Skip to main content
PMC home page
Journal of Anatomy logoLink to Journal of Anatomy
. 2000 May;196(Pt 4):519–525. doi: 10.1046/j.1469-7580.2000.19640519.x

Functional anatomy of movement disorders

A R CROSSMAN 1,✉
PMCID: PMC1468094  PMID: 10923984

Abstract

Models of basal ganglia function are described which encapsulate the principal pathophysiological mechanisms underlying parkinsonian akinesia on the one hand and abnormal involuntary movement disorders (dyskinesias) on the other. In Parkinson's disease, degeneration of the nigrostriatal dopamine system leads to overactivity of the ‘indirect’ striatopallidal projection to the lateral (external) segment of the globus pallidus. This causes inhibition of lateral pallidal neurons, which in turn project to the subthalamic nucleus. Disinhibition of the subthalamic nucleus leads to abnormal subthalamic overactivity and, as a consequence, overactivity of medial (internal) pallidal output neurons. Dyskinesias, such as are observed in Huntington's disease, levodopa-induced dyskinesia and ballism, share mechanistic features in common and are associated with decreased neuronal activity in both the subthalamic nucleus and the medial globus pallidus.

Keywords: Basal ganglia, Parkinson's disease, akinesia, dyskinesias

Full Text

The Full Text of this article is available as a PDF (149.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ALPERS B. J., JAEGER R. Hemiballism and its control by ablation of the motor cortex. Arch Neurol Psychiatry. 1950 Aug;64(2):285–287. [PubMed] [Google Scholar]
  2. Albin R. L., Qin Y., Young A. B., Penney J. B., Chesselet M. F. Preproenkephalin messenger RNA-containing neurons in striatum of patients with symptomatic and presymptomatic Huntington's disease: an in situ hybridization study. Ann Neurol. 1991 Oct;30(4):542–549. doi: 10.1002/ana.410300406. [DOI] [PubMed] [Google Scholar]
  3. Alexander G. E., Crutcher M. D., DeLong M. R. Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, "prefrontal" and "limbic" functions. Prog Brain Res. 1990;85:119–146. [PubMed] [Google Scholar]
  4. Asanuma C., Thach W. T., Jones E. G. Distribution of cerebellar terminations and their relation to other afferent terminations in the ventral lateral thalamic region of the monkey. Brain Res. 1983 May;286(3):237–265. doi: 10.1016/0165-0173(83)90015-2. [DOI] [PubMed] [Google Scholar]
  5. Aziz T. Z., Peggs D., Agarwal E., Sambrook M. A., Crossman A. R. Subthalamic nucleotomy alleviates parkinsonism in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-exposed primate. Br J Neurosurg. 1992;6(6):575–582. doi: 10.3109/02688699209002375. [DOI] [PubMed] [Google Scholar]
  6. Aziz T. Z., Peggs D., Sambrook M. A., Crossman A. R. Lesion of the subthalamic nucleus for the alleviation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in the primate. Mov Disord. 1991;6(4):288–292. doi: 10.1002/mds.870060404. [DOI] [PubMed] [Google Scholar]
  7. Barbeau A., Duvoisin R. C., Gerstenbrand F., Lakke J. P., Marsden C. D., Stern G. Classification of extrapyramidal disorders. Proposal for an international classification and glossary of terms. J Neurol Sci. 1981 Aug;51(2):311–327. doi: 10.1016/0022-510x(81)90109-x. [DOI] [PubMed] [Google Scholar]
  8. Baron M. S., Vitek J. L., Bakay R. A., Green J., Kaneoke Y., Hashimoto T., Turner R. S., Woodard J. L., Cole S. A., McDonald W. M. Treatment of advanced Parkinson's disease by posterior GPi pallidotomy: 1-year results of a pilot study. Ann Neurol. 1996 Sep;40(3):355–366. doi: 10.1002/ana.410400305. [DOI] [PubMed] [Google Scholar]
  9. Beal M. F., Ellison D. W., Mazurek M. F., Swartz K. J., Malloy J. R., Bird E. D., Martin J. B. A detailed examination of substance P in pathologically graded cases of Huntington's disease. J Neurol Sci. 1988 Mar;84(1):51–61. doi: 10.1016/0022-510x(88)90173-6. [DOI] [PubMed] [Google Scholar]
  10. Benabid A. L., Pollak P., Gross C., Hoffmann D., Benazzouz A., Gao D. M., Laurent A., Gentil M., Perret J. Acute and long-term effects of subthalamic nucleus stimulation in Parkinson's disease. Stereotact Funct Neurosurg. 1994;62(1-4):76–84. doi: 10.1159/000098600. [DOI] [PubMed] [Google Scholar]
  11. Benazzouz A., Gross C., Féger J., Boraud T., Bioulac B. Reversal of rigidity and improvement in motor performance by subthalamic high-frequency stimulation in MPTP-treated monkeys. Eur J Neurosci. 1993 Apr 1;5(4):382–389. doi: 10.1111/j.1460-9568.1993.tb00505.x. [DOI] [PubMed] [Google Scholar]
  12. Bergman H., Wichmann T., DeLong M. R. Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science. 1990 Sep 21;249(4975):1436–1438. doi: 10.1126/science.2402638. [DOI] [PubMed] [Google Scholar]
  13. Bergman H., Wichmann T., Karmon B., DeLong M. R. The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism. J Neurophysiol. 1994 Aug;72(2):507–520. doi: 10.1152/jn.1994.72.2.507. [DOI] [PubMed] [Google Scholar]
  14. Bird E. D., Iversen L. L. Huntington's chorea. Post-mortem measurement of glutamic acid decarboxylase, choline acetyltransferase and dopamine in basal ganglia. Brain. 1974 Sep;97(3):457–472. doi: 10.1093/brain/97.1.457. [DOI] [PubMed] [Google Scholar]
  15. Bird E. D., Mackay A. V., Rayner C. N., Iversen L. L. Reduced glutamic-acid-decarboxylase activity of post-mortem brain in Huntington's chorea. Lancet. 1973 May 19;1(7812):1090–1092. doi: 10.1016/s0140-6736(73)90398-x. [DOI] [PubMed] [Google Scholar]
  16. Blanchet P. J., Calon F., Martel J. C., Bédard P. J., Di Paolo T., Walters R. R., Piercey M. F. Continuous administration decreases and pulsatile administration increases behavioral sensitivity to a novel dopamine D2 agonist (U-91356A) in MPTP-exposed monkeys. J Pharmacol Exp Ther. 1995 Feb;272(2):854–859. [PubMed] [Google Scholar]
  17. Brotchie J. M., Crossman A. R. D-[3H]aspartate and [14C]GABA uptake in the basal ganglia of rats following lesions in the subthalamic region suggest a role for excitatory amino acid but not GABA-mediated transmission in subthalamic nucleus efferents. Exp Neurol. 1991 Aug;113(2):171–181. doi: 10.1016/0014-4886(91)90173-a. [DOI] [PubMed] [Google Scholar]
  18. Brotchie J. M., Mitchell I. J., Sambrook M. A., Crossman A. R. Alleviation of parkinsonism by antagonism of excitatory amino acid transmission in the medial segment of the globus pallidus in rat and primate. Mov Disord. 1991;6(2):133–138. doi: 10.1002/mds.870060208. [DOI] [PubMed] [Google Scholar]
  19. Burns R. S., Chiueh C. C., Markey S. P., Ebert M. H., Jacobowitz D. M., Kopin I. J. A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4546–4550. doi: 10.1073/pnas.80.14.4546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Burns R. S., Markey S. P., Phillips J. M., Chiueh C. C. The neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the monkey and man. Can J Neurol Sci. 1984 Feb;11(1 Suppl):166–168. doi: 10.1017/s0317167100046345. [DOI] [PubMed] [Google Scholar]
  21. CARPENTER M. B., CORRELL J. W., HINMAN A. Spinal tracts mediating subthalamic hyperkinesia. Physiological effects of selective partial cordotomies upon dyskinesia in rhesus monkey. J Neurophysiol. 1960 May;23:288–304. doi: 10.1152/jn.1960.23.3.288. [DOI] [PubMed] [Google Scholar]
  22. CARPENTER M. B., METTLER F. A. Analysis of subthalamic hyperkinesia in the monkey with special reference to ablations of a granular cortex. J Comp Neurol. 1951 Aug;95(1):125–157. doi: 10.1002/cne.900950108. [DOI] [PubMed] [Google Scholar]
  23. CARPENTER M. B., WHITTIER J. R., METTLER F. A. Analysis of choreoid hyperkinesia in the Rhesus monkey; surgical and pharmacological analysis of hyperkinesia resulting from lesions in the subthalamic nucleus of Luys. J Comp Neurol. 1950 Jun;92(3):293–331. doi: 10.1002/cne.900920303. [DOI] [PubMed] [Google Scholar]
  24. Calon F., Goulet M., Blanchet P. J., Martel J. C., Piercey M. F., Bédard P. J., Di Paolo T. Levodopa or D2 agonist induced dyskinesia in MPTP monkeys: correlation with changes in dopamine and GABAA receptors in the striatopallidal complex. Brain Res. 1995 May 22;680(1-2):43–52. doi: 10.1016/0006-8993(95)00229-j. [DOI] [PubMed] [Google Scholar]
  25. Chiueh C. C., Markey S. P., Burns R. S., Johannessen J. N., Jacobowitz D. M., Kopin I. J. Neurochemical and behavioral effects of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) in rat, guinea pig, and monkey. Psychopharmacol Bull. 1984 Summer;20(3):548–553. [PubMed] [Google Scholar]
  26. Clarke C. E., Sambrook M. A., Mitchell I. J., Crossman A. R. Levodopa-induced dyskinesia and response fluctuations in primates rendered parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). J Neurol Sci. 1987 May;78(3):273–280. doi: 10.1016/0022-510x(87)90041-4. [DOI] [PubMed] [Google Scholar]
  27. Crossman A. R., Clarke C. E., Boyce S., Robertson R. G., Sambrook M. A. MPTP-induced parkinsonism in the monkey: neurochemical pathology, complications of treatment and pathophysiological mechanisms. Can J Neurol Sci. 1987 Aug;14(3 Suppl):428–435. doi: 10.1017/s0317167100037859. [DOI] [PubMed] [Google Scholar]
  28. Crossman A. R., Mitchell I. J., Sambrook M. A. Regional brain uptake of 2-deoxyglucose in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in the macaque monkey. Neuropharmacology. 1985 Jun;24(6):587–591. doi: 10.1016/0028-3908(85)90070-x. [DOI] [PubMed] [Google Scholar]
  29. Crossman A. R., Sambrook M. A., Jackson A. Experimental hemiballismus in the baboon produced by injection of a gamma-aminobutyric acid antagonist into the basal ganglia. Neurosci Lett. 1980 Dec;20(3):369–372. doi: 10.1016/0304-3940(80)90176-7. [DOI] [PubMed] [Google Scholar]
  30. Crossman A. R., Sambrook M. A., Jackson A. Experimental hemichorea/hemiballismus in the monkey. Studies on the intracerebral site of action in a drug-induced dyskinesia. Brain. 1984 Jun;107(Pt 2):579–596. doi: 10.1093/brain/107.2.579. [DOI] [PubMed] [Google Scholar]
  31. Jackson A., Crossman A. R. Experimental choreoathetosis produced by injection of a gamma-aminobutyric acid antagonist into the lentiform nucleus in the monkey. Neurosci Lett. 1984 Apr 20;46(1):41–45. doi: 10.1016/0304-3940(84)90196-4. [DOI] [PubMed] [Google Scholar]
  32. Kita H., Kitai S. T. Intracellular study of rat globus pallidus neurons: membrane properties and responses to neostriatal, subthalamic and nigral stimulation. Brain Res. 1991 Nov 15;564(2):296–305. doi: 10.1016/0006-8993(91)91466-e. [DOI] [PubMed] [Google Scholar]
  33. Laitinen L. V. Ventroposterolateral pallidotomy. Stereotact Funct Neurosurg. 1994;62(1-4):41–52. doi: 10.1159/000098596. [DOI] [PubMed] [Google Scholar]
  34. Langston J. W., Ballard P., Tetrud J. W., Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science. 1983 Feb 25;219(4587):979–980. doi: 10.1126/science.6823561. [DOI] [PubMed] [Google Scholar]
  35. Langston J. W., Forno L. S., Rebert C. S., Irwin I. Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyrine (MPTP) in the squirrel monkey. Brain Res. 1984 Feb 6;292(2):390–394. doi: 10.1016/0006-8993(84)90777-7. [DOI] [PubMed] [Google Scholar]
  36. McGeer P. L., McGeer E. G. Enzymes associated with the metabolism of catecholamines, acetylcholine and gaba in human controls and patients with Parkinson's disease and Huntington's chorea. J Neurochem. 1976 Jan;26(1):65–76. [PubMed] [Google Scholar]
  37. Mitchell I. J., Boyce S., Sambrook M. A., Crossman A. R. A 2-deoxyglucose study of the effects of dopamine agonists on the parkinsonian primate brain. Implications for the neural mechanisms that mediate dopamine agonist-induced dyskinesia. Brain. 1992 Jun;115(Pt 3):809–824. doi: 10.1093/brain/115.3.809. [DOI] [PubMed] [Google Scholar]
  38. Mitchell I. J., Clarke C. E., Boyce S., Robertson R. G., Peggs D., Sambrook M. A., Crossman A. R. Neural mechanisms underlying parkinsonian symptoms based upon regional uptake of 2-deoxyglucose in monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neuroscience. 1989;32(1):213–226. doi: 10.1016/0306-4522(89)90120-6. [DOI] [PubMed] [Google Scholar]
  39. Mitchell I. J., Cross A. J., Sambrook M. A., Crossman A. R. Neural mechanisms mediating 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-induced parkinsonism in the monkey: relative contributions of the striatopallidal and striatonigral pathways as suggested by 2-deoxyglucose uptake. Neurosci Lett. 1986 Jan 2;63(1):61–65. doi: 10.1016/0304-3940(86)90013-3. [DOI] [PubMed] [Google Scholar]
  40. Mitchell I. J., Jackson A., Sambrook M. A., Crossman A. R. Common neural mechanisms in experimental chorea and hemiballismus in the monkey. Evidence from 2-deoxyglucose autoradiography. Brain Res. 1985 Jul 29;339(2):346–350. doi: 10.1016/0006-8993(85)90102-7. [DOI] [PubMed] [Google Scholar]
  41. Mitchell I. J., Jackson A., Sambrook M. A., Crossman A. R. The role of the subthalamic nucleus in experimental chorea. Evidence from 2-deoxyglucose metabolic mapping and horseradish peroxidase tracing studies. Brain. 1989 Dec;112(Pt 6):1533–1548. doi: 10.1093/brain/112.6.1533. [DOI] [PubMed] [Google Scholar]
  42. Mitchell I. J., Luquin R., Boyce S., Clarke C. E., Robertson R. G., Sambrook M. A., Crossman A. R. Neural mechanisms of dystonia: evidence from a 2-deoxyglucose uptake study in a primate model of dopamine agonist-induced dystonia. Mov Disord. 1990;5(1):49–54. doi: 10.1002/mds.870050113. [DOI] [PubMed] [Google Scholar]
  43. Nakanishi H., Kita H., Kitai S. T. Intracellular study of rat entopeduncular nucleus neurons in an in vitro slice preparation: response to subthalamic stimulation. Brain Res. 1991 May 24;549(2):285–291. doi: 10.1016/0006-8993(91)90469-c. [DOI] [PubMed] [Google Scholar]
  44. Penney J. B., Jr, Young A. B. Speculations on the functional anatomy of basal ganglia disorders. Annu Rev Neurosci. 1983;6:73–94. doi: 10.1146/annurev.ne.06.030183.000445. [DOI] [PubMed] [Google Scholar]
  45. Penney J. B., Jr, Young A. B. Striatal inhomogeneities and basal ganglia function. Mov Disord. 1986;1(1):3–15. doi: 10.1002/mds.870010102. [DOI] [PubMed] [Google Scholar]
  46. Sapp E., Ge P., Aizawa H., Bird E., Penney J., Young A. B., Vonsattel J. P., DiFiglia M. Evidence for a preferential loss of enkephalin immunoreactivity in the external globus pallidus in low grade Huntington's disease using high resolution image analysis. Neuroscience. 1995 Jan;64(2):397–404. doi: 10.1016/0306-4522(94)00427-7. [DOI] [PubMed] [Google Scholar]
  47. Schell G. R., Strick P. L. The origin of thalamic inputs to the arcuate premotor and supplementary motor areas. J Neurosci. 1984 Feb;4(2):539–560. doi: 10.1523/JNEUROSCI.04-02-00539.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Smith Y., Parent A. Neurons of the subthalamic nucleus in primates display glutamate but not GABA immunoreactivity. Brain Res. 1988 Jun 21;453(1-2):353–356. doi: 10.1016/0006-8993(88)90177-1. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Anatomy are provided here courtesy of Anatomical Society of Great Britain and Ireland

RESOURCES