (V-TIME) and Grant agreement n. 288586 (CuPiD Project).

Conflicts of interest

On behalf of all the authors, the corresponding author states that there is no conflict of interest.


  1. 1.
    Cowie D, Limousin P, Peters A, Day BL (2010) Insights into the neural control of locomotion from walking through doorways in Parkinson’s disease. Neuropsychologia 48:2750–2757CrossRefPubMedGoogle Scholar
  2. 2.
    Cowie D, Limousin P, Peters A, Hariz M, Day BL (2012) Doorway-provoked freezing of gait in Parkinson’s disease. Mov Disord 27:492–499CrossRefPubMedGoogle Scholar
  3. 3.
    Cummings JL (1993) Frontal-subcortical circuits and human behavior. Arch Neurol 50:873–880CrossRefPubMedGoogle Scholar
  4. 4.
    Earhart GM, Stevens ES, Perlmutter JS, Hong M (2007) Perception of active and passive turning in Parkinson disease. Neurorehabil Neural Repair 21:116–122CrossRefPubMedGoogle Scholar
  5. 5.
    Fling BW, Cohen RG, Mancini M, Nutt JG, Fair DA, Horak FB (2013) Asymmetric pedunculopontine network connectivity in parkinsonian patients with freezing of gait. Brain 136:2405–2418PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Giladi N, Hausdorff JM (2006) The role of mental function in the pathogenesis of freezing of gait in Parkinson’s disease. J Neurol Sci 248:173–176CrossRefPubMedGoogle Scholar
  7. 7.
    Giladi N, Horak FB, Hausdorff JM (2013) Classification of gait disturbances: distinguishing between continuous and episodic changes. Mov Disord 28:1469–1473CrossRefPubMedGoogle Scholar
  8. 8.
    Handojoseno AM, Shine JM, Nguyen TN, Tran Y, Lewis SJ, Nguyen HT (2012) The detection of Freezing of Gait in Parkinson’s disease patients using EEG signals based on Wavelet decomposition. Conf Proc IEEE Eng Med Biol Soc 2012:69–72PubMedGoogle Scholar
  9. 9.
    Heremans E, Nieuwboer A, Vercruysse S (2013) Freezing of gait in Parkinson’s disease: where are we now? Curr Neurol Neurosci Rep 13:350CrossRefPubMedGoogle Scholar
  10. 10.
    Herman T, Giladi N, Hausdorff JM (2013) Neuroimaging as a window into gait disturbances and freezing of gait in patients with Parkinson’s disease. Curr Neurol Neurosci Rep 13:411CrossRefPubMedGoogle Scholar
  11. 11.
    Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Knobl P, Kielstra L, Almeida Q (2012) The relationship between motor planning and freezing of gait in Parkinson’s disease. J Neurol Neurosurg Psychiatry 83:98–101CrossRefPubMedGoogle Scholar
  13. 13.
    Lewis SJ, Barker RA (2009) A pathophysiological model of freezing of gait in Parkinson’s disease. Parkinsonism Relat Disord 15:333–338CrossRefPubMedGoogle Scholar
  14. 14.
    Lowry KA, Brach JS, Nebes RD, Studenski SA, VanSwearingen JM (2012) Contributions of cognitive function to straight- and curved-path walking in older adults. Arch Phys Med Rehabil 93:802–807CrossRefPubMedGoogle Scholar
  15. 15.
    Maidan I, Plotnik M, Mirelman A, Weiss A, Giladi N, Hausdorff JM (2010) Heart rate changes during freezing of gait in patients with Parkinson’s disease. Mov Disord 25:2346–2354PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Mancini M, Horak FB, Zampieri C, Carlson-Kuhta P, Nutt JG, Chiari L (2011) Trunk accelerometry reveals postural instability in untreated Parkinson’s disease. Parkinsonism Relat Disord 17:557–562CrossRefPubMedGoogle Scholar
  17. 17.
    Mirelman A, Weiss A, Buchman A, Bennett DA, Giladi N (2013) Association between performance on timed up and go subtasks and mild cognitive impairment: further insights into the links between cognitive and motor functionGoogle Scholar
  18. 18.
    Mirelman A, Maidan I, Bernad-Elazari H, Nieuwhof F, Reelick M, Giladi N, Hausdorff JM (2014) Changes in frontal brain activation while walking and dual tasking: an fNIRS study in healthy young adultsGoogle Scholar
  19. 19.
    Mirelman A, Maidan I, Deutsch JE (2013) Virtual reality and motor imagery: promising tools for assessment and therapy in Parkinson’s disease. Mov Disord 28:1597–1608CrossRefPubMedGoogle Scholar
  20. 20.
    Miyai I, Tanabe HC, Sase I, Eda H, Oda I, Konishi I, Tsunazawa Y, Suzuki T, Yanagida T, Kubota K (2001) Cortical mapping of gait in humans: a near-infrared spectroscopic topography study. Neuroimage 14:1186–1192CrossRefPubMedGoogle Scholar
  21. 21.
    Muthalib M, Anwar AR, Perrey S, Dat M, Galka A, Wolff S, Heute U, Deuschl G, Raethjen J, Muthuraman M (2013) Multimodal integration of fNIRS, fMRI and EEG neuroimaging. Clin Neurophysiol 124:2060–2062CrossRefPubMedGoogle Scholar
  22. 22.
    Naismith SL, Shine JM, Lewis SJ (2010) The specific contributions of set-shifting to freezing of gait in Parkinson’s disease. Mov Disord 25:1000–1004CrossRefPubMedGoogle Scholar
  23. 23.
    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 53:695–699CrossRefPubMedGoogle Scholar
  24. 24.
    Nieuwboer A, Kwakkel G, Rochester L, Jones D, van Wegen E, Willems AM, Chavret F, Hetherington V, Baker K, Lim I (2007) Cueing training in the home improves gait-related mobility in Parkinson’s disease: the RESCUE trial. J Neurol Neurosurg Psychiatry 78:134–140PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Nutt JG, Bloem BR, Giladi N, Hallett M, Horak FB, Nieuwboer A (2011) Freezing of gait: moving forward on a mysterious clinical phenomenon. Lancet Neurol 10:734–744CrossRefPubMedGoogle Scholar
  26. 26.
    Pashler H (1994) Dual-task interference in simple tasks: data and theory. Psychol Bull 116:220–244CrossRefPubMedGoogle Scholar
  27. 27.
    Plotnik M, Giladi N, Hausdorff JM (2008) Bilateral coordination of walking and freezing of gait in Parkinson’s disease. Eur J Neurosci 27:1999–2006CrossRefPubMedGoogle Scholar
  28. 28.
    Pollmann S (2004) Anterior prefrontal cortex contributions to attention control. Exp Psychol 51:270–278CrossRefPubMedGoogle Scholar
  29. 29.
    Rosenberg-Katz K, Herman T, Jacob Y, Giladi N, Hendler T, Hausdorff JM (2013) Gray matter atrophy distinguishes between Parkinson disease motor subtypes. Neurology 80:1476–1484PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Schaafsma JD, Balash Y, Gurevich T, Bartels AL, Hausdorff JM, Giladi N (2003) Characterization of freezing of gait subtypes and the response of each to levodopa in Parkinson’s disease. Eur J Neurol 10:391–398CrossRefPubMedGoogle Scholar
  31. 31.
    Shine JM, Handojoseno AM, Nguyen TN, Tran Y, Naismith SL, Nguyen H, Lewis SJ (2014) Abnormal patterns of theta frequency oscillations during the temporal evolution of freezing of gait in Parkinson’s disease. Clin Neurophysiol 125:569–576CrossRefPubMedGoogle Scholar
  32. 32.
    Shine JM, Matar E, Ward PB, Bolitho SJ, Gilat M, Pearson M, Naismith SL, Lewis SJ (2013) Exploring the cortical and subcortical functional magnetic resonance imaging changes associated with freezing in Parkinson’s disease. Brain 136:1204–1215CrossRefPubMedGoogle Scholar
  33. 33.
    Sigman M, Dehaene S (2006) Dynamics of the central bottleneck: dual-task and task uncertainty. PLoS Biol 4:e220PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    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
  35. 35.
    Spildooren J, Vercruysse S, Desloovere K, Vandenberghe W, Kerckhofs E, Nieuwboer A (2010) Freezing of gait in Parkinson’s disease: the impact of dual-tasking and turning. Mov Disord 25:2563–2570CrossRefPubMedGoogle Scholar
  36. 36.
    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. Am J Neuroradiol 33:1804–1809CrossRefPubMedGoogle Scholar
  37. 37.
    Vandenbossche J, Deroost N, Soetens E, Spildooren J, Vercruysse S, Nieuwboer A, Kerckhofs E (2011) Freezing of gait in Parkinson disease is associated with impaired conflict resolution. Neurorehabil Neural Repair 25:765–773CrossRefPubMedGoogle Scholar
  38. 38.
    Vandenbossche J, Deroost N, Soetens E, Zeischka P, Spildooren J, Vercruysse S, Nieuwboer A, Kerckhofs E (2012) Conflict and freezing of gait in Parkinson’s disease: support for a response control deficit. Neuroscience 206:144–154CrossRefPubMedGoogle Scholar
  39. 39.
    Vercruysse S, Devos H, Munks L, Spildooren J, Vandenbossche J, Vandenberghe W, Nieuwboer A, Heremans E (2012) Explaining freezing of gait in Parkinson’s disease: motor and cognitive determinants. Mov Disord 27:1644–1651CrossRefPubMedGoogle Scholar
  40. 40.
    Wu T, Hallett M (2008) Neural correlates of dual task performance in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 79:760–766CrossRefPubMedGoogle Scholar
  41. 41.
    Yogev-Seligmann G, Hausdorff JM, Giladi N (2008) The role of executive function and attention in gait. Mov Disord 23:329–342CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Inbal Maidan
    • 1
    • 2
  • Hagar Bernad-Elazari
    • 1
  • Eran Gazit
    • 1
  • Nir Giladi
    • 1
    • 3
    • 4
  • Jeffery M. Hausdorff
    • 1
    • 3
    • 5
  • Anat Mirelman
    • 1
  1. 1.Center for the study of Movement, Cognition and Mobility, Department of NeurologyTel Aviv Sourasky Medical CenterTel-AvivIsrael
  2. 2.Rivers Lab, Department of Rehabilitation and Movement ScienceRutgers Biomedical and Health SciencesNewarkUSA
  3. 3.Sagol School of NeuroscienceTel Aviv UniversityTel AvivIsrael
  4. 4.Department of Neurology, Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  5. 5.Department of Physical Therapy, Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael

Personalised recommendations