Journal of Neural Transmission

, Volume 115, Issue 2, pp 249–260 | Cite as

Deficits in visuo-spatial working memory, inhibition and oculomotor control in boys with ADHD and their non-affected brothers

  • N. N. J. Rommelse
  • S. Van der Stigchel
  • J. Witlox
  • C. Geldof
  • J.-B. Deijen
  • J. Theeuwes
  • J. Oosterlaan
  • J. A. Sergeant


Few studies have assessed visuo-spatial working memory and inhibition in attention-deficit/hyperactivity disorder (ADHD) by recording saccades and consequently little additional knowledge has been gathered on oculomotor functioning in ADHD. Moreover, this is the first study to report the performance of non-affected siblings of children with ADHD, which may shed light on the familiality of deficits. A total of 14 boys with ADHD, 18 non-affected brothers, and 15 control boys aged 7–14 years, were administered a memory-guided saccade task with delays of three and seven seconds. Familial deficits were found in accuracy of visuo-spatial working memory, percentage of anticipatory saccades, and tendency to overshoot saccades relative to controls. These findings suggest memory-guided saccade deficits may relate to a familial predisposition for ADHD.

Keywords: ADHD; non-affected sibling; memory-guided saccade; endophenotype; overshoot; eye movement 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aman, DG, Carmichael, BD 1997High-resolution brain SPECT imaging in ADHDAnn Clin Psychiatry98186CrossRefGoogle Scholar
  2. American Psychiatric Association1994Diagnostic and statistical manual of mental disorders4American Psychiatric PressWashington DCGoogle Scholar
  3. Bakola, S, Gregoriou, GG, Moschovakis, AK, Raos, V, Savaki, HE 2007Saccade-related information in the superior temporal motion complex: quantitative functional mapping in the monkeyJ Neurosci2722242229PubMedCrossRefGoogle Scholar
  4. Becker, W, Fuchs, AF 1969Further properties of the human saccadic system: eye movements and correction with and without visual fixation pointsVision Res912471258PubMedCrossRefGoogle Scholar
  5. Brandt, SA, Ploner, CJ, Meyer, BU, Leistner, S, Villringer, A 1998Effects of repetitive transcranial magnetic stimulation over dorsolateral prefrontal and posterior parietal cortex on memory-guided saccadesExp Brain Res118197204PubMedCrossRefGoogle Scholar
  6. Brookes, K, Xu, X, Chen, W, Zhou, K, Neale, B, Lowe, N, Aneey, R, Franke, B, Gill, M, Ebstein, R, Buitelaar, J, Sham, P, Campbell, D, Knight, J, Andreou, P, Altink, M, Arnold, R, Boer, F, Buschgens, C, Butler, L, Christiansen, H, Feldman, L, Fleischman, K, Fliers, E, Howe-Forbes, R, Goldfarb, A, Heise, A, Gabriels, I, Korn-Lubetzki, I, Marco, R, Medad, S, Minderaa, R, Mulas, F, Muller, U, Mulligan, A, Rabin, K, Rommelse, N, Sethna, V, Sorohan, J, Uebel, H, Psychogiou, L, Weeks, A, Barrett, R, Craig, I, Banaschewski, T, Sonuga-Barke, E, Eisenberg, J, Kuntsi, J, Manor, I, McGuffin, P, Miranda, A, Oades, R, Plomin, R, Roeyers, H, Rothenberger, A, Sergeant, J, Steinhausen, H, Taylor, E, Thompson, M, Faraone, S, Asherson, P, Johansson, L 2006The analysis of 51 genes in DSM-IV combined type attention-deficit/hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genesMol Psychiatry11934953PubMedCrossRefGoogle Scholar
  7. Brozoski, TJ, Brown, RM, Rosvold, HE, Goldman, PS 1979Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkeyScience205929932PubMedCrossRefGoogle Scholar
  8. Cairney, S, Maruff, P, Vance, A, Barnett, R, Luk, E, Currie, J 2001Contextual abnormalities of saccadic inhibition in children with attention-deficit/hyperactivity disorderExp Brain Res141507518PubMedCrossRefGoogle Scholar
  9. Castellanos, FX, Giedd, JN, Berquin, PC, Walter, JM, Sharp, W, Tran, T, Vaituzis, AC, Blumenthal, JD, Nelson, J, Bastain, TM, Zijdenbos, A, Evans, AC, Rapoport, JL 2001Quantitative brain magnetic resonance imaging in girls with attention-deficit/hyperactivity disorderArch Gen Psychiatry58289295PubMedCrossRefGoogle Scholar
  10. Castellanos, FX, Giedd, JN, Marsh, WL, Hamburger, SD, Vaituzis, AC, Dickstein, DP, Sarfatti, SE, Vauss, YC, Snell, JW, Lange, N, Kaysen, D, Krain, AL, Ritchie, GF, Rajapakse, JC, Rapoport, JL 1996Quantitative brain magnetic resonance imaging in attention-deficit/hyperactivity disorderArch Gen Psychiatry53607616PubMedGoogle Scholar
  11. Castellanos, FX, Lee, PP, Sharp, W, Jeffries, NO, Greenstein, DK, Clasen, LS, Blumenthal, JD, James, RS, Ebens, CL, Walter, JM, Zijdenbos, A, Evans, AC, Giedd, JN, Rapoport, JL 2002Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorderJAMA28817401748PubMedCrossRefGoogle Scholar
  12. Castellanos, FX, Marvasti, FF, Ducharme, JL, Walter, JM, Israel, ME, Krain, A, Pavlovsky, C, Hommer, DW 2000Executive function oculomotor tasks in girls with ADHDJ Am Acad Child Adolesc Psychiatry39644650PubMedCrossRefGoogle Scholar
  13. Conners K (1996) Rating scales in ADHD. Duke University Medical CenterGoogle Scholar
  14. D’Esposito, M, Detre, JA, Alsop, DC, Shin, RK, Atlas, S, Grossman, M 1995The neural basis of the central executive system of working memoryNature378279281PubMedCrossRefGoogle Scholar
  15. Dickstein, SG, Bannon, K, Castellanos, FX, Milham, MP 2006The neural correlates of attention-deficit/hyperactivity disorder: an ALE meta-analysisJ Child Psychol Psychiatry4710511062PubMedCrossRefGoogle Scholar
  16. Durston, S, Hulshoff Pol, HE, Schnack, HG, Buitelaar, JK, Steenhuis, MP, Minderaa, RB, Kahn, RS, Van Engeland, H 2004Magnetic resonance imaging of boys with attention-deficit/hyperactivity disorder and their unaffected siblingsJ Am Acad Child Adolesc Psychiatry43332340PubMedCrossRefGoogle Scholar
  17. Durston, S, Tottenham, NT, Thomas, KM, Davidson, MC, Eigsti, JM, Yang, Y, Ulug, AM, Casey, BJ 2003Differential patterns of striatal activation in young children with and without ADHDBiol Psychiatry53871878PubMedCrossRefGoogle Scholar
  18. Ettinger, U, Antonova, E, Crawford, TJ, Mitterschiffthaler, MT, Goswani, S, Sharma, T, Kumari, V 2005Structural neural correlates of prosaccade and anti-saccade eye movements in healthy humansNeuroimage24487494PubMedCrossRefGoogle Scholar
  19. Faraone, SV, Biederman, J, Mick, E, Williamson, S, Wilens, T, Spencer, T, Weber, W, Jetton, J, Kraus, I, Pert, J, Zallen, B 2000Family study of girls with attention-deficit/hyperactivity disorderAm J Psychiatry15710771083PubMedCrossRefGoogle Scholar
  20. Feifel, D, Farber, RH, Clementz, BA, Perry, W, Anllo-Vento, L 2004Inhibitory deficits in ocular motor behaviour in adults with attention-deficit/hyperactivity disorderBiol Psychiatry56333339PubMedCrossRefGoogle Scholar
  21. Fuster, JM 1990Prefrontal cortex and the bridging of temporal gaps in the perception-action cycleAnn N Y Acad Sci608318329PubMedCrossRefGoogle Scholar
  22. Gnadt, JW, Bracewell, RM, Andersen, RA 1991Sensorimotor transformation during eye movements to remembered visual targetsVision Res31693715PubMedCrossRefGoogle Scholar
  23. Goodman, R 1997The strengths and difficulties questionnaire: a research noteJ Child Psychol Psychiatry38581586PubMedCrossRefGoogle Scholar
  24. Gottesman, II, Gould, TD 2003The endophenotype concept in psychiatry: etymology and strategic intentionsAm J Psychiatry160636645PubMedCrossRefGoogle Scholar
  25. Gould, TD, Bastain, TM, Israel, ME, Hommer, DW, Castallanos, FX 2001Altered performance on an ocular fixation task in attention-deficit/hyperactivity disorderBiol Psychiatry50633635PubMedCrossRefGoogle Scholar
  26. Groth-Marnat, G 1997Handbook of psychological assessment3WileyNew YorkGoogle Scholar
  27. Hall, WCMoschovakis, AK eds. 2003The superior colliculus: new approaches for studying sensorimotor integrationCRC PressBoca Roton, FLGoogle Scholar
  28. Hanisch, C, Radach, R, Holtkamp, K, Herpertz-Dahlmann, B, Konrad, K 2006Oculomotor inhibition in children with and without attention-deficit/hyperactivity disorder (ADHD)J Neural Transm113671684PubMedCrossRefGoogle Scholar
  29. Hazy, TE, Frank, MJ, O’Reilly, RC 2006Banishing the homunculus: making working memory workNeuroscience139105118PubMedCrossRefGoogle Scholar
  30. Henson, DB 1979Investigation into corrective saccadic eye movements for refixation amplitudes of 10 degrees and belowVision Res1910771082CrossRefGoogle Scholar
  31. Hopfinger, JB, Buonocore, MH, Mangun, GR 2000The neural mechanisms of top-down attentional controlNat Neurosci3284291PubMedCrossRefGoogle Scholar
  32. Klein, C, Raschke, A, Brandenbusch, A 2003Development of pro- and antisaccades in children with attention-deficit/hyperactivity disorder (ADHD) and healthy controlsPsychophysiology401728PubMedCrossRefGoogle Scholar
  33. Klein, C, Wendling, K, Huettner, P, Ruder, H, Peper, M 2006Intra-subject variability in attention-deficit/hyperactivity disorderBiol Psychiatry6010881097PubMedCrossRefGoogle Scholar
  34. Leigh, RJ, Kennard, C 2004Using saccades as a research tool in the clinical neurosciencesBrain127460477PubMedCrossRefGoogle Scholar
  35. Leigh, RJ, Zee, DS 1999The neurology of eye movements3Oxford University PressNew YorkGoogle Scholar
  36. Levy, F 1991The dopamine theory of attention-deficit/hyperactivity disorderAust N Z J Psychiatry25277283PubMedCrossRefGoogle Scholar
  37. Levy, F, Swanson, JM 2001Timing, space and ADHD: the dopamine theory revisitedAust N Z J Psychiatry35504511PubMedCrossRefGoogle Scholar
  38. Martinussen, R, Hayden, J, Hogg-Johnson, S, Tannock, R 2005A meta-analysis of working memory impairments in children with attention-deficit/hyperactivity disorderJ Am Acad Child Adolesc Psychiatry44377384PubMedCrossRefGoogle Scholar
  39. Moschovakis, AK 1996The superior colliculus and eye movement controlCurr Opin Neurobiol6811816PubMedCrossRefGoogle Scholar
  40. Mostofsky, SH, Lasker, AG, Cutting, LE, Denckla, MB, Zee, DS 2001Oculomotor abnormalities in attention-deficit/hyperactivity disorder. A preliminary studyNeurology57423430PubMedGoogle Scholar
  41. Munoz, DP 2002Commentary: saccadic eye movements: overview of neural circuitryProg Brain Res1408996PubMedGoogle Scholar
  42. Munoz, DP, Armstrong, IT, Hampton, KA, Moore, KD 2003Altered control of visual fixation and saccadic eye movements in attention-deficit/hyperactivity disorderJ Neurophysiol90503514PubMedCrossRefGoogle Scholar
  43. Niemi, P, Näätänen, R 1981Foreperiod and simple reaction timePsychol Bull89133162CrossRefGoogle Scholar
  44. Nitschke, MF, Binkofski, F, Buccino, G, Posse, S, Erdmann, C, Kömpf, D, Seitz, RJ, Heide, W 2004Activation of cerebellar hemispheres in spatial memorization of saccadic eye movements: an fMRI studyHum Brain Mapp22155164PubMedCrossRefGoogle Scholar
  45. Oosterlaan, J, Logan, GD, Sergeant, JA 1998Response inhibition in AD/HD, CD, comorbid AD/HD+CD, anxious, and control children: a meta-analysis of studies with the stop taskJ Child Psychol Psychiatry39411425PubMedCrossRefGoogle Scholar
  46. Ozonoff, S, Strayer, DL 2001Further evidence of intact working memory in autismJ Autism Dev Disord31257263PubMedCrossRefGoogle Scholar
  47. Pelham, WE, Aronoff, HR, Midlam, JK, Shapiro, CJ, Gnagy, EM, Chronis, AM, Onyango, AN, Forehand, G, Nguyen, A, Waxmonsky, J 1999A comparison of Ritalin and adderall: efficacy and time-course in children with attention-deficit/hyperactivity disorderPediatrics103e43PubMedCrossRefGoogle Scholar
  48. Pierrot-Deseiligny, C, Milea, D, Müri, RM 2004Eye movement control by the cerebral cortexCurr Opin Neurol171725CrossRefGoogle Scholar
  49. Pierrot-Deseiligny, C, Rivaud, S, Gaymard, B, Agid, Y 1991Cortical control of memory-guided saccades in manExp Brain Res83607617CrossRefGoogle Scholar
  50. Robinson, FR, Straube, A, Fuchs, AF 1993Role of the caudal fastigial nucleus in saccade generation. II. Effects of muscimol inactivationJ Neurophysiol7017411758PubMedGoogle Scholar
  51. Rommelse, NNJ, Oosterlaan, J, Buitelaar, J, Faraone, SV, Sergeant, JA 2007Time reproduction in children with ADHD and their non-affected siblingsJ Am Acad Child Adolesc Psychiatry46582590PubMedCrossRefGoogle Scholar
  52. Ross, RG, Harris, JG, Olincy, A, Radant, A 2000Eye movement task measures inhibition and spatial working memory in adults with schizophrenia, ADHD, and a normal comparison groupPsychiatry Res953542PubMedCrossRefGoogle Scholar
  53. Ross, RG, Hommer, D, Breiger, D, Varley, C, Radant, A 1994aEye movement task related to frontal lobe functioning in children with attention deficit disorderJ Am Acad Child Adolesc Psychiatry33869874CrossRefGoogle Scholar
  54. Ross, RG, Radant, AD, Young, DA, Hommer, DW 1994bSaccadic eye movements in normal children from 8 to 15 years of age: a developmental study of visuospatial attentionJ Autism Dev Disord24413431CrossRefGoogle Scholar
  55. Rubia, K, Overmeyer, S, Taylor, E, Brammer, M, Williams, SCR, Simmons, A, Bullmore, ET 1999Hypofrontality in attention-deficit/hyperactivity disorder during higher-order motor control: a study with functional MRIAm J Psychiatry156891896PubMedGoogle Scholar
  56. Sawaguchi, T, Goldman-Rakic, PS 1994The role of D1-dopamine receptor in working memory: local injections of dopamine antagonists into the prefrontal cortex of rhesus monkeys performing an oculomotor delayed-response taskJ Neurophysiol71515528PubMedGoogle Scholar
  57. Sawaguchi, T, Matsumura, M, Kubota, K 1988Dopamine enhances the neuronal activity of spatial short-term memory task in the primate prefrontal cortexNeurosci Res5465473PubMedCrossRefGoogle Scholar
  58. Schall, JD 1991

    Neuronal basis of saccadic eye movements

    Leventhal, AG eds. Vision and visual dysfunctionMacmillan PressLondon388442
    Google Scholar
  59. Schulz, KP, Fan, J, Tang, CY, Newcorn, JH, Buchsbaum, MS, Cheung, AM, Halperin, JM 2004Response inhibition in adolescents diagnosed with attention-deficit/hyperactivity disorder during childhood: an event-related fMRI studyAm J Psychiatry16116501657PubMedCrossRefGoogle Scholar
  60. Seidman, LJ, Biederman, J, Faraone, SV, Weber, W, Mennin, D, Jones, J 1997A pilot study of neuropsychological functioning in girls with ADHDJ Am Acad Child Adolesc Psychiatry36366373PubMedCrossRefGoogle Scholar
  61. Seidman, LJ, Biederman, J, Monuteaux, MC, Valera, E, Doyle, AE, Faraone, SV 2005Impact of gender and age on executive functioning: do girls and boys with and without attention-deficit/hyperactivity disorder differ neuropsychologically in preteen and teenage years?Dev Neuropsychol2779105PubMedCrossRefGoogle Scholar
  62. Sergeant, JA, Scholten, CA 1985On data limitations in hyperactivityJ Child Psychol Psychiatry26111124PubMedCrossRefGoogle Scholar
  63. Smith, EE, Jonides, J, Marshuetz, C, Koeppe, RA 1998Components of verbal working memory: evidence from neuroimagingProc Natl Acad Sci USA95876882PubMedCrossRefGoogle Scholar
  64. Sweeney, JA, Mintun, MA, Kwee, S, Wiseman, MB, Brown, DL, Rosenberg, DR, Carl, JR 1996Positron emission tomography study of voluntary saccadic eye movements and spatial working memoryJ Neurophysiol75454468PubMedGoogle Scholar
  65. Sweeney, JA, Takarae, Y, Macmillan, C, Luna, B, Minshew, NJ 2004Eye movements in neurodevelopmental disordersCurr Opin Neurol173742PubMedCrossRefGoogle Scholar
  66. Taylor, EA 1986Childhood hyperactivityBr J Psychiatry149562573PubMedCrossRefGoogle Scholar
  67. Taylor, E, Sandberg, S, Thorley, G, Giles, S 1991The epidemiology of childhood hyperactivityOxford University PressOxford, EnglandGoogle Scholar
  68. Their, P, Dicke, PW, Haas, R, Thielert, CD, Catz, N 2002The role of oculomotor vermis in the control of saccadic eye movementsAnn N Y Acad Sci9785062CrossRefGoogle Scholar
  69. Van der Stigchel S, Meeter M, Theeuwes J (in press) Top down influences make saccades deviate away: the case of endogenous cues. Acta PsycholGoogle Scholar
  70. Van der Stigchel, S, Rommelse, NNJ, Deijen, JB, Geldof, CJA, Witlox, J, Oosterlaan, J, Sergeant, JA, Theeuwes, J 2007Oculomotor capture in ADHDCogn Neuropsychol24535549CrossRefPubMedGoogle Scholar
  71. Van der Stigchel, S, Theeuwes, J 2006Our eyes deviate away from a location where a distractor is expected to appearExp Brain Res169338349PubMedCrossRefGoogle Scholar
  72. Waldman, ID 2005Statistical approaches to complex phenotypes: evaluating neuropsychological endophenotypes for attention-deficit/hyperactivity disorderBiol Psychiatry5713471356PubMedCrossRefGoogle Scholar
  73. Wechsler, D 2000WAIS-III Nederlandstalige bewerkingThe Psychological CorporationLondonGoogle Scholar
  74. Wechsler, D 2002WISC-III HandleidingThe Psychological CorporationLondonGoogle Scholar
  75. White, JM, Sparks, DL, Stanford, TR 1994Saccades to remembered target locations: an analysis of systematic and variable errorsVision Res347992PubMedCrossRefGoogle Scholar
  76. Yeo, RA, Hill, DE, Campbell, RA, Vigil, J, Petropoulos, H, Hart, B, Zamora, L, Brooks, WM 2003Proton magnetic resonance spectroscopy investigation of the right frontal lobe in children with attention-deficit/hyperactivity disorderJ Am Acad Child Adolesc Psychiatry42303310PubMedCrossRefGoogle Scholar
  77. Zametkin, AJ, Nordahl, TE, Gross, M, King, AC, Semple, W, Rumsey, J, Hamburger, S, Cohen, RM 1990Cerebral glucose metabolism in adults with hyperactivity of childhood onsetN Engl J Med32313611366PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • N. N. J. Rommelse
    • 1
  • S. Van der Stigchel
    • 2
  • J. Witlox
    • 1
  • C. Geldof
    • 1
  • J.-B. Deijen
    • 1
  • J. Theeuwes
    • 2
  • J. Oosterlaan
    • 1
  • J. A. Sergeant
    • 1
  1. 1.Department of Clinical NeuropsychologyVU University AmsterdamAmsterdamThe Netherlands
  2. 2.Department of Cognitive PsychologyVU University AmsterdamAmsterdamThe Netherlands

Personalised recommendations