Journal of the American Academy of Child & Adolescent Psychiatry
Volume 49, Issue 9 , Pages 944-953 , September 2010

Cognitive Inflexibility and Frontal-Cortical Activation in Pediatric Obsessive-Compulsive Disorder

A previous version of this work was presented at the American Academy of Child and Adolescent Psychiatry in October 2009.

  • Jennifer C. Britton, Ph.D.

      Affiliations

    • Mood and Anxiety Disorders Program at the National Institute of Mental Health in Bethesda, MD
    • ,
  • Scott L. Rauch, M.D.

      Affiliations

    • Brain Imaging Center at McLean Hospital in Belmont, MA
    • Massachusetts General Hospital in Boston, MA
    • ,
  • Isabelle M. Rosso, Ph.D.

      Affiliations

    • Brain Imaging Center at McLean Hospital in Belmont, MA
    • ,
  • William D.S. Killgore, Ph.D.

      Affiliations

    • Brain Imaging Center at McLean Hospital in Belmont, MA
    • ,
  • Lauren M. Price, B.A.

      Affiliations

    • Brain Imaging Center at McLean Hospital in Belmont, MA
    • ,
  • Jennifer Ragan, Ph.D.

      Affiliations

    • Massachusetts General Hospital in Boston, MA
    • ,
  • Anne Chosak, Ph.D.

      Affiliations

    • Massachusetts General Hospital in Boston, MA
    • ,
  • Dianne M. Hezel, B.A.

      Affiliations

    • Psychiatric and Neurodevelopmental Genetics Unit at Massachusetts General Hospital in Boston, MA
    • ,
  • Daniel S. Pine, M.D.

      Affiliations

    • Mood and Anxiety Disorders Program at the National Institute of Mental Health in Bethesda, MD
    • ,
  • Ellen Leibenluft, M.D.

      Affiliations

    • Mood and Anxiety Disorders Program at the National Institute of Mental Health in Bethesda, MD
    • ,
  • David L. Pauls, Ph.D.

      Affiliations

    • Psychiatric and Neurodevelopmental Genetics Unit at Massachusetts General Hospital in Boston, MA
    • ,
  • Michael A. Jenike, M.D.

      Affiliations

    • Massachusetts General Hospital in Boston, MA
    • ,
  • S. Evelyn Stewart, M.D.

      Affiliations

    • Massachusetts General Hospital in Boston, MA
    • Psychiatric and Neurodevelopmental Genetics Unit at Massachusetts General Hospital in Boston, MA
    • Corresponding Author InformationCorrespondence to S. Evelyn Stewart, M.D., Department of Psychiatry, Massachusetts General Hospital, Richard B. Simches Research Center, Psychiatric and Neurodevelopmental Genetics Unit, 185 Cambridge Street, 6th Floor, Boston, MA 02114

,Accepted 14 May 2010.

References 

  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders - Fourth Edition. Washington, DC: American Psychiatric Association; 1994;
  2. Kuelz AK, Hohagen F, Voderholzer U. Neuropsychological performance in obsessive-compulsive disorder: a critical review. Biol Psychol. 2004;65:185–236
  3. Lawrence NS, Wooderson S, Mataix-Cols D, David R, Speckens A, Phillips ML. Decision making and set shifting impairments are associated with distinct symptom dimensions in obsessive-compulsive disorder. Neuropsychology. 2006;20:409–419
  4. Bannon S, Gonsalvez CJ, Croft RJ, Boyce PM. Executive functions in obsessive-compulsive disorder: state or trait deficits?. Aust N Z J Psychiatry. 2006;40:1031–1038
  5. Remijnse PL, Nielen MM, van Balkom AJ, et al. Reduced orbitofrontal-striatal activity on a reversal learning task in obsessive-compulsive disorder. Arch Gen Psychiatry. 2006;63:1225–1236
  6. Gu BM, Park JY, Kang DH, et al. Neural correlates of cognitive inflexibility during task-switching in obsessive-compulsive disorder. Brain. 2008;131:155–164
  7. Chamberlain SR, Fineberg NA, Blackwell AD, Robbins TW, Sahakian BJ. Motor inhibition and cognitive flexibility in obsessive-compulsive disorder and trichotillomania. Am J Psychiatry. 2006;163:1282–1284
  8. Watkins LH, Sahakian BJ, Robertson MM, et al. Executive function in Tourette's syndrome and obsessive-compulsive disorder. Psychol Med. 2005;35:571–582
  9. Veale DM, Sahakian BJ, Owen AM, Marks IM. Specific cognitive deficits in tests sensitive to frontal lobe dysfunction in obsessive-compulsive disorder. Psychol Med. 1996;26:1261–1269
  10. Penades R, Catalan R, Rubia K, Andres S, Salamero M, Gasto C. Impaired response inhibition in obsessive compulsive disorder. Eur Psychiatry. 2007;22:404–410
  11. Bannon S, Gonsalvez CJ, Croft RJ, Boyce PM. Response inhibition deficits in obsessive-compulsive disorder. Psychiatry Res. 2002;110:165–174
  12. Rosenberg DR, Dick EL, O'Hearn KM, Sweeney JA. Response-inhibition deficits in obsessive-compulsive disorder: an indicator of dysfunction in frontostriatal circuits. J Psychiatry Neurosci. 1997;22:29–38
  13. Roth RM, Saykin AJ, Flashman LA, Pixley HS, West JD, Mamourian AC. Event-related functional magnetic resonance imaging of response inhibition in obsessive-compulsive disorder. Biol Psychiatry. 2007;62:901–909
  14. Page LA, Rubia K, Deeley Q, et al. A functional magnetic resonance imaging study of inhibitory control in obsessive-compulsive disorder. Psychiatry Res. 2009;174:202–209
  15. Shin MS, Choi H, Kim H, Hwang JW, Kim BN, Cho SC. A study of neuropsychological deficit in children with obsessive-compulsive disorder. Eur Psychiatry. 2008;23:512–520
  16. Rosenberg DR, Averbach DH, O'Hearn KM, Seymour AB, Birmaher B, Sweeney JA. Oculomotor response inhibition abnormalities in pediatric obsessive-compulsive disorder. Arch Gen Psychiatry. 1997;54:831–838
  17. Rubia K, Cubillo A, Smith AB, Woolley J, Heyman I, Brammer MJ. Disorder-specific dysfunction in right inferior prefrontal cortex during two inhibition tasks in boys with attention-deficit hyperactivity disorder compared to boys with obsessive-compulsive disorder. Hum Brain Mapp. 2010;31:287–299
  18. Woolley J, Heyman I, Brammer M, Frampton I, McGuire PK, Rubia K. Brain activation in paediatric obsessive compulsive disorder during tasks of inhibitory control. Br J Psychiatry. 2008;192:25–31
  19. Casey BJ, Davidson MC, Hara Y, et al. Early development of subcortical regions involved in non-cued attention switching. Dev Sci. 2004;7:534–542
  20. Kaufman J, Birmaher B, Brent D, et al. Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997;36:980–988
  21. Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale (II. Validity). Arch Gen Psychiatry. 1989;46:1012–1016
  22. Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale (I. Development, use, and reliability). Arch Gen Psychiatry. 1989;46:1006–1011
  23. Kovacs M. Child Depression Inventory. 1992. http://www.pearsonassessments.com/HAIWEB/Cultures/en-us/Productdetail.htm?Pid=015-8044-762&Mode=summary2009;Accessed February 18, 2010
  24. Leckman JF, Riddle MA, Hardin MT, et al. The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. J Am Acad Child Adolesc Psychiatry. 1989;28:566–573
  25. Spielberger CD, Edwards CD, Montuori J, Lushene R. STAI-C. http://www.mindgarden.com/products/staisch.htm#about, 2009Accessed February 18, 2010
  26. Leckman JF, Grice DE, Boardman J, et al. Symptoms of obsessive-compulsive disorder. Am J Psychiatry. 1997;154:911–917
  27. Stewart SE, Rosario MC, Baer L, et al. Four-factor structure of obsessive-compulsive disorder symptoms in children, adolescents, and adults. J Am Acad Child Adolesc Psychiatry. 2008;47:763–772
  28. Friston K. Statistical Parametric Mapping. http://www.fil.ion.ucl.ac.uk/spmAccessed February 18, 2010
  29. Rauch SL, Savage CR, Alpert NM, et al. Probing striatal function in obsessive-compulsive disorder: a PET study of implicit sequence learning. J Neuropsychiatry Clin Neurosci. 1997;9:568–573
  30. Rauch SL, Wedig MM, Wright CI, et al. Functional magnetic resonance imaging study of regional brain activation during implicit sequence learning in obsessive-compulsive disorder. Biol Psychiatry. 2007;61:330–336
  31. Ward BD AlphaSim. http://afni.nimh.nih.gov/afni/doc/manual/AlphaSim, 20102000;Accessed February 18, 2010
  32. Talairach J, Tournoux P. Co-Planar Stereotactic Atlas of the Human Brain. Stuttgart: Thieme; 1988;
  33. Brett M, Anton JL, Valabregue R, Poline JB. Region of interest analysis using an SPM toolbox. Paper presented at: 8th International Conference on Functional Mapping of the Human Brain 2002; Sendai, Japan.
  34. Dale AM, Fischl B, Sereno MI. Cortical surface-based analysis (I. Segmentation and surface reconstruction). Neuroimage. 1999;9:179–194
  35. Dove A, Pollmann S, Schubert T, Wiggins CJ, von Cramon DY. Prefrontal cortex activation in task switching: an event-related fMRI study. Brain Res Cogn Brain Res. 2000;9:103–109
  36. Monchi O, Petrides M, Petre V, Worsley K, Dagher A. Wisconsin Card Sorting revisited: distinct neural circuits participating in different stages of the task identified by event-related functional magnetic resonance imaging. J Neurosci. 2001;21:7733–7741
  37. Nakahara K, Hayashi T, Konishi S, Miyashita Y. Functional MRI of macaque monkeys performing a cognitive set-shifting task. Science. 2002;295:1532–1536
  38. Aron AR, Monsell S, Sahakian BJ, Robbins TW. A componential analysis of task-switching deficits associated with lesions of left and right frontal cortex. Brain. 2004;127:1561–1573
  39. Aron AR, Robbins TW, Poldrack RA. Inhibition and the right inferior frontal cortex. Trends Cogn Sci. 2004;8:170–177
  40. Garavan H, Ross TJ, Murphy K, Roche RA, Stein EA. Dissociable executive functions in the dynamic control of behavior: inhibition, error detection, and correction. Neuroimage. 2002;17:1820–1829
  41. MacDonald AW, Cohen JD, Stenger VA, Carter CS. Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control. Science. 2000;288:1835–1838
  42. Derrfuss J, Brass M, Neumann J, von Cramon DY. Involvement of the inferior frontal junction in cognitive control: meta-analyses of switching and Stroop studies. Hum Brain Mapp. 2005;25:22–34
  43. Konishi S, Hayashi T, Uchida I, Kikyo H, Takahashi E, Miyashita Y. Hemispheric asymmetry in human lateral prefrontal cortex during cognitive set shifting. Proc Natl Acad Sci U S A. 2002;99:7803–7808
  44. D'Esposito M, Postle BR, Jonides J, Smith EE. The neural substrate and temporal dynamics of interference effects in working memory as revealed by event-related functional MRI. Proc Natl Acad Sci U S A. 1999;96:7514–7519
  45. Sohn MH, Ursu S, Anderson JR, Stenger VA, Carter CS. Inaugural article: the role of prefrontal cortex and posterior parietal cortex in task switching. Proc Natl Acad Sci U S A. 2000;97:13448–13453
  46. Harrison BJ, Soriano-Mas C, Pujol J, et al. Altered corticostriatal functional connectivity in obsessive-compulsive disorder. Arch Gen Psychiatry. 2009;66:1189–1200
  47. Saxena S, Brody AL, Schwartz JM, Baxter LR. Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder. Br J Psychiatry Suppl. 1998;26–37
  48. Menzies L, Achard S, Chamberlain SR, et al. Neurocognitive endophenotypes of obsessive-compulsive disorder. Brain. 2007;130:3223–3236
  49. Chamberlain SR, Menzies L, Hampshire A, et al. Orbitofrontal dysfunction in patients with obsessive-compulsive disorder and their unaffected relatives. Science. 2008;321:421–422
  50. Mataix-Cols D, Alonso P, Pifarre J, Menchon JM, Vallejo J. Neuropsychological performance in medicated versus unmedicated patients with obsessive-compulsive disorder. Psychiatry Res. 2002;109:255–264
  51. Nakao T, Nakagawa A, Yoshiura T, et al. Brain activation of patients with obsessive-compulsive disorder during neuropsychological and symptom provocation tasks before and after symptom improvement: a functional magnetic resonance imaging study. Biol Psychiatry. 2005;57:901–910
  52. Vollm B, Richardson P, McKie S, Elliott R, Deakin JF, Anderson IM. Serotonergic modulation of neuronal responses to behavioural inhibition and reinforcing stimuli: an fMRI study in healthy volunteers. Eur J Neurosci. 2006;23:552–560
  53. Purcell R, Maruff P, Kyrios M, Pantelis C. Neuropsychological deficits in obsessive-compulsive disorder: a comparison with unipolar depression, panic disorder, and normal controls. Arch Gen Psychiatry. 1998;55:415–423
  54. Remijnse PL, Nielen MM, van Balkom AJ, et al. Differential frontal-striatal and paralimbic activity during reversal learning in major depressive disorder and obsessive-compulsive disorder. Psychol Med. 2009;39:1503–1518
  55. Baym CL, Corbett BA, Wright SB, Bunge SA. Neural correlates of tic severity and cognitive control in children with Tourette syndrome. Brain. 2008;131:165–179
  56. Marsh R, Zhu H, Wang Z, Skudlarski P, Peterson BS. A developmental fMRI study of self-regulatory control in Tourette's syndrome. Am J Psychiatry. 2007;164:955–966
  57. Smith AB, Taylor E, Brammer M, Toone B, Rubia K. Task-specific hypoactivation in prefrontal and temporoparietal brain regions during motor inhibition and task switching in medication-naive children and adolescents with attention deficit hyperactivity disorder. Am J Psychiatry. 2006;163:1044–1051

 This article was reviewed under and accepted by Ad Hoc Editor David R. Rosenberg, M.D.

 This research was supported by the David Judah Fund (J.C.B., S.E.S.) and in part by the Intramural Research Program of the National Institutes of Health and the National Institute of Mental Health (J.C.B., D.S.P., E.L.).

 Disclosure: Dr. Rauch has received funds for research through Massachusetts General Hospital (MGH) from Medtronics, Cyberonics, and Cephalon. He has received honoraria from Novartis, Neurogen, Sepracor, Primedia, and Medtronics, Inc. Dr. Rauch is a trustee at McLean Hospital and serves on the Board at the Massachusetts Society for Medical Research (MSMR) as well as on the National Foundation of Mental Health (NFMH) Board. Dr. Killgore works as a part-time contract researcher at the Department of Defense Contractor, GovSource, Inc., and does contract work for the Brain Institute, University of Utah. He has a U.S. Army Medical Research and Material Command grant and a patent pending: The Sleep History and Readiness Predictor (SHARP), a computer program developed for predicting cognitive performance from sleep and circadian rhythms. Dr. Killgore is affiliated with the U.S. Army Reserve. Dr. Pauls has obtained funds from the following sources: National Institutes of Health (National Institute of Neurological Disorders and Stroke, and National Institute of Mental Health), Autism Consortium, Ellison Foundation, Anonymous Donor, and has received an honorarium from the Mayo Clinic for giving course lectures. Drs. Britton, Rosso, Ragan, Chosak, Pine, Leibenluft, Jenike, and Stewart, and Ms. Price, and Ms. Hezel report no biomedical financial interests or potential conflicts of interest.

PII: S0890-8567(10)00416-8

doi: 10.1016/j.jaac.2010.05.006

Journal of the American Academy of Child & Adolescent Psychiatry
Volume 49, Issue 9 , Pages 944-953 , September 2010

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