Functional imaging of Parkinson’s disease: is it possible to detect brain areas for specific symptoms?

  • David J. Brooks
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 56)


H2 15O PET activation studies enable the brain systems involved in controlling different aspects of motor function to be defined. In Parkinson’s disease (PD) freely chosen limb movements are performed slowly. This bradykinesia is associated with selective underactivity of the supplementary motor area and dorsal prefrontal cortex, frontal association areas that receive subcortical input principally from the basal ganglia. At the same time there is compensatory overactivity of the lateral premotor and parietal cortex, areas that have a primary role in facilitating motor responses to visual and auditory cues. This finding explains why PD patients find it easier to perform cued as opposed to freely chosen actions. Levels of activation of the supplementary motor area and dorsal prefrontal cortex in PD can be restored with dopaminergic medication, implants of fetal mesencephalic tissue, internal pallidotomy or high frequency electrical subthalamic stimulation.

Activation studies suggest that Parkinsonian rest tremor arises from a combination of inappropriate overactivity of cerebellar connections and loss of dopaminergic function. When tremor is relieved by ventral thalamotomy or thalamic stimulation this cerebellar overactivity is corrected but at the expense of reducing levels of primary motor cortex activation.

It has been hypothesised that dyskinesias in PD arise due to altered dopamine receptor binding following chronic exposure to levodopa stimulation. Functional imaging findings, however, are against this hypothesis and rather suggest that downstream increases in basal ganglia opioid neurotransmission are more likely to be relevant.


Essential Tremor Postural Tremor Positron emISSIOn Tomography Activation Lateral Premotor Cortex Dorsal Prefrontal Cortex 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Alexander GE, Crutcher MD, Delong MR (1990) Basal ganglia thalamo-cortical circuits: parallel substrates for motor, oculomotor, “prefrontal” and “limbic” functions. Prog Brain Res 85: 119–146PubMedCrossRefGoogle Scholar
  2. Arcusa MJ, Barcia-Salorio JL, Burguera A, Pascual-Leone A (1996) Chronic, high frequency stimulation of the globus pallidus internus in Parkinson’s disease. Neurology 46 [Suppl 2]: A490Google Scholar
  3. Asenbaum S, Brucke T, Pirker W, Muller C, Wober C, Podreka I (1996) [123I]β-CIT-SPECT in Parkinson’s disase and essential tremor. Mov Disord 11 [Suppl 1]: 112Google Scholar
  4. Augood SJ, Emson PC, Mitchell IJ, Boyce S, Clarke CE, Crossman AR (1989) Cellular localisation of enkephalin gene expression in MPTP-treated cynomolgus monkeys. Mol Brain Res 6: 85–92PubMedCrossRefGoogle Scholar
  5. Baron MS, Vitek JL, Bakay RAE, Green J, Kaneoke Y, Hashimoto T, et al (1996) Treatment of advanced Parkinson’s disease by posterior GPi pallidotomy: 1-year results of a pilot study. Ann Neurol 40: 355–366PubMedCrossRefGoogle Scholar
  6. Bedard PJ, Gomez Mancilla B, Blanchette P, Gagnon C, Di Paolo T (1992) Levodopa-induced dyskinesia: facts and fantasy. What does the MPTP monkey tell us? Can J Neurol Sci 19: 134–137PubMedGoogle Scholar
  7. Benabid AL, Pollak P, Gervason C, Hoffman D, Gao DM, Hommel M, et al (1991) Long-term suppresion of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet 337: 403–406PubMedCrossRefGoogle Scholar
  8. Benecke R, Rothwell JC, Dick JP, Day BL, Marsden CD (1987) Disturbance of sequential movements in patients with Parkinson’s disease. Brain 110: 361–379PubMedCrossRefGoogle Scholar
  9. Blanchet P, Bedard PJ, Britton DR, Kebabian JW (1993) Differential effects of selective D-1 and D-2 dopamine agonists on levodopa-induced dyskinesia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-exposed monkeys. J Pharmacol Exp Therap 267: 275–279Google Scholar
  10. Boecker H, Ceballos-Baumann A, Dagher A, Samuel M, Passingham RE, Friston KJ, et al (1996) Central processing of increasingly complex learned finger sequences: Correlational analysis of 3D H2 15O PET data. Neurology 46 [Suppl]: A382Google Scholar
  11. Boecker H, Wills AJ, Ceballos-Baumann A, Samuel M, Thomas DGT, Marsden CD, et al (1997) Stereotactic thalamotomy in tremor-dominant Pakinson’s disease: A H2 15O PET motor activation study. Ann Neurol 41: 108–111PubMedCrossRefGoogle Scholar
  12. Boyce S, Clarke CE, Luquin R, Peggs D, Robertson RG, Mitchell IJ, et al (1990a) Induction of chorea and dystonia in Parkinsonian primates. Mov Disord 5: 3–7PubMedCrossRefGoogle Scholar
  13. Boyce S, Rupniak NMJ, Steventon MJ, Iversen SD (1990b) Differential effects of D1 and D2 agonists in MPTP-treated primates: Functional implications for Parkinson’s disease. Neurology 40: 927–933PubMedCrossRefGoogle Scholar
  14. Brooks DJ, Playford ED, Ibanez V, Sawle GV, Thompson PD, Findley LJ, et al (1992) Isolated tremor and disruption of the nigrostriatal dopaminergic system: An 18F-dopa PET study. Neurology 42: 1554–1560PubMedCrossRefGoogle Scholar
  15. Brooks DJ, Jenkins IH, Passingham RE (1993) Positron emission tomography studies on regional cerebral control of voluntary movement. In: Mano N, Hamada I, DeLong MR (eds) Role of the cerebellum and basal ganglia in voluntary movement. Excerpta Medica, Amsterdam, pp 267–274Google Scholar
  16. Burn DJ, Mark MH, Playford ED, Maraganore DM, Zimmerman Jr TR, Duvoisin RC, et al (1992) Parkinson’s disease in twins studied with 18F-dopa and positron emission tomography. Neurology 42: 1894–1900PubMedCrossRefGoogle Scholar
  17. Burn DJ, Rinne JO, Quinn NP, Lees AJ, Marsden CD, Brooks DJ (1995) Striatal opioid receptor binding in Parkinson’s disease, striatonigral degeneration, and Steele-Richardson-Olszewski syndrome: An 11C-diprenorphine PET study. Brain 118: 951–958PubMedCrossRefGoogle Scholar
  18. Ceballos-Baumann AO, Jenkins IH, Morrish PK, Brooks DJ, Rehncrona S, Odin P, et al (1996) Increase of movement-related activation of the supplementary motor area after embryonic mesencephalic grafting in Parkinson’s disease. Neurology 46 [Suppl]: A458CrossRefGoogle Scholar
  19. Ceballos-Baumann AO, Bartenstein P, Von Falkenhayn I, Boecker H, Riescher H, Schwaiger M, et al (1997) Parkinson’s disease ON and OFF subthalamic nucleus stimulation: A PET activation study. Neurology 48 [Suppl 2]: A250Google Scholar
  20. Crossman AR (1990) A hypothesis on the pathophysiological mechanisms that underlie levodopa-or dopamine agonist-induced dyskinesia in Parkinson’s disease: implications for future strategies in treatment. Mov Disord 5: 100–108PubMedCrossRefGoogle Scholar
  21. Dagher A, Owen AM, Brooks DJ (1997) Neuronal circuits involved in planning and spatial working memory in Parkinson’s disease and normal controls: A PET study. J Cereb Blood Flow Metabol 17 [Suppl 1]: S682Google Scholar
  22. Davis KD, Taub E, Houle S, Lang AE, Dostrovsky JO, Tasker RR, et al (1997) Globus pallidus stimulation activates the cortical motor system during alleviation of parkinsonian symptoms. Nat Med 3: 671–674PubMedCrossRefGoogle Scholar
  23. Deiber M-P, Pollak P, Passingham R, Landais P, Gervason C, Cinotti L, et al (1993) Thalamic stimulation and suppression of parkinsonisn tremor. Evidence of cerebellar deactivation using positron emission tomography. Brain 116: 267–279PubMedCrossRefGoogle Scholar
  24. Dick JPR, Rothwell JC, Day BL, Cantello R, Buruma O, Gioux M, et al (1989) The Bereitschaftspotential is abnormal in Parkinson’s disease. Brain 112: 233–244PubMedCrossRefGoogle Scholar
  25. Dogali M, Fazzini E, Kolodny E, Eidelberg D, Sterio D, Devinsky O, et al (1995) Stereotaxic ventral pallidotomy for Parkinson’s disease. Neurology 45: 753–761PubMedCrossRefGoogle Scholar
  26. Engber TM, Susel Z, Kuo S, et al (1991) Levodopa replacement therapy alters enzyme activities in striatum and neuropeptide content in striatal output neurons of 6-hydroxydopamine lesioned rats. Brain Res 552: 113–118PubMedCrossRefGoogle Scholar
  27. Fazzini E, Dogali M, Sterio D, Eidelberg D, Beric A (1997) Stereotactic pallidotomy for Parkinson’s disease: A long-term follow-up of unilateral pallidotomy. Neurology 48: 1273–1277PubMedCrossRefGoogle Scholar
  28. Fuxe K, Agnati LF, Kohler C, Kuonen D, Ogren SO, Andersson K, et al (1981) Characterisation of normal and supersensitive dopamine recetors: effects of ergot drugs and neuropeptides. J Neural Transm 51: 3–37PubMedCrossRefGoogle Scholar
  29. Gerfen CR, McGinty JF, Young III WS (1991) Dopamine differentially regulates dynorphin, substance P, and enkephalin expression in striatal neurons: in vivo hybridisation histochemical analysis. J Neurosci 11: 1016–1031PubMedGoogle Scholar
  30. Grafton ST, Waters C, Sutton J, Lew MF, Couldwell W (1995) Pallidotomy increases activity of motor association cortex in Parkinson’s disease — a positron emission tomographic study. Ann Neurol 37: 776–783PubMedCrossRefGoogle Scholar
  31. Henry B, Brotchie JM (1996) Potential of opioid antagonists in the treatment of levodopa-induced dyskinesias in Parkinson’s disease. Drugs Aging 9: 149–158PubMedCrossRefGoogle Scholar
  32. Hutchison WD, Lozano AM, Davis KD, Saint Cyr JA, Lang AE, Dostrovsky JO (1994) Differential neuronal activity in segments of globus pallidus in Parkinson’s disease patients. NeuroReport 5: 1533–1537PubMedCrossRefGoogle Scholar
  33. Jahanshahi M, Jenkins IH, Brown RG, Marsden CD, Passingham RE, Brooks DJ (1995) Self-initiated versus externally-triggered movements: Measurements of regional cerebral blood flow and movement-related potentials in normals and Parkinson’s disease. Brain 118: 913–933PubMedCrossRefGoogle Scholar
  34. Jenkins IH, Fernandez W, Playford ED, Lees AJ, Frackowiak RSJ, Passingham RE, et al (1992) Impaired activation of the supplementary motor area in Parkinson’s disease is reversed when akinesia is treated with apomorphine. Ann Neurol 32: 749–757PubMedCrossRefGoogle Scholar
  35. Jenkins IH, Bains PG, Colebatch JG, Thompson PD, Findley LJ, Frackowiak RSJ, et al (1993) A PET study of essential tremor: evidence for overactivity of cerebellar connections. Ann Neurol 34: 82–90PubMedCrossRefGoogle Scholar
  36. Jenkins IH, Brooks DJ, Nixon PD, Frackowiak RSJ, Passingham RE (1994) Motor sequence learning: A study with position emission tomography. J Neurosci 14: 3775–3790PubMedGoogle Scholar
  37. Jenkins IH, Jahanshahi M, Brown R, Jueptner M, Marsden CD, Passingham RE, et al (1996) Frontal activation during self-initiated finger movements and externally paced movements triggered by predictable and unpredictable stimuli. Neurology 46 [Suppl]: A382Google Scholar
  38. Laitinen LV, Bergenheim AT, Hariz MI (1992) Leksell’s posteroventral pallidotomy in the treatment of Parkinson’s disease. J Neurosurg 76: 53–61PubMedCrossRefGoogle Scholar
  39. Lamarre Y (1984) Animal models of tremor. In: Findley LJ, Capildeo R (eds) Movement disorders: tremor. MacMillan Press, London, pp 183–194Google Scholar
  40. Lamarre Y, Joffroy AJ (1979) Experimental tremor in the monkey: activity of thalamic and precentral cortical neurons in the absence of peripheral feedback. Adv Neurol 24: 109–122Google Scholar
  41. Larochelle L, Bedard P, Poirier LJ, Sourkes TL (1971) Correlative neuro-anatomical and neuropharmacological study of tremor and catatonia in the monkey. Neuropharmacology 10: 273–288PubMedCrossRefGoogle Scholar
  42. Lees AJ, Stern GM (1981) Sustained bromocriptine therapy in previously untreated patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 44: 1020–1023PubMedCrossRefGoogle Scholar
  43. Li SJ, Jiang HK, Satchowiak MS, et al (1990) Influence of nigrostriatal dopaminergic tone on the biosynthesis of dynorphin and enkephalin in rat striatum. Brain Res Mol Brain Res 8: 219–225PubMedCrossRefGoogle Scholar
  44. Liao K-K, Zeffiro T, Kertzman C, Hallett M (1992) Regional cerebral blood flow abnormalities in essential tremor. Mov Disord 7 [Suppl 1]: 46Google Scholar
  45. Limousin P, Pollak P, Benazzouz A, et al (1996) Effect on parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation. Lancet 345: 91–95CrossRefGoogle Scholar
  46. Limousin P, Greene J, Polak P, Rothwell JC, Benabid AL, Frackowiak RSJ (1997) Positron emission tomography (PET) study of modulation of cerebral activity by subthalamic nucleus (STN) and internal globus pallidus (GPi) stimulation in Parkinson’s disease. Neurology 48 [Suppl 2]: A249Google Scholar
  47. Luquin MR, Guillen J, Martinez-Vila E, Laguna J, Martinez Lage JM (1994) Functional interaction between dopamine D1 and D2 receptors in ‘MPTP’ monkeys. Eur J Pharmacol 253: 215–224PubMedCrossRefGoogle Scholar
  48. Mocchetti I, Naranjo J, Costa E (1987) Regulation of striatal enkephalin turnover in rats receiving antagonists of specific dopamine subtypes. J Pharmacol Exp Ther 241: 1120–1124PubMedGoogle Scholar
  49. Mouradian MM, Heuser IJE, Baronti F, Fabbrini G, Juncos JL, Chase TN (1989) Pathogenesis of dyskinesias in Parkinson’s disease. Ann Neurol 25: 523–526PubMedCrossRefGoogle Scholar
  50. Murata M, Kanazawa I (1993) Repeated L-dopa administration reduces the ability of dopamine storage and abolishes the supersensitivity of dopamine receptors in the striatum of intact rat. Neurosci Res 16: 15–23PubMedCrossRefGoogle Scholar
  51. Owen AM, Doyon J, Petrides M, Evans AC (1996) Planning and spatial working memory — a positron emission tomography study in humans. J Neurosci 8: 353–364CrossRefGoogle Scholar
  52. Parker F, Tzourio N, Blond S, Petit H, Mazoyer B (1992) Evidence for a common network of brain structures involved in parkinsonian tremor and voluntary repetitive movement. Brain Res 584: 11–17PubMedCrossRefGoogle Scholar
  53. Passingham RE (1987) Two cortical systems for directing movement. Motor areas of the cerebral cortex. Ciba Foundation 132: 151–164Google Scholar
  54. Penney Jr JB, Young AB (1986) Striatal inhomogeneities and basal ganglia function. Mov Disord 1: 3–15PubMedCrossRefGoogle Scholar
  55. Piccini P, Boecker H, Weeks RA, Brooks DJ (1997a) Dyskinesia correlated regional blood flow changes in Parkinson’s disease. Neurology 48 [Suppl 2]: A327Google Scholar
  56. Piccini P, Morrish PK, Turjanski N, Sawle GV, Mark MH, Maraganore DM, et al (1997b) Dopaminergic function in familial Parkinson’s disease: A clinical and 18F-dopa PET study. Ann Neurol 41: 222–229PubMedCrossRefGoogle Scholar
  57. Piccini P, Weeks RA, Brooks DJ (1997c) Opioid receptor binding in Parkinson’s patients with and without levodopa-induced dyskinesias. Ann Neurol 42: 720–726PubMedCrossRefGoogle Scholar
  58. Playford ED, Jenkins IH, Passingham RE, Nutt J, Frackowiak RSJ, Brooks DJ (1992) Impaired mesial frontal and putamen activation in Parkinson’s disease: a PET study. Ann Neurol 32: 151–161PubMedCrossRefGoogle Scholar
  59. Playford ED, Britton TC, Thompson PD, Brooks DJ, Findley LJ, Marsden CD (1995) Exacerbation of postural tremor with emergence of parkinsonism following neuroleptic administration. J Neurol Neurosurg Psychiatry 58: 487–489PubMedCrossRefGoogle Scholar
  60. Poirier LJ, Sourkes TL, Bouvier G, Boucher R, Carabin S (1966) Striatal amines, experimental tremor, and the effect of harmaline in the monkey. Brain 89: 37–52PubMedCrossRefGoogle Scholar
  61. Rascol O, Sabatini U, Fabre N, Brefel C, Loubinoux I, Celsis P, et al (1997) The ipsilateral cerebellar hemisphere is overactive during hand movements in akinetic parkinsonian patients. Brain 120: 103–110PubMedCrossRefGoogle Scholar
  62. Reches A, Wagner HR, Jackson-Lewis V, Yablonski-Alter E, Fahn S (1984) Chronic levodopa or pergolide administration induces downregulation of dopamine receptors in denervated striatum. Neurology 34: 1208–1212PubMedCrossRefGoogle Scholar
  63. Samuel M, Ceballos-Baumann AO, Blin J, Uema T, Boecker H, Brooks DJ (1997a) Evidence for lateral premotor and parietal overactivity in Parkinson’s disease during sequential and bimanual movements: A PET study. Brain 120: 963–976PubMedCrossRefGoogle Scholar
  64. Samuel M, Ceballos-Baumann AO, Turjanski N, Boecker H, Gorospe A, Linazasoro G, et al (1997b) Pallidotomy in Parkinson’s disease increases SMA and prefrontal activation during performance of volitional movements: An H2 15O PET study. Brain 120: 1301–1313PubMedCrossRefGoogle Scholar
  65. Samuel M, Caputo E, Brooks DJ, Scaravilli T, Branston N, Rothwell JC, et al (1998) A study of medial pallidotomy for Parkinson’s disease: Clinical outcome, MRI location and complications. Brain (In press)Google Scholar
  66. Sterio D, Beric A, Dogali M, Fazzini E, Alfaro G, Devinsky O (1994) Neurophysiological properties of pallidal neurons in Parkinson’s disease. Ann Neurol 35: 586–591PubMedCrossRefGoogle Scholar
  67. Trabucchi M, Bassi S, Frattola L (1982) Effect of naloxone on the “on-off” syndrome in patients receiving long-term levodopa therapy. Arch Neurol 39: 120–121PubMedCrossRefGoogle Scholar
  68. Turjanski N, Lees AJ, Brooks DJ (1997) PET studies on striatal dopaminergic receptor binding in drug naive and L-dopa treated Parkinson’s disease patients with and without dyskinesia. Neurology 49: 717–723PubMedCrossRefGoogle Scholar
  69. Wills AJ, Jenkins IH, Thompson PD, Frackowiak RSJ, Findley LJ, Brooks DJ (1994) Red nuclear and cerebellar but no olivary activation associated with essential tremor: A positron emission tomography study. Ann Neurol 36: 636–642PubMedCrossRefGoogle Scholar
  70. Young III WS, Bonner TI, Brann MR (1986) Mesencephalic dopamine neurons regulate the expression of neuropeptide mRNAs in the rat forebrain. Proc Natl Acad Sci USA 83: 9827–9831PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1999

Authors and Affiliations

  • David J. Brooks
    • 1
  1. 1.MRC Cyclotron Unit, Imperial College School of MedicineHammersmith Hospital and Institute of NeurologyLondonUK

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