Neurobiology of ADHD.

Attention-deficit hyperactivity disorder (ADHD) is a prevalent and debilitating disorder diagnosed on the basis of persistent and developmentally-inappropriate levels of overactivity, inattention and impulsivity. The etiology and pathophysiology of ADHD is incompletely understood. There is evidence of a genetic basis for ADHD but it is likely to involve many genes of small individual effect. Differences in the dimensions of the frontal lobes, caudate nucleus, and cerebellar vermis have been demonstrated. Neuropsychological testing has revealed a number of well documented differences between children with and without ADHD. These occur in two main domains: executive function and motivation although neither of these is specific to ADHD. In view of the recent advances in the neurobiology of reinforcement, we concentrate in this review on altered reinforcement mechanisms. Among the motivational differences, many pieces of evidence indicate that an altered response to reinforcement may play a central role in the symptoms of ADHD. In particular, sensitivity to delay of reinforcement appears to be a reliable finding. We review neurobiological mechanisms of reinforcement and discuss how these may be altered in ADHD, with particular focus on the neurotransmitter dopamine and its actions at the cellular and systems level. We describe how dopamine cell firing activity is normally associated with reinforcing events, and transfers to earlier time-points in the behavioural sequence as reinforcement becomes more predictable. We discuss how a failure of this transfer may give rise to many symptoms of ADHD, and propose that methylphenidate might act to compensate for the proposed dopamine transfer deficit.