Abstract
Prediction and time estimation are all but required for motor function in everyday life. In the context of eye movements, for instance, they allow predictive saccades and eye re-acceleration in anticipation of a target re-appearance. While the neural pathways involved are not fully understood, it is known that the frontal lobe plays an important role. As such, neurological disorders that affect it, such as frontotemporal (FTD) dementia, are likely to induce deficits in such movements. In this work, we study the performances of frontotemporal dementia patients in an oculomotor task designed to elicit predictive saccades at different rates, and compare them to young and older adults. Clear deficits in the production of predictive saccades were found in patients, in particular when the time between saccades was short (~500 ms). Furthermore, one asymptomatic C9ORF72 mutation bearer showed patterns of oculomotor behavior similar to FTD patients. He exhibited FTD symptoms within 3 years post-measure, suggesting that an impairment of oculomotor function could be an early clinical sign. Taken together, these results argue in favor of a role of the frontal lobe in predictive movements timing over short timescales, and suggest that predictive saccades in FTD patients warrant further investigation to fully assess their potential as a diagnostic aid.
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Anderson, T. J., & MacAskill, M. R. (2013). Eye movements in patients with neurodegenerative disorders. Nature Reviews Neurology, 9(2), 74–85. https://doi.org/10.1038/nrneurol.2012.273.
Antoniades, C. A., & Kennard, C. (2015). Ocular motor abnormalities in neurodegenerative disorders. Eye (Basingstoke), 29(2), 200–207. https://doi.org/10.1038/eye.2014.276.
Bang, J., Spina, S., & Miller, B. L. (2015). Frontotemporal dementia. The Lancet, 386(10004), 1672–1682. https://doi.org/10.1016/S0140-6736(15)00461-4.
Bigio, E. H. (2013). Making the diagnosis of Frontotemporal lobar degeneration. Archives of Pathology & Laboratory Medicine, 137(3), 314–325. https://doi.org/10.5858/arpa.2012-0075-RA.
Boxer, A. L., Garbutt, S., Rankin, K. P., Hellmuth, J., Neuhaus, J., Miller, B. L., & Lisberger, S. G. (2006). Medial versus lateral frontal lobe contributions to voluntary saccade control as revealed by the study of patients with frontal lobe degeneration. Journal of Neuroscience, 26(23), 6354–6363. https://doi.org/10.1523/JNEUROSCI.0549-06.2006.
Boxer, A. L., Garbutt, S., & Seeley, W. (2012). Saccade abnormalities in autopsy-confirmed Frontotemporal lobar degeneration and Alzheimer disease. Archives of Neurology, 69(4), 509–517. https://doi.org/10.1001/archneurol.2011.1021.Saccade.
Burr, D. C., & Morrone, C. (2006). Time perception: Space–time in the brain. Current Biology, 16(5), R171–R173. https://doi.org/10.1016/j.cub.2006.02.038.
Burrell, J. R., Hornberger, M., Carpenter, R. H. S., Kiernan, M. C., & Hodges, J. R. (2012). Saccadic abnormalities in frontotemporal dementia. Neurology, 78(23), 1816–1823. https://doi.org/10.1212/WNL.0b013e318258f75c.
Coppe, S., Orban de Xivry, J.-J., Yüksel, D., Ivanoiu, A., & Lefèvre, P. (2012). Dramatic impairment of prediction due to frontal lobe degeneration. Journal of Neurophysiology, 108(11), 2957–2966. https://doi.org/10.1152/jn.00582.2012.
Core Team, R. (2018). R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing Retrieved from https://www.r-project.org/.
Douglass, A., Walterfang, M., Velakoulis, D., & Abel, L. (2018). Behavioral variant frontotemporal dementia performance on a range of saccadic tasks. Journal of Alzheimer’s Disease, 65(1), 231–242. https://doi.org/10.3233/JAD-170797.
Field, A. P., & Wilcox, R. R. (2017). Robust statistical methods: A primer for clinical psychology and experimental psychopathology researchers. Behaviour Research and Therapy, 98, 19–38. https://doi.org/10.1016/j.brat.2017.05.013.
Findlay, J. M. (1981). Spatial and temporal factors in the predictive generation of saccadic eye movements. Vision Research, 21(3), 347–354. https://doi.org/10.1016/0042-6989(81)90162-0.
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975). Mini-mental state: A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12(3), 189–198.
Fukushima, K., Fukushima, J., Warabi, T., & Barnes, G. R. (2013). Cognitive processes involved in smooth pursuit eye movements: Behavioral evidence, neural substrate and clinical correlation. Frontiers in Systems Neuroscience, 7(March), 4. https://doi.org/10.3389/fnsys.2013.00004.
Garbutt, S., Matlin, A., Hellmuth, J., Schenk, A. K., Johnson, J. K., Rosen, H., Dean, D., Kramer, J., Neuhaus, J., Miller, B. L., Lisberger, S. G., & Boxer, A. L. (2008). Oculomotor function in frontotemporal lobar degeneration, related disorders and Alzheimer’s disease. Brain : A Journal of Neurology, 131(Pt 5), 1268–1281. https://doi.org/10.1093/brain/awn047.
Garibotto, V., Borroni, B., Agosti, C., Premi, E., Alberici, A., Eickhoff, S. B., Brambati, S. M., Bellelli, G., Gasparotti, R., Perani, D., & Padovani, A. (2011). Subcortical and deep cortical atrophy in Frontotemporal lobar degeneration. Neurobiology of Aging, 32(5), 875–884. https://doi.org/10.1016/j.neurobiolaging.2009.05.004.
Gaymard, B., Ploner, C. J., Rivaud, S., Vermersch, A. I., & Pierrot-Deseilligny, C. (1998). Cortical control of saccades. Experimental Brain Research, 123(1–2), 159–163. https://doi.org/10.1007/s002210050557.
Gijselinck, I., Van Langenhove, T., van der Zee, J., Sleegers, K., Philtjens, S., Kleinberger, G., et al. (2012). A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: A gene identification study. The Lancet Neurology, 11(1), 54–65. https://doi.org/10.1016/S1474-4422(11)70261-7.
Gorno-Tempini, M. L., Hillis, A. E., Weintraub, S., Kertesz, A., Mendez, M., Cappa, S. F., Ogar, J. M., Rohrer, J. D., Black, S., Boeve, B. F., Manes, F., Dronkers, N. F., Vandenberghe, R., Rascovsky, K., Patterson, K., Miller, B. L., Knopman, D. S., Hodges, J. R., Mesulam, M. M., & Grossman, M. (2011). Classification of primary progressive aphasia and its variants. Neurology, 76(11), 1006–1014. https://doi.org/10.1212/WNL.0b013e31821103e6.
Harrell, F., & Davis, C. E. (1982). A new distribution-free quantile estimator. Biometrika, 69(3), 635–640. https://doi.org/10.1093/biomet/69.3.635.
Henley, S. M. D., Downey, L. E., Nicholas, J. M., Kinnunen, K. M., Golden, H. L., Buckley, A., Mahoney, C. J., & Crutch, S. J. (2014). Degradation of cognitive timing mechanisms in behavioural variant frontotemporal dementia. Neuropsychologia, 65, 88–101. https://doi.org/10.1016/j.neuropsychologia.2014.10.009.
Hove, M. J., Fairhurst, M. T., Kotz, S. A., & Keller, P. E. (2013). Synchronizing with auditory and visual rhythms: An fMRI assessment of modality differences and modality appropriateness. NeuroImage, 67, 313–321. https://doi.org/10.1016/j.neuroimage.2012.11.032.
Irving, E. L., Steinbach, M. J., Lillakas, L., Babu, R. J., & Hutchings, N. (2006). Horizontal saccade dynamics across the human life span. Investigative Ophthalmology and Visual Science, 47(6), 2478–2484. https://doi.org/10.1167/iovs.05-1311.
Kleiner, M., Brainard, D. H., Pelli, D. G., Broussard, C., Wolf, T., & Niehorster, D. (2007). What’s new in Psychtoolbox-3? Perception, 36, S14. https://doi.org/10.1068/v070821.
Krauzlis, R. J. (2004). Recasting the smooth pursuit eye movement system. Journal of Neurophysiology, 91(2), 591–603. https://doi.org/10.1152/jn.00801.2003.
Krauzlis, R. J. (2005). The control of voluntary eye movements: New perspectives. The Neuroscientist : A Review Journal Bringing Neurobiology, Neurology and Psychiatry, 11(2), 124–137. https://doi.org/10.1177/1073858404271196.
Laforce, R. (2013). Behavioral and language variants of frontotemporal dementia: A review of key symptoms. Clinical Neurology and Neurosurgery, 115(12), 2405–2410. https://doi.org/10.1016/j.clineuro.2013.09.031.
Landin-Romero, R., Kumfor, F., Leyton, C. E., Irish, M., Hodges, J. R., & Piguet, O. (2017). Disease-specific patterns of cortical and subcortical degeneration in a longitudinal study of Alzheimer’s disease and behavioural-variant frontotemporal dementia. NeuroImage, 151(March 2016), 72–80. https://doi.org/10.1016/j.neuroimage.2016.03.032.
Lee, J., Joshua, M., Medina, J. F., & Lisberger, S. G. (2016a). Signal, noise, and variation in neural and sensory-motor latency. Neuron, 90(1), 165–176. https://doi.org/10.1016/j.neuron.2016.02.012.
Lee, S. M., Peltsch, A., Kilmade, M., Brien, D. C., Coe, B. C., Johnsrude, I. S., & Munoz, D. P. (2016b). Neural correlates of predictive saccades. Journal of Cognitive Neuroscience, 28(8), 1210–1227. https://doi.org/10.1162/jocn_a_00968.
Leigh, R. J., & Kennard, C. (2004). Using saccades as a research tool in the clinical neurosciences. Brain, 127(3), 460–477. https://doi.org/10.1093/brain/awh035.
Lewis, P., & Miall, R. (2003). Brain activation patterns during measurement of sub- and supra-second intervals. Neuropsychologia, 41(12), 1583–1592. https://doi.org/10.1016/S0028-3932(03)00118-0.
Lukasova, K., Nucci, M. P., & Neto, R. M. de A., Vieira, G., Sato, J. R., & Amaro, E. (2018). Predictive saccades in children and adults: A combined fMRI and eye tracking study. PLoS One, 13(5), e0196000. https://doi.org/10.1371/journal.pone.0196000.
Madelain, L., & Krauzlis, R. J. (2003). Effects of learning on smooth pursuit during transient disappearance of a visual target. Journal of Neurophysiology, 90(2), 972–982. https://doi.org/10.1152/jn.00869.2002.
Mair, P., & Wilcox, R. R. (2018). WRS2: Wilcox robust estimation and testing.
McIntire, L. K., McKinley, R. A., Goodyear, C., & McIntire, J. P. (2014). Detection of vigilance performance using eye blinks. Applied Ergonomics, 45(2 PB), 354–362. https://doi.org/10.1016/j.apergo.2013.04.020.
Merchant, H., Harrington, D. L., & Meck, W. H. (2013). Neural basis of the perception and estimation of time. Annual Review of Neuroscience, 36, 313–336. https://doi.org/10.1146/annurev-neuro-062012-170349.
Meyniel, C., Rivaud-Péchoux, S., Damier, P., & Gaymard, B. (2005). Saccade impairments in patients with fronto-temporal dementia. Journal of Neurology, Neurosurgery & Psychiatry, 76(11), 1581–1584. https://doi.org/10.1136/jnnp.2004.060392.
Nyffeler, T., Rivaud-Péchoux, S., Wattiez, N., & Gaymard, B. (2008). Involvement of the supplementary eye Field in Oculomotor predictive behavior. Journal of Cognitive Neuroscience, 20(9), 1583–1594. https://doi.org/10.1162/jocn.2008.20073.
Orban de Xivry, J.-J., & Lefèvre, P. (2007). Saccades and pursuit: Two outcomes of a single sensorimotor process. The Journal of Physiology, 584(Pt 1), 11–23. https://doi.org/10.1113/jphysiol.2007.139881.
Orban de Xivry, J.-J., Missal, M., & Lefèvre, P. (2008). A dynamic representation of target motion drives predictive smooth pursuit during target blanking. Journal of Vision, 8(15), 1–13. https://doi.org/10.1167/8.15.6.
Pierrot-Deseilligny, C., Müri, R. M., Ploner, C. J., Gaymard, B., Demeret, S., & Rivaud-Péchoux, S. (2003). Decisional role of the dorsolateral prefrontal cortex in ocular motor behaviour. Brain, 126(6), 1460–1473. https://doi.org/10.1093/brain/awg148.
Rascovsky, K., Hodges, J. R., Knopman, D., Mendez, M. F., Kramer, J. H., Neuhaus, J., van Swieten, J. C., Seelaar, H., Dopper, E. G. P., Onyike, C. U., Hillis, A. E., Josephs, K. A., Boeve, B. F., Kertesz, A., Seeley, W. W., Rankin, K. P., Johnson, J. K., Gorno-Tempini, M. L., Rosen, H., Prioleau-Latham, C. E., Lee, A., Kipps, C. M., Lillo, P., Piguet, O., Rohrer, J. D., Rossor, M. N., Warren, J. D., Fox, N. C., Galasko, D., Salmon, D. P., Black, S. E., Mesulam, M., Weintraub, S., Dickerson, B. C., Diehl-Schmid, J., Pasquier, F., Deramecourt, V., Lebert, F., Pijnenburg, Y., Chow, T. W., Manes, F., Grafman, J., Cappa, S. F., Freedman, M., Grossman, M., & Miller, B. L. (2011). Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain, 134(9), 2456–2477. https://doi.org/10.1093/brain/awr179.
Renton, A. E., Majounie, E., Waite, A., Simón-Sánchez, J., Rollinson, S., Gibbs, J. R., Schymick, J. C., Laaksovirta, H., van Swieten, J., Myllykangas, L., Kalimo, H., Paetau, A., Abramzon, Y., Remes, A. M., Kaganovich, A., Scholz, S. W., Duckworth, J., Ding, J., Harmer, D. W., Hernandez, D. G., Johnson, J. O., Mok, K., Ryten, M., Trabzuni, D., Guerreiro, R. J., Orrell, R. W., Neal, J., Murray, A., Pearson, J., Jansen, I. E., Sondervan, D., Seelaar, H., Blake, D., Young, K., Halliwell, N., Callister, J. B., Toulson, G., Richardson, A., Gerhard, A., Snowden, J., Mann, D., Neary, D., Nalls, M. A., Peuralinna, T., Jansson, L., Isoviita, V. M., Kaivorinne, A. L., Hölttä-Vuori, M., Ikonen, E., Sulkava, R., Benatar, M., Wuu, J., Chiò, A., Restagno, G., Borghero, G., Sabatelli, M., ITALSGEN Consortium, Heckerman, D., Rogaeva, E., Zinman, L., Rothstein, J. D., Sendtner, M., Drepper, C., Eichler, E. E., Alkan, C., Abdullaev, Z., Pack, S. D., Dutra, A., Pak, E., Hardy, J., Singleton, A., Williams, N. M., Heutink, P., Pickering-Brown, S., Morris, H. R., Tienari, P. J., & Traynor, B. J. (2011). A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron, 72(2), 257–268. https://doi.org/10.1016/j.neuron.2011.09.010.
Shelhamer, M., & Joiner, W. M. (2003). Saccades exhibit abrupt transition between reactive and predictive; predictive saccade sequences have long-term correlations. Journal of Neurophysiology, 90(4), 2763–2769. https://doi.org/10.1152/jn.00478.2003.
Stuphorn, V. (2015). The role of supplementary eye field in goal-directed behavior. Journal of Physiology-Paris, 109(1–3), 118–128. https://doi.org/10.1016/j.jphysparis.2015.02.002.
Turgeon, M., Lustig, C., & Meck, W. H. (2016). Cognitive aging and time perception: Roles of Bayesian optimization and degeneracy. Frontiers in Aging Neuroscience, 8(MAY), 1–17. https://doi.org/10.3389/fnagi.2016.00102.
Wilcox, R. R. (2017). One-way and higher designs for independent groups. In Introduction to Robust Estimation and Hypothesis Testing (pp. 319–415). Elsevier. https://doi.org/10.1016/B978-0-12-804733-0.00007-X.
Zhang, Y., Tartaglia, M. C., Schuff, N., Chiang, G. C., Ching, C., Rosen, H. J., Gorno-Tempini, M. L., Miller, B. L., & Weiner, M. W. (2013). MRI signatures of brain macrostructural atrophy and microstructural degradation in frontotemporal lobar degeneration subtypes. Journal of Alzheimer’s Disease, 33(2), 431–444. https://doi.org/10.3233/JAD-2012-121156.
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Deravet, N., Orban de Xivry, JJ., Ivanoiu, A. et al. Frontotemporal dementia patients exhibit deficits in predictive saccades. J Comput Neurosci 49, 357–369 (2021). https://doi.org/10.1007/s10827-020-00765-2
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DOI: https://doi.org/10.1007/s10827-020-00765-2