Abstract
Miniature yoked eye movements, fixational saccades, are critical to counteract visual fading. Fixational saccades are followed by a return saccades forming squarewaves. Present in healthy states, squarewaves, if too many or too big, affect visual stability. Parkinson’s disease (PD), where visual deficits are not uncommon, is associated with the squarewaves that are excessive in number or size. Our working hypothesis is that the basal ganglia are at the epicenter of the abnormal fixational saccades and squarewaves in PD; the effects are manifested through their connections to the superior colliculus (affecting saccade frequency and amplitude) and the cerebellum (affecting velocity and amplitude). We predict that the subthalamic deep brain stimulation (DBS) variably affects the amplitude, frequency, and velocity of fixational saccade and that the effect depends on the electrode’s proximity or the volume of activated tissue in the subthalamic nucleus’ connections with the superior colliculus or the cerebellum. We found that DBS modulated saccade amplitude, frequency, and velocity in 11 PD patients. Although all three parameters were affected, the extent of the effects varied amongst subjects. The modulation was dependent upon the location and size of the electrically activated volume of the subthalamic region.
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Abadi, R. V., & Gowen, E. (2004). Characteristics of saccadic intrusions. Vision Research, 44(23), 2675–2690. https://doi.org/10.1016/j.visres.2004.05.009.
Bergeron, A., & Guitton, D. (2001). The superior colliculus and its control of fixation behavior via projections to brainstem omnipause neurons. Progress in Brain Research, 134, 97–107. Elsevier. https://doi.org/10.1016/S0079-6123(01)34008-6.
Bergeron, A., & Guitton, D. (2002). In multiple-step gaze shifts: Omnipause (OPNs) and collicular fixation neurons encode gaze position error; OPNs gate saccades. Journal of Neurophysiology, 88(4), 1726–1742. https://doi.org/10.1152/jn.2002.88.4.1726.
Bergman, H., Wichmann, T., & DeLong, M. R. (1990). Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science, 249(4975), 1436–1438. https://doi.org/10.1126/science.2402638.
Borm, C. D. J. M., Visser, F., Werkmann, M., de Graaf, D., Putz, D., Seppi, K., Poewe, W., Vlaar, A. M. M., Hoyng, C., Bloem, B. R., Theelen, T., & de Vries, N. M. (2020). Seeing ophthalmologic problems in Parkinson disease: Results of a visual impairment questionnaire. Neurology, 94(14), e1539–e1547. https://doi.org/10.1212/WNL.0000000000009214.
Bostan, A. C., & Strick, P. L. (2010). The cerebellum and basal ganglia are interconnected. Neuropsychology Review, 20(3), 261–270. https://doi.org/10.1007/s11065-010-9143-9.
Büttner-Ennever, J. A., & Büttner, U. (1978). A cell group associated with vertical eye movements in the rostral mesencephalic reticular formation of the monkey. Brain Research, 151(1), 31–47. https://doi.org/10.1016/0006-8993(78)90948-4.
Büttner-Ennever, J. A., & Horn, A. K. E. (1994). Neuroanatomy of the saccadic omnipause neurons in the nucleus raphe interpositus. In Contemporary Ocular Motor and Vestibular Research: A Tribute to David A. Robinson (pp. 489–495). New York: Thieme Medical Publishers.
Büttner-Ennever, J. A., Horn, A. K. E., Henn, V., & Cohen, B. (1999). Projections from the superior colliculus motor map to omnipause neurons in monkey. Journal of Comparative Neurology, 413(1), 55–67. https://doi.org/10.1002/(SICI)1096-9861(19991011)413:1<55::AID-CNE3>3.0.CO;2-K.
Crawford, J. D., Cadera, W., & Vilis, T. (1991). Generation of torsional and vertical eye position signals by the interstitial nucleus of Cajal. Science, 252(5012), 1551–1553. https://doi.org/10.1126/science.2047862.
Cullen, K. E., & Guitton, D. (1997). Analysis of primate IBN spike trains using system identification techniques. I. Relationship to Eye Movement Dynamics During Head-Fixed Saccades. Journal of Neurophysiology, 78(6), 3259–3282. https://doi.org/10.1152/jn.1997.78.6.3259.
DeLong, M. R., & Wichmann, T. (2007). Circuits and circuit disorders of the basal ganglia. Archives of Neurology, 64(1), 20–24. https://doi.org/10.1001/archneur.64.1.20.
Evinger, C., Kaneko, C. R., & Fuchs, A. F. (1982). Activity of omnipause neurons in alert cats during saccadic eye movements and visual stimuli. Journal of Neurophysiology, 47(5), 827–844. https://doi.org/10.1152/jn.1982.47.5.827.
Fuchs, A. F., Kaneko, C. R. S., & Scudder, C. A. (1985). Brainstem control of saccadic eye movements. Annual Review of Neuroscience, 8(1), 307–337.
Hafed, Z. M., Goffart, L., & Krauzlis, R. J. (2009). A neural mechanism for microsaccade generation in the primate superior Colliculus. Science, 323(5916), 940–943. https://doi.org/10.1126/science.1166112.
Hepp, K., Henn, V., Vilis, T., & Cohen, B. (1989). Brainstem regions related to saccade generation. Reviews of Oculomotor Research, 3, 105.
Herishanu, Y. O., & Sharpe, J. A. (1981). Normal square wave jerks. Investigative Ophthalmology & Visual Science, 20(2), 268–272.
Hikosaka, O., & Wurtz, R. H. (1983a). Visual and oculomotor functions of monkey substantia nigra pars reticulata. II. Visual responses related to fixation of gaze. Journal of Neurophysiology, 49(5), 1254–1267. https://doi.org/10.1152/jn.1983.49.5.1254.
Hikosaka, O., & Wurtz, R. H. (1983b). Visual and oculomotor functions of monkey substantia nigra pars reticulata. IV. Relation of substantia nigra to superior colliculus. Journal of Neurophysiology, 49(5), 1285–1301. https://doi.org/10.1152/jn.1983.49.5.1285.
Kang, S. L., Shaikh, A. G., & Ghasia, F. F. (2018). Vergence and Strabismus in Neurodegenerative Disorders. Frontiers in Neurology, 9. https://doi.org/10.3389/fneur.2018.00299.
Kapoula, Z., Yang, Q., Otero-Millan, J., Xiao, S., Macknik, S. L., Lang, A., Verny, M., & Martinez-Conde, S. (2014). Distinctive features of microsaccades in Alzheimer’s disease and in mild cognitive impairment. AGE, 36(2), 535–543. https://doi.org/10.1007/s11357-013-9582-3.
Leigh, R. J., & Zee, D. S. (2015). The neurology of eye movements. Oxford: Oxford University Press.
Martinez-Conde, S., Macknik, S. L., Troncoso, X. G., & Dyar, T. A. (2006). Microsaccades counteract visual fading during fixation. Neuron, 49(2), 297–305. https://doi.org/10.1016/j.neuron.2005.11.033.
McCamy, M. B., Otero-Millan, J., Macknik, S. L., Yang, Y., Troncoso, X. G., Baer, S. M., Crook, S. M., & Martinez-Conde, S. (2012). Microsaccadic efficacy and contribution to Foveal and peripheral vision. Journal of Neuroscience, 32(27), 9194–9204. https://doi.org/10.1523/JNEUROSCI.0515-12.2012.
McIntyre, C. C., & Hahn, P. J. (2010). Network perspectives on the mechanisms of deep brain stimulation. Neurobiology of Disease, 38(3), 329–337. https://doi.org/10.1016/j.nbd.2009.09.022.
Moschovakis, A. K., Scudder, C. A., & Highstein, S. M. (1991). Structure of the primate oculomotor burst generator. I. Medium-lead burst neurons with upward on-directions. Journal of Neurophysiology, 65(2), 203–217.
Noecker, A. M., Choi, K. S., Riva-Posse, P., Gross, R. E., Mayberg, H. S., & McIntyre, C. C. (2018). StimVision software: Examples and applications in Subcallosal cingulate deep brain stimulation for depression. Neuromodulation: Technology at the Neural Interface, 21(2), 191–196. https://doi.org/10.1111/ner.12625.
Otero-Millan, J., Macknik, S. L., Serra, A., Leigh, R. J., & Martinez-Conde, S. (2011a). Triggering mechanisms in microsaccade and saccade generation: A novel proposal. Annals of the New York Academy of Sciences, 1233(1), 107–116. https://doi.org/10.1111/j.1749-6632.2011.06177.x.
Otero-Millan, J., Serra, A., Leigh, R. J., Troncoso, X. G., Macknik, S. L., & Martinez-Conde, S. (2011b). Distinctive features of saccadic intrusions and microsaccades in progressive Supranuclear palsy. Journal of Neuroscience, 31(12), 4379–4387. https://doi.org/10.1523/JNEUROSCI.2600-10.2011.
Otero-Millan, J., Schneider, R., Leigh, R. J., Macknik, S. L., & Martinez-Conde, S. (2013). Saccades during attempted fixation in Parkinsonian disorders and recessive Ataxia: From microsaccades to square-wave jerks. PLoS One, 8(3), e58535.
Otero-Millan, J., Castro, J. L. A., Macknik, S. L., & Martinez-Conde, S. (2014). Unsupervised clustering method to detect microsaccades. Journal of Vision, 14(2), 18–18. https://doi.org/10.1167/14.2.18.
Otero-Millan, J., Optican, L. M., Macknik, S. L., & Martinez-Conde, S. (2018). Modeling the triggering of saccades, microsaccades, and saccadic intrusions. Frontiers in Neurology, 9. https://doi.org/10.3389/fneur.2018.00346.
Pauli, W. M., Nili, A. N., & Tyszka, J. M. (2018). A high-resolution probabilistic in vivo atlas of human subcortical brain nuclei. Scientific Data, 5(1), 180063. https://doi.org/10.1038/sdata.2018.63.
Quaia, C., Lefèvre, P., & Optican, L. M. (1999). Model of the control of saccades by superior Colliculus and cerebellum. Journal of Neurophysiology, 82(2), 999–1018. https://doi.org/10.1152/jn.1999.82.2.999.
Racette, B. A., Gokden, M., Tychsen, L., & Perlmutter, J. S. (1999). Convergence insufficiency in idiopathic Parkinson’s disease responsive to levodopa. Strabismus, 7(3), 169–174. https://doi.org/10.1076/stra.7.3.169.636.
Rascol, O., Clanet, M., Montastruc, J. L., Simonetta, M., Soulier-Esteve, M. J., Doyon, B., & Rascol, A. (1989). Abnormal ocular movements in Parkinson’s disease evidence for involvement of dopaminergic systems. Brain, 112(5), 1193–1214. https://doi.org/10.1093/brain/112.5.1193.
Rascol, O., Sabatini, U., Simonetta-Moreau, M., Montastruc, J. L., Rascol, A., & Clanet, M. (1991). Square wave jerks in parkinsonian syndromes. Journal of Neurology, Neurosurgery & Psychiatry, 54(7), 599–602. https://doi.org/10.1136/jnnp.54.7.599.
Repka, M. X., Claro, M. C., Loupe, D. N., & Reich, S. G. (1996). Ocular motility in Parkinson’s disease. Journal of Pediatric Ophthalmology and Strabismus, 33(3), 144–147. https://doi.org/10.3928/0191-3913-19960501-04.
Rolfs, M., Kliegl, R., & Engbert, R. (2008). Toward a model of microsaccade generation: The case of microsaccadic inhibition. Journal of Vision, 8(11), 5–5. https://doi.org/10.1167/8.11.5.
Shaikh, A. G. (2019). Human gaze holding and its disorders. Annals of Otology and Neurotology, 02(01), 33–40. https://doi.org/10.1055/s-0039-1693834.
Shaikh, A. G., & Ghasia, F. F. (2013). Physiology and pathology of saccades and gaze holding. NeuroRehabilitation, 32(3), 493–505. https://doi.org/10.3233/NRE-130872.
Shaikh, A. G., Xu-Wilson, M., Grill, S., & Zee, D. S. (2011). “Staircase” square-wave jerks in early Parkinson’s disease. British Journal of Ophthalmology, 95(5), 705–709. https://doi.org/10.1136/bjo.2010.179630.
Sparks, D., Rohrer, W. H., & Zhang, Y. (2000). The role of the superior colliculus in saccade initiation: a study of express saccades and the gap effect. Vision Research, 40(20), 2763–2777. https://doi.org/10.1016/S0042-6989(00)00133-4.
Troncoso, X. G., Macknik, S. L., & Martinez-Conde, S. (2008). Microsaccades counteract perceptual filling-in. Journal of Vision, 8(14), 15–15. https://doi.org/10.1167/8.14.15.
Wark, H. A. C., Garell, P. C., Walker, A. L., & Basso, M. A. (2008). A case report on fixation instability in Parkinson’s disease with bilateral deep brain stimulation implants. Journal of Neurology, Neurosurgery & Psychiatry, 79(4), 443–447. https://doi.org/10.1136/jnnp.2007.117192.
Wichmann, T., & DeLong, M. R. (2003). Functional neuroanatomy of the basal ganglia in Parkinson’s disease. Functional Neuroanatomy of the Basal Ganglia in Parkinson’s Disease, 91, 9–18.
Wichmann, T., DeLong, M. R., Guridi, J., & Obeso, J. A. (2011). Milestones in research on the pathophysiology of Parkinson’s disease. Movement Disorders, 26(6), 1032–1041. https://doi.org/10.1002/mds.23695.
Wichmann, T., Bergman, H., & DeLong, M. R. (2018). Basal ganglia, movement disorders and deep brain stimulation: Advances made through non-human primate research. Journal of Neural Transmission (Vienna, Austria: 1996), 125(3), 419–430. https://doi.org/10.1007/s00702-017-1736-5.
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Beylergil, S.B., Murray, J., Noecker, A.M. et al. Effects of subthalamic deep brain stimulation on fixational eye movements in Parkinson’s disease. J Comput Neurosci 49, 345–356 (2021). https://doi.org/10.1007/s10827-020-00773-2
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DOI: https://doi.org/10.1007/s10827-020-00773-2