Elsevier

Clinical Neurophysiology

Volume 118, Issue 12, December 2007, Pages 2700-2708
Clinical Neurophysiology

Effects of stimulant medications on the EEG of girls with Attention-Deficit/Hyperactivity Disorder

https://doi.org/10.1016/j.clinph.2007.08.020Get rights and content

Abstract

Objective

Stimulant medications are the most commonly used treatments for Attention-Deficit/Hyperactivity Disorder (AD/HD) in North America and Australia, although it is still not entirely known how these medications work. This study investigated the effects of stimulant medications on the EEG of girls with AD/HD.

Methods

An initial EEG was recorded during an eyes-closed resting condition. Data from 19 electrode sites were Fourier transformed to provide absolute and relative power estimates for the delta, theta, alpha and beta bands. The data were then averaged into 9 regions and an analysis of both global and regional differences was performed. Subjects were placed on a six-month trial of a stimulant and a second EEG was recorded at the end of the trial.

Results

The unmedicated girls had significantly greater total power, absolute delta and theta, more relative theta especially in the frontal regions, and reduced frontal relative delta and beta activity compared with controls. Medication resulted in normalisation of theta power, but after medication, increased relative beta was also apparent in the AD/HD group.

Conclusions

These results indicate that stimulant medications result in a normalisation of slow wave activity in the EEG. In line with published research on the effects of arousal on the EEG, these results suggest that stimulant medications may have their therapeutic effect by improving the EEG substrate of processing deficits in these children. However, this requires further testing during active processing tasks.

Significance

This is the first study to investigate the effect of stimulant medications on the EEG of girls with AD/HD.

Introduction

Attention-Deficit/Hyperactivity Disorder (AD/HD) is one of the most common psychiatric conditions of childhood, affecting between 4% and 6% of school-age children (Lindgren et al., 1990, Pelham et al., 1992, APA, 1994). AD/HD can be a pervasive problem, with symptoms persisting into adulthood in between 40% and 70% of individuals (Bellak and Black, 1992). The disorder interferes with many areas of normal development and functioning in a child’s life, and predisposes the child to a greater degree of psychiatric and social pathology in later life (Wender, 1994).

A fundamental problem within the large body of AD/HD literature is that the vast majority of studies of AD/HD are conducted on boys with the disorder, with comparatively fewer studies on girls with AD/HD being undertaken. This is primarily due to the greater incidence of AD/HD in boys than girls, with clinical samples typically finding boys outnumbering girls by 4–1 (APA, 1994, De Quiros et al., 1994). However, this is problematic as girls with AD/HD present with different symptoms to boys, and the literature developed on boys is not always directly transferable to girls with the disorder. Compared with boys, girls are more likely to be inattentive without being excessively hyperactive or impulsive (Staller and Faraone, 2006), and hyperactivity in females is more likely to manifest as hypertalkativeness or emotional reactivity than excessive motor activity (Quinn, 2005). There are also differences in the profiles of comorbidities, with girls more likely to have comorbid internalizing disorders, and boys more likely to have comorbid externalizing disorders (Romano et al., 2005). AD/HD in girls is also more likely to lead to substance abuse disorders and sexual acting out in adolescence (Quinn, 2005). For these reasons it is important that research is undertaken specifically on girls with this disorder.

In North America and Australia, clinical guidelines recommend an initial trial of medication for the treatment of AD/HD before other interventions are explored (Swanson et al., 1998). In controlled trials (Wilens and Biederman, 1992), and clinical reports (Swanson et al., 1993), nearly 80% of children with AD/HD have demonstrated clinically significant improvements in the core symptoms of the disorder with treatment using stimulant medications.

EEG studies of children with and without AD/HD have typically found that AD/HD children have increased theta activity, which is often maximal in the frontal regions (Satterfield et al., 1972, Janzen et al., 1995, Chabot and Serfontein, 1996, Lazzaro et al., 1998, Clarke et al., 1998, Clarke et al., 2001a, Clarke et al., 2001c, Barry et al., 2003), increased posterior delta (Matousek et al., 1984, Clarke et al., 1998, Clarke et al., 2001a, Clarke et al., 2001c) and decreased alpha and beta activity (Dykman et al., 1982, Callaway et al., 1983, Barry et al., 2003), also most apparent in the posterior regions (Clarke et al., 1998, Clarke et al., 2001a, Clarke et al., 2001c, Lazzaro et al., 1998, Barry et al., 2003). However, the majority of these research have been conducted on males or mixed-sex samples, with only a few studies being conducted on females.

Clarke et al. (2001a) investigated sex differences in the EEG of children with both the Combined (AD/HDcom) and Predominantly Inattentive (AD/HDin) types of AD/HD. The total AD/HD group (including both males and females) had greater total power, greater absolute delta and theta, more relative theta, less relative alpha and beta, and higher theta/alpha and theta/beta ratios than the control group. Within the AD/HD sample, sex differences were found in total power, absolute alpha and beta, and relative delta and alpha. In all measures except total power, boys had more abnormal EEGs than girls, although the EEGs of the girls were not normal. In that study the analysis did not specifically examine differences between girls with or without AD/HD. In a follow-up study Clarke et al. (2003b) examined the EEG of 100 girls with AD/HD. Subjects had greater total power, more relative theta, and less relative delta, alpha and beta than control girls. Results also indicated that there was less variability within the sample than has been found in boys, with 96% of subjects having an EEG profile believed to represent cortical hypoarousal.

A few studies have investigated changes in the EEG due to stimulant medications, with the majority of studies, though not all, finding that the stimulants result in a normalisation of the EEG. Both Swartwood et al., 1998, Lubar et al., 1999 failed to identify any global changes in the EEG due to medication. Chabot et al. (1999) found that 56.9% of children with AD/HD showed a normalisation of the EEG after the administration of a stimulant, while 33.8% remained unchanged and 9.3% showed an increase in EEG abnormality. In a preliminary report, Loo et al. (1999) found that after administration of Methylphenidate good responders had decreased theta and alpha, and increased beta activity in the frontal regions, while poor responders showed the opposite EEG changes. Clarke et al., 2002a, Clarke et al., 2003a found that stimulant medications resulted in a normalisation of the EEG, with a reduction in theta activity and an increase in beta activity. These results were interpreted as indicating that stimulants acted at a cortical level, by increasing arousal, although complete normalisation was not found in the entire sample. Penberthy et al. (2006) found a normalisation of the Consistency Index with the administration of Methylphenidate in six boys with AD/HD. None of these studies have specifically examined the EEG effects of stimulants in girls with AD/HD.

Hence the aim of this study was to investigate the effects of stimulant medications on the EEG of girls with AD/HD.

Section snippets

Subjects

Eighteen girls with a diagnosis of AD/HD combined type and two with AD/HD predominantly inattentive type, according to DSM-IV criteria (APA, 1994), and 20 control girls, participated in this study. In the ADHD group, 9 children were treated with Methylphenidate and 11 with Dexamphetamine, with both the girls with an inattentive diagnosis being treated with Dexamphetamine. In both the groups, the children were between the ages of 7 and 12 years. Subjects had a full-scale WISC-III IQ score of 85

AD/HDoff versus control subjects

Globally, the AD/HDoff group had significantly greater total power (F = 4.40, p < .05), absolute delta (F = 4.40, p < .05) and theta (F = 5.86, p < .05), and more relative theta (F = 4.68, p < .05) than the control group (Fig. 1, Fig. 2). The difference between groups was greater in the frontal regions than in the posterior regions for relative delta (F = 5.68, p < .05), theta (F = 7.45, p < .01) and beta (F = 9.70, p < .01). For relative delta and beta, the AD/HDoff group had less power than the control group, whereas

Discussion

Past research on the EEG of children with AD/HD has found that these children have increased theta activity, which is often maximal in the frontal regions (Satterfield et al., 1972, Janzen et al., 1995, Chabot and Serfontein, 1996, Lazzaro et al., 1998, Clarke et al., 1998, Clarke et al., 2001a, Clarke et al., 2001c), increased posterior delta (Matousek et al., 1984, Clarke et al., 1998, Clarke et al., 2001a, Clarke et al., 2001c) and decreased alpha and beta activity (Dykman et al., 1982,

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