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Aim: Attention-deficit/hyperactivity disorder (ADHD) is a relatively common central nervous system disorder in school-age children, which may involve a specific disorder in cognition and/or information processing. Event-related potentials (ERP) are commonly used as physiological measures of cognitive function as they are easily measured and non-invasive. Thus, in the present study, we examined the effects of osmotic-release methylphenidate (MPH) (Concerta), a common treatment for childhood attention-deficit/hyperactivity disorder (ADHD), in ADHD children as measured by ERP.
Methods: Ten ADHD children participated after giving consent. Based on the guidelines for evoked potential measurement, mismatch negativity (MMN) and P300 were obtained by auditory odd-ball tasks. We measured both MMN and P300 in the drug-naive condition and after intake of osmotic-release MPH.
Results: The MMN amplitudes after intake of osmotic-release MPH were significantly greater than those in the drug-naive situation at Pz and C4. The P300 amplitudes after intake of osmotic-release MPH were significantly greater than those in the drug-naive situation at Cz and Pz.
Conclusion: MMN and P300 are sensitive tools for measuring the pharmacological effects of osmotic-release MPH in ADHD children.
ATTENTION-DEFICIT/HYPERACTIVITY DISORDER (ADHD) is a central nervous system (CNS) disorder estimated to occur in 3–7% of school-age children,1 and is considered to involve a specific disorder in cognition and/or information processing. Event-related potentials (ERP) are commonly used as physiological measures of cognitive function as they are easily measured and non-invasive. For instance, ERP have been used to examine cognitive disturbance in children with developmental disorder, and an early negative ERP has been shown to be strongly-related to attention deficit.
The mismatch negativity (MMN), which functions in a distinctive stimulus discrimination process that utilizes sensory memory of prior stimuli, is considered an important mechanism for rapid detection of changes in the outer world, except those concerning consciousness.2 As such, MMN reflects an automatic cerebral discrimination process, not under-attentive control. We previously reported that the amplitudes of both P300 and MMN were smaller in ADHD patients than in healthy subjects.3
With respect to the impulsivity observed in ADHD patients, we previously reported that the Hyperactivity-Impulsivity subscale score of the ADHD Rating Scale-IV-Japanese version (ADHD RS-IV-J) (Home Version)4 had a significantly strong positive correlation with the latency of MMN, and had a significant strong negative correlation with the amplitude of MMN, in predominantly hyperactive-impulsive type ADHD subjects.5 In other words, the more severe the impulsivity of ADHD subjects, the longer the MMN latency and the lower the MNN amplitude. Thus, ADHD children may have difficulty in referring to previous stimuli, causing increased sensitivity to and augmented anxiety about stimuli, which may account for the exhibited impulsivity.
Stimulating medications are commonly used for treatment of ADHD symptoms. Methylphenidate (MPH), for instance, has been used in ADHD children since 1937.6 In Japan, osmotic-release MPH (Concerta) was recently accepted as a treatment medication for ADHD children. Several studies have demonstrated a reduced P300 in ADHD children, which was normalized following MPH medication.7–9 However, to the best of our knowledge the effects of osmotic-release MPH on MMN in ADHD children have not been described. Thus, in the present study we examined the effects of MPH on MMN and P300, and on ameliorating cognitive function, especially attention function, in ADHD children.
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In the present study, although there seemed to be visual differences in most electrodes for both MMN and P300 following osmotic-release MPH treatment in ADHD children, significant increases in MMN or P300 amplitudes after osmotic-release MPH treatment were only observed in Pz and C4 or Cz and Pz. These discrepancies may relate to the small sample size and large standard deviation in the present study.
P300 is a potential generated in the final stage of sensory and cognitive processing. The improvement in P300 following osmotic-release MPH treatment in ADHD children is consistent with previous studies.7–9 As disturbance of the P300 component has been previously suggested as an indicator of impaired cognition,11,12 these data suggest that cognitive function in ADHD children was ameliorated by osmotic-release MPH treatment. However, P300 is likely to be affected by the cognitive factors present prior to P300 generation, thus limiting the significance of investigations employing solely P300 recordings. As such, we also evaluated MMN in ADHD children in the present study, the pre-P300 potentials that reflect information processing itself.3,5
In the present study, we reported that MMN amplitudes were increased after osmotic-release MPH treatment in ADHD children, suggesting that the automatic cerebral discrimination process might be ameliorated by osmotic-release MPH treatment, which in turn may have reduced the impulsiveness and hyperactivity in ADHD children.
With respect to the laterality of cerebral dysfunction in ADHD, it was proposed that ADHD children exhibit dysfunction in a right-sided frontal-striatal system.13 This comprehensive morphometric analysis was consistent with the hypothesized dysfunction of right-sided prefrontal-striatal systems in ADHD children.14 Furthermore, in an event-related functional magnetic resonance imaging (fMRI) study, ADHD children exhibited less right-sided activation in the anterior cingulate gyrus during alerting (one of the attentional networks) relative to controls.15
In the present study, there was no difference between the left (C3) and right (C4) P300 amplitudes or MMN amplitudes either before or after treatment, and there was no difference between the left (C3) and right (C4) P300 and MMN latencies either before or after treatment. However, the MMN amplitude after osmotic-release MPH treatment was significantly greater than that in the drug-naive situation at C4. Thus, we suggest that the right hemisphere may be competent following MPH treatment with respect to MMN.
There were two limitations to our study. First, the sample size was small. However, we examined 10 ADHD children who had no history of developmental disorder treatment, and our data showed significant changes. Second, we had no placebo-control subjects. Future studies with large samples and placebo-control subjects as measured by ERP are required to determine whether cognitive function in ADHD children was ameliorated by osmotic-release MPH treatment. In conclusion, the results of the present study suggest that both MMN and P300 are sensitive tools for measuring the pharmacological effects of osmotic-release MPH in ADHD children.