Drug therapies for attentional disorders alter the signal-to-noise ratio in the superior colliculus

Despite high levels of use, the mechanism of action of effective pharmacotherapies in attention deficit hyperactivity disorder (ADHD) is unknown. It has recently been hypothesized that one site of therapeutic action is the midbrain superior colliculus, a structure traditionally associated with visual processing, but also strongly implicated in distractibility, a core symptom of ADHD. We used male juvenile Wistar rats to examine the effects of therapeutically relevant doses of methylphenidate and d-amphetamine on collicular activity in vitro. Here we report a novel shared mechanism of the two drugs whereby they enhance the signal-to-noise ratio in the superior colliculus. The effects on the signal-to-noise ratio were mediated by serotonin (5-HT) via a pre-synaptic mechanism. This modulatory action would bias the system towards salient events and lead to an overall decrease in distractibility.