, Volume 35, Issue 5, pp 1637–1650 | Cite as

The role of working memory and attentional disengagement on inhibitory control: effects of aging and Alzheimer's disease

  • Trevor J. CrawfordEmail author
  • Steve Higham
  • Jenny Mayes
  • Mark Dale
  • Sandip Shaunak
  • Godwin Lekwuwa


Patients with Alzheimer's disease have an impairment of inhibitory control for reasons that are currently unclear. Using an eye-tracking task (the gap-overlap paradigm), we examined whether the uncorrected errors relate to the task of attentional disengagement in preparation for action. Alternatively, the difficulty in correcting for errors may be caused by the working memory representation of the task. A major aim of this study was to distinguish between the effects of healthy aging and neurodegenerative disease on the voluntary control of saccadic eye movements. Using the antisaccade task (AST) and pro-saccade task (PST) with the ‘gap’ and ‘overlap’ procedures, we obtained detailed eye-tracking measures in patients, with 18 patients with probable Alzheimer's disease, 25 patients with Parkinson's disease and 17 healthy young and 18 old participants. Uncorrected errors in the AST were selectively increased in Alzheimer's disease, but not in Parkinson's disease compared to the control groups. These uncorrected errors were strongly correlated with spatial working memory. There was an increase in the saccade reaction times to targets that were presented simultaneously with the fixation stimulus, compared to the removal of fixation. This ‘gap’ effect (i.e. overlap–gap) saccade reaction time was elevated in the older groups compared to young group, which yielded a strong effect of aging and no specific effect of neurodegenerative disease. Healthy aging, rather than neurodegenerative disease, accounted for the increase in the saccade reaction times to the target that are presented simultaneously with a fixation stimulus. These results suggest that the impairment of inhibitory control in the AST may provide a convenient and putative mark of working memory dysfunction in Alzheimer's disease.


Alzheimer's disease Parkinson's disease Attention Antisaccade Working memory Eye tracking 



This work was funded by the Lytham League of Friends, the Bial Foundation and The Sir John Fisher Foundation. We are grateful to T. Renvoize, J. Patel, A. Suriya, S. Tetley and the late Professor D. Mitchell for help with original data collection and to Ms. Lilith Kostandian for her help with processing of the PD data. We are grateful to two anonymous referees for their helpful comments on an earlier draft.


  1. Abel L, Troost B, Dell'Osso L (1983) The effects of age on normal saccadic characteristics and their variability. Vis Res 23:33–37PubMedCrossRefGoogle Scholar
  2. Amieva H, Phillips LH, Della Sala S, Henry JD (2004) Inhibitory functioning in Alzheimer's disease. Brain 127:949–964PubMedCrossRefGoogle Scholar
  3. APA (2000) Diagnostic and statistical manual of mental disorders. American Psychiatric Association, WashingtonGoogle Scholar
  4. Baddeley A (2007) Working memory, thought and action. Oxford University Press, OxfordCrossRefGoogle Scholar
  5. Baddeley A, Hitch G (1974) Working memory. In: Bower G (ed) The psychology of learning and motivation: advances in research and theory. Academic, New York, pp 47–89Google Scholar
  6. Boxer AL, Garbutt S, Rankin KP, Hellmuth J, Neuhaus J, Miller BL, Lisberger SG (2006) Medial versus lateral frontal lobe contributions to voluntary saccade control as revealed by the study of patients with frontal lobe degeneration. J Neurosci 26:6354–6363PubMedCrossRefGoogle Scholar
  7. Briand KA, Hening W, Poizner H, Sereno AB (2001) Automatic orienting of visuospatial attention in Parkinson's disease. Neuropsychologia 39:1240–1249PubMedCrossRefGoogle Scholar
  8. Broerse A, Crawford TJ, den Boer JA (2001) Parsing cognition in schizophrenia using saccadic eye movements: a selective overview. Neuropsychologia 39:742–756PubMedCrossRefGoogle Scholar
  9. Cameron IG, Watanabe M, Pari G, Munoz DP (2010) Executive impairment in Parkinson's disease: response automaticity and task switching. Neuropsychologia 48:1948–1957PubMedCrossRefGoogle Scholar
  10. Cameron IG, Pari G, Alahyane N, Brien DC, Coe BC, Stroman PW, Munoz DP (2012) Impaired executive function signals in motor brain regions in Parkinson's disease. NeuroImage 60:1156–1170PubMedCrossRefGoogle Scholar
  11. Castel AD, Balota DA, McCabe DB (2009) Memory efficiency and the strategic control of attention at encoding: impairments of value-directed remembering in Alzheimer's disease. Neuropsychology 23:297–306PubMedCrossRefGoogle Scholar
  12. Chambers J, Prescott T (2010) Response times for visually guided saccades in persons with Parkinson's disease: a meta-analytic review. Neuropsychologia 48:887–899PubMedCrossRefGoogle Scholar
  13. Chan F, Armstrong I, Pari G, Riopelle R, Munoz D (2005) Deficits in saccadic eye-movement control in Parkinson's disease. Neuropsychologia 43:784–796PubMedCrossRefGoogle Scholar
  14. Collette F, Schmidt C, Scherrer C, Adam S, Salmon E (2009) Specificity of inhibitory deficits in normal aging and Alzheimer's disease. Neurobiol Aging 30:875–889PubMedCrossRefGoogle Scholar
  15. Crawford TJ, Bennett D, Lekwuwa G, Shaunak S, Deakin JF (2002) Cognition and the inhibitory control of saccades in schizophrenia and Parkinson's disease. Prog Brain Res 140:449–466PubMedCrossRefGoogle Scholar
  16. 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
  17. Crawford TJ, Kean M, Klein RM, Hamm JP (2006) The effects of illusory line motion on incongruent saccades: implications for saccadic eye movements and visual attention. Exp Brain Res 173:498–506PubMedCrossRefGoogle Scholar
  18. Crawford TJ, Parker E, Solis-Trapala I, Mayes J (2011) Is the relationship of prosaccade reaction times and antisaccade errors mediated by working memory? Exp Brain Res 208:385–397PubMedCrossRefGoogle Scholar
  19. Crevits L, DeRidder K (1997) Disturbed striatoprefrontal mediated visual behaviour in moderate to severe parkinsonian patients. J Neurol Neurosurg Psychiatry 63:296–299PubMedCrossRefGoogle Scholar
  20. Crevits L, Vandierendonck A, Stuyven E, Verschaete S, Wildenbeest J (2004) Effect of intention and visual fixation disengagement on prosaccades in Parkinson's disease patients. Neuropsychologia 42:624–632PubMedCrossRefGoogle Scholar
  21. Duncan J, Emslie H, Williamms P, Johnson R, Freer C (1996) Intelligence and the frontal lobe: the organzation of goal-directed behaviour. Cogn Psychol 30:257–303PubMedCrossRefGoogle Scholar
  22. Eenshuistra RM, Ridderinkhof KR, van der Molen MW (2004) Age-related changes in antisaccade task performance: inhibitory control or working-memory engagement? Brain Cogn 56:177–188PubMedCrossRefGoogle Scholar
  23. Eenshuistra R, Ridderinkhof K, Weidema M, van der Molen M (2007) Developmental changes in oculomotor control and working-memory efficiency. Acta Psychol 124:139–158CrossRefGoogle Scholar
  24. Faust ME, Balota DA, Spieler DH, Ferraro FR (1999) Individual differences in information-processing rate and amount: implications for group differences in response latency. Psychol Bull 125:777–799PubMedCrossRefGoogle Scholar
  25. Fischer B, Weber H (1993) Express saccades and visual attention. Behav Brain Sci 16:553–610CrossRefGoogle Scholar
  26. Fischer B, Biscaldi M, Gezeck S (1997) On the development of voluntary and reflexive components in human saccade generation. Brain Res 754:285–297PubMedCrossRefGoogle Scholar
  27. Folstein M, Folstein S, McHugh P (1975) Mini-Mental State Examination. J Psychiatric Res 12:189–198CrossRefGoogle Scholar
  28. Fukushima J, Fukushima K, Miyasaka K, Yamashita I (1994) Voluntary control of saccadic eye movement in patients with frontal cortical lesions and parkinsonian patients in comparison with that in schizophrenics. Biol Psychiatry 36:21–30PubMedCrossRefGoogle Scholar
  29. 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 131:1268–1281PubMedCrossRefGoogle Scholar
  30. Greenwood PM, Parasuraman R, Alexander GE (1997) Controlling the focus of spatial attention during visual search: effects of advanced aging and Alzheimer's disease. Neuropsychology 11:3–12PubMedCrossRefGoogle Scholar
  31. Hallett P (1978) Primary and secondary saccades to goals defined by instructions. Vis Res 18:1279–1296PubMedCrossRefGoogle Scholar
  32. Hoehn M, Yahr M (1967) Parkinsonism: onset, progression and mortality. Neurology 17(5):427–442Google Scholar
  33. Hutton SB, Ettinger U (2006) The antisaccade task as a research tool in psychopathology: a critical review. Psychophysiol 43:302–313CrossRefGoogle Scholar
  34. Kaufman LD, Pratt J, Levine B, Black SE (2010) Antisaccades: a probe into the dorsolateral prefrontal cortex in Alzheimer's disease. A critical review. J Alzheimers Dis JAD 19:781–793Google Scholar
  35. Kaufman LD, Pratt J, Levine B, Black SE (2012) Executive deficits detected in mild Alzheimer's disease using the antisaccade task. Brain Behav 2:15–21PubMedCrossRefGoogle Scholar
  36. Kimberg D, Farah M (2000) Is there an inhibitory module in the prefrontal cortex? Working memory and the mechanisms underlying cognitive control. In: Monsell S, Driver J (eds) Attention and performance, vol. XVIII. MIT Press, CambridgeGoogle Scholar
  37. Kingstone A, Klein R, Morein-Zamir S, Hunt A, Fisk J, Maxner C (2002) Orienting attention in aging and Parkinson's disease: distinguishing modes of control. J Clin Exp Neuropsychol 24:951–967PubMedCrossRefGoogle Scholar
  38. Kitagawa M, Fukushima J, Tashiro K (1994) Relationship between antisaccades and the clinical symptoms in Parkinson's disease. Neurology 44:2285–2289PubMedCrossRefGoogle Scholar
  39. Leigh R, Kennard C (2004) Using saccades as a research tool in the clinical neurosciences. Brain 127:460–477PubMedCrossRefGoogle Scholar
  40. Lueck CJ, Tanyeri S, Crawford TJ, Henderson L, Kennard C (1990) Antisaccades and remembered saccades in Parkinson's disease. J Neurol Neurosurg Psychiatry 53:284–288PubMedCrossRefGoogle Scholar
  41. Milner B (1971) Interhemispheric differences in the localization of psychological processes in man. British Medical Bulletin 27. Br Med Bull 27:272–277PubMedGoogle Scholar
  42. Mitchell JP, Macrae C, Gilchrist ID (2002) Working memory and the suppression of reflexive saccades. J Cog Neurosci 14:95–103CrossRefGoogle Scholar
  43. Moschner C, Baloh RW (1994) Age-related-changes in visual tracking. J Gerontol 49:M235–M238PubMedCrossRefGoogle Scholar
  44. 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
  45. Posner M, Cohen Y (1984) Components of visual orienting. In: Bouma H, Bouwhuis D (eds) Components of visual orienting, vol. 10. Erlbaum, Hillsdale, pp 531–556Google Scholar
  46. Pratt J, Abrams R, Chasteen A (1997) Initiation and inhibition of saccadic eye movements in younger and older adults: an analysis of the gap effect. J Gerontololgy 52:P103–P107CrossRefGoogle Scholar
  47. Roberts J, Ralph J, Hager LD, Heron C (1994) Prefrontal cognitive processes: working memory and inhibition in the antisaccade task. J Exp Psychol Human 123:374–393CrossRefGoogle Scholar
  48. Salthouse TA (1992) Influence of processing speed on adult age differences in working memory. Acta Psychol 79:155–170CrossRefGoogle Scholar
  49. Saslow M (1967) Latency for saccadic eye movement. J Opt Soc Am 57(8):1030–1033, Optical Society of America, USPubMedCrossRefGoogle Scholar
  50. Schenkenberg T, Bradford DC, Ajax ET (1980) Line bisection and unilateral visual neglect in patients with neurological impairment. Neurology 30:509–517PubMedCrossRefGoogle Scholar
  51. Sharpe J, Zackon D (1987) Senescent saccades. Effects of aging on their accuracy, reaction time and velocity. Acta Otolaryngol 104:422–428PubMedCrossRefGoogle Scholar
  52. Spooner J, Sakala S, Baloh R (1980) Effect of aging on eye tracking. Arch Neurol 37:575–576PubMedCrossRefGoogle Scholar
  53. Tse C-S, Balota DA, Yap MJ, Duchek JM, McCabe DB (2010) Effects of healthy aging and early stage dementia of the Alzheimer's type on components of response time distributions in three attention tasks. Neuropsychology 24:300–315PubMedCrossRefGoogle Scholar
  54. Unsworth N, Schrock JC, Engle RW (2004) Working memory capacity and the antisaccade task: individual differences in voluntary saccade control. J Exp Psychol Learn Mem Cogn 30:1302–1321PubMedCrossRefGoogle Scholar
  55. van Koningsbruggen MG, Pender T, Machado L, Rafal RD (2009) Impaired control of the oculomotor reflexes in Parkinson's disease. Neuropsychologia 47:2909–2915PubMedCrossRefGoogle Scholar
  56. Vidailhet M, Rivaud S, Gouider-Khouja N, Pillon B et al (1994a) Eye movements in Parkinson's syndromes. Ann Neurol 35:420–426PubMedCrossRefGoogle Scholar
  57. Vidailhet M, Rivaud S, Gouiderkhouja N, Pillon B, Bonnet AM, Gaymard B, Agid Y, Pierrotdeseilligny C (1994b) Eye movements in Parkinsonian syndromes. Ann Neurol 35:487–490PubMedCrossRefGoogle Scholar
  58. Wechsler D (1997a) Wechsler Adult Intelligence Scale. The Psychological Corporation, San AntonioGoogle Scholar
  59. Wechsler D (1997b) Wechsler Memory Scale. The Psychological Corporation, San AntonioGoogle Scholar

Copyright information

© American Aging Association 2012

Authors and Affiliations

  • Trevor J. Crawford
    • 1
    Email author
  • Steve Higham
    • 2
  • Jenny Mayes
    • 1
  • Mark Dale
    • 2
  • Sandip Shaunak
    • 3
  • Godwin Lekwuwa
    • 3
  1. 1.Department of Psychology, Centre for Human Learning and Development, Centre for Aging ResearchLancaster UniversityLancasterUK
  2. 2.MAC Clinical ResearchBlackpool, LancashireUK
  3. 3.Royal Preston HospitalLancashire Teaching HospitalPrestonUK

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