Brain Structure and Function

, Volume 224, Issue 2, pp 567–582 | Cite as

Functional hierarchy of oculomotor and visual motion subnetworks within the human cortical optokinetic system

  • Ria Maxine RuehlEmail author
  • Felix Hoffstaedter
  • Andrew Reid
  • Simon Eickhoff
  • Peter zu Eulenburg
Original Article


Optokinetic look nystagmus (look OKN) is known to engage cortical visual motion and oculomotor hubs. Their functional network hierarchy, however, and the role of the cingulate eye field (CEF) and the dorsolateral prefrontal cortex (DLPFC) in particular have not been investigated. We used look OKN in fMRI to identify all cortical visual motion and oculomotor hubs involved. Using these activations as seed regions, we employed hierarchical clustering in two differing resting state conditions from a separate public data set. Robust activations in the CEF highlight its functional role in OKN and involvement in higher order oculomotor control. Deactivation patterns indicate a decreased modulatory involvement of the DLPFC. The hierarchical clustering revealed a changeable organization of the eye fields, hMT, V3A, and V6 depending on the resting state condition, segregating executive from higher order visual subnetworks. Overall, hierarchical clustering seems to allow for a robust delineation of physiological cortical networks.


Cingulate eye field Functional connectivity Hierarchical clustering Ocular motor control Optokinetic nystagmus 



This work was supported by the German Federal Ministry of Education and Research (BMBF 01 EO 0901).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9:357–381. CrossRefGoogle Scholar
  2. Andersen RA, Bracewell RM, Barash S, Gnadt JW, Fogassi L (1990) Eye position effects on visual, memory, and saccade-related activity in areas LIP and 7a of macaque. J Neurosci 10(4):1176–1196PubMedCrossRefGoogle Scholar
  3. Ashburner J (2007) A fast diffeomorphic image registration algorithm. NeuroImage 38(1):95–113. CrossRefGoogle Scholar
  4. Bense S, Janusch B, Schlindwein P, Bauermann T, Vucurevic G, Brandt T, Stoeter P, Dieterich M (2006) Direction-dependent visual cortex activation during horizontal optokinetic stimulation (fMRI study). Hum Brain Mapp 27(4):296–305. PubMedCrossRefGoogle Scholar
  5. Berman RA, Colby CL, Genovese CR, Voyvodic JT, Luna B, Thulborn KR, Sweeney JA (1999) Cortical networks subserving pursuit and saccadic eye movements in humans: an FMRI study. Hum Brain Mapp 8(4):209–225PubMedCrossRefGoogle Scholar
  6. Biswal B, Yetkin FZ, Haughton VM, Hyde JS (1995) Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med 34(4):537–541PubMedCrossRefGoogle Scholar
  7. Blanke O, Spinelli L, Thut G, Michel CM, Perrig S, Landis T, Seeck M (2000) Location of the human frontal eye field as defined by electrical cortical stimulation: anatomical, functional and electrophysiological characteristics. Neuroreport 11(9):1907–1913PubMedCrossRefGoogle Scholar
  8. Boileau I, Beauregar M, Beuter A, Breault C, Lecours AR (2002) Optokinetic stimulation and the egocentred midsagittal plane: an fMRI study. Neuroreport 13(1):61–65PubMedCrossRefGoogle Scholar
  9. Brotchie PR, Lee MB, Chen DY, Lourensz M, Jackson G, Bradley WG Jr (2003) Head position modulates activity in the human parietal eye fields. NeuroImage 18(1):178–184PubMedCrossRefGoogle Scholar
  10. Buchel C, Josephs O, Rees G, Turner R, Frith CD, Friston KJ (1998) The functional anatomy of attention to visual motion. A functional MRI study. Brain J Neurol 121(Pt 7):1281–1294CrossRefGoogle Scholar
  11. Bucher SF, Dieterich M, Seelos KC, Brandt T (1997) Sensorimotor cerebral activation during optokinetic nystagmus. A functional MRI study. Neurology 49(5):1370–1377PubMedCrossRefGoogle Scholar
  12. Cardin V, Smith AT (2011) Sensitivity of human visual cortical area V6 to stereoscopic depth gradients associated with self-motion. J Neurophysiol 106(3):1240PubMedPubMedCentralCrossRefGoogle Scholar
  13. Chapman LJ, Chapman JP (1987) The measurement of handedness. Brain Cogn 6(2):175–183PubMedCrossRefGoogle Scholar
  14. Chen M, Li B, Guang J, Wei L, Wu S, Liu Y, Zhang M (2016) Two subdivisions of macaque LIP process visual-oculomotor information differently. Proc Natl Acad Sci USA 113(41):E6263–E6270. PubMedCrossRefGoogle Scholar
  15. Cieslik EC, Zilles K, Caspers S, Roski C, Kellermann TS, Jakobs O, Langner R, Laird AR, Fox PT, Eickhoff SB (2013) Is there “one” DLPFC in cognitive action control? Evidence for heterogeneity from co-activation-based parcellation. Cereb Cortex 23(11):2677–2689. PubMedCrossRefGoogle Scholar
  16. DeSouza JF, Menon RS, Everling S (2003) Preparatory set associated with pro-saccades and anti-saccades in humans investigated with event-related FMRI. J Neurophysiol 89(2):1016–1023. PubMedCrossRefGoogle Scholar
  17. 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):1479–1495CrossRefGoogle Scholar
  18. Dieterich M, Bucher SF, Seelos KC, Brandt T (2000) Cerebellar activation during optokinetic stimulation and saccades. Neurology 54(1):148–155PubMedCrossRefGoogle Scholar
  19. 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(9):994–1007CrossRefGoogle Scholar
  20. 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(1):117–127. PubMedCrossRefGoogle Scholar
  21. 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. PubMedCrossRefGoogle Scholar
  22. 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(4):1325–1335. PubMedCrossRefGoogle Scholar
  23. Eickhoff SB, Schleicher A, Zilles K, Amunts K (2006) The human parietal operculum. I. Cytoarchitectonic mapping of subdivisions. Cereb Cortex 16(2):254–267. PubMedCrossRefGoogle Scholar
  24. Eickhoff SB, Grefkes C, Zilles K, Fink GR (2007a) The somatotopic organization of cytoarchitectonic areas on the human parietal operculum. Cereb Cortex 17(8):1800–1811. PubMedCrossRefGoogle Scholar
  25. Eickhoff SB, Paus T, Caspers S, Grosbras MH, Evans AC, Zilles K, Amunts K (2007b) Assignment of functional activations to probabilistic cytoarchitectonic areas revisited. NeuroImage 36(3):511–521. CrossRefPubMedGoogle Scholar
  26. Eickhoff SB, Grefkes C, Fink GR, Zilles K (2008) Functional lateralization of face, hand, and trunk representation in anatomically defined human somatosensory areas. Cereb Cortex 18(12):2820–2830. PubMedPubMedCentralCrossRefGoogle Scholar
  27. Everling S (2007) Where do I look? From attention to action in the frontal eye field. Neuron 56(3):417–419. PubMedCrossRefGoogle Scholar
  28. Felleman DJ, Van Essen DC (1991) Distributed hierarchical processing in the primate cerebral cortex. Cereb Cortex 1(1):1–47PubMedCrossRefGoogle Scholar
  29. Fox MD, Raichle ME (2007) Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci 8(9):700–711. PubMedCrossRefGoogle Scholar
  30. Friston KJ, Frith C, Turner R, Frackowiak RSJ (1995a) Characterizing evoked hemodynamics with fMRI. NeuroImage 2:157–165PubMedCrossRefGoogle Scholar
  31. 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 2:189–210CrossRefGoogle Scholar
  32. 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(2):149–159PubMedCrossRefGoogle Scholar
  33. Galletti C, Battaglini PP (1989) Gaze-dependent visual neurons in area V3A of monkey prestriate cortex. J Neurosci 9(4):1112PubMedCrossRefGoogle Scholar
  34. Galletti C, Gamberini M, Kutz DF, Fattori P, Luppino G, Matelli M (2001) The cortical connections of area V6: an occipito-parietal network processing visual information. Eur J Neurosci 13(8):1572–1588PubMedCrossRefGoogle Scholar
  35. 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(2):173–183PubMedCrossRefGoogle Scholar
  36. Gilaie-Dotan S (2016) Visual motion serves but is not under the purview of the dorsal pathway. Neuropsychologia 89:378–392. PubMedCrossRefGoogle Scholar
  37. Griffanti L, Salimi-Khorshidi G, Beckmann CF, Auerbach EJ, Douaud G, Sexton CE, Zsoldos E, Ebmeier KP, Filippini N, Mackay CE, Moeller S, Xu J, Yacoub E, Baselli G, Ugurbil K, Miller KL, Smith SM (2014) ICA-based artefact removal and accelerated fMRI acquisition for improved resting state network imaging. NeuroImage 95:232–247. PubMedPubMedCentralCrossRefGoogle Scholar
  38. Griffanti L, Rolinski M, Szewczyk-Krolikowski K, Menke RA, Filippini N, Zamboni G, Jenkinson M, Hu MTM, Mackay CE (2016) Challenges in the reproducibility of clinical studies with resting state fMRI: an example in early Parkinson’s disease. NeuroImage 124(Pt A):704–713. PubMedPubMedCentralCrossRefGoogle Scholar
  39. Hanakawa T, Dimyan MA, Hallett M (2008) The representation of blinking movement in cingulate motor areas: a functional magnetic resonance imaging study. Cereb Cortex 18(4):930–937. PubMedCrossRefGoogle Scholar
  40. Handel A, Glimcher PW (2000) Contextual modulation of substantia nigra pars reticulata neurons. J Neurophysiol 83(5):3042–3048PubMedCrossRefGoogle Scholar
  41. Huerta MF, Kaas JH (1990) Supplementary eye field as defined by intracortical microstimulation: connections in macaques. J Comp Neurol 293(2):299–330PubMedCrossRefGoogle Scholar
  42. 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(2):203–216. PubMedCrossRefGoogle Scholar
  43. Krauzlis RJ (2004) Recasting the smooth pursuit eye movement system. J Neurophysiol 91(2):591PubMedCrossRefGoogle Scholar
  44. Leigh RJ, Zee DS (2006) The neurology of eye movements, 4th edn. Oxford University Press, OxfordGoogle Scholar
  45. Liu X, Zhu XH, Qiu P, Chen W (2012) A correlation-matrix-based hierarchical clustering method for functional connectivity analysis. J Neurosci Methods 211(1):94–102. PubMedPubMedCentralCrossRefGoogle Scholar
  46. Liu D, Dong Z, Zuo X, Wang J, Zang Y (2013) Eyes-open/eyes-closed dataset sharing for reproducibility evaluation of resting state fMRI data analysis methods. Neuroinformatics 11(4):469–476. PubMedCrossRefGoogle Scholar
  47. Lynch JC, Tian JR (2006) Cortico-cortical networks and cortico-subcortical loops for the higher control of eye movements. Prog Brain Res 151:461–501. PubMedCrossRefGoogle Scholar
  48. Marrelec G, Krainik A, Duffau H, Pelegrini-Issac M, Lehericy S, Doyon J, Benali H (2006) Partial correlation for functional brain interactivity investigation in functional MRI. NeuroImage 32(1):228–237. PubMedCrossRefGoogle Scholar
  49. McKeefry DJ, Burton MP, Vakrou C, Barrett BT, Morland AB (2008) Induced deficits in speed perception by transcranial magnetic stimulation of human cortical areas V5/MT + and V3A. J Neurosci 28(27):6848–6857. PubMedPubMedCentralCrossRefGoogle Scholar
  50. Parton A, Nachev P, Hodgson TL, Mort D, Thomas D, Ordidge R, Morgan PS, Jackson S, Rees G, Husain M (2007) Role of the human supplementary eye field in the control of saccadic eye movements. Neuropsychologia 45(5-4):997–1008. PubMedPubMedCentralCrossRefGoogle Scholar
  51. Paus T, Petrides M, Evans AC, Meyer E (1993) Role of the human anterior cingulate cortex in the control of oculomotor, manual, and speech responses: a positron emission tomography study. J Neurophysiol 70(2):453–469PubMedCrossRefGoogle Scholar
  52. Pierrot-Deseilligny C, Muri RM, Ploner CJ, Gaymard B, Demeret S, Rivaud-Pechoux S (2003) Decisional role of the dorsolateral prefrontal cortex in ocular motor behaviour. Brain J Neurol 126(Pt 6):1460–1473CrossRefGoogle Scholar
  53. Pierrot-Deseilligny C, Milea D, Muri RM (2004) Eye movement control by the cerebral cortex. Curr Opin Neurol 17(1):17–25PubMedCrossRefGoogle Scholar
  54. Pitzalis S, Fattori P, Galletti C (2012) The functional role of the medial motion area V6. Front Behav Neurosci 6:91. PubMedCrossRefGoogle Scholar
  55. Pitzalis S, Fattori P, Galletti C (2015) The human cortical areas V6 and V6A. Vis Neurosci 32:E007. PubMedCrossRefPubMedCentralGoogle Scholar
  56. Ploner CJ, Gaymard BM, Rivaud-Pechoux S, Pierrot-Deseilligny C (2005) The prefrontal substrate of reflexive saccade inhibition in humans. Biol Psychiatry 57(10):1159–1165. PubMedCrossRefGoogle Scholar
  57. Poldrack RA, Fletcher PC, Henson RN, Worsley KJ, Brett M, Nichols TE (2008) Guidelines for reporting an fMRI study. NeuroImage 40(2):409–414. PubMedPubMedCentralCrossRefGoogle Scholar
  58. Press WA, Brewer AA, Dougherty RF, Wade AR, Wandell BA (2001) Visual areas and spatial summation in human visual cortex. Vis Res 41(10–11):1321–1332PubMedCrossRefGoogle Scholar
  59. Salimi-Khorshidi G, Douaud G, Beckmann CF, Glasser MF, Griffanti L, Smith SM (2014) Automatic denoising of functional MRI data: combining independent component analysis and hierarchical fusion of classifiers. NeuroImage 90:449–468. PubMedPubMedCentralCrossRefGoogle Scholar
  60. Schall JD, Morel A, Kaas JH (1993) Topography of supplementary eye field afferents to frontal eye field in macaque: implications for mapping between saccade coordinate systems. Vis Neurosci 10(2):385–393PubMedCrossRefGoogle Scholar
  61. Shin S, Sommer MA (2010) Activity of neurons in monkey globus pallidus during oculomotor behavior compared with that in substantia nigra pars reticulata. J Neurophysiol 103(4):1874–1887. PubMedPubMedCentralCrossRefGoogle Scholar
  62. Shipp S, Blanton M, Zeki S (1998) A visuo-somatomotor pathway through superior parietal cortex in the macaque monkey: cortical connections of areas V6 and V6A. Eur J Neurosci 10(10):3171–3193PubMedCrossRefGoogle Scholar
  63. Smith SM, Nichols TE, Vidaurre D, Winkler AM, Behrens TE, Glasser MF, Ugurbil K, Barch DM, Van Essen DC, Miller KL (2015) A positive-negative mode of population covariation links brain connectivity, demographics and behavior. Nat Neurosci 18(11):1565–1567. PubMedPubMedCentralCrossRefGoogle Scholar
  64. Stuphorn V, Schall JD (2002) Neuronal control and monitoring of initiation of movements. Muscle Nerve 26(3):326–339. PubMedCrossRefGoogle Scholar
  65. Tian JR, Lynch JC (1996) Corticocortical input to the smooth and saccadic eye movement subregions of the frontal eye field in Cebus monkeys. J Neurophysiol 76(4):2754–2771PubMedCrossRefGoogle Scholar
  66. Tootell RB, Mendola JD, Hadjikhani NK, Ledden PJ, Liu AK, Reppas JB, Sereno MI, Dale AM (1997) Functional analysis of V3A and related areas in human visual cortex. J Neurosci 17(18):7060–7078PubMedCrossRefGoogle Scholar
  67. Yoshida A, Tanaka M (2009) Neuronal activity in the primate globus pallidus during smooth pursuit eye movements. Neuroreport 20(2):121–125. PubMedCrossRefGoogle Scholar
  68. Zeki SM (1978) Uniformity and diversity of structure and function in rhesus monkey prestriate visual cortex. J Physiol 277:273–290PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Neurology, University HospitalLudwig-Maximilians-University MunichMunichGermany
  2. 2.German Center for Vertigo and Balance Disorders-IFB LMULudwig-Maximilians-University MunichMunichGermany
  3. 3.Institute of Neuroscience and Medicine (INM-7)JuelichGermany
  4. 4.Institute of Systems Neuroscience, Medical FacultyHeinrich Heine University DüsseldorfDuesseldorfGermany
  5. 5.School of PsychologyUniversity of NottinghamNottinghamUK

Personalised recommendations