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:

Cognitive interference is associated with neuronal marker N-acetyl aspartate in the anterior cingulate cortex: an in vivo 1H-MRS study of the Stroop Color-Word task

Molecular Psychiatry volume 6, pages 529–539 (2001)Cite this article

Abstract

The neurobiology of cognitive interference is unknown. Previous brain imaging studies using the Stroop Color-Word (SCW) task indicate involvement of the cingulate cortex cognitive division. The present study examines interrelationships between regional brain N-Acetyl aspartate (NAA) levels (as identified by in vivo proton magnetic resonance spectroscopy in the right and left anterior cingulate cortex (ACC), dorsolateral prefrontal cortex, orbitofrontal cortex and thalamus) and cognitive interference (as measured by the SCW task) in 15 normal subjects. The results show that brain chemistry depends on cognitive interference levels (high vs low). Reduction of NAA levels was demonstrated in the right ACC (ie, cognitive midsupracallosal division) of high interference subjects, as compared to the low interference group (P < 0.01, two-tailed t-test). Chemical-cognitive relationships were analyzed by calculating correlations between regional NAA levels and the SCW task scores. Cognitive interference was highly correlated with the right anterior cingulate NAA (r = 0.76, P < 0.001), and was unrelated to other studied regional NAA, including the left ACC (P < 0.025; comparing the difference between r values in the right and left ACC). The interrelationships between NAA across brain regions were examined using correlation analysis (square matrix correlation maps), which detected different connectivity patterns between the two groups. These findings provide evidence of ACC involvement in cognitive interference suggesting a possibility of neuronal reorganization in the physiological mechanism of interference (most likely due to genetically predetermined control of the number of neurons, dendrites and receptors, and their function). We conclude that spectroscopic brain mapping of NAA, the marker of neuronal density and function, to the SCW task measures differentiates between high and low interference in normal subjects. This neuroimaging/cognitive tool may be useful for documentation of interference in studying cognitive control mechanisms, and in diagnosis of neuropsychiatric disorders where dysfunction of cingulate cortex is expected.

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
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Stroop JR . Studies of interference in serial verbal reactions J Exp Psychol 1935 18: 643–661

    Article  Google Scholar 

  2. MacLeod CM . Half a century of research on the Stroop effect: an integrative review Psychol Bull 1991 109: 163–203

    Article  CAS  Google Scholar 

  3. Carter CS, Krener P, Chaderjian M, Northcutt C, Wolfe V . Abnormal processing of irrelevant information in attention deficit hyperactivity disorder Psychiatry Res 1995 56: 59–70

    Article  CAS  Google Scholar 

  4. Bush G, Frazier JA, Rauch SL, Seidman LJ, Whalen PJ, Jenike MA et al. Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the Counting Stroop Biol Psychiatry 1999 45: 1542–1552

    Article  CAS  Google Scholar 

  5. Hepp HH, Maier S, Hermle L, Spitzer M . The Stroop effect in schizophrenic patients Schizophr Res 1996 22: 187–195

    Article  CAS  Google Scholar 

  6. Phillips ML, Woodruff PW, David AS . Stroop interference and facilitation in the cerebral hemispheres in schizophrenia Schizophr Res 1996 20: 57–68

    Article  CAS  Google Scholar 

  7. Purdon SE . Olfactory identification and Stroop interference converge in schizophrenia J Psychiatry Neurosci 1998 23: 163–171

    PubMed  PubMed Central  CAS  Google Scholar 

  8. Boucart M, Mobarek N, Cuervo C, Danion JM . What is the nature of increased Stroop interference in schizophrenia? Acta Psychol (Amst) 1999 101: 3–25

    Article  CAS  Google Scholar 

  9. Fuentes LJ, Boucart M, Vivas AB, Alvarez R, Zimmerman MA . Inhibitory tagging in inhibition of return is affected in schizophrenia: evidence from the Stroop task Neuropsychology 2000 14: 134–140

    Article  CAS  Google Scholar 

  10. George MS, Ketter TA, Parekh PI, Rosinsky N, Ring HA, Pazzaglia PJ et al. Blunted left cingulate activation in mood disorder subjects during a response interference task (the Stroop) J Neuropsychiatry Clin Neurosci 1997 9: 55–63

    Article  CAS  Google Scholar 

  11. Thomas J, Raoux N, Everett J, Dantchev N, Widlocher D . Deficit in selective attention and its evolution in depression [French] Encephale 1997 23: 108–112

    PubMed  CAS  Google Scholar 

  12. Metzger LJ, Orr SP, Lasko NB, McNally RJ, Pitman RK . Seeking the source of emotional Stroop interference effects in PTSD: a study of P3s to traumatic words Integr Physiol Behav Sci 1997 32: 43–51

    Article  CAS  Google Scholar 

  13. Andrews TM, Anderson IM . Information processing in anxiety: a pilot study of the effect of manipulating 5-HT function J Psychopharmacol 1998 12: 155–160

    Article  CAS  Google Scholar 

  14. Lundh LG, Wikstrom J, Westerlund J, Ost LG . Preattentive bias for emotional information in panic disorder with agoraphobia J Abnorm Psychol 1999 108: 222–232

    Article  CAS  Google Scholar 

  15. Moradi AR, Taghavi MR, Neshat Doost HT, Yule W, Dalgleish T . Performance of children and adolescents with PTSD on the Stroop colour-naming task Psychol Med 1999 29: 415–419

    Article  CAS  Google Scholar 

  16. Rinne JO, Portin R, Ruottinen H, Nurmi E, Bergman J, Haaparanta M et al. Cognitive impairment and the brain dopaminergic system in Parkinson disease: [18F]fluorodopa positron emission tomographic study Arch Neurol 2000 57: 470–475

    Article  CAS  Google Scholar 

  17. Spieler DH, Balota DA, Faust ME . Stroop performance in healthy younger and older adults and in individuals with dementia of the Alzheimer's type J Exp Psychol Hum Percept Perform 1996 22: 461–479

    Article  CAS  Google Scholar 

  18. Hinkin CH, Castellon SA, Hardy DJ, Granholm E, Siegle G . Computerized and traditional stroop task dysfunction in HIV-1 infection Neuropsychology 1999 13: 306–316

    Article  CAS  Google Scholar 

  19. 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 

  20. Bench CJ, Frith CD, Grasby PM, Friston KJ, Paulesu E, Frackowiak RSJ et al. Investigations of the functional anatomy of attention using the Stroop test Neuropsychologia 1993 31: 907–922

    Article  CAS  Google Scholar 

  21. George MS, Ketter TA, Parekh PI, Rosinsky N, Ring HA, Casey BJ et al. Regional brain activity when selecting a response despite interference: an H215O PET study of the Stroop and an emotional Stroop Hum Brain Mapping 1994 1: 194–209

    Article  CAS  Google Scholar 

  22. Derbyshire SW, Vogt BA, Jones AK . Pain and Stroop interference tasks activate separate processing modules in anterior cingulate cortex Exp Brain Res 1998 118: 52–60

    Article  CAS  Google Scholar 

  23. Leung HC, Skudlarski P, Gatenby JC, Peterson BS, Gore JC . An event-related functional MRI study of the Stroop color word interference task Cereb Cortex 2000 10: 552–560

    Article  CAS  Google Scholar 

  24. MacDonald AW III, 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

    Article  Google Scholar 

  25. Bush G, Whalen PJ, Rosen BR, Jenike MA, McInerney SC, Rauch SL . The counting Stroop: an interference task specialized for functional neuroimaging—validation study with functional MRI Hum Brain Mapping 1998 6: 270–282

    Article  CAS  Google Scholar 

  26. Talairach J, Tournoux P . Co-planar Stereotactic Atlas of the Human Brain. 3-Dimensional Proportional System: An Approach to Cerebral Imaging Thieme: Stuttgart 1988

    Google Scholar 

  27. Whalen PJ, Bush G, McNally RJ, Wilhelm S, McInerney SC, Jenike MA et al. The emotional counting Stroop paradigm: a functional magnetic resonance imaging probe of the anterior cingulate affective division Biol Psychiatry 1998 44: 1219–1228

    Article  CAS  Google Scholar 

  28. Corbetta M, Miezin F, Dobmeyer S, Shulman G, Petersen S . Selective and divided attention during visual discriminations of shape, color, and speed: functional anatomy by positron emission tomography J Neurosci 1991 11: 2383–2402

    Article  CAS  Google Scholar 

  29. Carter CS, Braver TS, Barch DM, Botvinick MM, Noll D, Cohen JD . Anterior cingulate cortex, error detection, and the online monitoring of performance Science 1998 280: 747–749

    Article  CAS  Google Scholar 

  30. Menon V, Adleman NE, White CD, Glover GH, Reiss AL . Error-related brain activation during a Go/NoGo response inhibition task Hum Brain Mapping 2001 12: 131–143

    Article  CAS  Google Scholar 

  31. Carter CS, Botvinick MM, Cohen JD . The contribution of the anterior cingulate cortex to executive processes in cognition Rev Neurosci 1999 10: 49–57

    Article  CAS  Google Scholar 

  32. Carter CS, MacDonald AM, Botvinick MM, Ross LL, Stenger VA, Noll D et al. Parsing executive processes: strategic vs evaluative functions of the anterior cingulate cortex Proc Natl Acad Sci USA 2000 97: 1944–1948

    Article  CAS  Google Scholar 

  33. Rubia K, Russell T, Overmeyer S, Brammer MJ, Bullmore ET, Sharma T et al. Mapping motor inhibition: conjunctive brain activations across different versions of Go/No-Go and Stop tasks NeuroImage 2001 13: 250–261

    Article  CAS  Google Scholar 

  34. Zysset S, Muller K, Lohmann G, von Cramon DY . Color-word matching Stroop task: separating interference and response conflict NeuroImage 2001 13: 29–36

    Article  CAS  Google Scholar 

  35. Pujol J, Vendrell P, Deus J, Junque C, Bello J, Marti-Vilalta JL et al. The effect of medial frontal and posterior parietal demyelinating lesions on Stroop interference NeuroImage 2001 13: 68–75

    Article  CAS  Google Scholar 

  36. Grachev ID, Apkarian AV . Anxiety in healthy humans is associated with orbital frontal chemistry Mol Psychiatry 2000 5: 482–488

    Article  CAS  Google Scholar 

  37. Grachev ID, Apkarian AV . Chemical mapping of anxiety in the brain of healthy humans: an in vivo 1H MRS study on the effects of sex, age and brain region Hum Brain Mapping 2000 11: 261–272

    Article  CAS  Google Scholar 

  38. Grachev ID, Fredrickson BE, Apkarian AV . Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy study Pain 2000 89: 7–18

    Article  CAS  Google Scholar 

  39. Grachev ID, Fredrickson BE, Apkarian AV . Dissociating anxiety from pain: mapping the neuronal marker N-acetyl aspartate to perception distinguishes closely interrelated characteristics of chronic pain Mol Psychiatry 2001 6: 256–258

    Article  CAS  Google Scholar 

  40. Miller BL . A review of chemical issues in 1H NMR spectroscopy: N-acetyl-L-aspartate, creatine, and choline NMR Biomed 1991 4: 47–52

    Article  CAS  Google Scholar 

  41. Castillo M, Kwock L, Scatliff J, Mukherji S . Proton MR spectroscopy in neoplastic and non-neoplastic brain disorders Magn Reson Imaging Clin N Am 1998 6: 1–20

    PubMed  CAS  Google Scholar 

  42. Tsai G, Coyle JT . N-acetylaspartate in neuropsychiatric disorders [Review] Prog Neurobiol 1995 46: 531–540

    Article  CAS  Google Scholar 

  43. Manji HK, Moore GJ, Rajkowska G, Chen G . Neuroplasticity and cellular resilience in mood disorders Mol Psychiatry 2000 5: 578–593

    Article  CAS  Google Scholar 

  44. Stanley JA, Drost DJ, Williamson PC, Carr TJ . In vivo proton MRS study of glutamate and schizophrenia. In: Nasrallah HA, Pettegrew JW (eds) NMR Spectroscopy in Psychiatric Brain Disorders American Psychiatric Press: Washington 1995 pp 21–44

    Google Scholar 

  45. Nasrallah HA, Skinner TE, Schmalbrock P, Robitaille PM . In vivo 1H-NMR spectroscopy of the limbic temporal lobe in patients with schizophrenia. In: Nasrallah HA, Pettegrew JW (eds) NMR Spectroscopy in Psychiatric Brain Disorders American Psychiatric Press: Washington 1995 pp 1–20

    Google Scholar 

  46. Pfefferbaum A, Adalsteinsson E, Spielman D, Sullivan EV, Lim KO . In vivo brain concentrations of N-acetyl compounds, creatine, and choline in Alzheimer disease Arch Gen Psychiatry 1999 56: 185–192

    Article  CAS  Google Scholar 

  47. Winsberg ME, Sachs N, Tate DL, Adalsteinsson E, Spielman D, Ketter TA . Decreased dorsolateral prefrontal N-acetyl aspartate in bipolar disorder Biol Psychiatry 2000 47: 475–481

    Article  CAS  Google Scholar 

  48. Ebert D, Speck O, Konig A, Berger M, Hennig J, Hohagen F . 1H-magnetic resonance spectroscopy in obsessive-compulsive disorder: evidence for neuronal loss in the cingulate gyrus and the right striatum Psychiatry Res 1997 74: 173–176

    Article  CAS  Google Scholar 

  49. Bartha R, Stein MB, Williamson PC, Drost DJ, Neufeld RW, Carr TJ et al. A short echo 1H spectroscopy and volumetric MRI study of the corpus striatum in patients with obsessive-compulsive disorder and comparison subjects Am J Psychiatry 1998 155: 1584–1591

    Article  CAS  Google Scholar 

  50. Fitzgerald KD, Moore GJ, Paulson LA, Stewart CM, Rosenberg DR . Proton spectroscopic imaging of the thalamus in treatment-naive pediatric obsessive-compulsive disorder Biol Psychiatry 2000 47: 174–182

    Article  CAS  Google Scholar 

  51. Grachev ID, Berdichevsky D, Rauch SL, Heckers S, Kennedy DN, Caviness VS et al. A method for assessing the accuracy of intersubject registration of the human brain using anatomic landmarks NeuroImage 1999 9: 250–268

    Article  CAS  Google Scholar 

  52. Ono M, Kubik S, Abernathey CD . Atlas of the Cerebral Sulci Georg Thieme Verlag: Stuttgart, Germany 1990 pp 112–113

    Google Scholar 

  53. Salibi N, Brown MA . Clinical MR Spectroscopy: First Principles John Wiley & Sons: New York, NY 1998

    Google Scholar 

  54. Trenerry MR, Crosson B, DeBoe J, Leber WR . Stroop Neuropsychological Screening Test Manual Psychological Assessment Resources: Odessa FL 1988

    Google Scholar 

  55. Grachev ID, Apkarian AV . Chemical network of the living human brain: evidence of reorganization with aging Brain Res Cogn Brain Res 2001 11: 185–197

    Article  CAS  Google Scholar 

  56. Grachev ID, Swarnkar A, Szeverenyi NM, Ramachandran TS, Apkarian AV . Aging alters multi-chemical networking profile of the human brain: an in vivo 1H-MRS study of young vs middle-aged subjects J Neurochem 2001 77: 292–303

    Article  CAS  Google Scholar 

  57. Flood DG . Critical issues in the analysis of dendritic extent in aging humans, primates, and rodents Neurobiol Aging 1993 14: 649–654

    Article  CAS  Google Scholar 

  58. Flood DG, Coleman PD . Dendritic regression dissociated from neuronal death but associated with partial deafferentation in aging rat supraoptic nucleus Neurobiol Aging 1993 14: 575–587

    Article  CAS  Google Scholar 

  59. Auer DP, Putz B, Kraft E, Lipinski B, Schill J, Holsboer F . Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study Biol Psychiatry 2000 47: 305–313

    Article  CAS  Google Scholar 

  60. Vendrell P, Carme J, Pujol J, Jurado MA, Molet J, Grafman J . The role of prefrontal regions in the Stroop task Neuropsychologia 1995 33: 341–352

    Article  CAS  Google Scholar 

  61. Kingma A, Heij WL, Fasotti L, Elimg P . Stroop interference and disorders of selective attention Neuropsychologia 1996 34: 273–281

    Article  CAS  Google Scholar 

  62. Albanese AM, Merlo AB, Mascitti TA, Tornese EB, Gomez EE, Konopka V et al. Inversion of the hemispheric laterality of the anterior cingulate gyrus in schizophrenics Biol Psychiatry 1995 38: 13–21

    Article  CAS  Google Scholar 

  63. Davis KD, Taylor SJ, Crawley AP, Wood ML, Mikulis DJ . Functional MRI of pain- and attention-related activations in the human cingulate cortex J Neurophysiol 1997 77: 3370–3380

    Article  CAS  Google Scholar 

  64. Rainville P, Duncan GH, Price DD, Carrier B, Bushnell MC . Pain affect encoded in human anterior cingulate but not somatosensory cortex Science 1997 277: 968–971

    Article  CAS  Google Scholar 

  65. Peyron R, Garcia-Larrea L, Gregoire MC, Convers P, Lavenne F, Veyre L et al. Allodynia after lateral-medullary (Wallenberg) infarct: a PET study Brain 1998 121: 345–356

    Article  Google Scholar 

  66. Kwan CL, Crawley AP, Mikulis DJ, Davis KD . An fMRI study of the anterior cingulate cortex and surrounding medial wall activations evoked by noxious cutaneous heat and cold stimuli Pain 2000 85: 359–374

    Article  CAS  Google Scholar 

  67. Fuster JM . The Prefrontal Cortex: Anatomy, Physiology, and Neuropsychology of the Frontal Lobe Lippincott–Raven Publishers:Philadelphia, Pennsylvania 1997

    Google Scholar 

  68. Pandya DN, Yeterian EH . Comparison of prefrontal architecture and connections. In: Roberts AC, Robbins TW, Weiskrantz L (eds) The Prefrontal Cortex: Executive and Cognitive Functions Oxford University Press: New York 1998 pp 51–66

    Chapter  Google Scholar 

  69. Bechara A, Damasio AR, Damasio H, Anderson SW . Insensitivity to future consequences following damage to human prefrontal cortex Cognition 1994 50: 7–15

    Article  CAS  Google Scholar 

  70. Bechara A, Damasio H, Tranel D, Damasio AR . Deciding advantageously before knowing the advantageous strategy Science 1997 275: 1293–1295

    Article  CAS  Google Scholar 

  71. Damasio AR . The somatic marker hypothesis and the possible functions of the prefrontal cortex. In: Roberts AC, Robbins TW, Weiskrantz L (eds) The Prefrontal Cortex: Executive and Cognitive Functions Oxford University Press: New York 1998 pp 36–50

    Chapter  Google Scholar 

  72. Smith EE, Jonides J . Storage and executive processes in the frontal lobes Science 1999 283: 1657–1661

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank G Tillapaugh-Fay and N Horton for technical assistance, and P Sheehe for discussion of data analysis. The project was funded by Research Initiative Fund in Radiology (IDG, NMS) at SUNY Upstate Medical University.

Author information

Authors and Affiliations

  1. Department of Radiology, SUNY Upstate Medical University, Syracuse, 13210, NY, USA

    I D Grachev & N M Szeverenyi

  2. Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, 13210, NY, USA

    I D Grachev

  3. Department of Neurology, SUNY Upstate Medical University, Syracuse, 13210, NY, USA

    T S Ramachandran

  4. Chronic Pain and Fatigue Research Center, Georgetown University Medical Center, Washington, 20007, DC, USA

    R Kumar

Authors
  1. I D Grachev
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T S Ramachandran
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N M Szeverenyi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I D Grachev.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grachev, I., Kumar, R., Ramachandran, T. et al. Cognitive interference is associated with neuronal marker N-acetyl aspartate in the anterior cingulate cortex: an in vivo 1H-MRS study of the Stroop Color-Word task. Mol Psychiatry 6, 529–539 (2001). https://doi.org/10.1038/sj.mp.4000940

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4000940

Keywords

This article is cited by

Search

Advanced search

Quick links