Neural correlates (ERP/fMRI) of voluntary selection in adult ADHD patients

  • Susanne Karch
  • Tobias Thalmeier
  • Jürgen Lutz
  • Anja Cerovecki
  • Markus Opgen-Rhein
  • Bettina Hock
  • Gregor Leicht
  • Kristina Hennig-Fast
  • Thomas Meindl
  • Michael Riedel
  • Christoph Mulert
  • Oliver Pogarell
Original Paper


Deficits in executive functions, e.g. voluntary selection, are considered central to the attention-deficit/hyperactivity disorder (ADHD). The aim of this simultaneous EEG/fMRI study was to examine associated neural correlates in ADHD patients. Patients with ADHD and healthy subjects performed an adapted go/nogo task including a voluntary selection condition allowing participants to freely decide, whether to press the response button. Electrophysiologically, response inhibition and voluntary selection led to fronto-central responses. The fMRI data revealed increased medial/lateral frontal and parietal activity during the voluntary selection task. Frontal brain responses were reduced in ADHD patients compared to controls during free responses, whereas parietal brain functions seemed to be unaffected. These results may indicate that selection processes are related to dysfunctions, predominantly in frontal brain regions in ADHD patients.


Voluntary selection ADHD EEG–fMRI 



This study is part of the MD thesis of Tobias Thalmeier at the Faculty of Medicine, Ludwig-Maximilians-University, Munich. We thank Mije Hartmann who assisted with the proof-reading of the manuscript. All authors reported no biomedical financial interest or potential conflict of interest. This study was supported by the Faculty of Medicine, University of Munich (Förderprogramm für Forschung und Lehre; FöFoLe-572).


  1. 1.
    Aron AR, Poldrack RA (2005) The cognitive neuroscience of response inhibition: relevance for genetic research in attention-deficit/hyperactivity disorder. Biol Psychiatry 57:1285–1292CrossRefPubMedGoogle Scholar
  2. 2.
    Arrington CM, Logan GD (2004) The cost of a voluntary task switch. Psychol Sci 15:610–615CrossRefPubMedGoogle Scholar
  3. 3.
    Barkley RA (1997) Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. Psychol Bull 121:65–94CrossRefPubMedGoogle Scholar
  4. 4.
    Bartholow BD, Pearson MA, Dickter CL, Sher KJ, Fabiani M, Gratton G (2005) Strategic control and medial frontal negativity: beyond errors and response conflict. Psychophysiology 42:33–42CrossRefPubMedGoogle Scholar
  5. 5.
    Bekker EM, Kenemans JL, Verbaten MN (2004) Electrophysiological correlates of attention, inhibition, sensitivity and bias in a continuous performance task. Clin Neurophysiol 115:2001–2013CrossRefPubMedGoogle Scholar
  6. 6.
    Bekker EM, Overtoom CC, Kooij JJ, Buitelaar JK, Verbaten MN, Kenemans JL (2005) Disentangling deficits in adults with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 62:1129–1136CrossRefPubMedGoogle Scholar
  7. 7.
    Botvinick MM, Braver TS, Barch DM, Carter CS, Cohen JD (2001) Conflict monitoring and cognitive control. Psychol Rev 108:624–652CrossRefPubMedGoogle Scholar
  8. 8.
    Brass M, Derrfuss J, Forstmann B, von Cramon DY (2005) The role of the inferior frontal junction area in cognitive control. Trends Cogn Sci 9:314–316CrossRefPubMedGoogle Scholar
  9. 9.
    Braver TS, Barch DM, Kelley WM, Buckner RL, Cohen NJ, Miezin FM et al (2001) Direct comparison of prefrontal cortex regions engaged by working and long-term memory tasks. Neuroimage 14:48–59CrossRefPubMedGoogle Scholar
  10. 10.
    Bruin KJ, Wijers AA, van Staveren AS (2001) Response priming in a go/nogo task: do we have to explain the go/nogo N2 effect in terms of response activation instead of inhibition? Clin Neurophysiol 112:1660–1671CrossRefPubMedGoogle Scholar
  11. 11.
    Bush G, Frazier JA, Rauch SL, Seidman LJ, Whalen PJ, Jenike MA et al (1999) Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the Counting Stroop. Biol Psychiatry 45:1542–1552CrossRefPubMedGoogle Scholar
  12. 12.
    Bush G, Valera EM, Seidman LJ (2005) Functional neuroimaging of attention-deficit/hyperactivity disorder: a review and suggested future directions. Biol Psychiatry 57:1273–1284CrossRefPubMedGoogle Scholar
  13. 13.
    Cabeza R, Nyberg L (2000) Imaging cognition II: an empirical review of 275 PET and fMRI studies. J Cogn Neurosci 12:1–47CrossRefPubMedGoogle Scholar
  14. 14.
    Casey BJ, Castellanos FX, Giedd JN, Marsh WL, Hamburger SD, Schubert AB et al (1997) Implication of right frontostriatal circuitry in response inhibition and attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 36:374–383CrossRefPubMedGoogle Scholar
  15. 15.
    Casey BJ, Thomas KM, Welsh TF, Badgaiyan RD, Eccard CH, Jennings JR et al (2000) Dissociation of response conflict, attentional selection, and expectancy with functional magnetic resonance imaging. Proc Natl Acad Sci USA 97:8728–8733CrossRefPubMedGoogle Scholar
  16. 16.
    Connors CK, Erhardt D, Sparrow E (1999) Conners’ Adult ADHD Rating Scales (CAARS). Multi-Health Systems, North Tonawanda, New YorkGoogle Scholar
  17. 17.
    Debener S, Ullsperger M, Siegel M, Engel AK (2006) Single-trial EEG-fMRI reveals the dynamics of cognitive function. Trends Cogn Sci 10:558–563CrossRefPubMedGoogle Scholar
  18. 18.
    Debener S, Ullsperger M, Siegel M, Fiehler K, von Cramon DY, Engel AK (2005) Trial-by-trial coupling of concurrent electroencephalogram and functional magnetic resonance imaging identifies the dynamics of performance monitoring. J Neurosci 25:11730–11737CrossRefPubMedGoogle Scholar
  19. 19.
    Deiber MP, Passingham RE, Colebatch JG, Friston KJ, Nixon PD, Frackowiak RS (1991) Cortical areas and the selection of movement: a study with positron emission tomography. Exp Brain Res 84:393–402CrossRefPubMedGoogle Scholar
  20. 20.
    Dickstein SG, Bannon K, Castellanos FX, Milham MP (2006) The neural correlates of attention deficit hyperactivity disorder: an ALE meta-analysis. J Child Psychol Psychiatry 47:1051–1062CrossRefPubMedGoogle Scholar
  21. 21.
    Donchin E, Coles MGH (1988) Is the P300 component a manifestation of context updating? Behav Brain Sci 11:355–372Google Scholar
  22. 22.
    Donkers FC, van Boxtel GJ (2004) The N2 in go/no-go tasks reflects conflict monitoring not response inhibition. Brain Cogn 56:165–176PubMedGoogle Scholar
  23. 23.
    Durston S, Thomas KM, Worden MS, Yang Y, Casey BJ (2002) The effect of preceding context on inhibition: an event-related fMRI study. Neuroimage 16:449–453CrossRefPubMedGoogle Scholar
  24. 24.
    Eichele T, Specht K, Moosmann M, Jongsma ML, Quiroga RQ, Nordby H et al (2005) Assessing the spatiotemporal evolution of neuronal activation with single-trial event-related potentials and functional MRI. Proc Natl Acad Sci USA 102:17798–17803CrossRefPubMedGoogle Scholar
  25. 25.
    Falkenstein M, Hoormann J, Hohnsbein J (1999) ERP components in Go/Nogo tasks and their relation to inhibition. Acta Psychol (Amst) 101:267–291CrossRefGoogle Scholar
  26. 26.
    Fallgatter AJ, Ehlis AC, Seifert J, Strik WK, Scheuerpflug P, Zillessen KE et al (2004) Altered response control and anterior cingulate function in attention-deficit/hyperactivity disorder boys. Clin Neurophysiol 115:973–981CrossRefPubMedGoogle Scholar
  27. 27.
    Fassbender C, Schweitzer JB (2006) Is there evidence for neural compensation in attention deficit hyperactivity disorder? A review of the functional neuroimaging literature. Clin Psychol Rev 26:445–465CrossRefPubMedGoogle Scholar
  28. 28.
    Forstmann BU, Brass M, Koch I, von Cramon DY (2006) Voluntary selection of task sets revealed by functional magnetic resonance imaging. J Cogn Neurosci 18:388–398CrossRefPubMedGoogle Scholar
  29. 29.
    Forstmann BU, Ridderinkhof KR, Kaiser J, Bledowski C (2007) At your own peril: an ERP study of voluntary task set selection processes in the medial frontal cortex. Cogn Affect Behav Neurosci 7:286–296CrossRefPubMedGoogle Scholar
  30. 30.
    Frith CD, Friston K, Liddle PF, Frackowiak RS (1991) Willed action and the prefrontal cortex in man: a study with PET. Proc Biol Sci 244:241–246CrossRefPubMedGoogle Scholar
  31. 31.
    Gajewski PD, Stoerig P, Falkenstein M (2008) ERP-correlates of response selection in a response conflict paradigm. Brain Res 1189:127–134CrossRefPubMedGoogle Scholar
  32. 32.
    Garavan H, Ross TJ, Murphy K, Roche RA, Stein EA (2002) Dissociable executive functions in the dynamic control of behavior: inhibition, error detection, and correction. Neuroimage 17:1820–1829CrossRefPubMedGoogle Scholar
  33. 33.
    Garon N, Moore C, Waschbusch DA (2006) Decision making in children with ADHD only, ADHD-anxious/depressed, and control children using a child version of the Iowa Gambling Task. J Atten Disord 9:607–619CrossRefPubMedGoogle Scholar
  34. 34.
    Geurts HM, Verte S, Oosterlaan J, Roeyers H, Sergeant JA (2004) How specific are executive functioning deficits in attention deficit hyperactivity disorder and autism? J Child Psychol Psychiatry 45:836–854CrossRefPubMedGoogle Scholar
  35. 35.
    Goldberg II, Harel M, Malach R (2006) When the brain loses its self: prefrontal inactivation during sensorimotor processing. Neuron 50:329–339CrossRefPubMedGoogle Scholar
  36. 36.
    Harvey PO, Fossati P, Pochon JB, Levy R, Lebastard G, Lehericy S et al (2005) Cognitive control and brain resources in major depression: an fMRI study using the n-back task. Neuroimage 26:860–869CrossRefPubMedGoogle Scholar
  37. 37.
    Hyder F, Phelps EA, Wiggins CJ, Labar KS, Blamire AM, Shulman RG (1997) “Willed action”: a functional MRI study of the human prefrontal cortex during a sensorimotor task. Proc Natl Acad Sci USA 94:6989–6994CrossRefPubMedGoogle Scholar
  38. 38.
    Iaboni F, Douglas VI, Baker AG (1995) Effects of reward and response costs on inhibition in ADHD children. J Abnorm Psychol 104:232–240CrossRefPubMedGoogle Scholar
  39. 39.
    Ille N, Berg P, Scherg M (2002) Artifact correction of the ongoing EEG using spatial filters based on artifact and brain signal topographies. J Clin Neurophysiol 19:113–124CrossRefPubMedGoogle Scholar
  40. 40.
    Jahanshahi M, Jenkins IH, Brown RG, Marsden CD, Passingham RE, Brooks DJ (1995) Self-initiated versus externally triggered movements. I. An investigation using measurement of regional cerebral blood flow with PET and movement-related potentials in normal and Parkinson’s disease subjects. Brain 118(Pt 4):913–933CrossRefPubMedGoogle Scholar
  41. 41.
    Jueptner M, Stephan KM, Frith CD, Brooks DJ, Frackowiak RS, Passingham RE (1997) Anatomy of motor learning. I. Frontal cortex and attention to action. J Neurophysiol 77:1313–1324PubMedGoogle Scholar
  42. 42.
    Kamarajan C, Porjesz B, Jones KA, Choi K, Chorlian DB, Padmanabhapillai A et al (2005) Alcoholism is a disinhibitory disorder: neurophysiological evidence from a Go/No-Go task. Biol Psychol 69:353–373CrossRefPubMedGoogle Scholar
  43. 43.
    Karch S, Jager L, Karamatskos E, Graz C, Stammel A, Flatz W et al (2008) Influence of trait anxiety on inhibitory control in alcohol-dependent patients: simultaneous acquisition of ERPs and BOLD responses. J Psychiatr Res 42:734–745CrossRefPubMedGoogle Scholar
  44. 44.
    Karch S, Mulert C, Thalmeier T, Lutz J, Leicht G, Meindl T et al (2009) The free choice whether or not to respond after stimulus presentation. Hum Brain Mapp 30:2971–2985CrossRefPubMedGoogle Scholar
  45. 45.
    Kessler RC, Adler L, Ames M, Barkley RA, Birnbaum H, Greenberg P et al (2005) The prevalence and effects of adult attention deficit/hyperactivity disorder on work performance in a nationally representative sample of workers. J Occup Environ Med 47:565–572CrossRefPubMedGoogle Scholar
  46. 46.
    Kessler RC, Adler LA, Barkley R, Biederman J, Conners CK, Faraone SV et al (2005) Patterns and predictors of attention-deficit/hyperactivity disorder persistence into adulthood: results from the national comorbidity survey replication. Biol Psychiatry 57:1442–1451CrossRefPubMedGoogle Scholar
  47. 47.
    Kim MS, Kim YY, Yoo SY, Kwon JS (2007) Electrophysiological correlates of behavioral response inhibition in patients with obsessive-compulsive disorder. Depress Anxiety 24:22–31CrossRefPubMedGoogle Scholar
  48. 48.
    Konrad K, Gauggel S, Manz A, Scholl M (2000) Lack of inhibition: a motivational deficit in children with attention deficit/hyperactivity disorder and children with traumatic brain injury. Child Neuropsychol 6:286–296PubMedGoogle Scholar
  49. 49.
    Kramer AF, Strayer DL (1988) Assessing the development of automatic processing: an application of dual-task and event-related brain potential methodologies. Biol Psychol 26:231–267CrossRefPubMedGoogle Scholar
  50. 50.
    Krause KH, Krause J, Trott GE (1998) Hyperkinetic syndrome (attention deficit-hyperactivity disorder) in adulthood. Nervenarzt 69:543–556CrossRefPubMedGoogle Scholar
  51. 51.
    Lau H, Rogers RD, Passingham RE (2006) Dissociating response selection and conflict in the medial frontal surface. Neuroimage 29:446–451CrossRefPubMedGoogle Scholar
  52. 52.
    Lau HC, Rogers RD, Ramnani N, Passingham RE (2004) Willed action and attention to the selection of action. Neuroimage 21:1407–1415CrossRefPubMedGoogle Scholar
  53. 53.
    Matsuda T, Matsuura M, Ohkubo T, Ohkubo H, Atsumi Y, Tamaki M et al (2002) Influence of arousal level for functional magnetic resonance imaging (fMRI) study: simultaneous recording of fMRI and electroencephalogram. Psychiatry Clin Neurosci 56:289–290CrossRefPubMedGoogle Scholar
  54. 54.
    Menon V, Crottaz-Herbette S (2005) Combined EEG and fMRI studies of human brain function. Int Rev Neurobiol 66:291–321CrossRefPubMedGoogle Scholar
  55. 55.
    Mulert C, Jager L, Schmitt R, Bussfeld P, Pogarell O, Moller HJ et al (2004) Integration of fMRI and simultaneous EEG: towards a comprehensive understanding of localization and time-course of brain activity in target detection. Neuroimage 22:83–94CrossRefPubMedGoogle Scholar
  56. 56.
    Mulert C, Seifert C, Leicht G, Kirsch V, Ertl M, Karch S et al (2008) Single-trial coupling of EEG and fMRI reveals the involvement of early anterior cingulate cortex activation in effortful decision making. Neuroimage 42:158–168CrossRefPubMedGoogle Scholar
  57. 57.
    Nachev P, Rees G, Parton A, Kennard C, Husain M (2005) Volition and conflict in human medial frontal cortex. Curr Biol 15:122–128CrossRefPubMedGoogle Scholar
  58. 58.
    Nieuwenhuis S, Yeung N, van den Wildenberg W, Ridderinkhof KR (2003) Electrophysiological correlates of anterior cingulate function in a go/no-go task: effects of response conflict and trial type frequency. Cogn Affect Behav Neurosci 3:17–26CrossRefPubMedGoogle Scholar
  59. 59.
    Nigg JT (2001) Is ADHD a disinhibitory disorder? Psychol Bull 127:571–598CrossRefPubMedGoogle Scholar
  60. 60.
    Oosterlaan J, Sergeant JA (1998) Response inhibition and response re-engagement in attention-deficit/hyperactivity disorder, disruptive, anxious and normal children. Behav Brain Res 94:33–43CrossRefPubMedGoogle Scholar
  61. 61.
    Passingham RE (1995) The frontal lobes and voluntary action. Oxford University Press, OxfordGoogle Scholar
  62. 62.
    Playford ED, Jenkins IH, Passingham RE, Nutt J, Frackowiak RS, Brooks DJ (1992) Impaired mesial frontal and putamen activation in Parkinson’s disease: a positron emission tomography study. Ann Neurol 32:151–161CrossRefPubMedGoogle Scholar
  63. 63.
    Polich J, Kok A (1995) Cognitive and biological determinants of P300: an integrative review. Biol Psychol 41:103–146CrossRefPubMedGoogle Scholar
  64. 64.
    Retz-Junginger P, Retz W, Blocher D, Weijers HG, Trott GE, Wender PH et al (2002) Wender Utah rating scale. The short-version for the assessment of the attention-deficit hyperactivity disorder in adults. Nervenarzt 73:830–838CrossRefPubMedGoogle Scholar
  65. 65.
    Ridderinkhof KR, Ullsperger M, Crone EA, Nieuwenhuis S (2004) The role of the medial frontal cortex in cognitive control. Science 306:443–447CrossRefPubMedGoogle Scholar
  66. 66.
    Ritter W, Simson R, Vaughan HG Jr (1983) Event-related potential correlates of two stages of information processing in physical and semantic discrimination tasks. Psychophysiology 20:168–179CrossRefPubMedGoogle Scholar
  67. 67.
    Ritter W, Simson R, Vaughan HG Jr, Macht M (1982) Manipulation of event-related potential manifestations of information processing stages. Science 218:909–911CrossRefPubMedGoogle Scholar
  68. 68.
    Rubia K, Smith AB, Brammer MJ, Taylor E (2003) Right inferior prefrontal cortex mediates response inhibition while mesial prefrontal cortex is responsible for error detection. Neuroimage 20:351–358CrossRefPubMedGoogle Scholar
  69. 69.
    Rushworth MF, Buckley MJ, Behrens TE, Walton ME, Bannerman DM (2007) Functional organization of the medial frontal cortex. Curr Opin Neurobiol 17:220–227CrossRefPubMedGoogle Scholar
  70. 70.
    Schachar R, Mota VL, Logan GD, Tannock R, Klim P (2000) Confirmation of an inhibitory control deficit in attention-deficit/hyperactivity disorder. J Abnorm Child Psychol 28:227–235CrossRefPubMedGoogle Scholar
  71. 71.
    Schulz KP, Fan J, Tang CY, Newcorn JH, Buchsbaum MS, Cheung AM et al (2004) Response inhibition in adolescents diagnosed with attention deficit hyperactivity disorder during childhood: an event-related FMRI study. Am J Psychiatry 161:1650–1657CrossRefPubMedGoogle Scholar
  72. 72.
    Sergeant JA, Geurts H, Huijbregts S, Scheres A, Oosterlaan J (2003) The top and the bottom of ADHD: a neuropsychological perspective. Neurosci Biobehav Rev 27:583–592CrossRefPubMedGoogle Scholar
  73. 73.
    Sergeant JA, Geurts H, Oosterlaan J (2002) How specific is a deficit of executive functioning for attention-deficit/hyperactivity disorder? Behav Brain Res 130:3–28CrossRefPubMedGoogle Scholar
  74. 74.
    Siniatchkin M, Boor R, Jacobs J, Wolff S, Jansen O, Stephani U et al (2006) Correction of ballistocardiogram artefacts from EEG acquired in the MRI scanner using spatial filters based on artefact and brain signal topographies. Neuroimage 31:S86Google Scholar
  75. 75.
    Sirigu A, Daprati E, Ciancia S, Giraux P, Nighoghossian N, Posada A et al (2004) Altered awareness of voluntary action after damage to the parietal cortex. Nat Neurosci 7:80–84CrossRefPubMedGoogle Scholar
  76. 76.
    Smith JL, Johnstone SJ, Barry RJ (2004) Inhibitory processing during the Go/NoGo task: an ERP analysis of children with attention-deficit/hyperactivity disorder. Clin Neurophysiol 115:1320–1331CrossRefPubMedGoogle Scholar
  77. 77.
    Sonuga-Barke EJ, Dalen L, Daley D, Remington B (2002) Are planning, working memory, and inhibition associated with individual differences in preschool ADHD symptoms? Dev Neuropsychol 21:255–272CrossRefPubMedGoogle Scholar
  78. 78.
    Tamm L, Menon V, Ringel J, Reiss AL (2004) Event-related FMRI evidence of frontotemporal involvement in aberrant response inhibition and task switching in attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 43:1430–1440CrossRefPubMedGoogle Scholar
  79. 79.
    Turken AU, Swick D (1999) Response selection in the human anterior cingulate cortex. Nat Neurosci 2:920–924CrossRefPubMedGoogle Scholar
  80. 80.
    Vaidya CJ, Austin G, Kirkorian G, Ridlehuber HW, Desmond JE, Glover GH et al (1998) Selective effects of methylphenidate in attention deficit hyperactivity disorder: a functional magnetic resonance study. Proc Natl Acad Sci USA 95:14494–14499CrossRefPubMedGoogle Scholar
  81. 81.
    Walton ME, Devlin JT, Rushworth MF (2004) Interactions between decision making and performance monitoring within prefrontal cortex. Nat Neurosci 7:1259–1265CrossRefPubMedGoogle Scholar
  82. 82.
    Watanabe J, Sugiura M, Sato K, Sato Y, Maeda Y, Matsue Y et al (2002) The human prefrontal and parietal association cortices are involved in NO-GO performances: an event-related fMRI study. Neuroimage 17:1207–1216CrossRefPubMedGoogle Scholar
  83. 83.
    Williams D, Stott CM, Goodyer IM, Sahakian BJ (2000) Specific language impairment with or without hyperactivity: neuropsychological evidence for frontostriatal dysfunction. Dev Med Child Neurol 42:368–375CrossRefPubMedGoogle Scholar
  84. 84.
    Zametkin AJ, Nordahl TE, Gross M, King AC, Semple WE, Rumsey J et al (1990) Cerebral glucose metabolism in adults with hyperactivity of childhood onset. N Engl J Med 323:1361–1366PubMedCrossRefGoogle Scholar
  85. 85.
    Zang YF, Jin Z, Weng XC, Zhang L, Zeng YW, Yang L et al (2005) Functional MRI in attention-deficit hyperactivity disorder: evidence for hypofrontality. Brain Dev 27:544–550CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Susanne Karch
    • 1
  • Tobias Thalmeier
    • 1
  • Jürgen Lutz
    • 2
  • Anja Cerovecki
    • 1
  • Markus Opgen-Rhein
    • 1
  • Bettina Hock
    • 1
  • Gregor Leicht
    • 1
  • Kristina Hennig-Fast
    • 1
  • Thomas Meindl
    • 2
  • Michael Riedel
    • 1
  • Christoph Mulert
    • 1
  • Oliver Pogarell
    • 1
  1. 1.Department of Psychiatry and PsychotherapyLudwig-Maximilians-University MunichMunichGermany
  2. 2.Institute of Clinical RadiologyLudwig-Maximilians-UniversityMunichGermany

Personalised recommendations