Deep brain activation patterns involved in virtual gait without and with a doorway: An fMRI study

Autoři: Véronique Marchal aff001;  Jason Sellers aff001;  Mélanie Pélégrini-Issac aff002;  Cécile Galléa aff001;  Eric Bertasi aff001;  Romain Valabrègue aff001;  Brian Lau aff001;  Pierre Leboucher aff001;  Eric Bardinet aff001;  Marie-Laure Welter aff001;  Carine Karachi aff001
Působiště autorů: Sorbonne Universités, UPMC Univ Paris, CNRS, INSERM, AP HP GH Pitié Salpêtrière, Institut du Cerveau et de la Moelle épinière (ICM), Paris, France aff001;  Sorbonne Université, CNRS, INSERM, Laboratoire d’Imagerie Biomédicale, LIB, Paris, France aff002;  Centre de Neuroimagerie de recherche (CENIR), ICM, Paris, France aff003;  Plateforme PRISME, ICM, Paris, France aff004;  Service de Neurophysiologie, CHU Rouen, Université de Rouen, Rouen, France aff005;  Service de Neurochirurgie, AP-HP, GH Pitié-Salpêtrière, Paris, France aff006
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article


The human gait program involves many brain areas such as motor cortices, cerebellum, basal ganglia, brainstem, and spinal cord. The mesencephalic locomotor region (MLR), which contains the pedunculopontine (PPN) and cuneiform (CN) nuclei, is thought to be one of the key supraspinal gait generators. In daily life activities, gait primarily occurs in complex conditions, such as through narrow spaces, or while changing direction or performing motor or cognitive tasks. Here, we aim to explore the activity of these subcortical brain areas while walking through narrow spaces, using functional MRI in healthy volunteers and designing a virtual reality task mimicking walking down a hallway, without and with an open doorway to walk through. As a control, we used a virtual moving walkway in the same environment. Twenty healthy volunteers were scanned. Fifteen subjects were selected for second level analysis based on their ability to activate motor cortices. Using the contrast Gait versus Walkway, we found activated clusters in motor cortices, cerebellum, red nucleus, thalamus, and the left MLR including the CN and PPN. Using the contrast Gait with Doorway versus Walkway with Doorway, we found activated clusters in motor cortices, left putamen, left internal pallidum, left substantia nigra, right subthalamic area, and bilateral MLR involving the CN and PPN. Our results suggest that unobstructed gait involves a motor network including the PPN whereas gait through a narrow space requires the additional participation of basal ganglia and bilateral MLR, which may encode environmental cues to adapt locomotion.

Klíčová slova:

Biological locomotion – Cerebellum – Functional magnetic resonance imaging – Gait analysis – Walking – Basal ganglia – Caudate nucleus – Thalamus


1. Fukuyama H, Ouchi Y, Matsuzaki S, Nagahama Y, Yamauchi H, Ogawa M, et al. Brain functional activity during gait in normal subjects: a SPECT study. Neurosci Lett. 1997;228(3):183–6. doi: 10.1016/s0304-3940(97)00381-9 9218638

2. Miyai I, Tanabe HC, Sase I, Eda H, Oda I, Konishi I, et al. Cortical mapping of gait in humans: a near-infrared spectroscopic topography study. Neuroimage. 2001;14(5):1186–92. doi: 10.1006/nimg.2001.0905 11697950

3. Garcia-Rill E, Skinner RD, Fitzgerald JA. Activity in the mesencephalic locomotor region during locomotion. Exp Neurol. 1983;82(3):609–22. doi: 10.1016/0014-4886(83)90084-5 6653713

4. Mori S, Sakamoto T, Ohta Y, Takakusaki K, Matsuyama K. Site-specific postural and locomotor changes evoked in awake, freely moving intact cats by stimulating the brainstem. Brain Res. 1989;505(1):66–74. doi: 10.1016/0006-8993(89)90116-9 2611678

5. Takakusaki K, Habaguchi T, Ohtinata-Sugimoto J, Saitoh K, Sakamoto T. Basal ganglia efferents to the brainstem centers controlling postural muscle tone and locomotion: a new concept for understanding motor disorders in basal ganglia dysfunction. Neuroscience. 2003;119(1):293–308. doi: 10.1016/s0306-4522(03)00095-2 12763089

6. Roseberry TK, Lee AM, Lalive AL, Wilbrecht L, Bonci A, Kreitzer AC. Cell-Type-Specific Control of Brainstem Locomotor Circuits by Basal Ganglia. Cell. 2016;164(3):526–37. doi: 10.1016/j.cell.2015.12.037 26824660

7. Malouin F, Richards CL, Jackson PL, Dumas F, Doyon J. Brain activations during motor imagery of locomotor-related tasks: a PET study. Hum Brain Mapp. 2003;19(1):47–62. doi: 10.1002/hbm.10103 12731103

8. Jahn K, Deutschlander A, Stephan T, Kalla R, Wiesmann M, Strupp M, et al. Imaging human supraspinal locomotor centers in brainstem and cerebellum. Neuroimage. 2008;39(2):786–92. doi: 10.1016/j.neuroimage.2007.09.047 18029199

9. la Fougere C, Zwergal A, Rominger A, Forster S, Fesl G, Dieterich M, et al. Real versus imagined locomotion: a [18F]-FDG PET-fMRI comparison. Neuroimage. 2010;50(4):1589–98. doi: 10.1016/j.neuroimage.2009.12.060 20034578

10. Karachi C, Andre A, Bertasi E, Bardinet E, Lehericy S, Bernard FA. Functional parcellation of the lateral mesencephalus. J Neurosci. 2012;32(27):9396–401. doi: 10.1523/JNEUROSCI.0509-12.2012 22764247

11. Maillet A, Pollak P, Debu B. Imaging gait disorders in parkinsonism: a review. J Neurol Neurosurg Psychiatry. 2012;83(10):986–93. doi: 10.1136/jnnp-2012-302461 22773859

12. Fuchigami T, Morioka S. Differences in cortical activation between observing one's own gait and the gait of others: a functional near-infrared spectroscopy study. Neuroreport. 2015;26(4):192–6. doi: 10.1097/WNR.0000000000000312 25674903

13. Jiang D, Edwards MG, Mullins P, Callow N. The neural substrates for the different modalities of movement imagery. Brain Cogn. 2015;97:22–31. doi: 10.1016/j.bandc.2015.04.005 25956141

14. Dalla Volta R, Fasano F, Cerasa A, Mangone G, Quattrone A, Buccino G. Walking indoors, walking outdoors: an fMRI study. Front Psychol. 2015;6:1502. doi: 10.3389/fpsyg.2015.01502 26483745

15. Boyne P, Maloney T, DiFrancesco M, Fox MD, Awosika O, Aggarwal P, et al. Resting-state functional connectivity of subcortical locomotor centers explains variance in walking capacity. Hum Brain Mapp. 2018;39(12):4831–43. doi: 10.1002/hbm.24326 30052301

16. Maidan I, Rosenberg-Katz K, Jacob Y, Giladi N, Deutsch JE, Hausdorff JM, et al. Altered brain activation in complex walking conditions in patients with Parkinson's disease. Parkinsonism Relat Disord. 2016;25:91–6. doi: 10.1016/j.parkreldis.2016.01.025 26861167

17. 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(8):734–44. doi: 10.1016/S1474-4422(11)70143-0 21777828

18. 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(Pt 1):59–72. doi: 10.1093/brain/awq324 21126990

19. Fling BW, Cohen RG, Mancini M, Nutt JG, Fair DA, Horak FB. Asymmetric pedunculopontine network connectivity in parkinsonian patients with freezing of gait. Brain. 2013;136(Pt 8):2405–18. doi: 10.1093/brain/awt172 23824487

20. 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(6):e100291. doi: 10.1371/journal.pone.0100291 24937008

21. 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(3):e90634. doi: 10.1371/journal.pone.0090634 24595265

22. Peterson DS, Pickett KA, Duncan RP, Perlmutter JS, Earhart GM. Brain activity during complex imagined gait tasks in Parkinson disease. Clin Neurophysiol. 2014;125(5):995–1005. doi: 10.1016/j.clinph.2013.10.008 24210997

23. Peterson DS, Smulders K. Cues and Attention in Parkinsonian Gait: Potential Mechanisms and Future Directions. Frontiers in neurology. 2015;6:255. doi: 10.3389/fneur.2015.00255 26696955

24. Fasano A, Herman T, Tessitore A, Strafella AP, Bohnen NI. Neuroimaging of Freezing of Gait. J Parkinsons Dis. 2015;5(2):241–54. doi: 10.3233/JPD-150536 25757831

25. Canu E, Agosta F, Sarasso E, Volonte MA, Basaia S, Stojkovic T, et al. Brain structural and functional connectivity in Parkinson's disease with freezing of gait. Hum Brain Mapp. 2015;36(12):5064–78. doi: 10.1002/hbm.22994 26359798

26. Lenka A, Naduthota RM, Jha M, Panda R, Prajapati A, Jhunjhunwala K, et al. Freezing of gait in Parkinson's disease is associated with altered functional brain connectivity. Parkinsonism Relat Disord. 2016;24:100–6. doi: 10.1016/j.parkreldis.2015.12.016 26776567

27. Vervoort G, Alaerts K, Bengevoord A, Nackaerts E, Heremans E, Vandenberghe W, et al. Functional connectivity alterations in the motor and fronto-parietal network relate to behavioral heterogeneity in Parkinson's disease. Parkinsonism Relat Disord. 2016;24:48–55. doi: 10.1016/j.parkreldis.2016.01.016 26924603

28. Wang M, Jiang S, Yuan Y, Zhang L, Ding J, Wang J, et al. Alterations of functional and structural connectivity of freezing of gait in Parkinson's disease. J Neurol. 2016;263(8):1583–92. doi: 10.1007/s00415-016-8174-4 27230857

29. Mi TM, Mei SS, Liang PP, Gao LL, Li KC, Wu T, et al. Altered resting-state brain activity in Parkinson's disease patients with freezing of gait. Sci Rep. 2017;7(1):16711. doi: 10.1038/s41598-017-16922-0 29196699

30. Myers PS, McNeely ME, Pickett KA, Duncan RP, Earhart GM. Effects of exercise on gait and motor imagery in people with Parkinson disease and freezing of gait. Parkinsonism Relat Disord. 2018;53:89–95. doi: 10.1016/j.parkreldis.2018.05.006 29754837

31. Bharti K, Suppa A, Pietracupa S, Upadhyay N, Gianni C, Leodori G, et al. Abnormal Cerebellar Connectivity Patterns in Patients with Parkinson's Disease and Freezing of Gait. Cerebellum. 2018.

32. Li J, Yuan Y, Wang M, Zhang J, Zhang L, Jiang S, et al. Decreased interhemispheric homotopic connectivity in Parkinson's disease patients with freezing of gait: A resting state fMRI study. Parkinsonism Relat Disord. 2018;52:30–6. doi: 10.1016/j.parkreldis.2018.03.015 29602542

33. Bardinet E, Bhattacharjee M, Dormont D, Pidoux B, Malandain G, Schupbach M, et al. A three-dimensional histological atlas of the human basal ganglia. II. Atlas deformation strategy and evaluation in deep brain stimulation for Parkinson disease. J Neurosurg. 2009;110(2):208–19. doi: 10.3171/2008.3.17469 18976051

34. Hikosaka O, Isoda M. Switching from automatic to controlled behavior: cortico-basal ganglia mechanisms. Trends Cogn Sci. 2010;14(4):154–61. doi: 10.1016/j.tics.2010.01.006 20181509

35. Ricciardi L, Sarchioto M, Morgante F. Role of pedunculopontine nucleus in sleep-wake cycle and cognition in humans: A systematic review of DBS studies. Neurobiol Dis. 2019;128.

36. Cowie D, Limousin P, Peters A, Day BL. Insights into the neural control of locomotion from walking through doorways in Parkinson's disease. Neuropsychologia. 2010;48(9):2750–7. doi: 10.1016/j.neuropsychologia.2010.05.022 20519135

37. van der Meulen M, Allali G, Rieger SW, Assal F, Vuilleumier P. The influence of individual motor imagery ability on cerebral recruitment during gait imagery. Hum Brain Mapp. 2014;35(2):455–70. doi: 10.1002/hbm.22192 23015531

38. Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage. 2002;15(1):273–89. doi: 10.1006/nimg.2001.0978 11771995

39. Chumbley J, Worsley K, Flandin G, Friston K. Topological FDR for neuroimaging. Neuroimage. 2010;49(4):3057–64. doi: 10.1016/j.neuroimage.2009.10.090 19944173

40. Woo CW, Krishnan A, Wager TD. Cluster-extent based thresholding in fMRI analyses: pitfalls and recommendations. Neuroimage. 2014;91:412–9. doi: 10.1016/j.neuroimage.2013.12.058 24412399

41. Ryczko D, Dubuc R. The multifunctional mesencephalic locomotor region. Curr Pharm Des. 2013;19(24):4448–70. doi: 10.2174/1381612811319240011 23360276

42. Iseki K, Hanakawa T, Shinozaki J, Nankaku M, Fukuyama H. Neural mechanisms involved in mental imagery and observation of gait. Neuroimage. 2008;41(3):1021–31. doi: 10.1016/j.neuroimage.2008.03.010 18450480

43. Ekstrom AD, Kahana MJ, Caplan JB, Fields TA, Isham EA, Newman EL, et al. Cellular networks underlying human spatial navigation. Nature. 2003;425(6954):184–8. doi: 10.1038/nature01964 12968182

44. Jahn K, Deutschlander A, Stephan T, Strupp M, Wiesmann M, Brandt T. Brain activation patterns during imagined stance and locomotion in functional magnetic resonance imaging. Neuroimage. 2004;22(4):1722–31. doi: 10.1016/j.neuroimage.2004.05.017 15275928

45. Bakker M, De Lange FP, Helmich RC, Scheeringa R, Bloem BR, Toni I. Cerebral correlates of motor imagery of normal and precision gait. Neuroimage. 2008;41(3):998–1010. doi: 10.1016/j.neuroimage.2008.03.020 18455930

46. Shine JM, Matar E, Bolitho SJ, Dilda V, Morris TR, Naismith SL, et al. Modeling freezing of gait in Parkinson's disease with a virtual reality paradigm. Gait Posture. 2013;38(1):104–8. doi: 10.1016/j.gaitpost.2012.10.026 23218729

47. Heremans E, Nieuwboer A, Vercruysse S. Freezing of gait in Parkinson's disease: where are we now? Curr Neurol Neurosci Rep. 2013;13(6):350. doi: 10.1007/s11910-013-0350-7 23625316

48. Guillot A, Collet C, Nguyen VA, Malouin F, Richards C, Doyon J. Functional neuroanatomical networks associated with expertise in motor imagery. Neuroimage. 2008;41(4):1471–83. doi: 10.1016/j.neuroimage.2008.03.042 18479943

49. Roberts R, Callow N, Hardy L, Markland D, Bringer J. Movement imagery ability: development and assessment of a revised version of the vividness of movement imagery questionnaire. J Sport Exerc Psychol. 2008;30(2):200–21. 18490791

50. Guillot A, Collet C. Contribution from neurophysiological and psychological methods to the study of motor imagery. Brain Res Brain Res Rev. 2005;50(2):387–97. doi: 10.1016/j.brainresrev.2005.09.004 16271398

51. Malouin F, Richards CL, Durand A, Doyon J. Reliability of mental chronometry for assessing motor imagery ability after stroke. Archives of physical medicine and rehabilitation. 2008;89(2):311–9. doi: 10.1016/j.apmr.2007.11.006 18226656

52. Wang C, Wai Y, Weng Y, Yu J, Wang J. The cortical modulation from the external cues during gait observation and imagination. Neurosci Lett. 2008;443(3):232–5. doi: 10.1016/j.neulet.2008.07.084 18691632

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