Effects of prepulses and d-amphetamine on performance and event-related potential measures an an auditory discrimination task

Rationale: Prepulse inhibition (PPI) of the startle reflex is a measure of sensorimotor gating, that is the processing of the startle stimulus (S2) is inhibited by the interfering processing of a closely preceding prepulse (S 1). It has been demonstrated that PPI is disrupted in a variety of mental d isorders and that several neurotransmitter systems, including dopamine, par ticipate in the modulation of sensorimotor gating. Previous studies have al so shown that a task-relevant S1 enhances PPI in healthy subjects but not i n schizophrenic patients. These findings indicate an influence of attention al processes on sensorimotor gating and an impairment of this modulation in schizophrenia. Objective: Assuming a dopamine-mediated suppression of S1 p rocessing as a mechanism of resource management and selective attention, wh ich might be impaired in certain mental disorders, the present study invest igated the effects of the indirect dopaminergic agonist d-amphetamine on pr epulse-altered S2 discrimination and event related potentials (ERPs). Metho ds: Twelve healthy volunteers were tested in a double-blind, placebo-contro lled experimental design. Here, S2 is the target in a difficult Go/NoGo aud itory discrimination task. Results: Confirming our previous results, S2 pro cessing is "accentuated" by a weak acoustic prepulse in healthy subjects, t hus leading to a lower rate of errors of omission but also to more false al arms (i.e. a liberal response bias). This performance change correlated wit h a prepulse-induced increase in the amplitude of the P3 ERP towards non-ta rgets ("prepulse-induced non-target positivity"; PINTP). In addition, the r esults of the present study show that under prepulse conditions amphetamine disrupts "S2 accentuation" associated with a dose-related reduction of the P2 component of the S1 response and a plasma level related reduction of PI NTP. Conclusions: These data suggest an involuntary attentional shift towar ds S1 processing with increasing dopamine-release similar to that observed in patients with schizophrenia or OCD. It is concluded that sensory gating alters selective attention via dopaminergic modulation.