Skip to main content
SpringerLink
Log in

Delineating function and connectivity of optokinetic hubs in the cerebellum and the brainstem

  • Original Article
  • Published:
Brain Structure and Function Aims and scope Submit manuscript

Abstract

Optokinetic eye movements are crucial for keeping a stable image on the retina during movements of the head. These eye movements can be differentiated into a cortically generated response (optokinetic look nystagmus) and the highly reflexive optokinetic stare nystagmus, which is controlled by circuits in the brainstem and cerebellum. The contributions of these infratentorial networks and their functional connectivity with the cortical eye fields are still poorly understood in humans. To map ocular motor centres in the cerebellum and brainstem, we studied stare nystagmus using small-field optokinetic stimuli in the horizontal and vertical directions in 22 healthy subjects. We were able to differentiate ocular motor areas of the pontine brainstem and midbrain in vivo for the first time. Direction and velocity-dependent activations were found in the pontine brainstem (nucleus reticularis, tegmenti pontis, and paramedian pontine reticular formation), the uvula, flocculus, and cerebellar tonsils. The ocular motor vermis, on the other hand, responded to constant and accelerating velocity stimulation. Moreover, deactivation patterns depict a governing role for the cerebellar tonsils in ocular motor control. Functional connectivity results of these hubs reveal the close integration of cortico-cerebellar ocular motor and vestibular networks in humans. Adding to the cortical concept of a right-hemispheric predominance for visual-spatial processing, we found a complementary left-sided cerebellar dominance for our ocular motor task. A deeper understanding of the role of the cerebellum and especially the cerebellar tonsils for eye movement control in a clinical context seems vitally important and is now feasible with functional neuroimaging.

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
Fig. 5

Similar content being viewed by others

References

  • Afshar F, Watkins ES, Yap JC (1978) Stereotaxic atlas of the human brainstem and cerebellar nuclei: a variability study. vol Bd. 17. Raven Press

  • Ashburner J (2007) A fast diffeomorphic image registration algorithm NeuroImage 38:95–113. doi:10.1016/j.neuroimage.2007.07.007

    PubMed  Google Scholar 

  • Barmack NH, Pettorossi VE (1985) Effects of unilateral lesions of the flocculus on optokinetic and vestibuloocular reflexes of the rabbit. J Neurophysiol 53:481–496

    CAS  PubMed  Google Scholar 

  • Bense S et al (2006a) Direction-dependent visual cortex activation during horizontal optokinetic stimulation (fMRI study). Hum Brain Mapp 27:296–305. doi:10.1002/hbm.20185

    Article  PubMed  Google Scholar 

  • Bense S et al (2006b) Brainstem and cerebellar fMRI-activation during horizontal and vertical optokinetic stimulation experimental brain research 174:312–323

    PubMed  Google Scholar 

  • Boileau I, Beauregar M, Beuter A, Breault C, Lecours AR (2002) Optokinetic stimulation and the egocentred midsagittal plane: an fMRI study. NeuroReport 13:61–65

    Article  PubMed  Google Scholar 

  • Brandt T, Bartenstein P, Janek A, Dieterich M (1998) Reciprocal inhibitory visual-vestibular interaction. Visual motion stimulation deactivates the parieto-insular vestibular cortex. Brain J Neurol 121(Pt 9):1749–1758

    Article  Google Scholar 

  • Bremmer F, Klam F, Duhamel JR, Ben Hamed S, Graf W (2002) Visual-vestibular interactive responses in the macaque ventral intraparietal area (VIP). Eur J Neurosci 16:1569–1586

    Article  PubMed  Google Scholar 

  • Buttner U, Buttner-Ennever JA, Henn V (1977) Vertical eye movement related unit activity in the rostral mesencephalic reticular formation of the alert monkey. Brain Res 130:239–252

    Article  CAS  PubMed  Google Scholar 

  • Buttner-Ennever JA (2007) Anatomy of the oculomotor system. Dev Ophthalmol 40:1–14. doi:10.1159/0000100345

    Article  PubMed  Google Scholar 

  • Chao-Gan Y, Yu-Feng Z (2010) DPARSF: a MATLAB toolbox for “Pipeline” data analysis of resting-state fMRI. Front Syst Neurosci 4:13. doi:10.3389/fnsys.2010.00013

    PubMed  PubMed Central  Google Scholar 

  • Chapman LJ, Chapman JP (1987) The measurement of handedness. Brain Cogn 6:175–183

    Article  CAS  PubMed  Google Scholar 

  • Cohen B, Matsuo V, Raphan T (1977) Quantitative analysis of the velocity characteristics of optokinetic nystagmus and optokinetic after-nystagmus. J Physiol 270:321–344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crossland WJ, Hu XJ, Rafols JA (1994) Morphological study of the rostral interstitial nucleus of the medial longitudinal fasciculus in the monkey, Macaca mulatta, by Nissl, Golgi, and computer reconstruction and rotation methods. J Comp Neurol 347:47–63. doi:10.1002/cne.903470105

    Article  CAS  PubMed  Google Scholar 

  • de Jong BM, Shipp S, Skidmore B, Frackowiak RS, Zeki S (1994) The cerebral activity related to the visual perception of forward motion in depth. Brain J Neurol 117(Pt 5):1039–1054

    Article  Google Scholar 

  • de Schotten MT, Dell’Acqua F, Forkel SJ, Simmons A, Vergani F, Murphy DGM, Catani M (2011) A lateralized brain network for visuospatial attention. Nat Neurosci 14:1245–1246. doi:10.1038/nn.2905. http://www.nature.com/neuro/journal/v14/n10/abs/nn.2905.html (supplementary-information)

  • Devonshire IM, Papadakis NG, Port M, Berwick J, Kennerley AJ, Mayhew JE, Overton PG (2012) Neurovascular coupling is brain region-dependent. NeuroImage 59:1997–2006. doi:10.1016/j.neuroimage.2011.09.050

    Article  PubMed  Google Scholar 

  • Diedrichsen J (2006) A spatially unbiased atlas template of the human cerebellum. NeuroImage 33:127–138. doi:10.1016/j.neuroimage.2006.05.056

    Article  PubMed  Google Scholar 

  • Dieterich M, Bucher SF, Seelos KC, Brandt T (1998) Horizontal or vertical optokinetic stimulation activates visual motion-sensitive, ocular motor and vestibular cortex areas with right hemispheric dominance. An fMRI study. Brain J Neurol 121(Pt 8):1479–1495

    Article  Google Scholar 

  • Dieterich M, Bucher SF, Seelos KC, Brandt T (2000) Cerebellar activation during optokinetic stimulation and saccades. Neurology 54:148–155

    Article  CAS  PubMed  Google Scholar 

  • Dieterich M, Bense S, Lutz S, Drzezga A, Stephan T, Bartenstein P, Brandt T (2003a) Dominance for vestibular cortical function in the non-dominant hemisphere. Cereb Cortex 13:994–1007

    Article  CAS  PubMed  Google Scholar 

  • Dieterich M, Bense S, Stephan T, Yousry TA, Brandt T (2003b) fMRI signal increases and decreases in cortical areas during small-field optokinetic stimulation and central fixation. Exp Brain Res 148:117–127. doi:10.1007/s00221-002-1267-6

    Article  PubMed  Google Scholar 

  • Dieterich M, Muller-Schunk S, Stephan T, Bense S, Seelos K, Yousry TA (2009) Functional magnetic resonance imaging activations of cortical eye fields during saccades, smooth pursuit, and optokinetic nystagmus. Ann N Y Acad Sci 1164:282–292. doi:10.1111/j.1749-6632.2008.03718.x

    Article  PubMed  Google Scholar 

  • Eickhoff SB, Stephan KE, Mohlberg H, Grefkes C, Fink GR, Amunts K, Zilles K (2005) A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data. NeuroImage 25:1325–1335. doi:10.1016/j.neuroimage.2004.12.034

    Article  PubMed  Google Scholar 

  • Faull OK, Jenkinson M, Clare S, Pattinson KTS (2015) Functional subdivision of the human periaqueductal grey in respiratory control using 7 tesla fMRI NeuroImage 113:356–364. doi:10.1016/j.neuroimage.2015.02.026

  • Friston KJ, Frith C, Turner R, Frackowiak RSJ (1995a) Characterizing evoked hemodynamics with fMRI NeuroImage 2:157–165

    CAS  PubMed  Google Scholar 

  • Friston KJ, Holmes AP, Worsley KJ, Poline JB, Frith C, Frackowiak RSJ (1995b) Statistical parametric maps in functional imaging: a general linear approach. Hum Brain Mapp 2:189–210

    Article  Google Scholar 

  • Furman JM, Becker JT (1989) Vestibular responses in Wernicke’s encephalopathy. Ann Neurol 26:669–674. doi:10.1002/ana.410260513

    Article  CAS  PubMed  Google Scholar 

  • Galati G, Pappata S, Pantano P, Lenzi GL, Samson Y, Pizzamiglio L (1999) Cortical control of optokinetic nystagmus in humans: a positron emission tomography study. Exp Brain Res 126:149–159

    Article  CAS  PubMed  Google Scholar 

  • Gaymard B, Rivaud S, Cassarini JF, Dubard T, Rancurel G, Agid Y, Pierrot-Deseilligny C (1998) Effects of anterior cingulate cortex lesions on ocular saccades in humans. Exp Brain Res 120:173–183

    Article  CAS  PubMed  Google Scholar 

  • Gerrits N (1990) Vestibular nuclear complex. The human nervous system. Academic, Philadelphia, pp 863–888

    Chapter  Google Scholar 

  • Giaschi D et al (2003) Conscious visual abilities in a patient with early bilateral occipital damage. Dev Med Child Neurol 45:772–781

    Article  PubMed  Google Scholar 

  • Glasauer S, Stephan T, Kalla R, Marti S, Straumann D (2009) Up-down asymmetry of cerebellar activation during vertical pursuit eye movements. Cerebellum (London, England) 8:385–388. doi:10.1007/s12311-009-0109-5

  • Hasegawa T, Kato I, Harada K, Ikarashi T, Yoshida M, Koike Y (1994) The effect of uvulonodular lesions on horizontal optokinetic nystagmus and optokinetic after-nystagmus in cats. Acta Otolaryngol Suppl 511:126–130

    Article  CAS  PubMed  Google Scholar 

  • Heinen SJ, Keller EL (1996) The function of the cerebellar uvula in monkey during optokinetic and pursuit eye movements: single-unit responses and lesion effects. Exp Brain Res 110:1–14

    Article  CAS  PubMed  Google Scholar 

  • Hiramatsu T, Ohki M, Kitazawa H, Xiong G, Kitamura T, Yamada J, Nagao S (2008) Role of primate cerebellar lobulus petrosus of paraflocculus in smooth pursuit eye movement control revealed by chemical lesion. Neurosci Res 60:250–258. doi:10.1016/j.neures.2007.11.004

    Article  PubMed  Google Scholar 

  • Horn AK, Buttner U, Buttner-Ennever JA (1999) Brainstem and cerebellar structures for eye movement generation. Adv Otorhinolaryngol 55:1–25

    CAS  PubMed  Google Scholar 

  • Hu D, Shen H, Zhou Z (2008) Functional asymmetry in the cerebellum: a brief review. Cerebellum (London, England) 7:304–313. doi:10.1007/s12311-008-0031-2

  • Igarashi M, Takeda N, Chae S (1992) Uvula-nodulus and gravity direction (a study on vertical optokinetic-oculomotor functions). Acta Astronaut 27:25–30

    Article  CAS  PubMed  Google Scholar 

  • Ilg UJ, Hoffmann KP (1991) Responses of monkey nucleus of the optic tract neurons during pursuit and fixation. Neurosci Res 12:101–110

    Article  CAS  PubMed  Google Scholar 

  • Ilg UJ, Hoffmann KP (1996) Responses of neurons of the nucleus of the optic tract and the dorsal terminal nucleus of the accessory optic tract in the awake monkey. Eur J Neurosci 8:92–105

    Article  CAS  PubMed  Google Scholar 

  • Kashou NH, Leguire LE, Roberts CJ, Fogt N, Smith MA, Rogers GL (2010) Instruction dependent activation during optokinetic nystagmus (OKN) stimulation: an FMRI study at 3T. Brain Res 1336:10–21. doi:10.1016/j.brainres.2010.04.017

    Article  CAS  PubMed  Google Scholar 

  • Kheradmand A, Zee DS (2011) Cerebellum and ocular motor control. Front Neurol 2:53. doi:10.3389/fneur.2011.00053

    Article  PubMed  PubMed Central  Google Scholar 

  • Konen CS, Kleiser R, Seitz RJ, Bremmer F (2005) An fMRI study of optokinetic nystagmus and smooth-pursuit eye movements in humans. Exp Brain Res 165:203–216. doi:10.1007/s00221-005-2289-7

    Article  PubMed  Google Scholar 

  • Kralj-Hans I, Baizer JS, Swales C, Glickstein M (2007) Independent roles for the dorsal paraflocculus and vermal lobule VII of the cerebellum in visuomotor coordination. Exp Brain Res 177:209–222. doi:10.1007/s00221-006-0661-x

    Article  PubMed  Google Scholar 

  • Lee SH, Park SH, Kim JS, Kim HJ, Yunusov F, Zee DS (2014) Isolated unilateral infarction of the cerebellar tonsil: ocular motor findings. Ann Neurol 75:429–434

    Article  PubMed  Google Scholar 

  • Leigh RJ, Zee DS (2006) The neurology of eye movements. Contemporary neurology series, 4th edn, vol 70. Oxford Univ Press, Oxford

  • Mustari MJ, Fuchs AF (1990) Discharge patterns of neurons in the pretectal nucleus of the optic tract (NOT) in the behaving primate. J Neurophysiol 64:77–90

    CAS  PubMed  Google Scholar 

  • Mustari MJ, Ono S, Das VE (2009) Signal processing and distribution in cortical-brainstem pathways for smooth pursuit eye movements. Ann N Y Acad Sci 1164:147–154. doi:10.1111/j.1749-6632.2009.03859.x

    Article  PubMed  PubMed Central  Google Scholar 

  • Nagao S, Kitamura T, Nakamura N, Hiramatsu T, Yamada J (1997) Location of efferent terminals of the primate flocculus and ventral paraflocculus revealed by anterograde axonal transport methods. Neurosci Res 27:257–269. doi:10.1016/S0168-0102(97)01160-7

    Article  CAS  PubMed  Google Scholar 

  • Ohki M, Kitazawa H, Hiramatsu T, Kaga K, Kitamura T, Yamada J, Nagao S (2009) Role of primate cerebellar hemisphere in voluntary eye movement control revealed by lesion effects. J Neurophysiol 101:934–947. doi:10.1152/jn.90440.2009

    Article  PubMed  Google Scholar 

  • Ono S, Mustari MJ (2009) Smooth pursuit-related information processing in frontal eye field neurons that project to the NRTP. Cereb Cortex 19:1186–1197. doi:10.1093/cercor/bhn166

    Article  PubMed  Google Scholar 

  • Ono S, Das VE, Economides JR, Mustari MJ (2005) Modeling of smooth pursuit-related neuronal responses in the DLPN and NRTP of the rhesus macaque. J Neurophysiol 93:108–116. doi:10.1152/jn.00588.2004

    Article  PubMed  Google Scholar 

  • Pierrot-Deseilligny C, Milea D, Muri RM (2004) Eye movement control by the cerebral cortex. Curr Opin Neurol 17:17–25

    Article  PubMed  Google Scholar 

  • Poldrack RA, Fletcher PC, Henson RN, Worsley KJ, Brett M, Nichols TE (2008) Guidelines for reporting an fMRI study NeuroImage 40:409–414. doi:10.1016/j.neuroimage.2007.11.048

    PubMed  Google Scholar 

  • Robinson FR, Fuchs AF (2001) The role of the cerebellum in voluntary eye movements. Annu Rev Neurosci 24:981–1004. doi:10.1146/annurev.neuro.24.1.981

    Article  CAS  PubMed  Google Scholar 

  • Schmahmann JD (2000) MRI atlas of the human cerebellum. Academic Press, San Diego

    Google Scholar 

  • Schmahmann JD, Doyon J, Toga AW, Petrides M, Evans AC (2000) MRI Atlas of the human cerebellum. Academic Press, San Diego

    Google Scholar 

  • Schraa-Tam CK, van der Lugt A, Smits M, Frens MA, van Broekhoven PC, van der Geest JN (2008) fMRI of optokinetic eye movements with and without a contribution of smooth pursuit. J Neuroimaging Off J Am Soc Neuroimaging 18:158–167. doi:10.1111/j.1552-6569.2007.00204.x

  • Shojaku H, Grudt TJ, Barmack NH (1990) Vestibular and visual signals in the ventral paraflocculus of the cerebellum in rabbits. Neurosci Lett 108:99–104. doi:10.1016/0304-3940(90)90713-J

    Article  CAS  PubMed  Google Scholar 

  • Smith AT, Wall MB, Thilo KV (2012) Vestibular inputs to human motion-sensitive visual cortex. Cereb Cortex 22:1068–1077. doi:10.1093/cercor/bhr179

    Article  PubMed  Google Scholar 

  • Song XW et al (2011) REST: a toolkit for resting-state functional magnetic resonance imaging data processing. PLoS One 6:e25031. doi:10.1371/journal.pone.0025031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Straube A, Scheuerer W, Eggert T (1997) Unilateral cerebellar lesions affect initiation of ipsilateral smooth pursuit eye movements in humans. Ann Neurol 42:891–898. doi:10.1002/ana.410420611

    Article  CAS  PubMed  Google Scholar 

  • Takeichi N, Kaneko CR, Fuchs AF (2005) Discharge of monkey nucleus reticularis tegmenti pontis neurons changes during saccade adaptation. J Neurophysiol 94:1938–1951. doi:10.1152/jn.00113.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tan HS, Collewijn H, Van der Steen J (1992) Optokinetic nystagmus in the rabbit and its modulation by bilateral microinjection of carbachol in the cerebellar flocculus. Exp Brain Res 90:456–468

    Article  CAS  PubMed  Google Scholar 

  • Thielert CD, Thier P (1993) Patterns of projections from the pontine nuclei and the nucleus reticularis tegmenti pontis to the posterior vermis in the rhesus monkey: a study using retrograde tracers. J Comp Neurol 337:113–126. doi:10.1002/cne.903370108

    Article  CAS  PubMed  Google Scholar 

  • Vahedi K, Rivaud S, Amarenco P, Pierrot-Deseilligny C (1995) Horizontal eye movement disorders after posterior vermis infarctions. J Neurol Neurosurg Psychiatry 58:91–94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Voogd J, Barmack NH (2006) Oculomotor cerebellum. Prog Brain Res 151:231–268. doi:10.1016/s0079-6123(05)51008-2

    Article  PubMed  Google Scholar 

  • Voogd J, Schraa-Tam CK, van der Geest JN, De Zeeuw CI (2012) Visuomotor cerebellum in human and nonhuman primates. Cerebellum (London, England) 11:392–410. doi:10.1007/s12311-010-0204-7

  • Waespe W, Cohen B (1983) Flocculectomy and unit activity in the vestibular nuclei during visual–vestibular interactions. Exp Brain Res 51:23–35

    Article  CAS  PubMed  Google Scholar 

  • Worsley KJ, Marrett S, Neelin P, Vandal AC, Friston KJ, Evans AC (1996) A unified statistical approach for determining significant signals in images of cerebral activation. Hum Brain Mapp 4:58–73. doi:10.1002/(SICI)1097-0193(1996)4:1<58:AID-HBM4>3.0.CO;2-O

    Article  CAS  PubMed  Google Scholar 

  • Xiong G, Nagao S (2002) The lobulus petrosus of the paraflocculus relays cortical visual inputs to the posterior interposed and lateral cerebellar nuclei: an anterograde and retrograde tracing study in the monkey. Exp Brain Res 147:252–263. doi:10.1007/s00221-002-1241-3

    Article  PubMed  Google Scholar 

  • Yakushin SB, Gizzi M, Reisine H, Raphan T, Buttner-Ennever J, Cohen B (2000) Functions of the nucleus of the optic tract (NOT). II. Control of ocular pursuit. Exp Brain Res 131:433–447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zee DS, Yamazaki A, Butler PH, Gucer G (1981) Effects of ablation of flocculus and paraflocculus of eye movements in primate. J Neurophysiol 46:878–899

    CAS  PubMed  Google Scholar 

  • Zhang Y, Partsalis AM, Highstein SM (1993) Properties of superior vestibular nucleus neurons projecting to the cerebellar flocculus in the squirrel monkey. J Neurophysiol 69:642–645

    CAS  PubMed  Google Scholar 

  • zu Eulenburg P, Caspers S, Roski C, Eickhoff SB (2012) Meta-analytical definition and functional connectivity of the human vestibular cortex. NeuroImage 60:162–169. doi:10.1016/j.neuroimage.2011.12.032

Download references

Acknowledgements

The authors would like to thank Wibke Mueller-Forell and Sabine Esser for the profound support throughout this project.

Author information

Authors and Affiliations

  1. German Center for Vertigo and Balance Disorders, Ludwig-Maximilians-University, Feodor-Lynen-Str.19, 801377, Munich, Germany

    Ria Maxine Ruehl & Peter zu Eulenburg

  2. Department of Neurology, Ludwig-Maximilians-University, 801377, Munich, Germany

    Ria Maxine Ruehl

  3. Institute for Neuroradiology, Johannes Gutenberg University, 55131, Mainz, Germany

    Carolin Hinkel, Thomas Bauermann & Peter zu Eulenburg

Authors
  1. Ria Maxine Ruehl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carolin Hinkel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas Bauermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter zu Eulenburg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ria Maxine Ruehl.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ruehl, R.M., Hinkel, C., Bauermann, T. et al. Delineating function and connectivity of optokinetic hubs in the cerebellum and the brainstem. Brain Struct Funct 222, 4163–4185 (2017). https://doi.org/10.1007/s00429-017-1461-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00429-017-1461-8

Keywords

Search

Navigation