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AGE

, Volume 36, Issue 2, pp 535–543 | Cite as

Distinctive features of microsaccades in Alzheimer’s disease and in mild cognitive impairment

  • Zoi Kapoula
  • Qing Yang
  • Jorge Otero-Millan
  • Shifu Xiao
  • Stephen L. Macknik
  • Alexandre Lang
  • Marc Verny
  • Susana Martinez-Conde
Article

Abstract

During visual fixation, the eyes are never completely still, but produce small involuntary movements, called “fixational eye movements,” including microsaccades, drift, and tremor. In certain neurological disorders, attempted fixation results in abnormal fixational eye movements with distinctive characteristics. Thus, determining how normal fixation differs from pathological fixation has the potential to aid early and differential noninvasive diagnosis of neurological disease as well as the quantification of its progression and response to treatment. Here, we recorded the eye movements produced by patients with Alzheimer’s disease, patients with mild cognitive impairment, and healthy age-matched individuals during attempted fixation. We found that microsaccade magnitudes, velocities, durations, and intersaccadic intervals were comparable in the three subject groups, but microsaccade direction differed in patients versus healthy subjects. Our results indicate that microsaccades are more prevalently oblique in patients with Alzheimer’s disease or mild cognitive impairment than in healthy subjects. These findings extended to those microsaccades paired in square-wave jerks, supporting the hypothesis that microsaccades and square-wave jerks form a continuum, both in healthy subjects and in neurological patients.

Keywords

Fixational eye movements Fixation Saccadic intrusions Neurological disorder Dementia 

Notes

Acknowledgments

This study was supported by the following funding agencies: CNRS (grant PICS, no. 4197 to ZK), GIS-CNRS, Vieillissement et Longévité (to ZK), the Barrow Neurological Foundation (to SLM and SMC), the National Science Foundation (award 0852636 to SMC), the Arizona Alzheimer’s Consortium (to SMC), and the Science Foundation Arizona Bisgrove Award (to SLM).

Conflict of interest

The authors of this manuscript have no conflicts of interest to disclose.

Supplementary material

11357_2013_9582_MOESM1_ESM.doc (112 kb)
Supplementary Figure 1 (DOC 111 kb)

References

  1. Abadi RV, Gowen E (2004) Characteristics of saccadic intrusions. Vis Res 44:2675–2690PubMedCrossRefGoogle Scholar
  2. Belleville S, Chertkow H, Gauthier S (2007) Working memory and control of attention in persons with Alzheimer’s disease and mild cognitive impairment. Neuropsychology 21:458–469PubMedCrossRefGoogle Scholar
  3. Belleville S, Bherer L, Lepage E, Chertkow H, Gauthier S (2008) Task switching capacities in persons with Alzheimer’s disease and mild cognitive impairment. Neuropsychologia 46:2225–2233PubMedCrossRefGoogle Scholar
  4. Crawford TJ, Higham S, Renvoize T, Patel J, Dale M, Suriya A, Tetley S (2005) Inhibitory control of saccadic eye movements and cognitive impairment in Alzheimer’s disease. Biol Psychiatry 57:1052–1060PubMedCrossRefGoogle Scholar
  5. Cui J, Wilke M, Logothetis NK, Leopold DA, Liang H (2009) Visibility states modulate microsaccade rate and direction. Vision Res 49:228–236PubMedCentralPubMedCrossRefGoogle Scholar
  6. Di Stasi LL, McCamy MB, Catena A, Macknik SL, Cañas JJ, Martinez-Conde S (2013) Microsaccade and drift dynamics reflect mental fatigue. Eur J Neurosci 38:2389–2398PubMedCrossRefGoogle Scholar
  7. Engbert R (2006) Microsaccades: a microcosm for research on oculomotor control, attention, and visual perception. Prog Brain Res 154:177–192PubMedCrossRefGoogle Scholar
  8. Engbert R, Kliegl R (2003) Microsaccades uncover the orientation of covert attention. Vision Res 43:1035–1045PubMedCrossRefGoogle Scholar
  9. Engbert R, Mergenthaler K (2006) Microsaccades are triggered by low retinal image slip. Proc Natl Acad Sci U S A 103:7192–7197PubMedCentralPubMedCrossRefGoogle Scholar
  10. Fletcher WA, Sharpe JA (1986) Saccadic eye movement dysfunction in Alzheimer’s disease. Ann Neurol 20:464–471PubMedCrossRefGoogle Scholar
  11. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198PubMedCrossRefGoogle Scholar
  12. Garbutt S, Matlin A, Hellmuth J, Schenk AK, Johnson JK, Rosen H, Dean D, Kramer J, Neuhaus J, Miller BL, Lisberger SG, Boxer AL (2008) Oculomotor function in frontotemporal lobar degeneration, related disorders and Alzheimer’s disease. Brain 131:1268–1281PubMedCentralPubMedCrossRefGoogle Scholar
  13. Gowen E, Abadi RV, Poliakoff E, Hansen PC, Miall RC (2007) Modulation of saccadic intrusions by exogenous and endogenous attention. Brain Res 1141:154–167PubMedCrossRefGoogle Scholar
  14. Hershey LA, Whicker L, Abel LA, Dell'Osso LF, Traccis S, Grossniklaus D (1983) Saccadic latency measurements in dementia. Arch Neurol 40:592–593PubMedCrossRefGoogle Scholar
  15. Hotson JR, Steinke GW (1988) Vertical and horizontal saccades in aging and dementia: failure to inhibit anticipatory saccades. Neuroophthalmology 8:267–273CrossRefGoogle Scholar
  16. Kapoula Z, Robinson DA, Hain TC (1986) Motion of the eye immediately after a saccade. Exp Brain Res 61:386–394PubMedCrossRefGoogle Scholar
  17. Katzman R, Zhang M, Ouang-Ya-Qu, Wang Z, Liu WT, Yu E, Wong S-C, Salmon DP, Grant I (1988) A Chinese version of the mini-mental state examination; Impact of illiteracy in a Shanghai dementia survey. J Clin Epidemiol 41:971–978PubMedCrossRefGoogle Scholar
  18. Kaufman L, Pratt J, Levine B, Black S (2010) Antisaccades: a probe into the dorsolateral prefrontal cortex in Alzheimer’s disease. A critical review. J Alzheimers Dis 19:781–793PubMedGoogle Scholar
  19. Laubrock J, Engbert R, Kliegl R (2005) Microsaccade dynamics during covert attention. Vision Res 45:721–730PubMedCrossRefGoogle Scholar
  20. Leigh RJ, Zee DS (2006) The neurology of eye movements. Oxford Univ PressGoogle Scholar
  21. Levinoff EJ, Saumier D, Chertkow H (2005) Focused attention deficits in patients with Alzheimer’s disease and mild cognitive impairment. Brain Cogn 57:127–130PubMedCrossRefGoogle Scholar
  22. Martinez-Conde S (2006) Fixational eye movements in normal and pathological vision. In: Visual perception—fundamentals of vision: low and mid-level processes in perception, pp 151–176. Elsevier. Available at: http://www.sciencedirect.com.ezproxy1.lib.asu.edu/science/article/B7CV6-4M0C546-F/2/2321185cb4e661f44f2f859d714f5fbb [Accessed February 17, 2010]
  23. Martinez-Conde S, Macknik SL, Troncoso XG, Hubel DH (2009) Microsaccades: a neurophysiological analysis. Trends Neurosci 32:463–475PubMedCrossRefGoogle Scholar
  24. Møller F, Laursen M, Tygesen J, Sjølie A (2002) Binocular quantification and characterization of microsaccades. Graefes Arch Clin Exp Ophthalmol 240:765–770PubMedCrossRefGoogle Scholar
  25. Moser A, Kompf D, Olschinka J (1995) Eye movement dysfunction in dementia of the Alzheimer type. Dement Geriatr Cogn Disord 6:264–268CrossRefGoogle Scholar
  26. Mosimann UP, Müri RM, Burn DJ, Felblinger J, O'Brien JT, McKeith IG (2005) Saccadic eye movement changes in Parkinson's disease dementia and dementia with Lewy bodies. Brain 128:1267–1276PubMedCrossRefGoogle Scholar
  27. Munoz DP, Broughton JR, Goldring JE, Armstrong IT (1998) Age-related performance of human subjects on saccadic eye movement tasks. Exp Brain Res 121:391–400PubMedCrossRefGoogle Scholar
  28. Murakami I, Kitaoka A, Ashida H (2006) A positive correlation between fixation instability and the strength of illusory motion in a static display. Vis Res 46:2421–2431PubMedCrossRefGoogle Scholar
  29. Otero-Millan J, Troncoso XG, Macknik SL, Serrano-Pedraza I, Martinez-Conde S (2008) Saccades and microsaccades during visual fixation, exploration and search: foundations for a common saccadic generator. J Vis 8:14–21CrossRefGoogle Scholar
  30. Otero-Millan J, Macknik SL, Serra A, Leigh RJ, Martinez-Conde S (2011a) Triggering mechanisms in microsaccade and saccade generation: a novel proposal. Ann N Y Acad Sci 1233:107–116PubMedCrossRefGoogle Scholar
  31. Otero-Millan J, Serra A, Leigh RJ, Troncoso XG, Macknik SL, Martinez-Conde S (2011b) Distinctive features of saccadic intrusions and microsaccades in progressive supranuclear palsy. J Neurosci 31:4379–4387PubMedCentralPubMedCrossRefGoogle Scholar
  32. Pastukhov A, Vonau V, Stonkute S, Braun J (2013) Spatial and temporal attention revealed by microsaccades. Vis Res 85:45–57PubMedCrossRefGoogle Scholar
  33. Perry RJ, Hodges JR (1999) Attention and executive deficits in Alzheimer’s disease: a critical review. Brain 122:383–404PubMedCrossRefGoogle Scholar
  34. Petersen RC (2004) Mild cognitive impairment as a diagnostic entity. J Intern Med 256:183–194PubMedCrossRefGoogle Scholar
  35. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E (1999) Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 56:303–308PubMedCrossRefGoogle Scholar
  36. Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, Ritchie K, Rossor M, Thal L, Winblad B (2001) Current concepts in mild cognitive impairment. Arch Neurol 58:1985–1992PubMedCrossRefGoogle Scholar
  37. Rizzo M, Anderson SW, Dawson J, Myers R, Ball K (2000) Visual attention impairments in Alzheimer’s disease. Neurology 54:1954–1959PubMedCrossRefGoogle Scholar
  38. Rolfs M (2009) Microsaccades: small steps on a long way. Vision Res 49:2415–2441PubMedCrossRefGoogle Scholar
  39. Rolfs M, Laubrock J, Kliegl R (2006) Shortening and prolongation of saccade latencies following microsaccades. Exp Brain Res 169:369–376PubMedCrossRefGoogle Scholar
  40. Shafiq-Antonacci R, Maruff P, Masters C, Currie J (2003) Spectrum of saccade system function in Alzheimer disease. Arch Neurol 60:1272–1278PubMedCrossRefGoogle Scholar
  41. Sharpe JA, Zackon D (1987) Senescent saccades: effects of aging on their accuracy, latency and velocity. SOTO 104:422–428CrossRefGoogle Scholar
  42. Simic G, Stanic G, Mladinov M, Jovanov-Milosevic N, Kostovic I, Hof PR (2009) Does Alzheimer’s disease begin in the brainstem? Neuropathol Appl Neurobiol 35:532–554PubMedCentralPubMedCrossRefGoogle Scholar
  43. Tedeschi G, Di Costanzo A, Allocca S, Quattrone A, Casucci G, Russo L, Bonavita V (1989) Age-dependent changes in visually guided saccadic eye movements. Funct Neurol 4:363–367PubMedGoogle Scholar
  44. Troncoso XG, Macknik SL, Martinez-Conde S (2008a) Microsaccades counteract perceptual filling-in. J Vis 8:1–9CrossRefGoogle Scholar
  45. Troncoso XG, Macknik SL, Otero-Millan J, Martinez-Conde S (2008b) Microsaccades drive illusory motion in the Enigma illusion. Proc Natl Acad Sci U S A 105:16033–16038PubMedCentralPubMedCrossRefGoogle Scholar
  46. Tse PU, Sheinberg DS, Logothetis NK (2004) The distribution of microsaccade directions need not reveal the location of attention: reply to Rolfs, Engbert, and Kliegl. Psychol Sci 15:708–710CrossRefGoogle Scholar
  47. Valsecchi M, Turatto M (2008) Microsaccadic responses in a bimodal oddball task. Psychol Res 73:23–33PubMedCrossRefGoogle Scholar
  48. Valsecchi M, Betta E, Turatto M (2007) Visual oddballs induce prolonged microsaccadic inhibition. Exp Brain Res 177:196–208PubMedCrossRefGoogle Scholar
  49. Yang Q, Wang T, Su N, Liu Y, Xiao S, Kapoula Z (2011) Long latency and high variability in accuracy-speed of prosaccades in Alzheimer’s disease at mild to moderate stage. Dement Geriatr Cogn Disord Extra 1:318–329CrossRefGoogle Scholar
  50. Yang Q, Wang T, Xiao S, Kapoula Z (2013) Specific saccade deficits in patients with Alzheimer’s disease at mild to moderate stage and in patients with amnestic mild cognitive impairment. Age 35(4):1287–1298PubMedCrossRefGoogle Scholar

Copyright information

© American Aging Association 2013

Authors and Affiliations

  1. 1.CeSeM, UMR 8194, CNRS University Paris V IRIS group, Ophthalmology service European Hospital Georges PompidouParisFrance
  2. 2.Department of NeurobiologyBarrow Neurological InstitutePhoenixUSA
  3. 3.University of VigoVigoSpain
  4. 4.Geriatric Psychiatry Department, Shanghai Mental Health CenterShanghai Jiaotong University School of MedicineShanghaiChina
  5. 5.Department of NeurosurgeryBarrow Neurological InstitutePhoenixUSA
  6. 6.Department of Geriatric NeurologySalpetrière HospitalParisFrance

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