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Patterns of Brain Activity Linked to Positive Medication Response
A recent issue of the journal Biological Psychiatry contains a brief but very interesting report that relates patterns of brain activity in children with ADHD to a positive response to medication. This study is interesting for at least 2 reasons. First, the finding that only children with ADHD who show a particular change in brain activity in response to medication show behavioral improvement supports a current theory that ADHD is associated with underactivity in the prefrontal cortex. Second, the findings to be discussed below also provide support for the theory and practice that underlies the use of neurofeedback treatment for ADHD.
Before describing the study, some brief background information will be useful to review. First, current theories of ADHD, such as the recent theory proposed by Dr. Russell Barkley, suggest that the symptoms of ADHD reflect a pattern of underactivity in the prefrontal cortex. It is this region of the brain that is believed to be primarily responsible for what Barkley and others refer to as "behavioral inhibition" - i.e. the ability to inhibit or refrain from one's immediate response tendencies so that situations can be thought through and various options considered. In Barkley's theory, this core deficit in behavioral inhibition leads to a variety of other difficulties and eventually to the observable symptoms of ADHD.
There have been several recent studies in which EEG measures in individuals with and without ADHD have been compared and found to differ. (An EEG is a procedure for measuring the pattern of activity in different brain regions.) Studies using this procedure have found that children with ADHD exhibit an excess of slow wave activity (these types of brain waves are referred to as theta or alpha depending on their exact frequency) and a reduced amount of beta (these are higher frequency brain waves that are associated with attention and concentration). The basic idea is that children with ADHD demonstrate a pattern of underactivity in the prefrontal cortical areas, and that this is the basis within the central nervous system for many of the symptoms they display. Some support for this hypothesis was provided in a study reviewed in the April issue of ADHD RESEARCH UPDATE, in which measures of prefrontal cortical activity was found to do a very accurate job of differentiating individuals with ADHD from those without the diagnosis.
Studies such as these that report an association between particular patterns of brain activity and ADHD symptoms are an initial step in determining whether such EEG patterns play a causal role in a child's - or adult's - symptoms of ADHD. Merely demonstrating that these things are related, however, is not sufficient to establish causality. Instead, to get closer to making any causal conclusion about patterns of brain activity and ADHD symptoms, one would want to try and change these underlying EEG patterns, and then observe where there is any corresponding change in ADHD symptoms.
This is essentially what the authors of this interesting preliminary investigation attempted to do (Loo, S.K. et.al.; (1999). EEG correlates of methylphenidate response among children with ADHD: Preliminary findings. Biological Psychiatry, 45, 1657- 1660). Participants in this study were 10 children (8 boys and 2 girls) between the ages of 8 and 13 who had a confirmed diagnosis of ADHD. Children in the study were brought to the lab on 2 separate days that were about 1 week apart. On each day, EEG recordings were taken two separate times. The first time was a baseline reading to obtain a measure of the child's typical EEG activity. The second time was about 1.5 hours after taking either a 10 mg. tablet of methylphenidate or a placebo.
There was one other important step in this study. Right after the second EEG recording, children were given the Conners Continuous Performance Test (CPT), a computerized measure of sustained attention and impulsivity. In this test, the child sits in front of a computer terminal and is instructed to press the space bar each time any letter except X is presented on the screen. A variety of measures are computed from this test including reaction time, errors of omission (i.e. failing to press the space bar when letters besides X are displayed; such omissions are associated with failing to pay attention), and errors of commission (i.e. pressing the space bar when an X is displayed; such errors of responding when one has been instructed not to is associated with impulsivity).
Prior research has documented that children with ADHD perform differently from children without ADHD on the Conners CPT, and this measure is often used to assist in the diagnostic process. In addition, a child's CPT performance has been shown to improve significantly in response to stimulant medication treatment. Thus, by comparing the CPT results that each child obtained after taking the placebo pill with the results obtained after taking the actual medication, children could be classified as "responders" or "non-responders" to the medication (i.e. those classified as responders had significantly better CPT results after medication than after placebo while the CPT results for non-responders did not show any significant change.) Then, by comparing the EEG changes after medication for the responders and non-responders, the authors could examine what specific changes in brain activity were associated with a positive response to medication.
Results
When response vs. no response to medication was determined as described above, 7 of the 10 children were found to have a positive medication response. The crucial question, then, is how EEG changes following medication in the responders compared to EEG changes in the non-responders. The prediction would be that medication responders would show a decrease in slow wave activity (i.e. alpha and theta) because these wave patterns are associated with daydreaming and lack of concentration and an increase in beta activity which is associated with better attention. For the non-responders, no such changes should have been evident.
In general, this is exactly what was found. Responders showed small but consistent decreases in alpha and theta activity and increases in beta activity. Non-responders, in contrast, showed the exact opposite pattern. As the authors note "...medication appears to increase cortical arousal and increase high frequency activity (i.e. beta) associated with concentration and attention among children who are positive medication responders."
The authors also examined the correlation between changes in CPT performance between the medication and placebo condition and changes in beta activity during these conditions. This correlation was strongly positive which means that children who showed the most improvement on the CPT were those who showed the greatest increase in beta activity. This suggests - but does not prove - that increased beta activity is what caused the better CPT performance.
Summary And Implications
Because of the small sample size, the results of this study certainly needed to be considered preliminary, and replication with a larger sample would be an important extension of this work. With this caution in mind, however, this is potentially a very important study.
This study demonstrated that children who responded positively to stimulant medication as assessed by their CPT performance were those whose EEG results indicated increased beta and reduced alpha and theta activity following medication. Thus, the children who improved showed increased cortical activity after medication. This supports current views that ADHD reflects lower levels of cortical activity (some have referred to this as a "sluggish brain"), and that increasing this activity is associated with improvement in ADHD symptoms.
The results of this study also have potentially important implications for the use of neurofeedback as a treatment for ADHD. This is a treatment approach whose efficacy is still not considered firmly established by most ADHD experts, but which has yielded promising results in a number of studies. In neurofeedback treatment, children with ADHD are specifically taught how to decrease slow wave activity (i.e. alpha and theta) and to increase higher frequency beta activity. Several studies have demonstrated that a majority of children with ADHD can be taught to produce these changes. In addition, unlike such changes which result from medication and last only a matter of hours, neurofeedback-induced changes are reported to persist over time. The results of the current study appear supportive of neurofeedback treatment because they show that EEG changes associated with a positive medication response are the same types of changes that are targeted by neurofeedback.
This is certainly not "proof" that neurofeedback treatment works, but it does suggest that the premise underlying such treatment - i.e. train children to decrease slow wave brain activity and increase higher frequency activity - is a plausible account of what successful treatment may involve.
Note: This article originally appeared in Attention Research Update, an online newsletter written by Dr. David Rabiner, a Duke University psychologist and former member of CHADD's Professional Advisory Board. You can learn more about Attention Research Update and sign up for a free subscription at www.helpforadd.com.