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Brain network markers of abnormal cerebral glucose metabolism and blood flow in Parkinson’s disease

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Abstract

Neuroimaging of cerebral glucose metabolism and blood flow is ideally suited to assay widely-distributed brain circuits as a result of local molecular events and behavioral modulation in the central nervous system. With the progress in novel analytical methodology, this endeavor has succeeded in unraveling the mechanisms underlying a wide spectrum of neurodegenerative diseases. In particular, statistical brain mapping studies have made significant strides in describing the pathophysiology of Parkinson’s disease (PD) and related disorders by providing signature biomarkers to determine the systemic abnormalities in brain function and evaluate disease progression, therapeutic responses, and clinical correlates in patients. In this article, we review the relevant clinical applications in patients in relation to healthy volunteers with a focus on the generation of unique spatial covariance patterns associated with the motor and cognitive symptoms underlying PD. These characteristic biomarkers can be potentially used not only to improve patient recruitment but also to predict outcomes in clinical trials.

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References

  1. Thobois S, Jahanshahi M, Pinto S, Frackowiak R, Limousin-Dowsey P. PET and SPECT functional imaging studies in Parkinsonian syndromes: from the lesion to its consequences. Neuroimage 2004, 23: 1–16.

    Article  PubMed  CAS  Google Scholar 

  2. Peng S, Doudet DJ, Dhawan V, Ma Y. Dopamine PET imaging and Parkinson’s disease. PET Clin 2013, 8: 469–485.

    Article  Google Scholar 

  3. Ma Y, Tang C, Moeller JR, Eidelberg D. Abnormal regional brain function in Parkinson’s disease: truth or fiction? Neuroimage 2009, 45: 260–266.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 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: 483–495.

    Article  PubMed  Google Scholar 

  5. Wichmann T, DeLong MR. Functional neuroanatomy of the basal ganglia in Parkinson’s disease. Adv. Neurol. 2003, 91: 9–18.

    PubMed  Google Scholar 

  6. Braak H, Del Tredici K. Cortico-basal ganglia-cortical circuitry in Parkinson’s disease reconsidered. Exp Neurol 2008, 212: 226–229.

    Article  PubMed  Google Scholar 

  7. Brownell AL, Canales K, Chen YI, Jenkins BG, Owen C, Livni E, et al. Mapping of brain function after MPTP-induced neurotoxicity in a primate Parkinson’s disease model. Neuroimage 2003, 20: 1064–1075.

    Article  PubMed  Google Scholar 

  8. Guigoni C, Dovero S, Aubert I, Li Q, Bioulac BH, Bloch B, et al. Levodopa-induced dyskinesia in MPTP-treated macaques is not dependent on the extent and pattern of nigrostrial lesioning. Eur. J. Neurosci. 2005, 22: 283–287.

    Article  PubMed  Google Scholar 

  9. Fukuda M, Mentis MJ, Ma Y, Dhawan V, Antonini A, Lang AE, et al. Networks mediating the clinical effects of pallidal brain stimulation for Parkinson’s disease: a PET study of resting-state glucose metabolism. Brain 2001, 124: 1601–1609.

    Article  PubMed  CAS  Google Scholar 

  10. Eckert T, Barnes A, Dhawan V, Frucht S, Gordon MF, Feigin AS, et al. FDG PET in the differential diagnosis of parkinsonian disorders. Neuroimage 2005, 26: 912–921.

    Article  PubMed  Google Scholar 

  11. Teune LK, Bartels AL, de Jong BM, Willemsen AT, Eshuis SA, de Vries JJ, et al. Typical cerebral metabolic patterns in neurodegenerative brain diseases. Mov Disord 2010, 25: 2395–2404.

    Article  PubMed  Google Scholar 

  12. Powers WJ, Videen TO, Markham J, Black KJ, Golchin N, Perlmutter JS. Cerebral mitochondrial metabolism in early Parkinson’s disease. J Cereb Blood Flow Metab 2008, 28: 1754–1760.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Ghaemi M, Raethjen J, Hilker R, Rudolf J, Sobesky J, Deuschl G, et al. Monosymptomatic resting tremor and Parkinson’s disease: a multitracer positron emission tomographic study. Mov Disord 2002, 17: 782–788.

    Article  PubMed  Google Scholar 

  14. Hilker R, Voges J, Weisenbach S, Kalbe E, Burghaus L, Ghaemi M, et al. Subthalamic nucleus stimulation restores glucose metabolism in associative and limbic cortices and in cerebellum: evidence from a FDG-PET study in advanced Parkinson’s disease. J Cereb Blood Flow Metab 2004, 24: 7–16.

    Article  PubMed  CAS  Google Scholar 

  15. Lozza C, Marie RM, Baron JC. The metabolic substrates of bradykinesia and tremor in uncomplicated Parkinson’s disease. Neuroimage 2002, 17: 688–699.

    Article  PubMed  CAS  Google Scholar 

  16. Trost M, Su S, Su P, Yen RF, Tseng HM, Barnes A, et al. Network modulation by the subthalamic nucleus in the treatment of Parkinson’s disease. Neuroimage 2006, 31: 301–307.

    Article  PubMed  Google Scholar 

  17. Bohnen NI, Minoshima S, Giordani B, Frey KA, Kuhl DE. Motor correlates of occipital glucose hypometabolism in Parkinson’s disease without dementia. Neurology 1999, 52: 541–546.

    Article  PubMed  CAS  Google Scholar 

  18. Hosokai Y, Nishio Y, Hirayama K, Takeda A, Ishioka T, Sawada Y, et al. Distinct patterns of regional cerebral glucose metabolism in Parkinson’s disease with and without mild cognitive impairment. Mov Disord 2009, 24: 854–862.

    Article  PubMed  Google Scholar 

  19. Berti V, Polito C, Ramat S, Vanzi E, De Cristofaro MT, Pellicano G, et al. Brain metabolic correlates of dopaminergic degeneration in de novo idiopathic Parkinson’s disease. Eur J Nucl Med Mol Imaging 2010, 37: 537–544.

    Article  PubMed  CAS  Google Scholar 

  20. Arahata Y, Hirayama M, Ieda T, Koike Y, Kato T, Tadokoro M, et al. Parieto-occipital glucose hypometabolism in Parkinson’s disease with autonomic failure. J Neurol Sci 1999, 163: 119–126.

    Article  PubMed  CAS  Google Scholar 

  21. Wu JC, Iacono R, Ayman M, Salmon E, Lin SD, Carlson J, et al. Correlation of intellectual impairment in Parkinson’s disease with FDG PET scan. Neuroreport 2000, 11: 2139–2144.

    Article  PubMed  CAS  Google Scholar 

  22. Liepelt I, Reimold M, Maetzler W, Godau J, Reischl G, Gaenslen A, et al. Cortical hypometabolism assessed by a metabolic ratio in Parkinson’s disease primarily reflects cognitive deterioration-[18F]FDG-PET. Mov Disord 2009, 24: 1504–1511.

    Article  PubMed  Google Scholar 

  23. Boecker H, Ceballos-Baumann A, Bartenstein P, Weindl A, Siebner HR, Fassbender T, et al. Sensory processing in Parkinson’s and Huntington’s disease: investigations with 3D H(2)(15)O-PET. Brain 1999, 122: 1651–1665.

    Article  PubMed  Google Scholar 

  24. Fukuda M, Mentis M, Ghilardi MF, Dhawan V, Antonini A, Hammerstad J, et al. Functional correlates of pallidal stimulation for Parkinson’s disease. Ann Neurol 2001, 49: 155–164.

    Article  PubMed  CAS  Google Scholar 

  25. Imon Y, Matsuda H, Ogawa M, Kogure D, Sunohara N. SPECT image analysis using statistical parametric mapping in patients with Parkinson’s disease. J Nucl Med 1999, 40: 1583–1589.

    PubMed  CAS  Google Scholar 

  26. Kikuchi A, Takeda A, Kimpara T, Nakagawa M, Kawashima R, Sugiura M, et al. Hypoperfusion in the supplementary motor area, dorsolateral prefrontal cortex and insular cortex in Parkinson’s disease. J Neurol Sci 2001, 193: 29–36.

    Article  PubMed  CAS  Google Scholar 

  27. Abe Y, Kachi T, Kato T, Arahata Y, Yamada T, Washimi Y, et al. Occipital hypoperfusion in Parkinson’s disease without dementia: correlation to impaired cortical visual processing. J Neurol Neurosurg Psychiatry 2003, 74: 419–422.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  28. Matsui H, Nishinaka K, Oda M, Hara N, Komatsu K, Kubori T, et al. Heterogeneous factors in dementia with Parkinson’s disease: IMP-SPECT study. Parkinsonism Relat Disord 2007, 13: 174–181.

    Article  PubMed  Google Scholar 

  29. Firbank MJ, Colloby SJ, Burn DJ, McKeith IG, O’Brien JT. Regional cerebral blood flow in Parkinson’s disease with and without dementia. Neuroimage 2003, 20: 1309–1319.

    Article  PubMed  CAS  Google Scholar 

  30. Osaki Y, Morita Y, Fukumoto M, Akagi N, Yoshida S, Doi Y. Three-dimensional stereotactic surface projection SPECT analysis in Parkinson’s disease with and without dementia. Mov Disord 2005, 20: 999–1005.

    Article  PubMed  Google Scholar 

  31. Spetsieris PG, Eidelberg D. Scaled subprofile modeling of resting state imaging data in Parkinson’s disease: methodological issues. Neuroimage 2011, 54: 2899–2914.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Moeller JR, Ishikawa T, Dhawan V, Spetsieris P, Mandel F, Alexander GE, et al. The metabolic topography of normal aging. J Cereb Blood Flow Metab 1996, 16: 385–398.

    Article  PubMed  CAS  Google Scholar 

  33. Hsu JL, Jung TP, Hsu CY, Hsu WC, Chen YK, Duann JR, et al. Regional CBF changes in Parkinson’s disease: a correlation with motor dysfunction. Eur J Nucl Med Mol Imaging 2007, 34: 1458–1466.

    Article  PubMed  Google Scholar 

  34. Mentis MJ, McIntosh AR, Perrine K, Dhawan V, Berlin B, Feigin A, et al. Relationships among the metabolic patterns that correlate with mnemonic, visuospatial, and mood symptoms in Parkinson’s disease. Am J Psychiatry 2002, 159: 746–754.

    Article  PubMed  Google Scholar 

  35. Chen K, Reiman EM, Huan Z, Caselli RJ, Bandy D, Ayutyanont N, et al. Linking functional and structural brain images with multivariate network analyses: a novel application of the partial least square method. Neuroimage 2009, 47: 602–610.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Friston KJ, Holmes A, Poline JB, Price CJ, Frith CD. Detecting activations in PET and fMRI: levels of inference and power. Neuroimage 1996, 4: 223–235.

    Article  PubMed  CAS  Google Scholar 

  37. McIntosh AR, Bookstein FL, Haxby JV, Grady CL. Spatial pattern analysis of functional brain images using partial least squares. Neuroimage 1996, 3: 143–157.

    Article  PubMed  CAS  Google Scholar 

  38. Carbon M, Eidelberg D. Function al imaging of sequence learning in Parkinson’s disease. J Neurol Sci 2006, 248: 72–77.

    Article  PubMed  Google Scholar 

  39. Ma Y, Tang C, Spetsieris PG, Dhawan V, Eidelberg D. Abnormal metabolic network activity in Parkinson’s disease: test-retest reproducibility. J Cereb Blood Flow Metab 2007, 27: 597–605.

    Article  PubMed  Google Scholar 

  40. Niethammer M, Eidelberg D. Metabo lic brain networks in translational neurology: Concepts and Applications. Ann Neurol 2012.

    Google Scholar 

  41. Kaasinen V, Maguire RP, Hundemer HP, Leenders KL. Corticostriatal covariance patterns of 6-[18F]fluoro-L-dopa and [18F]fluorodeoxyglucose PET in Parkinson’s disease. J Neurol 2006, 253: 340–348.

    Article  PubMed  CAS  Google Scholar 

  42. Huang C, Tang C, Feigin A, Lesser M, Ma Y, Pourfar M, et al. Changes in network activity with the progression of Parkinson’s disease. Brain 2007, 130: 1834–1846.

    Article  PubMed  Google Scholar 

  43. Moeller JR, Nakamura T, Mentis MJ, Dhawan V, Spetsieres P, Antonini A, et al. Reproducibility of Regional Metabolic Covariance Patterns: Comparison of Four Populations. Journal of Nuclear Medicine 1999, 40: 1264–1269.

    PubMed  CAS  Google Scholar 

  44. Wu P, Wang J, Peng S, Ma Y, Zhang H, Guan Y, et al. Metabolic brain network in the Chinese patients with Parkinson’s disease based on 18F-FDG PET imaging. Parkinsonism Relat Disord 2013, 19: 622–627.

    Article  PubMed  Google Scholar 

  45. Teune LK, Renken RJ, Mudali D, De Jong BM, Dierckx RA, Roerdink JB, et al. Validation of parkinsonian disease-related metabolic brain patterns. Mov Disord 2013, 28: 547–551.

    Article  PubMed  CAS  Google Scholar 

  46. Ma Y, Peng S, Spetsieris PG, Sossi V, Eidelberg D, Doudet DJ. Abnormal metabolic brain networks in a nonhuman primate model of parkinsonism. J Cereb Blood Flow Metab 2012, 32: 633–642.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  47. Eckert T, Tang C, Ma Y, Brown N, Lin T, Frucht S, et al. Abnormal metabolic networks in atypical parkinsonism. Mov Disord 2008, 23: 727–733.

    Article  PubMed  Google Scholar 

  48. Poston KL, Tang CC, Eckert T, Dhawan V, Frucht S, Vonsattel JP, et al. Network correlates of disease severity in multiple system atrophy. Neurology 2012, 78: 1237–1244.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  49. Mure H, Hirano S, Tang CC, Isaias IU, Antonini A, Ma Y, et al. Parkinson’s disease tremor-related metabolic network: characterization, progression, and treatment effects. Neuroimage 2011, 54: 1244–1253.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Huang C, Mattis P, Tang C, Perrine K, Carbon M, Eidelberg D. Metabolic brain networks associated with cognitive function in Parkinson’s disease. Neuroimage 2007, 34: 714–723.

    Article  PubMed  Google Scholar 

  51. Lozza C, Baron JC, Eidelberg D, Mentis MJ, Carbon M, Marie RM. Executive processes in Parkinson’s disease: FDG-PET and network analysis. Hum Brain Mapp 2004, 22: 236–245.

    Article  PubMed  Google Scholar 

  52. Eidelberg D, Moeller JR, Kazumata K, Antonini A, Sterio D, Dhawan V, et al. Metabolic correlates of pallidal neuronal activity in Parkinson’s disease. Brain 1997, 120: 1315–1324.

    Article  PubMed  Google Scholar 

  53. Lin TP, Carbon M, Tang C, Mogilner AY, Sterio D, Beric A, et al. Metabolic correlates of subthalamic nucleus activity in Parkinson’s disease. Brain 2008, 131: 1373–1380.

    Article  PubMed  Google Scholar 

  54. Feigin A, Antonini A, Fukuda M, De Notaris R, Benti R, Pezzoli G, et al. Tc-99m ethylene cysteinate dimer SPECT in the differential diagnosis of parkinsonism. Mov Disord 2002, 17: 1265–1270.

    Article  PubMed  Google Scholar 

  55. Eckert T, Van Laere K, Tang C, Lewis DE, Edwards C, Santens P, et al. Quantification of Parkinson’s disease-related network expression with ECD SPECT. Eur J Nucl Med Mol Imaging 2007, 34: 496–501.

    Article  PubMed  Google Scholar 

  56. Ma Y, Eidelberg D. Functional imaging of cerebral blood flow and glucose metabolism in Parkinson’s disease and Huntington’s disease. Mol Imaging Biol 2007, 9: 223–233.

    Article  PubMed  Google Scholar 

  57. Ma Y, Huang C, Dyke JP, Pan H, Alsop D, Feigin A, et al. Parkinson’s disease spatial covariance pattern: noninvasive quantification with perfusion MRI. J Cereb Blood Flow Metab 2010, 30: 505–509.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Melzer TR, Watts R, MacAskill MR, Pearson JF, Rueger S, Pitcher TL, et al. Arterial spin labelling reveals an abnormal cerebral perfusion pattern in Parkinson’s disease. Brain 2011, 134: 845–855.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Feigin A, Fukuda M, Dhawan V, Przedborski S, Jackson-Lewis V, Mentis MJ, et al. Metabolic correlates of levodopa response in Parkinson’s disease. Neurology 2001, 57: 2083–2088.

    Article  PubMed  CAS  Google Scholar 

  60. Hilker R, Voges J, Thiel A, Ghaemi M, Herholz K, Sturm V, et al. Deep brain stimulation of the subthalamic nucleus versus levodopa challenge in Parkinson’s disease: measuring the on- and off-conditions with FDG-PET. J Neural Transm 2002, 109: 1257–1264.

    Article  PubMed  CAS  Google Scholar 

  61. Hirano S, Asanuma K, Ma Y, Tang C, Feigin A, Dhawan V, et al. Dissociation of metabolic and neurovascular responses to levodopa in the treatment of Parkinson’s disease. J Neurosci 2008, 28: 4201–4209.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  62. Krack P, Batir A, Van Blercom N, Chabardes S, Fraix V, Ardouin C, et al. Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson’s disease. The New England journal of medicine 2003, 349: 1925–1934.

    Article  PubMed  CAS  Google Scholar 

  63. Follett KA, Weaver FM, Stern M, Hur K, Harris CL, Luo P, et al. Pallidal versus subthalamic deep-brain stimulation for Parkinson’s disease. N Engl J Med 2010, 362: 2077–2091.

    Article  PubMed  CAS  Google Scholar 

  64. Fasano A, Daniele A, Albanese A. Treatment of motor and non-motor features of Parkinson’s disease with deep brain stimulation. Lancet Neurol 2012, 11: 429–442.

    Article  PubMed  Google Scholar 

  65. Payoux P, Remy P, Miloudi M, Houeto JL, Stadler C, Bejjani BP, et al. Contrasting changes in cortical activation induced by acute high-frequency stimulation within the globus pallidus in Parkinson’s disease. J Cereb Blood Flow Metab 2009, 29: 235–243.

    Article  PubMed  Google Scholar 

  66. Fukuda M, Barnes A, Simon ES, Holmes A, Dhawan V, Giladi N, et al. Thalamic stimulation for parkinsonian tremor: correlation between regional cerebral blood flow and physiological tremor characteristics. Neuroimage 2004, 21: 608–615.

    Article  PubMed  Google Scholar 

  67. Asanuma K, Tang C, Ma Y, Dhawan V, Mattis P, Edwards C, et al. Network modulation in the treatment of Parkinson’s disease. Brain 2006, 129: 2667–2678.

    Article  PubMed  Google Scholar 

  68. Trost M, Su PC, Barnes A, Su SL, Yen RF, Tseng HM, et al. Evolving metabolic changes during the first postoperative year after subthalamotomy. J Neurosurg 2003, 99: 872–878.

    Article  PubMed  Google Scholar 

  69. Wang J, Ma Y, Huang Z, Sun B, Guan Y, Zuo C. Modulation of me tabolic brain function by bilateral subthalamic nucleus stimulation in the treatment of Parkinson’s disease. J Neurol 2010, 257: 72–78.

    Article  PubMed  Google Scholar 

  70. Karimi M, Golchin N, Tabbal SD, Hershey T, Videen TO, Wu J, et al. Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease. Brain 2008, 131: 2710–2719.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  71. Geday J, Ostergaard K, Johnsen E, Gjedde A. STN-stimulation in Parkinson’s disease restores striatal inhibition of thalamocortical projection. Hum Brain Mapp 2009, 30: 112–121.

    Article  PubMed  Google Scholar 

  72. Sestini S, Ramat S, Formiconi AR, Ammannati F, Sorbi S, Pupi A. Brain networks underlying the clinical effects of long-term subthalamic stimulation for Parkinson’s disease: a 4-year follow-up study with rCBF SPECT. J Nucl Med 2005, 46: 1444–1454.

    PubMed  Google Scholar 

  73. Limousin P, Greene J, Pollak P, Rothwell J, Benabid AL, Frackowiak R. Changes in cerebral activity pattern due to subthalamic nucleus or internal pallidum stimulation in Parkinson’s disease. Ann Neurol 1997, 42: 283–291.

    Article  PubMed  CAS  Google Scholar 

  74. Thobois S, Hotton GR, Pinto S, Wilkinson L, Limousin-Dowsey P, Brooks DJ, et al. STN stimulation alters pallidal-frontal coupling during response selection under competition. J Cereb Blood Flow Metab 2007, 27: 1173–1184.

    Article  PubMed  Google Scholar 

  75. Ballanger B, Lozano AM, Moro E, van Eimeren T, Hamani C, Chen R, et al. Cerebral blood flow changes induced by pedunculopontine nucleus stimulation in patients with advanced Parkinson’s disease: A [(15)O] H(2)O PET study. Hum Brain Mapp 2009, 30: 3901–3909.

    Article  PubMed  Google Scholar 

  76. Alessandro S, Ceravolo R, Brusa L, Pierantozzi M, Costa A, Galati S, et al. Non-motor functions in parkinsonian patients implanted in the pedunculopontine nucleus: focus on sleep and cognitive domains. J Neurol Sci 2010, 289: 44–48.

    Article  PubMed  Google Scholar 

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Peng, S., Eidelberg, D. & Ma, Y. Brain network markers of abnormal cerebral glucose metabolism and blood flow in Parkinson’s disease. Neurosci. Bull. 30, 823–837 (2014). https://doi.org/10.1007/s12264-014-1472-x

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