Journal of Neural Transmission

, Volume 123, Issue 7, pp 751–767 | Cite as

Our first decade of experience in deep brain stimulation of the brainstem: elucidating the mechanism of action of stimulation of the ventrolateral pontine tegmentum

  • Paolo Mazzone
  • Osvaldo Vilela Filho
  • Fabio Viselli
  • Angelo Insola
  • Stefano Sposato
  • Flora Vitale
  • Eugenio Scarnati
Translational Neurosciences - Review Article

Abstract

The region of the pedunculopontine tegmental nucleus (PPTg) has been proposed as a novel target for deep brain stimulation (DBS) to treat levodopa resistant symptoms in motor disorders. Recently, the anatomical organization of the brainstem has been revised and four new distinct structures have been represented in the ventrolateral pontine tegmentum area in which the PPTg was previously identified. Given this anatomical reassessment, and considering the increasing of our experience, in this paper we revisit the value of DBS applied to that area. The reappraisal of clinical outcomes in the light of this revisitation may also help to understand the consequences of DBS applied to structures located in the ventrolateral pontine tegmentum, apart from the PPTg. The implantation of 39 leads in 32 patients suffering from Parkinson’s disease (PD, 27 patients) and progressive supranuclear palsy (PSP, four patients) allowed us to reach two major conclusions. The first is that the results of the advancement of our technique in brainstem DBS matches the revision of brainstem anatomy. The second is that anatomical and functional aspects of our findings may help to explain how DBS acts when applied in the brainstem and to identify the differences when it is applied either in the brainstem or in the subthalamic nucleus. Finally, in this paper we discuss how the loss of neurons in brainstem nuclei occurring in both PD and PSP, the results of intraoperative recording of somatosensory evoked potentials, and the improvement of postural control during DBS point toward the potential role of ascending sensory pathways and/or other structures in mediating the effects of DBS applied in the ventrolateral pontine tegmentum region.

Keywords

Deep brain stimulation Ventrolateral pontine tegmentum Pedunculopontine tegmental nucleus Parkinson’s disease Atypical parkinsonisms Somatosensory evoked potentials 

Notes

Acknowledgments

The authors wish to thank Prof. Edgar Garcia-Rill for his critical reading of the manuscript and suggestions. We are also grateful to Prof Francesco Masedu and Dr. Annamaria Capozzo, University of L’Aquila, for evaluating data and carrying out statistics concerning correlations between SEPs and anatomical landmarks, and Prof. Paolo Arena, DIEEI, University of Catania, for evaluating the electrical fields generated by DBS.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Ethical standard statement

All the procedures described in the present paper have been conducted according to ethical standards, approved by local ethical committees and patients gave their informed consent to participate to the described studies.

References

  1. Alam M, Schwabe K, Krauss JK (2011) The pedunculopontine nucleus area: critical evaluation of interspecies differences relevant for its use as a target for deep brain stimulation. Brain 134:11–23CrossRefPubMedGoogle Scholar
  2. Albin RL, Young AB, Penney JB (1995) The functional anatomy of disorders of the basal ganglia. Trends Neurosci 18:63–64CrossRefPubMedGoogle Scholar
  3. Aravamuthan BR, Angelaki DE (2012) Vestibular responses in the macaque pedunculopontine nucleus and central mesencephalic reticular formation. Neuroscience 223:183–199CrossRefPubMedPubMedCentralGoogle Scholar
  4. Aravamuthan BR, Muthusamy KA, Stein JF, Aziz TZ, Johansen-Berg H (2007) Topography of cortical and subcortical connections of the human pedunculopontine and subthalamic nuclei. Neuroimage 37:694–705CrossRefPubMedGoogle Scholar
  5. Aravamuthan BR, Stein JF, Aziz TZ (2008) The anatomy and localization of the pedunculopontine nucleus determined using probabilistic diffusion tractography [corrected]. Br J Neurosurg 22(Suppl 1):S25–S32CrossRefPubMedGoogle Scholar
  6. Bartolic A, Pirtosek Z, Rozman J, Ribaric S (2005) Postural stability of Parkinson’s disease patients is improved by decreasing rigidity. Eur J Neurol 12:156–159CrossRefPubMedGoogle Scholar
  7. Bejjani BP, Gervais D, Arnulf I, Papadopoulos S, Demeret S, Bonnet AM, Cornu P, Damier P, Agid Y (2000) Axial parkinsonian symptoms can be improved: the role of levodopa and bilateral subthalamic stimulation. J Neurol Neurosurg Psychiatry 68:595–600CrossRefPubMedPubMedCentralGoogle Scholar
  8. Bergman H, Wichmann T, Karmon B, DeLong MR (1994) The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism. J Neurophysiol 72:507–520PubMedGoogle Scholar
  9. Beuter A, Hernandez R, Rigal R, Modolo J, Blanchet PJ (2008) Postural sway and effect of levodopa in early Parkinson’s disease. Can J Neurol Sci 35:65–68CrossRefPubMedGoogle Scholar
  10. Blaszczyk JW, Orawiec R (2011) Assessment of postural control in patients with Parkinson’s disease: sway ratio analysis. Hum Mov Sci 30:396–404CrossRefPubMedGoogle Scholar
  11. Bonnet AM, Loria Y, Saint-Hilaire MH, Lhermitte F, Agid Y (1987) Does long-term aggravation of Parkinson’s disease result from nondopaminergic lesions? Neurology 37:1539–1542CrossRefPubMedGoogle Scholar
  12. Braak H, Del Tredici K (2008) Cortico-basal ganglia-cortical circuitry in Parkinson’s disease reconsidered. Exp Neurol 212:226–229CrossRefPubMedGoogle Scholar
  13. Braak H, Ghebremedhin E, Rub U, Bratzke H, Del TK (2004) Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 318:121–134CrossRefPubMedGoogle Scholar
  14. Caliandro P, Insola A, Scarnati E, Padua L, Russo G, Granieri E, Mazzone P (2011) Effects of unilateral pedunculopontine stimulation on electromyographic activation patterns during gait in individual patients with Parkinson’s disease. J Neural Transm 118:1477–1486CrossRefPubMedGoogle Scholar
  15. Dautan D, Huerta-Ocampo I, Witten IB, Deisseroth K, Bolam JP, Gerdjikov T, Mena-Segovia J (2014) A major external source of cholinergic innervation of the striatum and nucleus accumbens originates in the brainstem. J Neurosci 34:4509–4518CrossRefPubMedPubMedCentralGoogle Scholar
  16. DeLong MR (1990) Primate models of movement disorders of basal ganglia origin. Trends Neurosci 13:281–285CrossRefPubMedGoogle Scholar
  17. Deniau JM, Degos B, Bosch C, Maurice N (2010) Deep brain stimulation mechanisms: beyond the concept of local functional inhibition. Eur J Neurosci 32:1080–1091CrossRefPubMedGoogle Scholar
  18. Edley SM, Graybiel AM (1983) The afferent and efferent connections of the feline nucleus tegmenti pedunculopontinus, pars compacta. J Comp Neurol 217:187–215CrossRefPubMedGoogle Scholar
  19. Ferraye MU, Debu B, Fraix V, Goetz L, Ardouin C, Yelnik J, Henry-Lagrange C, Seigneuret E, Piallat B, Krack P, Le Bas JF, Benabid AL, Chabardes S, Pollak P (2010) Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson’s disease. Brain 133:205–214CrossRefPubMedGoogle Scholar
  20. Futami T, Takakusaki K, Kitai ST (1995) Glutamatergic and cholinergic inputs from the pedunculopontine tegmental nucleus to dopamine neurons in the substantia nigra pars compacta. Neurosci Res 21:331–342CrossRefPubMedGoogle Scholar
  21. Garcia-Rill E (2015) Waking and the reticular activating system in health and disease. Elsevier-Academic Press, AmsterdamGoogle Scholar
  22. Garcia-Rill E, Skinner RD, Miyazato H, Homma Y (2001) Pedunculopontine stimulation induces prolonged activation of pontine reticular neurons. Neuroscience 104:455–465CrossRefPubMedGoogle Scholar
  23. Grofova I, Keane S (1991) Descending brainstem projections of the pedunculopontine tegmental nucleus in the rat. Anat Embryol (Berl) 184:275–290CrossRefGoogle Scholar
  24. Gut NK, Winn P (2015) Deep brain stimulation of different pedunculopontine targets in a novel rodent model of parkinsonism. J Neurosci 35:4792–4803CrossRefPubMedPubMedCentralGoogle Scholar
  25. Hazrati LN, Parent A (1992) Projection from the deep cerebellar nuclei to the pedunculopontine nucleus in the squirrel monkey. Brain Res 585:267–271CrossRefPubMedGoogle Scholar
  26. Hirsch EC, Graybiel AM, Duyckaerts C, Javoy-Agid F (1987) Neuronal loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy. Proc Natl Acad Sci USA 84:5976–5980CrossRefPubMedPubMedCentralGoogle Scholar
  27. Hong S, Hikosaka O (2014) Pedunculopontine tegmental nucleus neurons provide reward, sensorimotor, and alerting signals to midbrain dopamine neurons. Neuroscience 282C:139–155CrossRefGoogle Scholar
  28. Insola A, Valeriani M, Mazzone P (2012) Targeting the pedunculopontine nucleus: a new neurophysiological method based on somatosensory evoked potentials to calculate the distance of the deep brain stimulation lead from the Obex. Neurosurgery 71:96–103PubMedGoogle Scholar
  29. Insola A, Padua L, Mazzone P, Scarnati E, Valeriani M (2014) Low and high-frequency somatosensory evoked potentials recorded from the human pedunculopontine nucleus. Clin Neurophysiol 125:1859–1869CrossRefPubMedGoogle Scholar
  30. Jackson A, Crossman AR (1983) Nucleus tegmenti pedunculopontinus: efferent connections with special reference to the basal ganglia, studied in the rat by anterograde and retrograde transport of horseradish peroxidase. Neuroscience 10:725–765CrossRefPubMedGoogle Scholar
  31. Jellinger K (1988) The pedunculopontine nucleus in Parkinson’s disease, progressive supranuclear palsy and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 51:540–543CrossRefPubMedPubMedCentralGoogle Scholar
  32. Jenkinson N, Nandi D, Miall RC, Stein JF, Aziz TZ (2004) Pedunculopontine nucleus stimulation improves akinesia in a Parkinsonian monkey. Neuroreport 15:2621–2624CrossRefPubMedGoogle Scholar
  33. Karachi C, Andre A, Bertasi E, Bardinet E, Lehericy S, Bernard FA (2012) Functional parcellation of the lateral mesencephalus. J Neurosci 32:9396–9401CrossRefPubMedGoogle Scholar
  34. Khan S, Javed S, Mooney L, White P, Plaha P, Whone A, Gill SS (2012) Clinical outcomes from bilateral versus unilateral stimulation of the pedunculopontine nucleus with and without concomitant caudal zona incerta region stimulation in Parkinson’s disease. Br J Neurosurg 26:722–725CrossRefPubMedGoogle Scholar
  35. Kobayashi Y, Isa T (2002) Sensory-motor gating and cognitive control by the brainstem cholinergic system. Neural Netw 15:731–741CrossRefPubMedGoogle Scholar
  36. Krauthamer GM, Grunwerg BS, Krein H (1995) Putative cholinergic neurons of the pedunculopontine tegmental nucleus projecting to the superior colliculus consist of sensory responsive and unresponsive populations which are functionally distinct from other mesopontine neurons. Neuroscience 69:507–517CrossRefPubMedGoogle Scholar
  37. Lau B, Welter ML, Belaid H, Fernandez VS, Bardinet E, Grabli D, Karachi C (2015) The integrative role of the pedunculopontine nucleus in human gait. Brain 138:1284–1296CrossRefPubMedGoogle Scholar
  38. Lavoie B, Parent A (1994a) Pedunculopontine nucleus in the squirrel monkey: projections to the basal ganglia as revealed by anterograde tract-tracing methods. J Comp Neurol 344:210–231CrossRefPubMedGoogle Scholar
  39. Lavoie B, Parent A (1994b) Pedunculopontine nucleus in the squirrel monkey: cholinergic and glutamatergic projections to the substantia nigra. J Comp Neurol 344:232–241CrossRefPubMedGoogle Scholar
  40. Lee HJ, Rye DB, Hallanger AE, Levey AI, Wainer BH (1988) Cholinergic vs. noncholinergic efferents from the mesopontine tegmentum to the extrapyramidal motor system nuclei. J Comp Neurol 275:469–492CrossRefPubMedGoogle Scholar
  41. Mancini M, Carlson-Kuhta P, Zampieri C, Nutt JG, Chiari L, Horak FB (2012) Postural sway as a marker of progression in Parkinson’s disease: a pilot longitudinal study. Gait Posture 36:471–476CrossRefPubMedPubMedCentralGoogle Scholar
  42. Mazzone P, Stanzione P, Lozano A, Sposato S, Scarnati E, Stefani A (2005a) Brain stimulation and movement disorders: Where are we going? In: Meglio M (ed) Proceedings of the 14th meeting of the World Society for Stereotactic and Functional Neurosurgery (WSSFN) Monduzzi, Bologna, ItalyGoogle Scholar
  43. Mazzone P, Lozano A, Stanzione P, Galati S, Scarnati E, Peppe A, Stefani A (2005b) Implantation of human pedunculopontine nucleus: a safe and clinically relevant target in Parkinson’s disease. Neuroreport 16:1877–1881CrossRefPubMedGoogle Scholar
  44. Mazzone P, Sposato S, Insola A, Dilazzaro V, Scarnati E (2008) Stereotactic surgery of nucleus tegmenti pedunculopontine. Br J Neurosurg 22(Suppl 1):S33–S40CrossRefPubMedGoogle Scholar
  45. Mazzone P, Insola A, Sposato S, Scarnati E (2009) The deep brain stimulation of the pedunculopontine tegmental nucleus. Neuromodulation 12:191–204CrossRefPubMedGoogle Scholar
  46. Mazzone P, Sposato S, Insola A, Scarnati E (2011) The deep brain stimulation of the pedunculopontine tegmental nucleus: towards a new stereotactic neurosurgery. J Neural Transm 118:1431–1451CrossRefPubMedGoogle Scholar
  47. Mazzone P, Padua L, Falisi G, Insola A, Florio TM, Scarnati E (2012) Unilateral deep brain stimulation of the pedunculopontine tegmental nucleus improves oromotor movements in Parkinson’s disease. Brain Stimul 5:634–641CrossRefPubMedGoogle Scholar
  48. Mazzone P, Sposato S, Insola A, Scarnati E (2013) The clinical effects of deep brain stimulation of the pedunculopontine tegmental nucleus in movement disorders may not be related to the anatomical target, leads location, and setup of electrical stimulation. Neurosurgery 73:894–906CrossRefPubMedGoogle Scholar
  49. Mazzone P, Paoloni M, Mangone M, Santilli V, Insola A, Fini M, Scarnati E (2014) Unilateral deep brain stimulation of the pedunculopontine tegmental nucleus in idiopathic Parkinson’s disease: effects on gait initiation and performance. Gait Posture 40:357–362CrossRefPubMedGoogle Scholar
  50. Moro E, Hamani C, Poon YY, Al-Khairallah T, Dostrovsky JO, Hutchison WD, Lozano AM (2010) Unilateral pedunculopontine stimulation improves falls in Parkinson’s disease. Brain 133:215–224CrossRefPubMedGoogle Scholar
  51. Muller ML, Albin RL, Kotagal V, Koeppe RA, Scott PJ, Frey KA, Bohnen NI (2013) Thalamic cholinergic innervation and postural sensory integration function in Parkinson’s disease. Brain 136:3282–3289CrossRefPubMedPubMedCentralGoogle Scholar
  52. Muthusamy KA, Aravamuthan BR, Kringelbach ML, Jenkinson N, Voets NL, Johansen-Berg H, Stein JF, Aziz TZ (2007) Connectivity of the human pedunculopontine nucleus region and diffusion tensor imaging in surgical targeting. J Neurosurg 107:814–820CrossRefPubMedGoogle Scholar
  53. Okada K, Kobayashi Y (2013) Reward prediction-related increases and decreases in tonic neuronal activity of the pedunculopontine tegmental nucleus. Front Integr Neurosci 7:36CrossRefPubMedPubMedCentralGoogle Scholar
  54. Okada K, Kobayashi Y (2014) Fixational saccade-related activity of pedunculopontine tegmental nucleus neurons in behaving monkeys. Eur J Neurosci 40:2641–2651CrossRefPubMedGoogle Scholar
  55. Olszewski J, Baxter D (1954) Cytoarchitecture of the human brainstem. Lippincott, PhiladelphiaGoogle Scholar
  56. Pahapill PA, Lozano AM (2000) The pedunculopontine nucleus and Parkinson’s disease. Brain 123:1767–1783CrossRefPubMedGoogle Scholar
  57. Panyakaew P, Anan C, Bhidayasiri R (2015) Visual deprivation elicits subclinical postural inflexibilities in early Parkinson’s disease. J Neurol Sci 349:214–219CrossRefPubMedGoogle Scholar
  58. Paxinos G, Huang XF (1995) Atlas of the human brainstem. Academic Press, San DiegoGoogle Scholar
  59. Paxinos G, Huang X, Sengul G, Watson (2012) Organization of brainstem nuclei. The human nervous system. Elsevier Academic Press, Amsterdam, pp 260–327CrossRefGoogle Scholar
  60. Pierantozzi M, Palmieri MG, Galati S, Stanzione P, Peppe A, Tropepi D, Brusa L, Pisani A, Moschella V, Marciani MG, Mazzone P, Stefani A (2008) Pedunculopontine nucleus deep brain stimulation changes spinal cord excitability in Parkinson’s disease patients. J Neural Transm 115:731–735CrossRefPubMedGoogle Scholar
  61. Plaha P, Gill SS (2005) Bilateral deep brain stimulation of the pedunculopontine nucleus for Parkinson’s disease. NeuroReport 16:1883–1887CrossRefPubMedGoogle Scholar
  62. Reese NB, Garcia-Rill E, Skinner RD (1995a) Auditory input to the pedunculopontine nucleus: II. Unit responses. Brain Res Bull 37:265–273CrossRefPubMedGoogle Scholar
  63. Reese NB, Garcia-Rill E, Skinner RD (1995b) Auditory input to the pedunculopontine nucleus: I. Evoked potentials. Brain Res Bull 37:257–264CrossRefPubMedGoogle Scholar
  64. Reese NB, Garcia-Rill E, Skinner RD (1995c) The pedunculopontine nucleus–auditory input, arousal and pathophysiology. Prog Neurobiol 47:105–133CrossRefPubMedGoogle Scholar
  65. Rinne JO, Ma SY, Lee MS, Collan Y, Roytta M (2008) Loss of cholinergic neurons in the pedunculopontine nucleus in Parkinson’s disease is related to disability of the patients. Parkinsonism Relat Disord 14:553–557CrossRefPubMedGoogle Scholar
  66. Rocchi L, Chiari L, Horak FB (2002) Effects of deep brain stimulation and levodopa on postural sway in Parkinson’s disease. J Neurol Neurosurg Psychiatry 73:267–274CrossRefPubMedPubMedCentralGoogle Scholar
  67. Ruggiero DA, Anwar M, Golanov EV, Reis DJ (1997) The pedunculopontine tegmental nucleus issues collaterals to the fastigial nucleus and rostral ventrolateral reticular nucleus in the rat. Brain Res 760:272–276CrossRefPubMedGoogle Scholar
  68. Rye DB, Saper CB, Lee HJ, Wainer BH (1987) Pedunculopontine tegmental nucleus of the rat: cytoarchitecture, cytochemistry, and some extrapyramidal connections of the mesopontine tegmentum. J Comp Neurol 259:483–528CrossRefPubMedGoogle Scholar
  69. Rye DB, Lee HJ, Saper CB, Wainer BH (1988) Medullary and spinal efferents of the pedunculopontine tegmental nucleus and adjacent mesopontine tegmentum in the rat. J Comp Neurol 269:315–341CrossRefPubMedGoogle Scholar
  70. Scarnati E, Florio T, Capozzo A, Confalone G, Mazzone P (2011) The pedunculopontine tegmental nucleus: implications for a role in modulating spinal cord motoneuron excitability. J Neural Transm 118:1409–1421CrossRefPubMedGoogle Scholar
  71. Schaltenbrand G, Wahren W (1977) Atlas for stereotaxy of the human brain. Thieme, New YorkGoogle Scholar
  72. Schrader C, Seehaus F, Capelle HH, Windhagen A, Windhagen H, Krauss JK (2013) Effects of pedunculopontine area and pallidal DBS on gait ignition in Parkinson’s disease. Brain StimulGoogle Scholar
  73. Sherman D, Fuller PM, Marcus J, Yu J, Zhang P, Chamberlin NL, Saper CB, Lu J (2015) Anatomical location of the mesencephalic locomotor region and its possible role in locomotion, posture, cataplexy, and parkinsonism. Front Neurol 6:140CrossRefPubMedPubMedCentralGoogle Scholar
  74. Skinner RD, Garcia-Rill E (1984) The mesencephalic locomotor region (MLR) in the rat. Brain Res 323:385–389CrossRefPubMedGoogle Scholar
  75. Skinner RD, Kinjo N, Henderson V, Garcia-Rill E (1990) Locomotor projections from the pedunculopontine nucleus to the spinal cord. Neuroreport 1:183–186CrossRefPubMedGoogle Scholar
  76. Stefani A, Lozano AM, Peppe A, Stanzione P, Galati S, Tropepi D, Pierantozzi M, Brusa L, Scarnati E, Mazzone P (2007) Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson’s disease. Brain 130:1596–1607CrossRefPubMedGoogle Scholar
  77. Sugimoto T, Hattori T (1984) Organization and efferent projections of nucleus tegmenti pedunculopontinus pars compacta with special reference to its cholinergic aspects. Neuroscience 11:931–946CrossRefPubMedGoogle Scholar
  78. Sutton AC, O’Connor KA, Pilitsis JG, Shin DS (2015) Stimulation of the subthalamic nucleus engages the cerebellum for motor function in parkinsonian rats. Brain Struct Funct 220:3595–3609CrossRefPubMedGoogle Scholar
  79. Takakusaki K, Habaguchi T, Ohtinata-Sugimoto J, Saitoh K, Sakamoto T (2003) Basal ganglia efferents to the brainstem centers controlling postural muscle tone and locomotion: a new concept for understanding motor disorders in basal ganglia dysfunction. Neuroscience 119:293–308CrossRefPubMedGoogle Scholar
  80. Takakusaki K, Habaguchi T, Saitoh K, Kohyama J (2004) Changes in the excitability of hindlimb motoneurons during muscular atonia induced by stimulating the pedunculopontine tegmental nucleus in cats. Neuroscience 124:467–480CrossRefPubMedGoogle Scholar
  81. Talairach J, David M, Tornoux P, Korredor H, Kvasina T (1957) Atlas d’anatomie stereotaxique des noyaux gris centraux. Masson, ParisGoogle Scholar
  82. Tattersall TL, Stratton PG, Coyne TJ, Cook R, Silberstein P, Silburn PA, Windels F, Sah P (2014) Imagined gait modulates neuronal network dynamics in the human pedunculopontine nucleus. Nat Neurosci 17:449–454CrossRefPubMedGoogle Scholar
  83. Thevathasan W, Coyne TJ, Hyam JA, Kerr G, Jenkinson N, Aziz TZ, Silburn PA (2011) Pedunculopontine nucleus stimulation improves gait freezing in Parkinson disease. Neurosurgery 69:1248–1253CrossRefPubMedGoogle Scholar
  84. Thevathasan W, Cole MH, Graepel CL, Hyam JA, Jenkinson N, Brittain JS, Coyne TJ, Silburn PA, Aziz TZ, Kerr G, Brown P (2012) A spatiotemporal analysis of gait freezing and the impact of pedunculopontine nucleus stimulation. Brain 135:1446–1454CrossRefPubMedPubMedCentralGoogle Scholar
  85. Tjernstrom F, Bjorklund M, Malmstrom EM (2014) Romberg ratio in quiet stance posturography-test to retest reliability. Gait PostureGoogle Scholar
  86. Vitale F, Mattei C, Capozzo A, Pietrantoni I, Mazzone P, Scarnati E (2016) Cholinergic excitation from the pedunculopontine tegmental nucleus to the dentate nucleus in the rat. Neuroscience 317:12–22CrossRefPubMedGoogle Scholar
  87. Wang HL, Morales M (2009) Pedunculopontine and laterodorsal tegmental nuclei contain distinct populations of cholinergic, glutamatergic and GABAergic neurons in the rat. Eur J Neurosci 29:340–358CrossRefPubMedGoogle Scholar
  88. Weinberger M, Hamani C, Hutchison WD, Moro E, Lozano AM, Dostrovsky JO (2008) Pedunculopontine nucleus microelectrode recordings in movement disorder patients. Exp Brain Res 188:165–174CrossRefPubMedGoogle Scholar
  89. Welter ML, Demain A, Ewenczyk C, Czernecki V, Lau B, El HA, Belaid H, Yelnik J, Francois C, Bardinet E, Karachi C, Grabli D (2015) PPNa-DBS for gait and balance disorders in Parkinson’s disease: a double-blind, randomised study. J NeurolGoogle Scholar
  90. Wichmann T, DeLong MR (2001) Basal ganglia circuits in movement and movement disorders. In: Kultas-Ilinsky K, Ilinsky IA (eds) Basal ganglia and thalamus in health and movement disorders. KluverAcademic/Plenum Publishers, New York, pp 11–25CrossRefGoogle Scholar
  91. Wichmann T, Bergman H, DeLong MR (1994) The primate subthalamic nucleus. III. Changes in motor behavior and neuronal activity in the internal pallidum induced by subthalamic inactivation in the MPTP model of parkinsonism. J Neurophysiol 72:521–530PubMedGoogle Scholar
  92. Winn P (2008) Experimental studies of pedunculopontine functions: are they motor, sensory or integrative? Parkinsonism Relat Disord 14(Suppl 2):S194–S198CrossRefPubMedGoogle Scholar
  93. Young RF, Tronnier V, Rinaldi PC (1992) Chronic stimulation of the Kolliker-Fuse nucleus region for relief of intractable pain in humans. J Neurosurg 76:979–985CrossRefPubMedGoogle Scholar
  94. Zrinzo L, Zrinzo LV, Tisch S, Limousin PD, Yousry TA, Afshar F, Hariz MI (2008) Stereotactic localization of the human pedunculopontine nucleus: atlas-based coordinates and validation of a magnetic resonance imaging protocol for direct localization. Brain 131:1588–1598CrossRefPubMedGoogle Scholar
  95. Zweig RM, Jankel WR, Hedreen JC, Mayeux R, Price DL (1989) The pedunculopontine nucleus in Parkinson’s disease. Ann Neurol 26:41–46CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Paolo Mazzone
    • 1
  • Osvaldo Vilela Filho
    • 2
  • Fabio Viselli
    • 3
  • Angelo Insola
    • 4
  • Stefano Sposato
    • 5
  • Flora Vitale
    • 6
  • Eugenio Scarnati
    • 6
  1. 1.Operative Unit for Stereotactic and Functional Neurosurgery, Regional Center for Functional Neurosurgery and DBSCTO Hospital, ASL Roma 2RomeItaly
  2. 2.Stereotactic and Functional Neurosurgery ServiceMedical School, Federal University of GoiasGoiâniaBrazil
  3. 3.Department of NeurologySt. John the Baptist HospitalRomeItaly
  4. 4.Operative Unit for NeurophysiopathologyASL RMCRomeItaly
  5. 5.Department of NeuroradiologyUniversity HospitalZurichSwitzerland
  6. 6.Department of Biotechnological and Applied Biomedical Sciences (DISCAB)University of L’AquilaL’AquilaItaly

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