Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Research Article
  • Published:

Associations between prepulse inhibition and executive visual attention in children with the 22q11 deletion syndrome

Molecular Psychiatry volume 10, pages 553–562 (2005)Cite this article

Abstract

The 22q11 deletion syndrome (DS) results in the loss of approximately 30 gene copies and is associated with possible physical anomalies, varied learning disabilities, and a specific cluster of neurocognitive deficits, including primary impairment in working memory, executive visual attention, and sensorimotor processing. Retrospective studies have suggested that children with 22q11DS are at 25 times greater risk of developing schizophrenia, thus specification of early brain network vulnerabilities among children with 22q11DS is critical. Previously, we reported that children with 22q11DS as compared with sibling controls had selective deficits in visual executive attention, and subsequently found lowered prepulse inhibition (PPI) in these same children. Visual executive attention and PPI recruit the same brain pathways linking prefrontal cortex to basal ganglia structures. To test the specificity of brain pathway vulnerability among children with 22q11DS, we examined visual executive attention and PPI paradigm data collected during the same test session from 21 children with 22q11DS and 25 sibling controls. We predicted lower %PPI and less efficient executive attention scores, and a significant inverse correlation between measures. %PPI in children with 22q11DS as compared with sibling controls was 20% lower, and visual executive attention efficiency scores 40% worse. As predicted, %PPI was inversely correlated only with executive attention efficiency scores. The implications of these findings with regard to brain pathway vulnerability in children with 22q11DS are considered. These results suggest that children with 22q11DS have early functional abnormality in pathways linking the prefrontal cortex and basal ganglia.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Botto LD, May K, Fernhoff PM, Correa A, Coleman K, Rasmussen SA et al. A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. Pediatrics 2003; 112 (Part 1): 101–107.

    Article  Google Scholar 

  2. Morrow B, Goldberg R, Carlson C, Das Gupta R, Sirotkin H, Collins J et al. Molecular definition of the 22q11 deletions in velo-cardio-facial syndrome. Am J Hum Genet 1995; 56: 1391–1403.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Ryan AK, Goodship JA, Wilson DI, Philip N, Levy A, Seidel H et al. Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study (see comment). J Med Genet 1997; 34: 798–804.

    Article  CAS  Google Scholar 

  4. Pulver AE, Nestadt G, Goldberg R, Shprintzen RJ, Lamacz M, Wolyniec PS et al. Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives. J Nerv Ment Dis 1994; 182: 476–478.

    Article  CAS  Google Scholar 

  5. Murphy KC, Jones LA, Owen MJ . High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch Gen Psychiatry 1999; 56: 940–945.

    Article  CAS  Google Scholar 

  6. Woodin M, Wang PP, Aleman D, McDonald-McGinn D, Zackai E, Moss E . Neuropsychological profile of children and adolescents with the 22q11.2 microdeletion. Genet Med 2001; 3: 34–39.

    Article  CAS  Google Scholar 

  7. Sobin C, Kiley-Brabeck K, Khuri J, Taylor L, Karayiorgou M . Neuropsychological characteristics of children with the 22q11 deletion syndrome: a descriptive analysis. Child Neuropsychol, in press.

  8. Sobin C, Kiley-Brabeck K, Daniels S, Blundell M, Anyane-Yeboa K, Karayiorgou M . Networks of attention in children with the 22q11 deletion syndrome. Dev Neuropsychol 2004; 26: 611–626.

    Article  Google Scholar 

  9. Graham FK . Presidential Address, 1974. The more or less startling effects of weak prestimulation. Psychophysiology 1975; 12: 238–248.

    Article  CAS  Google Scholar 

  10. Koch M, Kungel M, Herbert H . Cholinergic neurons in the pedunculopontine tegmental nucleus are involved in the mediation of prepulse inhibition of the acoustic startle response in the rat. Exp Brain Res 1993; 97: 71–82.

    Article  CAS  Google Scholar 

  11. Koch M, Lingenhohl K, Pilz PK . Loss of the acoustic startle response following neurotoxic lesions of the caudal pontine reticular formation: possible role of giant neurons. Neuroscience 1992; 49: 617–625.

    Article  CAS  Google Scholar 

  12. Swerdlow NR, Geyer MA . Neurophysiology and neuropharmacology of short lead interval startle modification. In: Dawson ME, Schell AM, Bohmelt AH (eds). Startle Modification. New York: Cambridge University Press, 1999, pp 114–133.

    Chapter  Google Scholar 

  13. Ornitz EM . Developmental aspects of neurophysiology. In: Lewis M (ed). Child and Adolescent Psychiatry: A Comprehensive Textbook, 3rd edn. Baltimore: Williams and Wilkens, 2002, pp 87–92.

    Google Scholar 

  14. Ornitz EM, Guthrie D, Sadeghpour M, Sugiyama T . Maturation of prestimulation-induced startle modulation in girls. Psychophysiology 1991; 28: 11–20.

    Article  CAS  Google Scholar 

  15. Ornitz EM, Guthrie D, Kaplan AR, Lane SJ, Norman RJ . Maturation of startle modulation. Psychophysiology 1986; 23: 624–634.

    Article  CAS  Google Scholar 

  16. Castellanos FX, Fine EJ, Kaysen D, Marsh WL, Rapoport JL, Hallett M . Sensorimotor gating in boys with Tourette's syndrome and ADHD: preliminary results. Biol Psychiatry 1996; 39: 33–41.

    Article  CAS  Google Scholar 

  17. Ornitz EM, Pynoos RS . Startle modulation in children with posttraumatic stress disorder (see comment). Am J Psychiatry 1989; 146: 866–870.

    Article  CAS  Google Scholar 

  18. Frankland P, Wang Y, Rosner B, Shimizu T, Balleine B, Dykens EM et al. Sensorimotor gating abnormalities in young males with fragile X syndrome and Fmr1-knockout mice. Mol Psychiatry 2004 adv pub online.

  19. Ornitz EM, Hanna GL, de Traversay J . Prestimulation-induced startle modulation in attention-deficit hyperactivity disorder and nocturnal enuresis. Psychophysiology 1992; 29: 437–451.

    Article  CAS  Google Scholar 

  20. Schall U, Schon A, Zerbin D, Eggers C, Oades RD . Event-related potentials during an auditory discrimination with prepulse inhibition in patients with schizophrenia, obsessive–compulsive disorder and healthy subjects. Int J Neurosci 1996; 84: 15–33.

    Article  CAS  Google Scholar 

  21. Swerdlow NR, Benbow CH, Zisook S, Geyer MA, Braff DL . A preliminary assessment of sensorimotor gating in patients with obsessive compulsive disorder. Biol Psychiatry 1993; 33: 298–301.

    Article  CAS  Google Scholar 

  22. Ludewig S, Ludewig K, Geyer MA, Hell D, Vollenweider FX . Prepulse inhibition deficits in patients with panic disorder. Depress Anxiety 2002; 15: 55–60.

    Article  CAS  Google Scholar 

  23. Larsen DK, Norton GR, Walker JR, Stein M . Analysis of startle responses in patients with panic disorder and social phobia. Cogn Behav Ther 2002; 31: 156–169.

    Article  Google Scholar 

  24. McAlonan GM, Daly E, Kumari V, Critchley HD, van Amelsvoort T, Suckling J et al. Brain anatomy and sensorimotor gating in Asperger's syndrome. Brain 2002; 125 (Part 7): 1594–1606.

    Article  Google Scholar 

  25. Swerdlow NR, Paulsen J, Braff DL, Butters N, Geyer MA, Swenson MR . Impaired prepulse inhibition of acoustic and tactile startle response in patients with Huntington's disease. J Neurol Neurosurg Psychiatry 1995; 58: 192–200.

    Article  CAS  Google Scholar 

  26. Perry W, Minassian A, Feifel D, Braff DL . Sensorimotor gating deficits in bipolar disorder patients with acute psychotic mania. Biol Psychiatry 2001; 50: 418–424.

    Article  CAS  Google Scholar 

  27. Braff DL, Geyer MA, Light GA, Sprock J, Perry W, Cadenhead KS et al. Impact of prepulse characteristics on the detection of sensorimotor gating deficits in schizophrenia. Schizophr Res 2001; 49: 171–178.

    Article  CAS  Google Scholar 

  28. Swerdlow NR, Caine SB, Geyer MA . Regionally selective effects of intracerebral dopamine infusion on sensorimotor gating of the startle reflex in rats. Psychopharmacology (Berl) 1992; 108: 189–195.

    Article  CAS  Google Scholar 

  29. Sobin C, Kiley-Brabeck K, Karayiorgou M . Lowered prepulse inhibition in children with the 22q11 deletion syndrome. Am J Psychiatry, in press.

  30. Posner MI, Boies SJ . Components of attention. Psychol Rev 1971; 78: 391–408.

    Article  Google Scholar 

  31. Mesulam MM . A cortical network for directed attention and unilateral neglect. Ann Neurol 1981; 10: 309–325.

    Article  CAS  Google Scholar 

  32. Mesulam MM . Large-scale neurocognitive networks and distributed processing for attention, language, and memory. Ann Neurol 1990; 28: 597–613.

    Article  CAS  Google Scholar 

  33. Posner MI, Imhoff A, Friedrich FJ, Cohen A . Isolating attentional systems: a cognitive-anatomical analysis. Psychobiology 1987; 15: 107–121.

    Google Scholar 

  34. Posner MI, Petersen SE, Fox PT, Raichle ME . Localization of cognitive operations in the human brain. Science 1988; 240: 1627–1631.

    Article  CAS  Google Scholar 

  35. Sprafkin J, Gadow KD, Salisbury H, Schneider J, Loney J . Further evidence of reliability and validity of the Child Symptom Inventory-4: parent checklist in clinically referred boys. J Clin Child Adolesc Psychol 2002; 31: 513–524.

    Article  Google Scholar 

  36. Shaffer D, Fisher P, Lucas CP, Dulcan MK, Schwab-Stone ME . NIMH Diagnostic Interview Schedule for Children Version IV (NIMH DISC-IV): description, differences from previous versions, and reliability of some common diagnoses. J Am Acad Child Adolesc Psychiatry 2000; 39: 28–38.

    Article  CAS  Google Scholar 

  37. Flaten MA . Startle reflex facilitation as a function of classical eyeblink conditioning in humans. Psychophysiology 1993; 30: 581–588.

    Article  CAS  Google Scholar 

  38. Graham FK, Putnam LE, Leavitt LA . Lead-stimulation effects of human cardiac orienting and blink reflexes. J Exp Psychol Hum Percept Perform 1975; 104: 175–182.

    CAS  PubMed  Google Scholar 

  39. Blumenthal TD . Inhibition of the human startle response is affected by both prepulse intensity and eliciting stimulus intensity. Biol Psychol 1996; 44: 85–104.

    Article  CAS  Google Scholar 

  40. Fan J, McCandliss BD, Sommer T, Raz A, Posner MI . Testing the efficiency and independence of attentional networks. J Cogn Neurosci 2002; 14: 340–347.

    Article  Google Scholar 

  41. Rueda MR, Fan J, Halparin J, Gruber D, Lercari LP, Mc Candliss BD et al. Development of attention during childhood. Neuropsychologia 2004; 42: 1029–1040.

    Article  Google Scholar 

  42. Daniel W . Biostatistics: A Foundation for Analysis in the Health Sciences. New York: John Wiley & Sons, 1991.

    Google Scholar 

  43. Posner MI, Dehaene S . Attentional networks. Trends Neurosci 1994; 17: 75–79.

    Article  CAS  Google Scholar 

  44. Bench CJ, Frith CD, Grasby PM, Friston KJ, Paulesu E, Frackowiak RS et al. Investigations of the functional anatomy of attention using the Stroop test. Neuropsychologia 1993; 31 (9): 907–922.

    Article  CAS  Google Scholar 

  45. Corbetta M, Miezin FM, Dobmeyer S, Shulman GL, Petersen SE . Selective and divded attention during visual discrimination of shape, color, and speed: functional anatomy by positron emission tomography. J Neurosci 1991; 11: 2383–2492.

    Article  CAS  Google Scholar 

  46. Pardo JV, Pardo PJ, Janer KW, Raichle ME . The anterior cingulate cortex mediates processing selection in the Stroop attentional conflict paradigm. Proc Natl Acad Sci USA 1990; 87: 256–259.

    Article  CAS  Google Scholar 

  47. Martin JH . The visual system. In: Martin JH (ed). Neuroanatomy. Norwalk: Appleton and Lange, 1989, pp 135–163.

    Google Scholar 

  48. Mountcastle VB . Brain mechanisms for directed attention. J R Soc Med 1978; 71: 14–28.

    Article  CAS  Google Scholar 

  49. Wurtz RH, Goldberg ME, Robinson DL . Behavioral modulation of visual responses in monkeys. Progr Psychobiol Physiol Psychol 1980; 9: 42–83.

    Google Scholar 

  50. Petersen SE, Robinson DL, Morris JD . Contributions of the pulvinar to visual spatial attention. Neuropsychol Rev 1987; 25: 97–105.

    Article  CAS  Google Scholar 

  51. LeBerge D, Buchsbaum MS . Attention filtering and the pulvinar: evidence from PET scan measures. Program of the 29th Annual Meeting Psychonometric Society, 1988, p 4.

  52. Corbetta M, Akbudak E, Conturo TE, Snyder AZ, Ollinger JM, Drury HA et al. A common network for functional areas for attention and eye movements. Neuron 1998; 21: 761–773.

    Article  CAS  Google Scholar 

  53. Kastner S, Pinks MA, De Weerd P, Desimone R, Ungerleider LG . Increased activity in human visual cortex during directed attention in the absence of visual stimulation. Neuron 1999; 22: 751–761.

    Article  CAS  Google Scholar 

  54. Shute CCD, Lewis PR . The ascending cholinergic reticular system: neocortical, olfactory and subcortical projections. Brain 1967; 90: 497–520.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the children in this study for their hard work, ongoing participation, and invaluable feedback regarding our procedures, and of course, their parents, for their generous commitment to our work. Samantha Monk continues to provide excellent and invaluable assistance with data tracking, data entry, and study administration. We would also like to thank Maude Blundell, MS, for her important contribution to the early recruitment phase of the study, and Kawame Anyane-Yeboa, MD, for his participant referrals. This research was supported by a grant from the Child Health and Human Development Branch of the National Institutes of Health (K08-HD040321, to CS) and also by a General Clinical Research Center grant (M01-RR00102) from the National Center for Research Resources, National Institutes of Health.

Author information

Authors and Affiliations

  1. The Rockefeller University, New York, NY, USA

    C Sobin, K Kiley-Brabeck & M Karayiorgou

Authors
  1. C Sobin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K Kiley-Brabeck
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Karayiorgou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C Sobin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sobin, C., Kiley-Brabeck, K. & Karayiorgou, M. Associations between prepulse inhibition and executive visual attention in children with the 22q11 deletion syndrome. Mol Psychiatry 10, 553–562 (2005). https://doi.org/10.1038/sj.mp.4001609

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4001609

Keywords

This article is cited by

Search

Advanced search

Quick links