Abstract
The prolonged reaction times seen in Parkinson's disease (PD) have been linked to a dopaminergic-dependent deficit in using prior information to prepare responses, but also have been explained by an altered temporal processing. However, an underlying cognitive mechanism linking dopamine, temporal processing and response preparation remains elusive.To address this, we studied PD patients, with or without medication, and age-matched healthy individuals using a variable foreperiod task requiring speeded responses to a visual stimulus occurring at variable onset-times, with block-wise changes in the temporal predictability of visual stimuli.Compared with controls, unmedicated patients showed impaired use of prior information to prepare their responses, as reflected by slower reaction times, regardless of the level of temporal predictability. Crucially, after dopamine administration normal performance was restored, with faster responses for high temporal predictability.Using Bayesian hierarchical drift-diffusion modelling, we estimated the parameters that determine temporal preparation. In this theoretical framework, impaired temporal preparation under dopaminergic depletion was driven by inflexibly high decision boundaries (i.e. participants were always extremely cautious). This indexes high levels of uncertainty about temporal predictions irrespectively of stimulus onset predictability.Our results suggest that dopaminergic depletion in PD affects the uncertainty of predictions about the timing of future events (temporal predictions), which are crucial for the anticipatory preparation of responses. Dopamine, which is affected in PD, controls the ability to predict the timing of future events.
Highlights
Our ‘beliefs’ about the external world allow for generating predictions about the possible timing of future events
Our results suggest that dopaminergic depletion in Parkinson's disease (PD) affects the uncertainty of predictions about the timing of future events, which are crucial for the anticipatory preparation of responses
Temporal predictions carry a degree of uncertainty that scales with the length and variability of the delay preceding an event
Summary
Our ‘beliefs’ about the external world allow for generating predictions about the possible timing of future events (temporal predictions, Nobre et al, 2007). Temporal predictions carry a degree of uncertainty (temporal uncertainty) that scales with the length and variability (predictability) of the delay preceding an event (foreperiod; Gibbon et al, 1997). When the length and/or variability of foreperiods increases, temporal predictions become more uncertain, leading to slower RTs (Klemmer, 1956). When long fixed foreperiods precede reward delivery (Bromberg-Martin et al, 2010; Nomoto et al, 2010), or when the foreperiods are variable (variable foreperiod), dopamine midbrain cells respond in relation to the temporal predictability of the reward delivery time (Pasquereau and Turner, 2015). Suppression of dopaminergic neurotransmission impairs temporal judgments (Soares et al, 2016) and the ability to form temporal predictions (Tomassini et al, 2015), possibly through a dopamine-dependent increase in uncertainty about the underlying temporal structure of events
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