Skip to main content
SpringerLink
Log in

Functional MRI in Idiopathic Parkinson Disease and Parkinsonism

  • Chapter
  • First Online:
Neuroimaging of Movement Disorders

Part of the book series: Current Clinical Neurology ((CCNEU,volume 44))

Abstract

In the last 20 years, functional MRI (fMRI) has been an exciting development. Since its appearance, it has been extensively used in studies on movement disorders. This chapter will briefly introduce a basic overview of fMRI. We will then focus on the successful application of blood oxygen level-dependent (BOLD) fMRI in idiopathic Parkinson disease (iPD), a common and critical movement disorder. BOLD fMRI has been extensively used to understand the neural correlates of motor deficits in iPD from both a regional brain activity and network basis. This technique has also provided new insight into nonmotor deficits such as cognitive, psychiatric, and olfactory impairments. fMRI studies on asymptomatic gene mutation carriers have found a compensatory reorganization of striatocortical motor loops to maintain motor function in the preclinical stage. More recent resting-state fMRI studies have identified iPD-specific spontaneous neural activity or network connectivity patterns. The role of arterial spin labeling (ASL) perfusion MRI in iPD is discussed. fMRI findings in atypical parkinsonism, including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and dementia with Lewy bodies (DLB) are also presented. Despite some limitations, future fMRI studies will enhance our understanding of pathophysiological changes in movement disorders. fMRI also has potential to be developed as a neuroimaging biomarker of iPD, with the potential to improve early diagnosis, monitor disease progression, differentiate iPD from other parkinsonisms on an individual basis, and may identify novel targets for future therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ogawa S, Lee TM, Kay AR, Tank DW. Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci U S A. 1990;87:9868–72.

    Article  PubMed  CAS  Google Scholar 

  2. Ogawa S, Menon RS, Tank DW, Kim SG, Merkle H, Ellermann JM, Ugurbil K. Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model. Biophys J. 1993;64:803–12.

    Article  PubMed  CAS  Google Scholar 

  3. Sabatini U, Boulanouar K, Fabre N, Martin F, Carel C, Colonnese C, Bozzao L, Berry I, Montastruc JL, Chollet F, Rascol O. Cortical motor reorganization in akinetic patients with Parkinson’s disease: a functional MRI study. Brain. 2000;123:394–403.

    Article  PubMed  Google Scholar 

  4. Haslinger B, Erhard P, Kampfe N, Boecker H, Rummeny E, Schwaiger M, Conrad B, Ceballos-Baumann AO. Event-related functional magnetic resonance imaging in Parkinson’s disease before and after levodopa. Brain. 2001;124:558–70.

    Article  PubMed  CAS  Google Scholar 

  5. Buhmann C, Glauche V, Sturenburg HJ, Oechsner M, Weiller C, Buchel C. Pharmacologically modulated fMRI—cortical responsiveness to levodopa in drug-naïve hemiparkinsonian patients. Brain. 2003;126:451–61.

    Article  PubMed  CAS  Google Scholar 

  6. Wu T, Hallett M. A functional MRI study of automatic movements in patients with Parkinson’s disease. Brain. 2005;128:2250–9.

    Article  PubMed  Google Scholar 

  7. Yu H, Sternad D, Corcos DM, Vaillancourt DE. Role of hyperactive cerebellum and motor cortex in Parkinson’s disease. Neuroimage. 2007;35(1):222–33.

    Article  PubMed  Google Scholar 

  8. Wu T, Wang L, Hallett M, Li K, Chan P. Neural correlates of bimanual anti-phase and in-phase movements in Parkinson’s disease. Brain. 2010;133:2394–409.

    Article  PubMed  Google Scholar 

  9. Tessa C, Lucetti C, Diciotti S, Paoli L, Cecchi P, Giannelli M, Baldacci F, Ginestroni A, Vignali C, Mascalchi M, Bonuccelli U. Hypoactivation of the primary sensorimotor cortex in de novo Parkinson’s disease: a motor fMRI study under controlled conditions. Neuroradiology. 2012;554(3):261–8.

    Article  Google Scholar 

  10. Deiber MP, Passingham RE, Colebatch JG, Friston KJ, Nixon PD, Frackowiak RS. Cortical areas and the selection of movement: a study with positron emission tomography. Exp Brain Res. 1991;84:393–402.

    Article  PubMed  CAS  Google Scholar 

  11. Jenkins IH, Jahanshahi M, Jueptner M, Passingham RE, Brooks DJ. Self-initiated versus externally triggered movements. II. The effect of movement predictability on regional cerebral blood flow. Brain. 2000;123:1216–28.

    Article  PubMed  Google Scholar 

  12. Cunnington R, Windischberger C, Deecke L, Moser E. The preparation and execution of self-initiated and externally-triggered movement: a study of event-related fMRI. Neuroimage. 2002;15:373–85.

    Article  PubMed  CAS  Google Scholar 

  13. Schell GR, Strick PL. The origin of thalamic inputs to the arcuate premotor and supplementary motor areas. J Neurosci. 1984;4:539–60.

    PubMed  CAS  Google Scholar 

  14. Rascol O, Sabatini U, Fabre N, Brefel C, Loubinoux I, Celsis P, Senard JM, Montastruc JL, Chollet F. The ipsilateral cerebellar hemisphere is overactive during hand movements in akinetic parkinsonian patients. Brain. 1997;120:103–10.

    Article  PubMed  Google Scholar 

  15. Catalan MJ, Ishii K, Honda M, Samii A, Hallett M. A PET study of sequential finger movements of varying length in patients with Parkinson’s disease. Brain. 1999;122:483–95.

    Article  PubMed  Google Scholar 

  16. Appel-Cresswell S, de la Fuente-Fernandez R, Galley S, McKeown MJ. Imaging of compensatory mechanisms in Parkinson’s disease. Curr Opin Neurol. 2010;23:407–12.

    Article  PubMed  Google Scholar 

  17. Werheid K, Zysset S, Müller A, Reuter M, von Cramon DY. Rule learning in a serial reaction time task: an fMRI study on patients with early Parkinson’s disease. Brain Res Cogn Brain Res. 2003;16:273–84.

    Article  PubMed  Google Scholar 

  18. Mallol R, Barrós-Loscertales A, López M, Belloch V, Parcet MA, Avila C. Compensatory cortical mechanisms in Parkinson’s disease evidenced with fMRI during the performance of pre-learned sequential movements. Brain Res. 2007;1147:265–71.

    Article  PubMed  CAS  Google Scholar 

  19. Bédard P, Sanes JN. On a basal ganglia role in learning and rehearsing visual-motor associations. Neuroimage. 2009;47(4):1701–10.

    Article  PubMed  Google Scholar 

  20. Ponsen MM, Daffertshofer A, van den Heuvel E, Wolters ECH, Beek PJ, Berendse HW. Bimanual coordination dysfunction in early, untreated Parkinson’s disease. Parkinsonism Relat Disord. 2006;12:246–52.

    Article  PubMed  Google Scholar 

  21. Wu T, Hallett M. Neural correlates of dual task performance in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2008;79:760–6.

    Article  PubMed  CAS  Google Scholar 

  22. Friston KJ. Functional and effective connectivity in neuroimaging: a synthesis. Hum Brain Mapp. 1994;2:56–78.

    Article  Google Scholar 

  23. Rowe J, Stephan KE, Friston K, Frackowiak R, Lees A, Passingham R. Attention to action in Parkinson’s disease: impaired effective connectivity among frontal cortical regions. Brain. 2002;125:276–89.

    Article  PubMed  Google Scholar 

  24. Rowe JB, Hughes LE, Barker RA, Owen AM. Dynamic causal modelling of effective connectivity from fMRI: are results reproducible and sensitive to Parkinson’s disease and its treatment? Neuroimage. 2010;52:1015–26.

    Article  PubMed  CAS  Google Scholar 

  25. Helmich RC, de Lange FP, Bloem BR, Toni I. Cerebral compensation during motor imagery in Parkinson’s disease. Neuropsychologia. 2007;45:2201–15.

    Article  PubMed  Google Scholar 

  26. Helmich RC, Aarts E, de Lange FP, Bloem BR, Toni I. Increased dependence of action selection on recent motor history in Parkinson’s disease. J Neurosci. 2009;29:6105–13.

    Article  PubMed  CAS  Google Scholar 

  27. Palmer SJ, Eigenraam L, Hoque T, McCaig RG, Troiano A, McKeown MJ. Levodopa-sensitive, dynamic changes in effective connectivity during simultaneous movements in Parkinson’s disease. Neuroscience. 2009;158:693–704.

    Article  PubMed  CAS  Google Scholar 

  28. van Eimeren T, Monchi O, Ballanger B, Strafella AP. Dysfunction of the default mode network in Parkinson disease. A functional magnetic resonance imaging study. Arch Neurol. 2009;66:877–83.

    Article  PubMed  Google Scholar 

  29. Jahanshahi M, Jones CR, Zijlmans J, Katzenschlager R, Lee L, Quinn N, Frith CD, Lees AJ. Dopaminergic modulation of striato-frontal connectivity during motor timing in Parkinson’s disease. Brain. 2010;133:727–45.

    Article  PubMed  Google Scholar 

  30. Wu T, Chan P, Hallett M. Effective connectivity of neural networks in automatic movements in Parkinson’s disease. Neuroimage. 2010;49:2581–87.

    Article  PubMed  CAS  Google Scholar 

  31. Wu T, Wang L, Hallett M, Chen Y, Li K, Chan P. Effective connectivity of brain networks during self-initiated movement in Parkinson’s disease. Neuroimage. 2011;55:204–15.

    Article  PubMed  Google Scholar 

  32. Palmer SJ, Li J, Wang ZJ, McKeown MJ. Joint amplitude and connectivity compensatory mechanisms in Parkinson’s disease. Neuroscience. 2010;166:1110–8.

    Article  PubMed  CAS  Google Scholar 

  33. Di Martino A, Scheres A, Margulies DS, Kelly AM, Uddin LQ, Shehzad Z, Biswal B, Walters JR, Castellanos FX, Milham MP. Functional connectivity of human striatum: a resting state FMRI study. Cereb Cortex. 2008;18:2735–47.

    Article  PubMed  CAS  Google Scholar 

  34. Grossman M, Cooke A, DeVita C, Lee C, Alsop D, Detre J, Gee J, Chen W, Stern MB, Hurtig HI. Grammatical and resource components of sentence processing in Parkinson’s disease: an fMRI study. Neurology. 2003;60:775–81.

    Article  PubMed  CAS  Google Scholar 

  35. Lewis SJ, Dove A, Robbins TW, Barker RA, Owen AM. Cognitive impairments in early Parkinson’s disease are accompanied by reductions in activity in frontostriatal neural circuitry. J Neurosci. 2003;23:6351–6.

    PubMed  CAS  Google Scholar 

  36. Monchi O, Petrides M, Doyon J, Postuma RB, Worsley K, Dagher A. Neural bases of set-shifting deficits in Parkinson’s disease. J Neurosci. 2004;24:702–10.

    Article  PubMed  CAS  Google Scholar 

  37. Monchi O, Petrides M, Strafella AP, Worsley K, Doyon J. Functional role of the basal ganglia in planning and execution of actions. Ann Neurol. 2006;59:257–64.

    Article  PubMed  Google Scholar 

  38. Monchi O, Petrides M, Mejia-Constain B, Strafella AP. Cortical activity in Parkinson’s disease during executive processing depends on striatal involvement. Brain. 2007;130:233–44.

    Article  PubMed  Google Scholar 

  39. Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL. A default mode of brain function. Proc Natl Acad Sci U S A. 2001;98:676–82.

    Article  PubMed  CAS  Google Scholar 

  40. Greicius MD, Krasnow B, Reiss AL, Menon V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci U S A. 2003;100:253–8.

    Article  PubMed  CAS  Google Scholar 

  41. Voon V, Dalley JW. Parkinson disease: impulsive choice-Parkinson disease and dopaminergic therapy. Nat Rev Neurol. 2011;7:541–2.

    Article  PubMed  CAS  Google Scholar 

  42. Voon V, Pessiglione M, Brezing C, Gallea C, Fernandez, HH, Dolan RJ, Hallett M. Mechanisms underlying dopamine-mediated reward bias in compulsive behaviors. Neuron. 2010;65:135–42.

    Article  PubMed  CAS  Google Scholar 

  43. Voon V, Gao J, Brezing C, Symmonds M, Ekanayake V, Fernandez H, Dolan RJ, Hallett M. Dopamine agonists and risk: impulse control disorders in Parkinson’s disease. Brain. 2011;134:1438–46.

    Article  PubMed  Google Scholar 

  44. Stebbins GT, Goetz CG, Carrillo MC, Bangen KJ, Turner DA, Glover GH, Gabrieli JD. Altered cortical visual processing in PD with hallucinations: an fMRI study. Neurology. 2004;63:1409–16.

    Article  PubMed  CAS  Google Scholar 

  45. Cardoso EF, Maia FM, Fregni F, Myczkowski ML, Melo LM, Sato JR, Marcolin MA, Rigonatti SP, Cruz AC Jr, Barbosa ER, Amaro E Jr. Depression in Parkinson’s disease: convergence from voxel-based morphometry and functional magnetic resonance imaging in the limbic thalamus. Neuroimage. 2009;47:467–72.

    Article  PubMed  Google Scholar 

  46. Moessnang C, Frank G, Bogdahn U, Winkler J, Greenlee MW, Klucken J. Altered activation patterns within the olfactory network in Parkinson’s disease. Cereb Cortex. 2011;221:1246–53.

    Article  Google Scholar 

  47. Biswal B, Yetkin FZ, Haughton VM, Hyde JS. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med. 1995;34:537–41.

    Article  PubMed  CAS  Google Scholar 

  48. Fox MD, Greicius M. Clinical applications of resting state functional connectivity. Front Syst Neurosci. 2010;4:19.

    PubMed  Google Scholar 

  49. Wu T, Long X, Zang Y, Wang L, Hallett M, Li K, Chan P. Regional homogeneity changes in patients with Parkinson’s disease. Hum Brain Mapp. 2009;30:1502–10.

    Article  PubMed  Google Scholar 

  50. Zang YF, Jiang TZ, Lu YL, He Y, Tian LX. Regional homogeneity approach to fMRI data analysis. Neuroimage. 2004;22:394–400.

    Article  PubMed  Google Scholar 

  51. Zang YF, He Y, Zhu CZ, Cao QJ, Sui MQ, Liang M, Tian LX, Jiang TZ, Wang YF. Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI. Brain Dev. 2007;29(2):83–91.

    Article  PubMed  Google Scholar 

  52. Skidmore FM, Yang M, Baxter L, von Deneen KM, Collingwood J, He G, White K, Korenkevych D, Savenkov A, Heilman KM, Gold M, Liu Y. Reliability analysis of the resting state can sensitively and specifically identify the presence of Parkinson disease. Neuroimage. 2011 Sep 6. (in press).

    Google Scholar 

  53. Skidmore FM, Yang M, Baxter L, von Deneen KM, Collingwood J, He G, Tandon R, Korenkevych D, Savenkov A, Heilman KM, Gold M, Liu Y. Apathy, depression, and motor symptoms have distinct and separable resting activity patterns in idiopathic Parkinson disease. Neuroimage 2011 Jul 14. (in press).

    Google Scholar 

  54. Wu T, Wang L, Chen Y, Zhao C, Li K, Chan P. Changes of functional connectivity of the motor network in the resting state in Parkinson’s disease. Neurosci Lett. 2009;460:6–10.

    Article  PubMed  CAS  Google Scholar 

  55. Helmich RC, Derikx LC, Bakker M, Scheeringa R, Bloem BR, Toni I. Spatial remapping of cortico-striatal connectivity in Parkinson’s disease. Cereb Cortex. 2010;20:1175–86.

    Article  PubMed  Google Scholar 

  56. Wu T, Long X, Wang L, Hallett M, Zang Y, Li K, Chan P. Functional connectivity of cortical motor areas in the resting state in Parkinson’s disease. Hum Brain Mapp. 2011;32:1443–57.

    Article  PubMed  Google Scholar 

  57. Baudrexel S, Witte T, Seifried C, von Wegner F, Beissner F, Klein JC, Steinmetz H, Deichmann R, Roeper J, Hilker R. Resting state fMRI reveals increased subthalamic nucleus-motor cortex connectivity in Parkinson’s disease. Neuroimage 2011;55:1728–38.

    Article  PubMed  Google Scholar 

  58. Seibert TM, Murphy EA, Kaestner EJ, Brewer JB. Interregional correlations in Parkinson disease and Parkinson-related dementia with resting functional MR imaging. Radiology. 2012 Apr;263(1):226–34.

    Article  Google Scholar 

  59. Braak H, Del TK, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging. 2003;24:197–211.

    Article  PubMed  Google Scholar 

  60. Fearnley JM, Lees AJ. Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain. 1991;14:2283–230.

    Article  Google Scholar 

  61. Buhmann C, Binkofski F, Klein C, Büchel C, van Eimeren T, Erdmann C, Hedrich K, Kasten M, Hagenah J, Deuschl G, Pramstaller PP, Siebner HR. Motor reorganization in asymptomatic carriers of a single mutant Parkin allele: a human model for presymptomatic parkinsonism. Brain. 2005;128:2281–90.

    Article  PubMed  CAS  Google Scholar 

  62. van Nuenen BF, Weiss MM, Bloem BR, Reetz K, van Eimeren T, Lohmann K, Hagenah J, Pramstaller PP, Binkofski F, Klein C, Siebner HR. Heterozygous carriers of a Parkin or PINK1 mutation share a common functional endophenotype. Neurology. 2009;72:1041–7.

    Article  PubMed  CAS  Google Scholar 

  63. van Eimeren T, Binkofski F, Buhmann C, Hagenah J, Strafella AP, Pramstaller PP, Siebner HR, Klein C. Imaging movement-related activity in medicated Parkin-associated and sporadic Parkinson’s disease. Parkinsonism Relat Disord. 2010;16:384–7.

    Article  PubMed  Google Scholar 

  64. Detre JA, Leigh JS, Williams DS, Koretsky AP. Perfusion imaging. Magn Reson Med. 1992;23:37–45.

    Article  PubMed  CAS  Google Scholar 

  65. Melzer TR, Watts R, MacAskill MR, Pearson JF, Rüeger S, Pitcher TL, Livingston L, Graham C, Keenan R, Shankaranarayanan A, Alsop DC, Dalrymple-Alford JC, Anderson TJ. Arterial spin labelling reveals an abnormal cerebral perfusion pattern in Parkinson’s disease. Brain. 2011;134:845–55.

    Article  PubMed  Google Scholar 

  66. Ma Y, Huang C, Dyke JP, Pan H, Alsop D, Feigin A, Eidelberg D. Parkinson’s disease spatial covariance pattern: noninvasive quantification with perfusion MRI. J Cereb Blood Flow Metab. 2010;30:505–9.

    Article  PubMed  Google Scholar 

  67. You H, Wang J, Wang H, Zang YF, Zheng FL, Meng CL, Feng F. Altered regional homogeneity in motor cortices in patients with multiple system atrophy. Neurosci Lett. 2011;502(1):18–23.

    Article  PubMed  CAS  Google Scholar 

  68. Whitwell JL, Avula R, Master A, Vemuri P, Senjem ML, Jones DT, Jack CR Jr, Josephs KA. Disrupted thalamocortical connectivity in PSP: a resting-state fMRI, DTI, and VBM study. Parkinsonism Relat Disord. 2011;17:599–605.

    Article  PubMed  Google Scholar 

  69. Zwergal A, la Fougère C, Lorenzl S, Rominger A, Xiong G, Deutschenbaur L, Linn J, Krafczyk S, Dieterich M, Brandt T, Strupp M, Bartenstein P, Jahn K. Postural imbalance and falls in PSP correlate with functional pathology of the thalamus. Neurology. 2011;77(2):101–9.

    Article  PubMed  CAS  Google Scholar 

  70. McKeith IG, Dickson DW, Lowe Emre M, O’Brien JT, Feldman H, Cummings J, Duda JE, Lippa C, Perry EK, Aarsland D, Arai H, Ballard CG, Boeve B, Burn DJ, Costa D, Del Ser T, Dubois B, Galasko D, Gauthier S, Goetz CG, Gomez-Tortosa E, Halliday G, Hansen LA, Hardy J, Iwatsubo T, Kalaria RN, Kaufer D, Kenny RA, Korczyn A, Kosaka K, Lee VM, Lees A, Litvan I, Londos E, Lopez OL, Minoshima S, Mizuno Y, Molina JA, Mukaetova-Ladinska EB, Pasquier F, Perry RH, Schulz JB, Trojanowski JQ, Yamada M; Consortium on DLB. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology. 2005;65:1863–72.

    Google Scholar 

  71. Lee JE, Park HJ, Park B, Song SK, Sohn YH, Lee JD, Lee PH. A comparative analysis of cognitive profiles and white-matter alterations using voxel-based diffusion tensor imaging between patients with Parkinson’s disease dementia and dementia with Lewy bodies. J Neurol Neurosurg Psychiatry. 2010;81:320–26.

    Article  PubMed  Google Scholar 

  72. Galvin JE, Price JL, Yan Z, Morris JC, Sheline YI. Resting bold fMRI differentiates dementia with Lewy bodies vs. Alzheimer disease. Neurology. 2011;76:1797–803.

    Article  PubMed  CAS  Google Scholar 

  73. Kenny ER, Blamire AM, Firbank MJ, O’Brien JT. Functional connectivity in cortical regions in dementia with Lewy bodies and Alzheimer’s disease. Brain. 2012;135:569–81.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurobiology, Xuanwu Hospital, 45 Changchun Street, 100053, Bejing, China

    Prof. Tao Wu MD

  2. Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 7D37, 10 Center Drive, 20892-1428, Bethesda, MD, USA

    Mark Hallett MD

Authors
  1. Prof. Tao Wu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark Hallett MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tao Wu MD .

Editor information

Editors and Affiliations

  1. , Department of Neuroscience, University of California at San Diego, Gilman Dr 9500, La Jolla, 92093, California, USA

    Fatta B. Nahab

  2. , Neurorehabilitation Research Institute, Morinomiya Hospital, Morinomiya 2-1-88, Joto-ku,Osaka-shi, 536-0025, Osaka, Japan

    Noriaki Hattori

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Wu, T., Hallett, M. (2013). Functional MRI in Idiopathic Parkinson Disease and Parkinsonism. In: Nahab, F., Hattori, N. (eds) Neuroimaging of Movement Disorders. Current Clinical Neurology, vol 44. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-471-5_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-471-5_9

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-470-8

  • Online ISBN: 978-1-62703-471-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation