Skip to main content
SpringerLink
Log in

Functional neuroanatomy of the human premotor oculomotor brainstem nuclei: insights from postmortem and advanced in vivo imaging studies

  • Review
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

Considerable progress has been made recently in the field of the functional neuroanatomy of the primate oculomotor system, which has also improved our understanding of the structure, organization and function of the human oculomotor system. In the present review we provide for the first time an overview of the neuroanatomical basis of eye movement control in humans as revealed by a series of post-mortem studies in which the human premotor oculomotor brainstem nuclei were identified using unconventional 100 μm thick serial tissue sections stained for Nissl substance and lipofuscin pigment (Nissl-pigment stain according to Braak). Data from control brains and from patients suffering from spinocerebellar ataxia type 3, a neurodegenerative disease that severely impairs oculomotor function are discussed and recommendations for the identification of human premotor oculomotor brainstem nuclei in post-mortem studies are given. To visualize premotor brainstem nuclei in living patients, modern brain imaging techniques have been employed, albeit with limited success. Establishing topographic markers of brainstem nuclei may be a necessary next step to further elucidate the functional neuroanatomy of the premotor oculomotor brainstem network in human patients. This will help radiologists to identify these nuclei in living patients and will enable clinicians to monitor the progression of neurological disorders affecting the oculomotor system.

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
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Balcer LJ (2001) Anatomic and topographic diagnosis. Ophthalmol Clin North Am 14:1–21

    PubMed  CAS  Google Scholar 

  • Barmack NH (2003) Central vestibular system and posterior cerebellum. Brain Res Bull 60:511–541

    Article  PubMed  Google Scholar 

  • Bense S, Janusch B, Vucurevic G, Bauermann T, Schlindwein P, Brandt T, Stoeter P, Dieterich M (2006) Brainstem and cerebellar fMRI-activation during horizontal and vertical optokinetic stimulation. Exp Brain Res 174:312–323

    Article  PubMed  Google Scholar 

  • Bianchi R, Gioia M (1990) Accessory oculomotor nuclei of man. I. The nucleus of Darkschewitsch: A Nissl and Golgi study. Acta Anat 139:349–356

    Article  PubMed  CAS  Google Scholar 

  • Bianchi R, Gioia M (1991) Accessory oculomotor nuclei of man. II. The interstitial nucleus of Cajal: A Nissl and Golgi study. Acta Anat 142:357–365

    PubMed  CAS  Google Scholar 

  • Braak H (1970) On the nuclei of the human brain stem. II. The raphe nuclei. Z Zellforsch Mikrosk Anat 107:123–141

    Article  PubMed  CAS  Google Scholar 

  • Braak H, Rüb U, Del Tredici K (2003) Involvement of precerebellar nuclei in multiple system atrophy. Neuropathol Appl Neurobiol 29:60–76

    Article  PubMed  CAS  Google Scholar 

  • Bürk K, Fetter M, Abele M, Laccone F, Brice A, Dichgans J, Klockgether T (1999) Autosomal dominant cerebellar ataxia type I: oculomotor abnormalities in families with SCA1, SCA2 and SCA3. J Neurol 246:789–797

    Article  PubMed  Google Scholar 

  • Büttner U, Büttner-Ennever JA (2006) Present concepts of oculomotor organization. Prog Brain Res 151:1–42

    PubMed  Google Scholar 

  • Büttner-Ennever JA (2006) The extraocular motor nuclei: organization and functional neuroanatomy. Prog Brain Res 151:95–125

    PubMed  Google Scholar 

  • Büttner-Ennever JA, Horn AKE (1997) Anatomical substrates of oculomotor control. Curr Opin Neurobiol 7:872–879

    Article  PubMed  Google Scholar 

  • Büttner-Ennever JA, Horn AKE (2004) Reticular formation: eye movements, gaze, and blinks. In: Paxinos G, Mai JK (eds) The human nervous system. 2nd edn. Elsevier, Amsterdam, pp 479–510

    Google Scholar 

  • Büttner-Ennever JA, Büttner U, Cohen B, Baumgartner G (1982) Vertical glaze paralysis and the rostral interstitial nucleus of the medial longitudinal fasciculus. Brain 105:125–149

    Article  PubMed  Google Scholar 

  • Büttner-Ennever JA, Cohen B, Pause M, Fries W (1988) Raphe nucleus of the pons containing omnipause neurons of the oculomotor system in the monkey, and its homologue in man. J Comp Neurol 267:307–321

    Article  PubMed  Google Scholar 

  • Buttner N Geschwind D, Jen JC, Perlman S, Pulst SM, Baloh RW (1998) Oculomotor phenotypes in autosomal dominant ataxias. Arch Neurol 55:1353–1357

    Article  Google Scholar 

  • Crawford JD, Cadera W, Vilis T (1991) Generation of torsional and vertical eye position signals by the interstitial nucleus of Cajal. Science 252:1551–1553

    Article  PubMed  CAS  Google Scholar 

  • Deoni SC, Josseau MJ, Rutt BK, Peters TM (2005) Visualization of thalamic nuclei on high resolution, multi-averaged T1 and T2 maps acquired at 1.5 T. Hum Brain Mapp 25:353–359

    Article  PubMed  Google Scholar 

  • Eggert T (2007) Eye movement recordings: methods. Dev Ophthalmol 40:15–34

    PubMed  Google Scholar 

  • Fukushima K (1987) The interstitial nucleus of Cajal and its role in the control of movements of head and eyes. Prog Neurobiol 29:107–192

    Article  PubMed  CAS  Google Scholar 

  • Gerrits NM (1991) Vestibular nuclear complex. In: Paxinos G (ed) The human nervous system. 1st edn. Academic Press, San Diego, pp 863–888

    Google Scholar 

  • Gierga K, Bürk K, Bauer M, Orozco Diaz G, Auburger G, Schultz C, Vuksic M, Schöls L, de Vos RA, Braak H, Deller T, Rüb U (2005) Involvement of the cranial nerves and their nuclei in spinocerebellar ataxia type 2 (SCA2). Acta Neuropathol 109:617–631

    Article  PubMed  CAS  Google Scholar 

  • Golding CV, Danchaivijtr C, Hodgson TL, TraBizi SJ, Kennart C (2006) Identification of an oculomotor biomarker of preclinical Huntington disease. Neurology 67:485–487

    Article  PubMed  CAS  Google Scholar 

  • Habas C, Cabanis EA (2007) Anatomical parcellation of the brainstem and cerebellar white matter: a preliminary probabilistic tractography study at 3 T. Neuroradiology 49:849–863

    Article  PubMed  Google Scholar 

  • Heinsen H, Heinsen YL (1991) Serial thick, frozen, gallocyanin stained sections of human central nervous system. J Histotechnol 14:167–173

    Google Scholar 

  • Helmchen C, Rambold H, Kempermann U, Büttner-Ennever JA, Büttner U (2002) Localizing value of torsional nystagmus in small midbrain lesions. Neurology 59:1956–1964

    PubMed  CAS  Google Scholar 

  • Horn AKE (2006) The reticular formation. Prog Brain Res 151:127–155

    PubMed  Google Scholar 

  • Horn AKE, Büttner-Ennever JA (1998) Premotor neurons for vertical eye movements in the rostral mesencephalon of monkey and human: Histologic identification by parvalbumin immunostaining. J Comp Neurol 392:413–427

    Article  PubMed  CAS  Google Scholar 

  • Horn AKE, Büttner-Ennever JA, Wahle P, Reichenberger I (1994) Neurotransmitter profile of saccadic omnipause neurons in nucleus raphe interpositus. J Neurosci 14:2032–2046

    PubMed  CAS  Google Scholar 

  • Horn AKE, Büttner-Ennever JA, Suzuki A, Henn V (1995) Histological identification of premotor neurons for horizontal saccades in monkeys and man by parvalbumin immunostaining. J Comp Neurol 359:350–363

    Article  PubMed  CAS  Google Scholar 

  • Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S, Kawakami H, Nakamura S, Nishimura M, Akiguchi I, Kimura J, Narumiya S, Kakizuka A (1994) CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet 8:221–228

    Article  PubMed  CAS  Google Scholar 

  • Komisaruk BR, Mosier KM, Liu WC, Criminale C, Zaborszky L, Whipple B, Kalnin A (2002) Functional localization of brainstem and cervical spinal cord nuclei in humans with fMRI. AJNR Am J Neuroradiol 23:609–617

    PubMed  Google Scholar 

  • Koutcherov Y, Huang XF, Halliday G, Paxinos G (2004) Organization of human brain stem nuclei. In: Paxinos G, Mai JK (eds) The human nervous system. 2nd edn. Elsevier, Amsterdam, pp 267–320

    Google Scholar 

  • Krauzlis RJ, Stone LS (1999) Tracking with the mind’s eye. Trends Neurosci 22:544–550

    Article  PubMed  CAS  Google Scholar 

  • Leigh RJ, Kennard C (2004) Using saccades as a research tool in the clinical neurosciences. Brain 127:460–477

    Article  PubMed  CAS  Google Scholar 

  • Leigh RJ, Zee DS (2006) The neurology of eye movements. 4th edn. Oxford University Press, Oxford

    Google Scholar 

  • Malessa S, Hirsch EC, Cervera P, Javoy-Agid F, Duyckaerts C, Hauw JJ, Agid Y (1991) Progressive supranuclear palsy: loss of choline-acetyltransferase-like immunoreactive neurons in the pontine reticular formation. Neurology 41:1593–1597

    PubMed  CAS  Google Scholar 

  • Martin GF, Holstege G, Mehler WR (1991) Reticular formation of the pons and medullla. In: Paxinos G (ed) The human nervous system. 1st edn. Academic Press, San Diego, pp 203–220

    Google Scholar 

  • May PJ (2006) The mammalian superior colliculus: laminar structure and connections. Prog Brain Res 151:321–378

    PubMed  Google Scholar 

  • Miller MJ, Mark LP, Ho KC, Haughton VM (1997) Anatomic relationship of the oculomotor nuclear complex and medial longitudinal fasciculus in the midbrain. AJNR AM J Neuroradiol 18:111–113

    PubMed  CAS  Google Scholar 

  • Nagae-Poetscher LM, Jiang H, Wakana S, Golay X, van Zijl PCM, Mori S (2004) High-resolution diffusion tensor imaging of the brain stem at 3 T. AJNR Am J Neuroradiol 25:1325–1330

    PubMed  Google Scholar 

  • Napadow V, Dhond R, Kennedy D, Hui KK, Makris N (2006) Automated brainstem co-registration (ABC) for MRI. Neuroimage 32:1113–1119

    Article  PubMed  Google Scholar 

  • Oikawa H, Sasaki M, Tamakawa Y, Ehara S, Tohyama K (2002) The substantia nigra in Parkinson disease: Proton density-weighted spin-echo and fast short inversion time inversion-recovery MR findings. AJNR Am J Neuroradiol 23:1747–1756

    PubMed  Google Scholar 

  • Olszewski J, Baxter D (1982) Cytoarchitecture of the human brain stem. 2nd edn. Karger, Basel

    Google Scholar 

  • Paxinos G, Huang XF (1995) Atlas of the human brainstem. Academic press, San Diego

    Google Scholar 

  • Pfefferbaum A, Sullivan EV, Adalsteinsson E, Garrick T, Harper C (2004) Postmortem MR imaging of formalin-fixed human brain. Neuroimage 21:1585–1595

    Article  PubMed  Google Scholar 

  • Riess O, Rüb U, Pastore A, Bauer P, Schöls L (2007) SCA3: Neurological features, pathogenesis and animal models. Cerebellum 30:1–13

    Article  Google Scholar 

  • Robinson DA (1963) A method of measuring eye movement using a scleral search coil in a magnetic field. IEEE Trans Biomed Eng 10:137–145

    PubMed  CAS  Google Scholar 

  • Rubin AJ, King WM, Reinbold KA, Shoulson I (1993) Quantitative longitudinal assessment of saccades in Huntington’s disease. Clin Neuroophthalmol 13:59–66

    Article  CAS  Google Scholar 

  • Rüb U, Del Tredici K, Schultz C, Büttner-Ennever J, Braak E, Braak H (2001a) The premotor region for rapid vertical eye movements shows early involvement in Alzheimer’s disease-related cytoskeletal pathology. Vision Res 41:2149–2156

    Article  PubMed  Google Scholar 

  • Rüb U, Schultz C, Del Tredici K, Braak H (2001b) Early involvement of the tegmentopontine reticular nucleus during the evolution of the Alzheimer’s disease-related cytoskeletal pathology. Brain Res 908:107–112

    Article  PubMed  Google Scholar 

  • Rüb U, Brunt ER, Del Turco D, de Vos RAI, Gierga K, Paulson H, Braak H (2003a) Guidelines for the pathoanatomical examination of the lower brain stem in ingestive and swallowing disorders and its application to a dysphagic spinocerebellar ataxia type 3 patient. Neuropathol Appl Neurobiol 29:1–13

    Article  PubMed  Google Scholar 

  • Rüb U, Brunt ER, de Vos RAI, Del Turco D, Del Tredici K, Gierga K, Schultz C, Ghebremedhin E, Bürk K, Auburger G, Braak H (2003b) Degeneration of the central vestibular system in spinocerebellar ataxia type 3 patients and its possible clinical significance. Neuropathol Appl Neurobiol 30:402–414

    Article  Google Scholar 

  • Rüb U, Brunt ER, Gierga K, Schultz C, Paulson H, de Vos RAI, Braak H (2003c) The nucleus raphe interpositus in spinocerebellar ataxia type 3 (Machado-Joseph disease). J Chem Neuroanat 25:115–122

    Article  PubMed  CAS  Google Scholar 

  • Rüb U, Bürk K, Schöls L, Brunt ER, de Vos RAI, Orozco Diaz G, Gierga K, Ghebremedhin E, Schultz C, Del Turco D, Mittelbronn M, Auburger G, Deller T, Braak H (2003d) Damage to the reticulotegmental nucleus of the pons in spinocerebellar ataxia type 1, 2, and 3. Neurology 63:1258–1263

    Google Scholar 

  • Rüb U, Schultz C, Del Tredici K, Gierga K, Reifenberger G, De Vos RAI, Seifried C, Braak H, Auburger G (2003e) Anatomically-based guidelines for systematic investigations of the central somatosensory system and their application to a spinocerebellar ataxia type 2 (SCA2) patient. Neuropathol Appl Neurobiol 29:418–433

    Article  PubMed  Google Scholar 

  • Rüb U, Brunt ER, Gierga K, Seidel K, Schultz C, Schöls L, Auburger G, Heinsen H, Ippel PF, Glimmerveen WF, Wittebol-Post D, Arai K, Deller T, de Vos RA (2005a) Spinocerebellar ataxia type 7 (SCA7): first report of a systematic neuropathological study of the brain of a patient with a very short expanded CAG-repeat. Brain Pathol 15:287–295

    PubMed  Google Scholar 

  • Rüb U, Gierga K, Brunt ER, de Vos RA, Bauer M, Schöls L, Bürk K, Auburger G, Bohl J, Schultz C, Vuksic M, Burbach GJ, Braak H, Deller T (2005b) Spinocerebellar ataxias types 2 and 3: degeneration of the precerebellar nuclei isolates the three phylogenetically defined regions of the cerebellum. J Neural Transm 112:1523–1545

    Article  PubMed  Google Scholar 

  • Rüb U, Brunt ER, Deller T (2008) New insights into the pathoanatomy of spinocerebellar ataxia type 3 (Machado-Joseph disease). Curr Opin Neurol (in press)

  • Seo SW, Shin HY, Kim SH, Han SW, Lee KY, Kim SM, Heo JH (2004) Vestibular imbalance associated with a lesion in the nucleus prepositus hypoglossi area. Arch Neurol 61:1440–1443

    Article  PubMed  Google Scholar 

  • Steffen H (2006) Diagnosis of supranuclear eye movement disorders. Part I: different types of eye movements. Ophthalmologe 103:901–909

    Article  PubMed  CAS  Google Scholar 

  • Stieltjes B, Kaufmann WE, van Zijl PC, Fredericksen K, Pearlson GD, Solaiyappan M, Mori S (2001) Diffusion tensor imaging and axonal tracking in the human brainstem. Neuroimage 14:723–735

    Article  PubMed  CAS  Google Scholar 

  • Wakana S, Jiang H, Nagae-Poetscher LM, van Zijl PC, Mori S (2004) Fiber tract-based atlas of human white matter anatomy. Radiology 230:77–87

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Supported by grants from the Deutsche Forschungsgemeinschaft (RU 1215/1-2), the Deutsche Heredo-Ataxie-Gesellschaft (DHAG), the ADCA-Vereniging Nederland, the Bernd Fink-Stiftung (Düsseldorf, Germany) and the National Institutes of Health R01 EY15311. The skillful assistance of I. Szasz (graphics) and M. Hütten (technical support) is gratefully acknowledged. The authors thank Ewout Brunt for providing clinical SCA3 data.

Author information

Authors and Affiliations

  1. Institute for Clinical Neuroanatomy, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590, Frankfurt/Main, Germany

    Udo Rüb, Heiko Braak & Thomas Deller

  2. Department of Neurology, University of California School of Medicine, Los Angeles, CA, 90095, USA

    Joanna C. Jen

Authors
  1. Udo Rüb
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joanna C. Jen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Heiko Braak
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas Deller
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Udo Rüb.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rüb, U., Jen, J.C., Braak, H. et al. Functional neuroanatomy of the human premotor oculomotor brainstem nuclei: insights from postmortem and advanced in vivo imaging studies. Exp Brain Res 187, 167–180 (2008). https://doi.org/10.1007/s00221-008-1342-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00221-008-1342-8

Keywords

Search

Navigation