Skip to main content
SpringerLink
Log in

Commentary: The pedunculopontine nucleus: clinical experience, basic questions and future directions

  • Movement Disorders - Original Article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

This issue is dedicated to a potential new target for the treatment of movement disorders, the pedunculopontine tegmental nucleus (PPTg), or, more simply, the pedunculopontine nucleus, that some authors abbreviate as PPN. We provide an overview of the field as an introduction to the general reader, beginning with the clinical experience to date of Mazzone and co-workers in Rome, some basic questions that need to be addressed, and potential future directions required in order to ensure that the potential benefits of this work are realized.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Breit S, Schulz JB, Benabid AL (2004) Deep brain stimulation. Cell Tissue Res 318:275–288

    Article  PubMed  Google Scholar 

  • Chaturvedi A, Butson CR, Cooper SE, McIntyre CC (2006) Subthalamic nucleus deep brain stimulation: accurate axonal threshold prediction with diffusion tensor based electric field models. Conf Proc IEEE Eng Med Biol Soc 1:1240–1243

    Article  PubMed  Google Scholar 

  • de Paor AM, Lowery MM (2009) Analysis of the mechanism of action of deep brain stimulation using the concepts of dither injection and the equivalent nonlinearity. IEEE Trans Biomed Eng 56:2717–2720

    Article  PubMed  Google Scholar 

  • 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, Pollack P (2010) Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson’s disease. Brain 133:205–214

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Rill E (1986) The basal ganglia and the locomotor regions. Brain Res Rev 11:47–63

    Article  Google Scholar 

  • Garcia-Rill E (1991) The pedunculopontine nucleus. Prog Neurobiol 36:363–389

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Rill E, Skinner RD (1991) Modulation of rhythmic functions by the brainstem. In: Shimamura M, Grillner S, Edgerton VR (eds) Neurobiological basis of human locomotion. Japan Sci Press, Tokyo, pp 137–158

    Google Scholar 

  • Garcia-Rill E, Skinner RD, Fitzgerald JA (1985) Chemical activation of the mesencephalic locomotor region. Brain Res 330:43–54

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Rill E, Houser CR, Skinner RD, Smith W, Woodward DJ (1987) Locomotion-inducing sites in the vicinity of the pedunculopontine nucleus. Brain Res Bull 18:731–738

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Rill E, Kinjo N, Atsuta Y, Ishikawa Y, Webber M, Skinner RD (1990) Posterior midbrain-induced locomotion. Brain Res Bull 24:499–508

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Rill E, Biedermann JA, Chambers T, Skinner RD, Mrak RE, Husain M, Karson CN (1995) Mesopontine neurons in schizophrenia. Neuroscience 66:321–335

    Article  PubMed  CAS  Google Scholar 

  • Irnich W (1980) The chronaxie time and its practical implications. Pacing Clin Electrophysiol 3:292–301

    Article  PubMed  CAS  Google Scholar 

  • Jenkinson N, Nandi D, Miall RC, Stein JF, Aziz TZ (2004) Pedunculopontine nucleus stimulation improves akinesia in a parkinsonian monkey. Neuroreport 15:2621–2624

    Article  PubMed  Google Scholar 

  • Karson CN, Garcia-Rill E, Biedermann JA, Mrak RE, Husain M, Skinner RD (1991) The brain stem reticular formation in schizophrenia. Psychiat Res 40:31–48

    Article  CAS  Google Scholar 

  • Lai YY, Siegel JM (1991) Pontomedullary glutamate receptors mediating locomotion and muscle tone suppression. J Neurosci 11:2931–2937

    PubMed  CAS  Google Scholar 

  • Mazzone P (2003) Deep brain stimulation in Parkinson’s disease: bilateral implantation of globus pallidus and subthalamic nucleus. J.Neurosurg Sci 47:47–51

    PubMed  CAS  Google Scholar 

  • Mazzone P, Scarnati E (2009) Deep brain stimulation (DBS) of the medial thalamus for movement disorders: the role of the centromedianum–parafascicular complex. In: Krames ES, Peckham PH, Rezai AR (eds) Neuromodulation. Elsevier-Academic Press, New York, pp 599–615

    Chapter  Google Scholar 

  • 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 14th Meeting of the World Society of Stereotactic and Functional Neurosurgery (WSSFN). Monduzzi, Bologna

    Google Scholar 

  • 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 16:1877–1881

    Article  PubMed  Google Scholar 

  • Mazzone P, Stocchi F, Galati S, Insola A, Altibrandi MG, Modugno N, Tropepi D, Brusa L, Stefani A (2006) Bilateral implantation of centromedian parafascicularis complex and GPi: a new combination of unconventional targets for deep brain stimulation in severe Parkinson’s disease. Neuromodulation 9:221–228

    Article  Google Scholar 

  • Mazzone P, Sposato S, Insola A, Di Lazzaro V, Scarnati E (2008) Stereotactic surgery of nucleus tegmenti pedunculopontini. Br J Neurosurg 22(Suppl 1):S33–S40

    Article  PubMed  Google Scholar 

  • Mazzone P, Insola A, Sposato S, Scarnati E (2009) The deep brain stimulation of the pedunculopontine tegmental nucleus. Neuromodulation 12:191–204

    Article  Google Scholar 

  • Modolo J, Beuter A (2009) Linking brain dynamics, neural mechanisms, and deep brain stimulation in Parkinson’s disease: an integrated perspective. Med Eng Phys 31:615–623

    Article  PubMed  Google Scholar 

  • Moro E, Hamani C, Poon Y, Al-Khairallah T, Dostrovsky IO, Hutchison WD, Lozano AM (2010a) Unilateral pedunculopontine stimulation improves falls in parkinson’s disease. Brain 133:215–224

    Article  PubMed  Google Scholar 

  • Moro E, Lozano AM, Pollak P, Agid Y, Rehncrona S, Volkmann J, Kulisevsky J, Obeso JA, Albanese A, Hariz MI, Quinn NP, Speelman JD, Benabid AL, Fraix V, Mendes A, Welter ML, Houeto JL, Cornu P, Dormont D, Tornqvist AL, Ekberg R, Schnitzler A, Timmermann L, Wojtecki L, Gironell A, Rodriguez-Oroz MC, Guridi J, Bentivoglio AR, Contarino MF, Romito L, Scerrati M, Janssens M, Lang AE (2010b) Long-term results of a multicenter study on subthalamic and pallidal stimulation in Parkinson’s disease. Mov Disord 25:578–586

    Article  PubMed  Google Scholar 

  • Munro-Davies L, Winter J, Aziz TZ, Stein J (2001) Kainate acid lesions of the pedunculopontine region in the normal behaving primate. Mov Disord 16:150–151

    Article  PubMed  CAS  Google Scholar 

  • Nandi D, Aziz TZ, Giladi N, Winter J, Stein JF (2002) Reversal of akinesia in experimental parkinsonism by GABA antagonist microinjections in the pedunculopontine nucleus. Brain 125:2418–2430

    Article  PubMed  Google Scholar 

  • Nandi D, Jenkinson N, Stein J, Aziz T (2008) The pedunculopontine nucleus in Parkinson’s disease: primate studies. Br J Neurosurg 22(Suppl 1):S4–S8

    Article  PubMed  Google Scholar 

  • Nowak LG, Bullier J (1998) Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter. Exp Brain Res 118:477–488

    Article  PubMed  CAS  Google Scholar 

  • Okun MS, Fernandez HH, Wu SS, Kirsch-Darrow L, Bowers D, Bova F, Suelter M, Jacobson CE, Wang X, Gordon CW Jr, Zeilman P, Romrell J, Martin P, Ward H, Rodriguez RL, Foote KD (2009) Cognition and mood in Parkinson’s disease in subthalamic nucleus versus globus pallidus interna deep brain stimulation: the COMPARE trial. Ann Neurol 65:586–595

    Article  PubMed  Google Scholar 

  • Piallat B, Chabardès S, Torres N, Fraix V, Goetz L, Seigneuret E, Bardinet E, Ferraye M, Debu B, Krack P, Yelnik J, Pollack P, Benabid AL (2009) Gait is associated with an increase in tonic firing of the subcuneiform nucleus neurons. Neuroscience 158:1201–1205

    Article  PubMed  CAS  Google Scholar 

  • Reese NB, Garcia-Rill E, Skinner RD (1995) The pedunculopontine nucleus-auditory input, arousal and pathophysiology. Prog Neurobiol 47:105–133

    Article  PubMed  CAS  Google Scholar 

  • Shik ML, Severin FV, Orlovski GN (1966) Control of walking and running by means of electrical stimulation of mid-brain. Biophysica (USSR) 11:756

    Google Scholar 

  • Skinner RD, Garcia-Rill E (1984) The mesencephalic locomotor region (MLR) in the rat. Brain Res 323:385–389

    Article  PubMed  CAS  Google Scholar 

  • Stefani A, Lozano AM, Peppe A, Stanzione P, Galati S, Tropepi D, Pierantozzi M, Brusa L, Scarnati E, Mazzone P (2007) Bilateral deep bain stimulation of the peunculopontine and subthalamic nuclei in severe Parkinson’s disease. Brain 130:1596–1607

    Article  PubMed  Google Scholar 

  • Strafella AP, Lozano AM, Ballanger B, Poon YY, Lang AE, Moro E (2008) rCBF changes associated with PPTG stimulation in a patient with Parkinson’s disease: a PET study. Mov Disord 15:1051–1054

    Article  Google Scholar 

  • Takakusaki K, Saitoh K, Harada H, Kashiwayanagi M (2004) Role of basal ganglia-brainstem pathways in the control of motor behaviors. Neurosci Res 50:137–151

    Article  PubMed  CAS  Google Scholar 

  • Teo C, Rasco L, Al-Mefty K, Skinner RD, Garcia-Rill E (1997) Decreased habituation of midlatency auditory evoked responses in Parkinson’s disease. Mov Disord 12:655–664

    Article  PubMed  CAS  Google Scholar 

  • Teo C, Rasco L, Skinner RD, Garcia-Rill E (1998) Disinhibition of the sleep state-dependent P1 potential in Parkinson’s disease-improvement after pallidotomy. Sleep Res Online 1:62–70

    PubMed  CAS  Google Scholar 

  • Volkmann J, Albanese A, Kulisevsky J, Tornqvist AL, Houeto JL, Pidoux B, Bonnet AM, Mendes A, Benabid AL, Fraix V, Van Blercom N, Xie J, Obeso J, Rodriguez-Oroz MC, Guridi J, Schnitzler A, Timmermann L, Gironell AA, Molet J, Pascual-Sedano B, Rehncrona S, Moro E, Lang AC, Lozano AM, Bentivoglio AR, Scerrati M, Contarino MF, Romito L, Janssens M, Agid Y (2009) Long-term effects of pallidal or subthalamic deep brain stimulation on quality of life in Parkinson’s disease. Mov Disord 24:1154–1161

    Article  PubMed  Google Scholar 

  • Walker HC, Watts RL, Guthrie S, Wang D, Guthrie BL (2009) Bilateral effects of unilateral subthalamic deep brain stimulation on Parkinson’s disease at 1 year. Neurosurgery 65:302–309

    Article  PubMed  Google Scholar 

  • Weinberger M, Hamani C, Hutchison WD, Moro E, Lozano AM, Dostrovsky JO (2008) Pedunculopontine nucleus microelectrode recordings in movement disorder patients. Exp Brain Res 188:165–174

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Supported by NIH awards RR20146 and NS20246 to EGR; RIA and PRIN 2008 to ES.

Author information

Authors and Affiliations

  1. Functional and Stereotactic Neurosurgery, CTO Hospital ASL Roma C, Via San Nemesio 21, 00145, Rome, Italy

    P. Mazzone

  2. Department of Biomedical Sciences and Technologies (STB), University of L’Aquila, Via Vetoio Coppito 2, 67100, L’Aquila, Italy

    E. Scarnati

  3. Department of Neurobiology and Developmental Sciences College of Medicine, Center for Translational Neuroscience, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 847, Little Rock, AR, 72205, USA

    E. Garcia-Rill

Authors
  1. P. Mazzone
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Scarnati
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Garcia-Rill
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. Garcia-Rill.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mazzone, P., Scarnati, E. & Garcia-Rill, E. Commentary: The pedunculopontine nucleus: clinical experience, basic questions and future directions. J Neural Transm 118, 1391–1396 (2011). https://doi.org/10.1007/s00702-010-0530-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-010-0530-4

Keywords

Search

Navigation