Altered response control and anterior cingulate function in attention-deficit/hyperactivity disorder boys

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Abstract

Objective: To investigate mechanisms and structures underlying prefrontal response control and inhibition in boys suffering from attention-deficit/hyperactivity disorder (ADHD).

Method: Sixteen boys with ADHD and 19 healthy controls were investigated electrophysiologically during performance of a visual Go-Nogo task (Continuous Performance Test, CPT). An electrophysiological source localization method was employed to further analyze the data.

Results: The ADHD boys showed a significantly diminished central Nogo-P3, due to a lack of Nogo-related frontalization of the positive brain electrical field in this group. This two-dimensional effect was associated with a significantly reduced activation of the anterior cingulate cortex (ACC) in the ADHD boys in the Nogo condition of the CPT. Both groups did not significantly differ regarding the amplitude of the Nogo-N2.

Conclusions: The results indicate deficits in prefrontal response control in unmedicated ADHD boys that do not seem to be specifically inhibitory in nature. A supposed dysfunction of the ACC in ADHD was confirmed.

Introduction

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common childhood disabilities (Shaywitz et al., 1994) and is characterized by developmentally inappropriate symptoms of inattention, impulsivity and hyperactivity. It has been suggested that a core deficit in inhibitory control accounts for many deficits in executive function observed in ADHD that underlie most of the dysfunctional behaviors associated with this syndrome (Barkley, 1997). In accordance with this view, children suffering from ADHD very often exhibit deficits in response inhibition and perform poorly on tasks of inhibitory control such as the Stop-Signal Task or Go-Nogo paradigms (Bayliss and Roodenrys, 2000, Konrad et al., 2000, Nigg, 1999, Rubia et al., 2001, Schachar and Logan, 1990, Schachar et al., 2000). In addition to these behavioral signs of disturbed mechanisms of response inhibition, electrophysiological data have also been interpreted as reflecting deficits in inhibitory control in ADHD. ADHD children were, for example, found to exhibit decreased right inferior-frontal N200 amplitudes in a Stop-Signal Task (Pliszka et al., 2000), the N200 being interpreted as a neurophysiological correlate of response inhibition. Studies employing Go-Nogo tasks also partly reported decreased frontal N200 amplitudes in ADHD children, but mostly interpreted their findings in the light of a more general attentional deficit in ADHD children, not exclusively related to response inhibition. Yong-Liang et al. (2000), for example, observed a reduced N200 amplitude in ADHD children only when the Go-Nogo task was performed second, after a stimulus-response compatibility task. Overtoom et al. (1998) investigated ADHD children by means of a Continuous Performance Test (CPT) and found decreased N200 amplitudes only in a particular subgroup of ADHD children; for the group of ADHD children as a whole, the N200 component did not differentiate patients and control children. However, the ADHD children exhibited a reduced target P300, suggesting deficient attentional processes rather than specific disturbances in response inhibition. Brandeis et al. (2002) also employed the CPT to investigate children suffering from ADHD, and observed an impaired orientation to cues in these children. Furthermore, they reported an attenuation of several Nogo-related components (frontal N2, central P3, right posterior P300) linked to frontal functions.

Functional imaging studies have provided further evidence for ADHD-related disturbances in processes and structures underlying inhibitory control. Functional magnetic resonance imaging (fMRI) during a Go-Nogo paradigm (Vaidya et al., 1998) showed atypical activation of frontal-striatal structures in ADHD children that was associated with deficits in inhibitory control. Also employing fMRI, Rubia et al. (1999) found a reduced activation of right-prefrontal areas in ADHD adolescents in a Stop-Signal Task, and Rubia et al. (2001) reported diminished right-prefrontal activation during higher level inhibition and delay management in addition to behavioral disturbances of response inhibition in ADHD adolescents. In contrast to these findings, Vaidya et al. (1998) observed enhanced frontal lobe activity bilaterally in ADHD children performing a Go-Nogo task, which was attributed to an increased inhibitory effort in these children.

For the present study, the CPT (Rosvold et al., 1956) was used to further investigate neurophysiological mechanisms of inhibitory control in children suffering from ADHD. Electrophysiological studies employing Go-Nogo tasks such as the CPT usually report some characteristic differences in the event-related potentials (ERPs) following Go and Nogo stimuli. Firstly, in the Nogo ERPs a negative deflection with a frontocentral maximum occurs around 200–400 ms after stimulus onset (Nogo-N2). This N2 has been suggested to reflect the inhibitory process associated with Nogo trials, although some contradictory findings have questioned this inhibition concept of the N2 (Falkenstein et al., 1995). The other characteristic difference between Go and Nogo ERPs concerns the topography of the P300 which is located more anterior (maximum typically at Cz) in Nogo as compared to Go (parietal maximum, typically at Pz) trials (e.g. Bokura et al., 2001). This effect has also been suggested to be associated with processes of response inhibition. A useful parameter quantifying this frontalization of the positive brain electrical field is the ‘Nogo-anteriorization’ (NGA; Fallgatter et al., 1997, Fallgatter et al., 2000, Fallgatter and Strik, 1999) that has been shown to be a highly reliable neurophysiological correlate of prefrontal/cognitive response control (Fallgatter et al., 2001, Fallgatter et al., 2002). An electrophysiological source localization method (LORETA) (Pascual-Marqui et al., 1994) related the Nogo-evoked P300 activity to an activation of certain prefrontal structures, particularly the anterior cingulate cortex (ACC) (Fallgatter et al., 2002, Strik et al., 1998).

The aim of the present study was to examine neurophysiological correlates of prefrontal response control in a group of children suffering from ADHD. The two major questions were if the electrophysiological data (N2, P3) would indicate a specific deficit in response inhibition in ADHD children and if these children would differ from healthy controls regarding the localization and/or strength of electrical activity underlying the scalp potentials.

Section snippets

Subjects

A total of 18 boys suffering from uncomplicated attention deficit and hyperactivity disorder without any comorbidity (F90.0 according to ICD10) and a control sample of 19 healthy boys were investigated electrophysiologically after written informed consent was obtained. Due to an insufficient number of artifact-free EEG-epochs, two of the ADHD children had to be excluded from further analyses. The remaining 16 children (mean age±SD: 9.55±1.52 years; range: 7.17–11.67 years) were all patients at

Reaction times and error rates

The group of ADHD children exhibited significantly longer reaction times to target (Go) stimuli than the control group (493±75 vs. 429±64 ms; t33=2.711, P<0.05). Omission errors consisted of Go-stimuli subjects did not respond to, whereas commission errors occurred whenever subjects responded to a non-target stimulus (Nogo). Mann-Whitney U tests revealed that the ADHD group made significantly more omission errors than the control group (U=53.0, P<0.001), whereas both groups did not differ

Response control versus response inhibition

The major finding of the present study is a diminished Nogo-related anteriorization of the P300 topography with reduced Cz amplitudes in ADHD boys that goes along with a significantly diminished Nogo-related activation of the anterior cingulate cortex (ACC) in these children as compared to a healthy control group.

The highly significant increase of the P300 amplitude at frontal and central electrode positions (Fz, Cz) in CPT Nogo as compared to Go trials within the group of healthy children

Acknowledgements

The authors would like to thank B. Neuhauser, Ch. Schwarz and I. Gröbner for skillful and dedicated technical support.

References (41)

  • C Mulert et al.

    Reduced event-related current density in the anterior cingulate cortex in schizophrenia

    Neuroimage

    (2001)
  • R.C Oldfield

    The assessment and analysis of handedness: the Edinburgh inventory

    Neuropsychologia

    (1971)
  • C.C Overtoom et al.

    Associations between event-related potentials and measures of attention and inhibition in the Continuous Performance Task in children with ADHD and normal controls

    J Am Acad Child Adolesc Psychiatry

    (1998)
  • R.D Pascual-Marqui et al.

    Low resolution electromagnetic tomography, a new method for localizing electrical activity in the brain

    Int J Psychophysiol

    (1994)
  • R.D Pascual-Marqui et al.

    Low resolution brain electromagnetic tomography (LORETA) functional imaging in acute, neuroleptic-naive, first-episode, productive schizophrenia

    Psychiatry Res

    (1999)
  • S.R Pliszka et al.

    Inhibitory control in children with attention-deficit/hyperactivity disorder: event-related potentials identify the processing component and timing of an impaired right-frontal response-inhibition mechanism

    Biol Psychiatry

    (2000)
  • W.K Strik et al.

    Three dimensional tomography of event-related potentials during response inhibition: evidence for phasic frontal lobe activation

    Electroenceph clin Neurophysiol

    (1998)
  • K.E Zillessen et al.

    Changes of the brain electrical fields during the continuous performance test in attention-deficit hyperactivity disorder-boys depending on methylphenidate medication

    Clin Neurophysiol

    (2001)
  • R.A Barkley

    ADHD and the nature of self-control

    (1997)
  • D.M Bayliss et al.

    Executive processing and attention deficit hyperactivity disorder: an application of the supervisory attentional system

    Dev Neuropsychol

    (2000)
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