Elsevier

Biological Psychiatry

Volume 56, Issue 8, 15 October 2004, Pages 597-606
Biological Psychiatry

Original articles
Effect of methylphenidate on executive functioning in adults with attention-deficit/hyperactivity disorder: Normalization of behavior but not related brain activity

https://doi.org/10.1016/j.biopsych.2004.07.011Get rights and content

Background

We examined the effect of prolonged methylphenidate (MPH) treatment on the functional neuroanatomy of executive functioning in adult men with attention-deficit/hyperactivity disorder (ADHD).

Methods

Positron emission tomography with [15O] water measured alterations of regional cerebral blood flow (rCBF) during the Paced Auditory Serial Addition Task and a control task in 10 ADHD and 11 normal control men. Attention-deficit/hyperactivity disorder men were imaged unmedicated and after a clinically optimal dose of MPH for 3 weeks.

Results

Methylphenidate improved ADHD task performance, reduced rCBF in the prefrontal cortex (PFC), and increased rCBF in the right thalamus and precentral gyrus. Comparisons between the ADHD and normal control groups showed that normal control participants exhibited greater anterior cingulate cortex and temporal gyrus rCBF than ADHD participants under both conditions. Executive functioning was associated with greater subcortical (basal ganglia and cerebellar vermis) activation in the ADHD than normal control group under both conditions.

Conclusions

Methylphenidate does not normalize task-related activity in ADHD. Task-related rCBF decreases in the PFC may be due to improved filtering out of task-irrelevant stimuli by way of MPH-mediated dopamine release in the PFC.

Section snippets

Participants

The initial subject sample consisted of 13 men diagnosed with ADHD, combined type (American Psychiatric Association 1994), and a group of 11 healthy normal control (NC) subjects matched for age, gender, and general intelligence (Table 1). Two of the ADHD men in the unmedicated condition did not participate in the medicated condition, and brain positron emission tomography (PET) data from one of the ADHD participants in the off-medication condition was incomplete. Therefore, the final ADHD

MPH effects on ADHD symptoms and PASAT performance

The mean daily dose of MPH was 19 mg (SD = 9.07) administered over a mean of 2.9 (SD = .74) divided doses per day. Methylphenidate pharmacotherapy was statistically effective in reducing ADHD symptoms as measured by the CGI and self and other’s ratings on the Adult ADHD DSM-IV Rating Scale (Table 2). Methylphenidate improved PASAT performance accuracy of 82% (SD = 12.90) at baseline to 89% (SD = 6.15) at end point (t = 2.73, df = 9, p = .02). The NC group performed significantly better on the

Discussion

Similar to Mehta et al (2000), we found that MPH administration reduced EF-related activity in the PFC. We speculate that reductions in rCBF in the PFC are due to the release of dopamine by MPH in the PFC that, in turn, act on dopamine D1 and D2 receptors. Increases in dopamine have been shown to cause reductions in the firing activity of PFC neurons (Isacson et al 2004; Parfitt et al 1990; Zhou and Hablitz 1999). Dopamine, acting through D1 receptors, appears to inhibit local excitatory

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