Stimulus-dependent dopamine release in attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is related to an attenuated and dysfunctional dopamine system. Normally, a high extracellular dopamine level yields a tonic dopaminergic input that down-regulates stimuli-evoked phasic dopamine responses through autoreceptors. Abnormally low tonic extracellular dopamine in ADHD up-regulates the autoreceptors so that stimuli-evoked phasic dopamine is boosted. The authors propose that these boosted phasic responses yield hypersensitivity to environmental stimuli in ADHD. Stimuli evoking moderate brain arousal lead to well-functioning performance, whereas either too little or too much stimuli attenuate cognitive performance. Strong, salient stimuli may easily disrupt attention, whereas an environment with impoverished stimuli causes low arousal, which is typically compensated for by hyperactivity. Stochastic resonance is the phenomenon that makes a moderate noise facilitate stimulus discrimination and cognitive performance. Computational modeling shows that more noise is required for stochastic resonance to occur in dopamine-deprived neural systems in ADHD. This prediction is supported by empirical data.