Brain Topography

, Volume 29, Issue 2, pp 334–343 | Cite as

Neurological Gait Abnormalities Moderate the Functional Brain Signature of the Posture First Hypothesis

  • Roee Holtzer
  • Joe Verghese
  • Gilles Allali
  • Meltem Izzetoglu
  • Cuiling Wang
  • Jeannette R. Mahoney
Original Paper


The posture first hypothesis suggests that under dual-task walking conditions older adults prioritize gait over cognitive task performance. Functional neural confirmation of this hypothesis, however, is lacking. Herein, we determined the functional neural correlates of the posture first hypothesis and hypothesized that the presence of neurological gait abnormalities (NGA) would moderate associations between brain activations, gait and cognitive performance. Using functional near-infrared spectroscopy we assessed changes in oxygenated hemoglobin levels in the pre-frontal cortex (PFC) during normal walk and walk while talk (WWT) conditions in a large cohort of non-demented older adults (n = 236; age = 75.5 ± 6.49 years; female = 51.7 %). NGA were defined as central (due to brain diseases) or peripheral (neuropathic gait) following a standardized neurological examination protocol. Double dissociations between brain activations and behavior emerged as a function of NGA. Higher oxygenation levels during WWT were related to better cognitive performance (estimate = 0.145; p < 0.001) but slower gait velocity (estimate = −6.336, p < 0.05) among normals. In contrast, higher oxygenation levels during WWT among individuals with peripheral NGA were associated with worse cognitive performance (estimate = −0.355; p < 0.001) but faster gait velocity (estimate = 14.855; p < 0.05). Increased activation in the PFC during locomotion may have a compensatory function that is designed to support gait among individuals with peripheral NGA.


Locomotion Aging Brain Near-infrared spectroscopy 



This research was supported by the National Institutes on Aging R01AG036921 (PI: R. Holtzer) and R01AG044007 (PI: J. Verghese).

Compliance with Ethical Standards

Conflicts of Interest

Dr. Izzetoglu has a very minor share in the company that manufactures the fNIRS device used in this study. All other authors have no conflicts of interest to report in relation to the current article.


  1. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders (text revision ed.). American Psychiatric Press, Washington, DCGoogle Scholar
  2. Ayaz H, Izzetoglu M, Platek SM, Bunce S, Izzetoglu K, Pourrezaei K, Onaral B (2006) Registering fNIR data to brain surface image using MRI templates. Conf Proc IEEE Eng Med Biol Soc 1:2671–2674. doi: 10.1109/IEMBS.2006.260835 PubMedGoogle Scholar
  3. Ayers EI, Tow AC, Holtzer R, Verghese J (2014) Walking while talking and falls in aging. Gerontology 60(2):108–113. doi: 10.1159/000355119 PubMedCentralCrossRefPubMedGoogle Scholar
  4. Bloem BR, Grimbergen YA, van Dijk JG, Munneke M (2006) The “posture second” strategy: a review of wrong priorities in Parkinson’s disease. J Neurol Sci 248(1–2):196–204. doi: 10.1016/j.jns.2006.05.010 CrossRefPubMedGoogle Scholar
  5. Blumen HM, Holtzer R, Brown LL, Gazes Y, Verghese J (2014) Behavioral and neural correlates of imagined walking and walking-while-talking in the elderly. Hum Brain Mapp. doi: 10.1002/hbm.22461 PubMedCentralGoogle Scholar
  6. Cabeza R (2002). Hemispheric asymmetry reduction in older adults: the HAROLD model. Psychol Aging 17(1), 85–100.
  7. Cooper RJ, Selb J, Gagnon L, Phillip D, Schytz HW, Iversen HK, Boas DA (2012) A systematic comparison of motion artifact correction techniques for functional near-infrared spectroscopy. Front Neurosci 6:147. doi: 10.3389/fnins.2012.00147 PubMedCentralCrossRefPubMedGoogle Scholar
  8. Drew T, Prentice S, Schepens B (2004) Cortical and brainstem control of locomotion. Prog Brain Res 143:251–261.
  9. Duff K, Humphreys Clark JD, O’Bryant SE, Mold JW, Schiffer RB, Sutker PB (2008) Utility of the RBANS in detecting cognitive impairment associated with Alzheimer’s disease: sensitivity, specificity, and positive and negative predictive powers. Arch Clin Neuropsychol 23(5):603–612. doi: 10.1016/j.acn.2008.06.004 PubMedCentralCrossRefPubMedGoogle Scholar
  10. England SE, Verghese J, Mahoney JR, Trantzas C, Holtzer R (2015) Three-level rating of turns while walking. Gait Posture 41(1):300–303. doi: 10.1016/j.gaitpost.2014.09.010 PubMedCentralCrossRefPubMedGoogle Scholar
  11. Erdogan SB, Yucel MA, Akin A (2014) Analysis of task-evoked systemic interference in fNIRS measurements: insights from fMRI. Neuroimage 87:490–504. doi: 10.1016/j.neuroimage.2013.10.024 CrossRefPubMedGoogle Scholar
  12. Gerin-Lajoie M, Richards CL, McFadyen BJ (2005) The negotiation of stationary and moving obstructions during walking: anticipatory locomotor adaptations and preservation of personal space. Motor Control 9(3):242–269PubMedGoogle Scholar
  13. Harada T, Miyai I, Suzuki M, Kubota K (2009) Gait capacity affects cortical activation patterns related to speed control in the elderly. Exp Brain Res 193(3):445–454. doi: 10.1007/s00221-008-1643-y CrossRefPubMedGoogle Scholar
  14. Holtzer R, Verghese J, Xue X, Lipton RB (2006) Cognitive processes related to gait velocity: results from the Einstein Aging Study. Neuropsychology 20(2):215–223. doi: 10.1037/0894-4105.20.2.215 CrossRefPubMedGoogle Scholar
  15. Holtzer R, Verghese J, Wang C, Hall CB, Lipton RB (2008) Within-person across-neuropsychological test variability and incident dementia. JAMA 300(7):823–830. doi: 10.1001/jama.300.7.823 PubMedCentralCrossRefPubMedGoogle Scholar
  16. Holtzer R, Mahoney JR, Izzetoglu M, Izzetoglu K, Onaral B, Verghese J (2011) fNIRS study of walking and walking while talking in young and old individuals. J Gerontol A Biol Sci Med Sci 66(8):879–887. doi: 10.1093/gerona/glr068 CrossRefPubMedGoogle Scholar
  17. Holtzer R, Wang C, Lipton R, Verghese J (2012a) The protective effects of executive functions and episodic memory on gait speed decline in aging defined in the context of cognitive reserve. J Am Geriatr Soc 60(11):2093–2098. doi: 10.1111/j.1532-5415.2012.04193.x PubMedCentralPubMedGoogle Scholar
  18. Holtzer R, Wang C, Verghese J (2012b) The relationship between attention and gait in aging: facts and fallacies. Motor Control 16(1):64–80.
  19. Holtzer R, Epstein N, Mahoney JR, Izzetoglu M, Blumen HM (2014a) Neuroimaging of mobility in aging: a targeted review. J Gerontol A Biol Sci Med Sci 69(11):1375–1388. doi: 10.1093/gerona/glu052 PubMedCentralCrossRefPubMedGoogle Scholar
  20. Holtzer R, Epstein N, Mahoney JR, Izzetoglu M, Blumen HM (2014b) Neuroimaging of mobility in aging: a targeted review. J Gerontol A Biol Sci Med Sci. doi: 10.1093/gerona/glu052 Google Scholar
  21. Holtzer R, Mahoney J, Verghese J (2014c) Intraindividual variability in executive functions but not speed of processing or conflict resolution predicts performance differences in gait speed in older adults. J Gerontol A Biol Sci Med Sci 69(8):980–986. doi: 10.1093/gerona/glt180 PubMedCentralCrossRefPubMedGoogle Scholar
  22. Holtzer R, Wang C, Verghese J (2014d) Performance variance on walking while talking tasks: theory, findings, and clinical implications. Age (Dordr) 36(1):373–381. doi: 10.1007/s11357-013-9570-7 CrossRefGoogle Scholar
  23. Holtzer R, Mahoney CJ, Wang C, England SE, Verghese J (2015) Online fronto-cortical control of simple and attention-demanding locomotion in humans. Neuroimage 112:152–159CrossRefPubMedGoogle Scholar
  24. Izzetoglu M, Bunce SC, Izzetoglu K, Onaral B, Pourrezaei K (2007) Functional brain imaging using near-infrared technology. IEEE Eng Med Biol Mag 26(4):38–46.
  25. Izzetoglu M, Chitrapu P, Bunce S, Onaral B (2010) Motion artifact cancellation in NIR spectroscopy using discrete Kalman filtering. Biomed Eng Online 9:16. doi: 10.1186/1475-925X-9-16 PubMedCentralCrossRefPubMedGoogle Scholar
  26. Jobsis FF (1977) Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science 198(4323):1264–1267.
  27. Kirilina E, Jelzow A, Heine A, Niessing M, Wabnitz H, Bruhl R, Tachtsidis I (2012) The physiological origin of task-evoked systemic artefacts in functional near infrared spectroscopy. Neuroimage 61(1):70–81. doi: 10.1016/j.neuroimage.2012.02.074 PubMedCentralCrossRefPubMedGoogle Scholar
  28. Li KZH, Lindenberger U, Freund AM, Baltes PB (2001) Walking while memorizing: age-related differences in compensatory behavior. Psychol Sci 12(3):230–237CrossRefPubMedGoogle Scholar
  29. Lindenberger U, Marsiske M, Baltes PB (2000) Memorizing while walking: increase in dual-task costs from young adulthood to old age. Psychol Aging 15(3):417–436CrossRefPubMedGoogle Scholar
  30. MacDonald AW 3rd, Cohen JD, Stenger VA, Carter CS (2000) Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control. Science 288(5472):1835–1838CrossRefPubMedGoogle Scholar
  31. Mirelman A, Maidan I, Bernad-Elazari H, Nieuwhof F, Reelick M, Giladi N, Hausdorff JM (2014) Increased frontal brain activation during walking while dual tasking: an fNIRS study in healthy young adults. J Neuroeng Rehabil 12(11):85. doi: 10.1186/1743-0003-11-85 CrossRefGoogle Scholar
  32. Miyake A, Friedman NP, Emerson MJ, Witzki AH, Howerter A, Wager TD (2000) The unity and diversity of executive functions and their contributions to complex “Frontal Lobe” tasks: a latent variable analysis. Cognit Psychol 41(1):49–100. doi: 10.1006/cogp.1999.0734 CrossRefPubMedGoogle Scholar
  33. Nutt JG, Marsden CD, Thompson PD (1993) Human walking and higher-level gait disorders, particularly in the elderly. Neurology 43(2):268–279.
  34. Oh-Park M, Xue X, Holtzer R, Verghese J (2011) Transient versus persistent fear of falling in community-dwelling older adults: incidence and risk factors. J Am Geriatr Soc 59(7):1225–1231. doi: 10.1111/j.1532-5415.2011.03475.x PubMedCentralCrossRefPubMedGoogle Scholar
  35. Reuter-Lorenz PA, Jonides J, Smith EE, Hartley A, Miller A, Marshuetz C, Koeppe RA (2000) Age differences in the frontal lateralization of verbal and spatial working memory revealed by PET. J Cogn Neurosci 12(1):174–187.
  36. Rosso AL, Studenski SA, Chen WG, Aizenstein HJ, Alexander NB, Bennett DA, Rosano C (2013) Aging, the central nervous system, and mobility. J Gerontol A Biol Sci Med Sci 68(11):1379–1386. doi: 10.1093/gerona/glt089 PubMedCentralCrossRefPubMedGoogle Scholar
  37. Schaefer S, Schellenbach M, Lindenberger U, Woollacott M (2015) Walking in high-risk settings: do older adults still prioritize gait when distracted by a cognitive task? Exp Brain Res 233(1):79–88. doi: 10.1007/s00221-014-4093-8 CrossRefPubMedGoogle Scholar
  38. Schwenk M, Zieschang T, Oster P, Hauer K (2010) Dual-task performances can be improved in patients with dementia: a randomized controlled trial. Neurology 74(24):1961–1968. doi: 10.1212/WNL.0b013e3181e39696 CrossRefPubMedGoogle Scholar
  39. Stern Y (2009) Cognitive reserve. Neuropsychologia 47(10):2015–2028. doi: 10.1016/j.neuropsychologia.2009.03.004 PubMedCentralCrossRefPubMedGoogle Scholar
  40. Studenski S, Perera S, Patel K, Rosano C, Faulkner K, Inzitari M, Guralnik J (2011) Gait speed and survival in older adults. JAMA 305(1):50–58. doi: 10.1001/jama.2010.1923 PubMedCentralCrossRefPubMedGoogle Scholar
  41. Verghese J, Lipton RB, Hall CB, Kuslansky G, Katz MJ, Buschke H (2002) Abnormality of gait as a predictor of non-Alzheimer’s dementia. N Engl J Med 347(22):1761–1768. doi: 10.1056/NEJMoa020441 CrossRefPubMedGoogle Scholar
  42. Verghese J, LeValley A, Hall CB, Katz MJ, Ambrose AF, Lipton RB (2006) Epidemiology of gait disorders in community-residing older adults. J Am Geriatr Soc 54(2):255–261. doi: 10.1111/j.1532-5415.2005.00580.x PubMedCentralCrossRefPubMedGoogle Scholar
  43. Verghese J, Derby C, Katz MJ, Lipton RB (2007) High risk neurological gait syndrome and vascular dementia. J Neural Transm 114(10):1249–1252. doi: 10.1007/s00702-007-0762-0 CrossRefPubMedGoogle Scholar
  44. Verghese J, Robbins M, Holtzer R, Zimmerman M, Wang C, Xue X, Lipton RB (2008) Gait dysfunction in mild cognitive impairment syndromes. J Am Geriatr Soc 56(7):1244–1251. doi: 10.1111/j.1532-5415.2008.01758.x PubMedCentralCrossRefPubMedGoogle Scholar
  45. Verghese J, Ambrose AF, Lipton RB, Wang C (2010a) Neurological gait abnormalities and risk of falls in older adults. J Neurol 257(3):392–398. doi: 10.1007/s00415-009-5332-y PubMedCentralCrossRefPubMedGoogle Scholar
  46. Verghese J, Mahoney J, Ambrose AF, Wang C, Holtzer R (2010b) Effect of cognitive remediation on gait in sedentary seniors. J Gerontol A Biol Sci Med Sci 65(12):1338–1343. doi: 10.1093/gerona/glq127 CrossRefPubMedGoogle Scholar
  47. Verghese J, Holtzer R, Lipton RB, Wang C (2012) Mobility stress test approach to predicting frailty, disability, and mortality in high-functioning older adults. J Am Geriatr Soc 60(10):1901–1905. doi: 10.1111/j.1532-5415.2012.04145.x PubMedCentralCrossRefPubMedGoogle Scholar
  48. Yogev-Seligmann G, Hausdorff JM, Giladi N (2008) The role of executive function and attention in gait. Mov Disord 23(3):329–342. doi: 10.1002/mds.21720 CrossRefGoogle Scholar
  49. Yogev-Seligmann G, Giladi N, Brozgol M, Hausdorff JM (2012) A training program to improve gait while dual tasking in patients with Parkinson’s disease: a pilot study. Arch Phys Med Rehabil 93(1):176–181. doi: 10.1016/j.apmr.2011.06.005 CrossRefPubMedGoogle Scholar
  50. Yuan J, Blumen HM, Verghese J, Holtzer R (2014) Functional connectivity associated with gait velocity during walking and walking-while-talking in aging: a resting-state fMRI study. Hum Brain Mapp. doi: 10.1002/hbm.22717 Google Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Roee Holtzer
    • 1
    • 2
  • Joe Verghese
    • 1
    • 5
  • Gilles Allali
    • 1
    • 6
  • Meltem Izzetoglu
    • 3
  • Cuiling Wang
    • 4
  • Jeannette R. Mahoney
    • 1
  1. 1.Department of NeurologyAlbert Einstein College of Medicine of Yeshiva UniversityBronxUSA
  2. 2.Ferkauf Graduate School of Psychology of Yeshiva UniversityBronxUSA
  3. 3.School of Biomedical EngineeringDrexel UniversityPhiladelphiaUSA
  4. 4.Department of EpidemiologyAlbert Einstein College of Medicine of Yeshiva UniversityBronxUSA
  5. 5.Department of MedicineAlbert Einstein College of Medicine of Yeshiva UniversityBronxUSA
  6. 6.Department of Clinical NeurosciencesGeneva University Hospitals and University of GenevaGenevaSwitzerland

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