Saturday, December 1, 2007

Selective Effects of Ritalin in ADHD

Vaidya, C.J., Austin, G., Kirkorian, G., Ridlehuber, H.W., Desmond, J.E., Glover, G.H., & Gabrieli, J.D.E. (November 1998). Selective effects of methylphenidate in attention deficit hyperactivity disorder: A functional magnetic resonance study, Neurobiology, 95, 14494-14499.

ADHD is the most common developmental disorder of childhood and has been associated with such adverse life outcomes as lower educational and occupational achievement, as well as increased risk for various disorders in adulthood. Evidence suggests that ADHD is characterized by dysfunction in transmission of dopamine to the frontal lobes and striatal (basal ganglia) structures of the brain since ADHD symptoms typically respond favorably to stimulant medications (e.g. methylphenidate) that release and inhibit reuptake of dopamine in these regions. However, prior to this study, there was no direct evidence to indicate differences in dopaminergic modulation between ADHD and normal children. Therefore, the purpose of this study was to see: (a) how performance in response inhibition tasks differs between ADHD children and normal children, (b) how administration of methylphenidate improved performance in response inhibition tasks in ADHD children in comparison with normal children, (c) how baseline frontal-striatal function differ in ADHD and control children, and (d) how methylphenidate modulates frontal-striatal function differently in ADHD and control children. Since inhibition of motor responses is known to depend on the integrity of both frontal and striatal structures, functional magnetic resonance imaging (fMRI) was used to image the frontal lobes, as well as the head of the caudate nucleus and the anterior portion of the putamen during response inhibition tasks to assess the four aforementioned points.

Each subject in the study was presented with various computer-generated stimuli and instructed to respond with a button-press on a hand-held joystick. In one block, they were told to respond to all stimuli presented. In another block, they were told to respond to all stimuli except for one (inhibition). Their behavioral performance was measured by the percentage of errors committed during the task. At the same time, activation of certain brain regions was gathered during the trials via fMRI. With the different independent variables and levels, the overall design looks something like the following table for the "stimulus-controlled" task (for brevity, I will neglect to mention the "response-controlled" task and results):

The results can be condensed as follows: (a) The ADHD group made more errors than the control group on the response inhibition task. (b) Both the ADHD and the control groups showed significant improvements on the task with the administration of MPH. (c) Baseline striatal activation was shown to be lower in ADHD subjects than in the control group. (d) Administration of MPH increased striatal activation in ADHD subjects but decreased striatal activation in control subjects.

The results support the hypothesis that there are indeed differences between ADHD children and normal children, both in performance on response inhibition tasks and in their striatal activation in the absence of stimulant medication. And further, when administered stimulant medication, ADHD children showed different functional reactions to the medication in the striatum than their control group counterparts. These are important findings, especially given the neural specificity of the results.

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