title: The Role of Dopamine in Temporal Uncertainty.
abstract: The temporal preparation of motor responses to external events (temporal preparation) relies on internal representations of the accumulated elapsed time (temporal representations) before an event occurs and on estimates about its most likely time of occurrence (temporal expectations). The precision (inverse of uncertainty) of temporal preparation, however, is limited by two sources of uncertainty. One is intrinsic to the nervous system and scales with the length of elapsed time such that temporal representations are least precise for longest time durations. The other is external and arises from temporal variability of events in the outside world. The precision of temporal expectations thus decreases if events become more variable in time. It has long been recognized that the processing of time durations within the range of hundreds of milliseconds (interval timing) strongly depends on dopaminergic (DA) transmission. The role of DA for the precision of temporal preparation in humans, however, remains unclear. This study therefore directly assesses the role of DA in the precision of temporal preparation of motor responses in healthy humans. In a placebo-controlled double-blind design using a selective D2-receptor antagonist (sulpiride) and D1/D2 receptor antagonist (haloperidol), participants performed a variable foreperiod reaching task, under different conditions of internal and external temporal uncertainty. DA blockade produced a striking impairment in the ability of extracting temporal expectations across trials and on the precision of temporal representations within a trial. Large Weber fractions for interval timing, estimated by fitting subjective hazard functions, confirmed that this effect was driven by an increased uncertainty in the way participants were experiencing time. This provides novel evidence that DA regulates the precision with which we process time when preparing for an action.
authors.affiliation: University College London.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Tomassini
authors.affiliation: University College London.
authors.forename: Diane
authors.initials: D
authors.lastname: Ruge
authors.affiliation: University College London.|University of Birmingham.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Galea
authors.affiliation: University College London.
authors.forename: William
authors.initials: W
authors.lastname: Penny
authors.affiliation: University College London.
authors.forename: Sven
authors.initials: S
authors.lastname: Bestmann
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004311:Double-Blind Method; D005246:Feedback / Q000187:drug effects; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D033182:Intention; D008297:Male; D008960:Models, Psychological; D009068:Movement / Q000187:drug effects / Q000502:physiology*; D010775:Photic Stimulation; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013469:Sulpiride / Q000494:pharmacology; D013997:Time Factors; D013998:Time Perception / Q000187:drug effects / Q000502:physiology*; D035501:Uncertainty; D055815:Young Adult
chemical_list: D018492:Dopamine Antagonists; D013469:Sulpiride; D006220:Haloperidol; D004298:Dopamine