A positron emission tomography study of methylphenidate in adults with ADHD: Alterations in resting blood flow and predicting treatment response

A hallmark symptom of attention-deficit hyperactivity disorder (ADHD) is an excess of motoric behavior or hyperactivity. Methylphenidate (MPH) is known to reduce hyperactivity in individuals with ADHD. Yet little is known about how it alters neural activity and how this relates to its clinical effects. The goal of this study is to examine MPH-induced changes during resting brain metabolism, and to examine how these changes correlate with measures of behavioral response to the drug. Measures of regional cerebral blood flow (rCBF) using positron emission tomography (PET) were acquired at rest for ten adult subjects with ADHD during both an unmedicated state and after a 3-week period of chronic dosing with a clinically optimal dose of MPH. Compared with the on-MPH condition, the off-MPH condition was associated with relative increases in rCBF bilaterally in the precentral gyri, left caudate nucleus, and right claustrum. The on-MPH condition was associated with relative increases in rCBF in the cerebellar vermis. A correlational analysis measured the relation between rCBF in the off-medication condition to change in ADHD ratings between the off- and on-MPH condition to identify brain regions associated with treatment response. The degree of change in the ratings was negatively correlated with rCBF increases in the midbrain, cerebellar vermis, and the precentral and middle frontal gyri in the off-MPH condition, The majority of these brain regions are involved in the planning and execution of motor behavior. These data suggest that MPH modulates brain regions associated with motor function to achieve a reduction in ADHD symptoms.