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White matter abnormalities and their impact on attentional performance in adult attention-deficit/hyperactivity disorder

  • Andreas KonradEmail author
  • Thomas F. Dielentheis
  • Dschamil El Masri
  • Paulo R. Dellani
  • Peter Stoeter
  • Goran Vucurevic
  • Georg Winterer
Original Paper

Abstract

Inattention is the most important behavioral feature of adult patients with attention-deficit/hyperactivity disorder (ADHD). Neuroimaging studies in ADHD have demonstrated abnormalities primarily in the frontostriatal circuitry and were mostly conducted in children. We investigated white matter (WM) integrity in adult ADHD patients and the correlation of WM microstructure and neuropsychological parameters in 37 (21 men) never-medicated adult ADHD patients and 34 age- and gender-matched healthy controls. All subjects underwent clinical interviews, rating scales, and neuropsychological tests of attentional performance. Diffusion tensor imaging (DTI) was acquired, and 12 WM regions-of-interest (ROIs) within the attentional network were chosen. Group differences of mean fractional anisotropy (FA) and mean diffusivity (MD) values were calculated for each ROI, and patients’ DTI measures were then correlated with measures of attentional performance. FA values in ADHD patients were significantly reduced in the left inferior longitudinal fasciculus (ILF), while MD values were significantly increased in ADHD patients in the frontal portion of the left frontooccipital fasciculus (IFO). In ADHD patients, MD values were negatively correlated with attentional performance in the left ILF. Our findings provide further support for disturbed frontostriatal structural connectivity and also point to an involvement of the left temporal white matter with an impact on attentional performance.

Keywords

Attention-deficit/hyperactivity disorder Diffusion tensor imaging Fractional anisotropy Mean diffusivity Attention 

Notes

Acknowledgments

This study was supported by the MAIFOR grant of the Johannes Gutenberg-University Mainz, Germany. We thank the patients and volunteers who participated in our study.

Conflict of interest

None.

References

  1. 1.
    Ashtari M, Kumra S, Bhaskar SL, Clarke T, Thaden E, Cervellione KL, Rhinewine J, Kane JM, Adesman A, Milanaik R, Maytal J, Diamond A, Szeszko P, Ardekani BA (2005) Attention-deficit/hyperactivity disorder: a preliminary diffusion tensor imaging study. Biol Psychiatry 57:448–455PubMedCrossRefGoogle Scholar
  2. 2.
    Basser PJ, Mattiello J, LeBihan D (1994) Estimation of the effective self-diffusion tensor from the NMR spin echo. J Magn Reson B 103:247–254PubMedCrossRefGoogle Scholar
  3. 3.
    Basser PJ, Pierpaoli C (1996) Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J Magn Reson B 111:209–219PubMedCrossRefGoogle Scholar
  4. 4.
    Bayerl M, Dielentheis TF, Vucurevic G, Gesierich T, Vogel F, Fehr C, Stoeter P, Huss M, Konrad A (2010) Disturbed brain activation during a working memory task in drug-naive adult patients with ADHD. Neuroreport 21:442–446Google Scholar
  5. 5.
    Beaulieu C (2002) The basis of anisotropic water diffusion in the nervous system—a technical review. NMR Biomed 15:435–455PubMedCrossRefGoogle Scholar
  6. 6.
    Beck AT, Steer RA (1987) Beck Depression Inventory (BDI). The Psychological Corporation Inc, San AntonioGoogle Scholar
  7. 7.
    Beidel DC, Borden JW, Turner SM, Jacob RG (1989) The social phobia and anxiety inventory: concurrent validity with a clinic sample. Behav Res Ther 27:573–576PubMedCrossRefGoogle Scholar
  8. 8.
    Brown TE (1996) Brown Attention-Deficit Disorder Scales (BADDS). The Psychological Corporation. Harcourt Brace & Company, San AntonioGoogle Scholar
  9. 9.
    Bush G, Frazier JA, Rauch SL, Seidman LJ, Whalen PJ, Jenike MA, Rosen BR, Biederman J (1999) Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the Counting Stroop. Biol Psychiatry 45:1542–1552PubMedCrossRefGoogle Scholar
  10. 10.
    Bush G, Valera EM, Seidman LJ (2005) Functional neuroimaging of attention-deficit/hyperactivity disorder: a review and suggested future directions. Biol Psychiatry 57:1273–1284PubMedCrossRefGoogle Scholar
  11. 11.
    Casey BJ, Epstein JN, Buhle J, Liston C, Davidson MC, Tonev ST, Spicer J, Niogi S, Millner AJ, Reiss A, Garrett A, Hinshaw SP, Greenhill LL, Shafritz KM, Vitolo A, Kotler LA, Jarrett MA, Glover G (2007) Frontostriatal connectivity and its role in cognitive control in parent-child dyads with ADHD. Am J Psychiatry 164:1729–1736PubMedCrossRefGoogle Scholar
  12. 12.
    Castellanos FX (1997) Toward a pathophysiology of attention-deficit/hyperactivity disorder. Clin Pediatr (Phila) 36:381–393CrossRefGoogle Scholar
  13. 13.
    Castellanos FX, Hyde Z (2010) Diffusion tensor imaging provides new clues in adults with ADHD (Commentary on Konrad et al.). Eur J Neurosci 31:910–911CrossRefGoogle Scholar
  14. 14.
    Castellanos FX, Tannock R (2002) Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes. Nat Rev Neurosci 3:617–628PubMedGoogle Scholar
  15. 15.
    Clarke AR, Barry RJ, Heaven PC, McCarthy R, Selikowitz M, Byrne MK (2008) EEG coherence in adults with attention-deficit/hyperactivity disorder. Int J Psychophysiol 67:35–40PubMedCrossRefGoogle Scholar
  16. 16.
    Durston S, Mulder M, Casey BJ, Ziermans T, van Engeland H (2006) Activation in ventral prefrontal cortex is sensitive to genetic vulnerability for attention-deficit hyperactivity disorder. Biol Psychiatry 60:1062–1070PubMedCrossRefGoogle Scholar
  17. 17.
    Epstein JN, Casey BJ, Tonev ST, Davidson MC, Reiss AL, Garrett A, Hinshaw SP, Greenhill LL, Glover G, Shafritz KM, Vitolo A, Kotler LA, Jarrett MA, Spicer J (2007) ADHD- and medication-related brain activation effects in concordantly affected parent-child dyads with ADHD. J Child Psychol Psychiatry 48:899–913PubMedCrossRefGoogle Scholar
  18. 18.
    Faraone SV, Biederman J, Spencer T, Wilens T, Seidman LJ, Mick E, Doyle AE (2000) Attention-deficit/hyperactivity disorder in adults: an overview. Biol Psychiatry 48:9–20PubMedCrossRefGoogle Scholar
  19. 19.
    Fellgiebel A, Wille P, Muller MJ, Winterer G, Scheurich A, Vucurevic G, Schmidt LG, Stoeter P (2004) Ultrastructural hippocampal and white matter alterations in mild cognitive impairment: a diffusion tensor imaging study. Dement Geriatr Cogn Disord 18:101–108PubMedCrossRefGoogle Scholar
  20. 20.
    Fydrich T, Renneberg B, Schmitz B, Wittchen HU (1997) Strukturiertes Klinisches Interview für DSM-IVAchse II: Persönlichkeitsstörungen. Interviewheft, Hogrefe, GöttingenGoogle Scholar
  21. 21.
    Giedd JN, Blumenthal J, Molloy E, Castellanos FX (2001) Brain imaging of attention deficit/hyperactivity disorder. Ann N Y Acad Sci 931:33–49PubMedCrossRefGoogle Scholar
  22. 22.
    Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, Heninger GR, Charney DS (1989) The Yale-Brown obsessive compulsive scale. I. Development, use, and reliability. Arch Gen Psychiatry 46:1006–1011PubMedCrossRefGoogle Scholar
  23. 23.
    Greenberg LM, Kindschi CL (1996) TOVA test of variables of attention: clinical guide. TOVA Research Foundation, St. Paul, MNGoogle Scholar
  24. 24.
    Hamilton LS, Levitt JG, O’Neill J, Alger JR, Luders E, Phillips OR, Caplan R, Toga AW, McCracken J, Narr KL (2008) Reduced white matter integrity in attention-deficit hyperactivity disorder. Neuroreport 19:1705–1708PubMedCrossRefGoogle Scholar
  25. 25.
    Hesslinger B, van Tebartz Elst L, Thiel T, Haegele K, Hennig J, Ebert D (2002) Frontoorbital volume reductions in adult patients with attention deficit hyperactivity disorder. Neurosci Lett 328:319–321PubMedCrossRefGoogle Scholar
  26. 26.
    Hofer S, Frahm J (2006) Topography of the human corpus callosum revisited–comprehensive fiber tractography using diffusion tensor magnetic resonance imaging. Neuroimage 32:989–994PubMedCrossRefGoogle Scholar
  27. 27.
    Horn W (1983) Leistungsprüfsystem (LPS) (Performance test system). Hogrefe, GöttingenGoogle Scholar
  28. 28.
    Jacob CP, Nguyen TT, Dempfle A, Heine M, Windemuth-Kieselbach C, Baumann K, Jacob F, Prechtl J, Wittlich M, Herrmann MJ, Gross-Lesch S, Lesch KP, Reif A (2010) A gene-environment investigation on personality traits in two independent clinical sets of adult patients with personality disorder and attention deficit/hyperactive disorder. Eur Arch Psychiatry Clin Neurosci 260:317–326PubMedCrossRefGoogle Scholar
  29. 29.
    Karch S, Thalmeier T, Lutz J, Cerovecki A, Opgen-Rhein M, Hock B, Leicht G, Hennig-Fast K, Meindl T, Riedel M, Mulert C, Pogarell O (2010) Neural correlates (ERP/fMRI) of voluntary selection in adult ADHD patients. Eur Arch Psychiatry Clin Neurosci 260:427–440PubMedCrossRefGoogle Scholar
  30. 30.
    Kobel M, Bechtel N, Specht K, Klarhofer M, Weber P, Scheffler K, Opwis K, Penner IK (2010) Structural and functional imaging approaches in attention deficit/hyperactivity disorder: does the temporal lobe play a key role? Psychiatry Res 183:230–236PubMedCrossRefGoogle Scholar
  31. 31.
    Konrad A, Dielentheis TF, El Masri D, Bayerl M, Fehr C, Gesierich T, Vucurevic G, Stoeter P, Winterer G (2010) Disturbed structural connectivity is related to inattention and impulsivity in adult attention deficit hyperactivity disorder. Eur J Neurosci 31:912–919PubMedCrossRefGoogle Scholar
  32. 32.
    Konrad A, Vucurevic G, Musso F, Stoeter P, Winterer G (2009) Correlation of brain white matter diffusion anisotropy and mean diffusivity with reaction time in an oddball task. Neuropsychobiology 60:55–66PubMedCrossRefGoogle Scholar
  33. 33.
    Krause J, Krause K-H (2002) ADHD im Erwachsenenalter: häufige psychiatrische Erkrankungen. In: Voss H (ed) Unaufmerksam und hyperaktiv. Kirchheim, Mainz, pp 166–182Google Scholar
  34. 34.
    Madden DJ, Whiting WL, Huettel SA, White LE, MacFall JR, Provenzale JM (2004) Diffusion tensor imaging of adult age differences in cerebral white matter: relation to response time. Neuroimage 21:1174–1181PubMedCrossRefGoogle Scholar
  35. 35.
    Makris N, Biederman J, Valera EM, Bush G, Kaiser J, Kennedy DN, Caviness VS, Faraone SV, Seidman LJ (2007) Cortical thinning of the attention and executive function networks in adults with attention-deficit/hyperactivity disorder. Cereb Cortex 17:1364–1375PubMedCrossRefGoogle Scholar
  36. 36.
    Makris N, Buka SL, Biederman J, Papadimitriou GM, Hodge SM, Valera EM, Brown AB, Bush G, Monuteaux MC, Caviness VS, Kennedy DN, Seidman LJ (2008) Attention and executive systems abnormalities in adults with childhood ADHD: A DT-MRI study of connections. Cereb Cortex 18:1210–1220PubMedCrossRefGoogle Scholar
  37. 37.
    Murias M, Swanson JM, Srinivasan R (2007) Functional connectivity of frontal cortex in healthy and ADHD children reflected in EEG coherence. Cereb Cortex 17:1788–1799PubMedCrossRefGoogle Scholar
  38. 38.
    Papadakis NG, Xing D, Houston GC, Smith JM, Smith MI, James MF, Parsons AA, Huang CL, Hall LD, Carpenter TA (1999) A study of rotationally invariant and symmetric indices of diffusion anisotropy. Magn Reson Imaging 17:881–892PubMedCrossRefGoogle Scholar
  39. 39.
    Paul RH, Grieve SM, Niaura R, David SP, Laidlaw DH, Cohen R, Sweet L, Taylor G, Clark RC, Pogun S, Gordon E (2008) Chronic cigarette smoking and the microstructural integrity of white matter in healthy adults: a diffusion tensor imaging study. Nicotine Tob Res 10:137–147PubMedCrossRefGoogle Scholar
  40. 40.
    Rapport MD, Bolden J, Kofler MJ, Sarver DE, Raiker JS, Alderson RM (2009) Hyperactivity in boys with attention-deficit/hyperactivity disorder (ADHD): a ubiquitous core symptom or manifestation of working memory deficits? J Abnorm Child Psychol 37:521–534PubMedCrossRefGoogle Scholar
  41. 41.
    Retz-Junginger P, Retz W, Blocher D, Stieglitz RD, Georg T, Supprian T, Wender PH, Rosler M (2003) Reliability and validity of the Wender-Utah-Rating-Scale short form. Retrospective assessment of symptoms for attention deficit/hyperactivity disorder. Nervenarzt 74:987–993PubMedCrossRefGoogle Scholar
  42. 42.
    Retz-Junginger P, Retz W, Blocher D, Weijers HG, Trott GE, Wender PH, Rossler M (2002) Wender Utah rating scale. The short-version for the assessment of the attention-deficit hyperactivity disorder in adults. Nervenarzt 73:830–838PubMedCrossRefGoogle Scholar
  43. 43.
    Rosler M, Retz W, Retz-Junginger P, Stieglitz RD, Kessler H, Reimherr F, Wender PH (2008) Attention deficit hyperactivity disorder in adults. Benchmarking diagnosis using the Wender-Reimherr adult rating scale. Nervenarzt 79:320–327PubMedCrossRefGoogle Scholar
  44. 44.
    Rubia K, Smith AB, Brammer MJ, Taylor E (2007) Temporal lobe dysfunction in medication-naive boys with attention-deficit/hyperactivity disorder during attention allocation and its relation to response variability. Biol Psychiatry 62:999–1006PubMedCrossRefGoogle Scholar
  45. 45.
    Rusch N, Weber M, Il’yasov KA, Lieb K, Ebert D, Hennig J, van Elst LT (2007) Inferior frontal white matter microstructure and patterns of psychopathology in women with borderline personality disorder and comorbid attention-deficit hyperactivity disorder. Neuroimage 35:738–747PubMedCrossRefGoogle Scholar
  46. 46.
    Schmithorst VJ, Holland SK, Dardzinski BJ (2008) Developmental differences in white matter architecture between boys and girls. Hum Brain Mapp 29(6):696–710PubMedCrossRefGoogle Scholar
  47. 47.
    Schmithorst VJ, Wilke M, Dardzinski BJ, Holland SK (2002) Correlation of white matter diffusivity and anisotropy with age during childhood and adolescence: a cross-sectional diffusion-tensor MR imaging study. Radiology 222:212–218PubMedCrossRefGoogle Scholar
  48. 48.
    Schneider MF, Krick CM, Retz W, Hengesch G, Retz-Junginger P, Reith W, Rosler M (2010) Impairment of fronto-striatal and parietal cerebral networks correlates with attention deficit hyperactivity disorder (ADHD) psychopathology in adults—a functional magnetic resonance imaging (fMRI) study. Psychiatry Res 183:75–84PubMedCrossRefGoogle Scholar
  49. 49.
    Schulz KP, Fan J, Tang CY, Newcorn JH, Buchsbaum MS, Cheung AM, Halperin JM (2004) Response inhibition in adolescents diagnosed with attention deficit hyperactivity disorder during childhood: an event-related FMRI study. Am J Psychiatry 161:1650–1657PubMedCrossRefGoogle Scholar
  50. 50.
    Schulz KP, Tang CY, Fan J, Marks DJ, Newcorn JH, Cheung AM, Halperin JM (2005) Differential prefrontal cortex activation during inhibitory control in adolescents with and without childhood attention-deficit/hyperactivity disorder. Neuropsychology 19:390–402PubMedCrossRefGoogle Scholar
  51. 51.
    Seidman LJ, Doyle A, Fried R, Valera E, Crum K, Matthews L (2004) Neuropsychological function in adults with attention-deficit/hyperactivity disorder. Psychiatr Clin North Am 27:261–282PubMedCrossRefGoogle Scholar
  52. 52.
    Seidman LJ, Valera EM, Makris N (2005) Structural brain imaging of attention-deficit/hyperactivity disorder. Biol Psychiatry 57:1263–1272PubMedCrossRefGoogle Scholar
  53. 53.
    Seidman LJ, Valera EM, Makris N, Monuteaux MC, Boriel DL, Kelkar K, Kennedy DN, Caviness VS, Bush G, Aleardi M, Faraone SV, Biederman J (2006) Dorsolateral prefrontal and anterior cingulate cortex volumetric abnormalities in adults with attention-deficit/hyperactivity disorder identified by magnetic resonance imaging. Biol Psychiatry 60:1071–1080PubMedCrossRefGoogle Scholar
  54. 54.
    Shafritz KM, Marchione KE, Gore JC, Shaywitz SE, Shaywitz BA (2004) The effects of methylphenidate on neural systems of attention in attention deficit hyperactivity disorder. Am J Psychiatry 161:1990–1997PubMedCrossRefGoogle Scholar
  55. 55.
    Spencer TJ, Biederman J, Wilens TE, Faraone SV (2002) Overview and neurobiology of attention-deficit/hyperactivity disorder. J Clin Psychiatry 63(Suppl 12):3–9PubMedGoogle Scholar
  56. 56.
    Spreen O, Strauss E (1991) A compendium of neuropsychological tests. Oxford University Press, New YorkGoogle Scholar
  57. 57.
    Sturm W, Willmes K (1983) LPS-K—Eine Kurzform des Leistungsprüfsystems für hirngeschädigte Patienten mit Instruktionen für die psychometrische Einzelfalldiagnostik (LPS-K—a short form of the Leistungspruefsystem for brain-damaged patients with instructions for psychometric single case diagnosis). Diagnostica 29:346–358Google Scholar
  58. 58.
    Valera EM, Faraone SV, Murray KE, Seidman LJ (2007) Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder. Biol Psychiatry 61:1361–1369PubMedCrossRefGoogle Scholar
  59. 59.
    Ward MF, Wender PH, Reimherr FW (1993) The wender Utah rating scale: an aid in the retrospective diagnosis of childhood attention deficit hyperactivity disorder. Am J Psychiatry 150:885–890PubMedGoogle Scholar
  60. 60.
    Wittchen HU, Wunderlich U, Gruschwitz S, Zaudig M (1997) Strukturiertes Klinisches Interview für DSM-IV. Achse I: Psychische Störungen. Interviewheft und Beurteilungsheft. Eine deutschsprachige, erweiterte Bearbeitung der amerikanischen Originalversion des SCID I. Hogrefe, GöttingenGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Andreas Konrad
    • 1
    Email author
  • Thomas F. Dielentheis
    • 2
  • Dschamil El Masri
    • 1
  • Paulo R. Dellani
    • 3
  • Peter Stoeter
    • 4
  • Goran Vucurevic
    • 4
  • Georg Winterer
    • 5
  1. 1.Department of Psychiatry and PsychotherapyUniversity Medical CentreMainzGermany
  2. 2.The Rhineland Regional Council (LVR), Clinic LangenfeldLangenfeldGermany
  3. 3.Department of NeurologyUniversity Medical CentreMainzGermany
  4. 4.Institute of NeuroradiologyUniversity Medical CentreMainzGermany
  5. 5.Institute for GeneticsUniversity of CologneCologneGermany

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