Dopamine Precursor Depletion in Healthy Volunteers Impairs Processing of Duration but Not Temporal Order

Chassignolle, Morgane; Jovanović, Ljubica; Schmidt-Mutter, Catherine; Behr, Guillaume; Giersch, Anne; Coull, Jennifer T.

doi:10.1162/jocn_a_01700

Cited by 11 publications

(12 citation statements)

References 85 publications

(130 reference statements)

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“…Although there is sufficient evidence for a D2 receptor-based dopaminergic modulation of duration estimates in the subsecond range [66, 67, 64, 68, 69], most studies have been performed in the seconds to minutes range [2, 65]. However, we emphasize that the basic mechanism of dopaminergic modulation is not necessarily restricted to the subsecond range.…”

Section: Discussionmentioning

confidence: 92%

“…Numerous studies report that decreasing dopaminergic activity, e.g., by dopaminergic antagonists, can slow down the internal clock leading to an underestimation of timing intervals, while increasing levels of DA, e.g., by dopaminergic agonists, speeds up the internal clock [12, 89, 95]. Although most of these studies have been conducted for intervals in the seconds to minutes range [12, 72], similar effects have also been found for shorter intervals, investigating, for example, dopaminergic drugs in healthy humans [18, 19, 20, 37] and mice [95] and dopamine-related conditions such as ADHD [4, 90, 101].…”

Section: Introductionmentioning

confidence: 99%

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Testing the state-dependent model of subsecond time perception against experimental evidence

Ravichandran-Schmidt

Haß

2022

Preprint

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Coordinated movements, speech and other actions are impossible without precise timing. Realistic computational models of interval timing in the mammalian brain are expected to provide key insights into the underlying mechanisms of timing. Existing computational models of time perception have only been partially replicating experimental observations, such as the linear increase of time, the dopaminergic modulation of this increase, and the scalar property, i.e., the linear increase of the standard deviation of temporal estimates. In this work, we incorporate the state-dependent computational model, which encodes time in the dynamic evolution of network states without the need for a specific network structure into a biologically plausible prefrontal cortex (PFC) model based on in vivo and in vitro recordings of rodents. Specifically, we stimulated 1000 neurons in the beginning and in the end of a range of different time intervals, extracted states of neurons and trained the readout layer based on these states using least squares to predict the respective inter stimulus interval. We show that the naturally occurring heterogeneity in cellular and synaptic parameters in the PFC is sufficient to encode time over several hundreds of milliseconds. The readout faithfully represents the duration between two stimuli applied to the superficial layers of the network, thus fulfilling the requirement of a linear encoding of time. A simulated activation of the D2 dopamine receptor leads to an overestimation and an inactivation to an underestimation of time, in line with experimental results. Furthermore, we show that the scalar property holds true for intervals of several hundred milliseconds, and provide a mechanistic explanation for the origin of the scalar property as well as its deviations. We conclude that this model can represent durations up to 750 ms in a biophysically plausible setting, compatible with experimental findings in this regime.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Testing the state-dependent model of subsecond time perception against experimental evidence

Ravichandran-Schmidt

Haß

2022

Preprint

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“…Pharmacological studies in animals 1 – 4 , as well as direct manipulation of dopamine signalling 5 , suggest that dopamine affects behaviour in various temporal tasks. In humans, the administration of dopaminergic antagonists impairs the discrimination of temporal intervals 6 – 8 , and biases performance in (re)production of recently presented temporal intervals 9 – 12 , although this relationship might be more intricate than in rodents 9 , 10 , 12 .…”

Section: Introductionmentioning

confidence: 99%

“…In the work presented here, we used the acute phenylalanine and tyrosine depletion method (APTD, 25 , 26 ) to decrease dopamine synthesis, which has previously been shown to decrease temporal estimation accuracy in both perceptual 6 and motor 9 , 12 timing tasks. We asked participants to reproduce the duration of the revolution of a disc that moved around a circular path at varying speeds, and contrasted performance in two temporal reproduction tasks.…”

Section: Introductionmentioning

confidence: 99%

Dopamine precursor depletion affects performance and confidence judgements when events are timed from an explicit, but not an implicit onset

Jovanovic,

Chassignolle,

Schmidt-Mutter

et al. 2023

Sci Rep

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Dopamine affects processing of temporal information, but most previous work has tested its role in prospective tasks, where participants know in advance when the event to be timed starts. However, we are often exposed to events whose onset we do not know in advance. We can evaluate their duration after they have elapsed, but mechanisms underlying this ability are still elusive. Here we contrasted effects of acute phenylalanine and tyrosine depletion (APTD) on both forms of timing in healthy volunteers, in a within-subject, placebo-controlled design. Participants were presented with a disc moving around a circular path and asked to reproduce the duration of one full revolution and to judge their confidence in performance. The onset of the revolution was either known in advance (explicit onset) or revealed only at the end of the trial (implicit onset). We found that APTD shortened reproduced durations in the explicit onset task but had no effect on temporal performance in the implicit onset task. This dissociation is corroborated by effects of APTD on confidence judgements in the explicit task only. Our findings suggest that dopamine has a specific role in prospective encoding of temporal intervals, rather than the processing of temporal information in general.

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“…Clinical symptoms are related to these temporal alterations (Foucher et al, 2007;Giersch et al, 2015;Martin et al, 2017Martin et al, , 2014. Unfortunately, these symptoms persist with medication, as hitherto dopamine does not appear involved (Chassignolle et al, 2021). Nonetheless, new leads for treatment may be found in video game studies.…”

Section: Introductionmentioning

confidence: 99%

Enhanced temporal resolution of vision in action video game players

Foerster¹,

Chidharom²,

Giersch³

2022

Preprint

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Video game play has been suggested to improve visual and attention processing. Nevertheless, while action video game play is highly dynamic, there is scarce research on how information is processed in time. This cross-sectional study investigates whether temporal discrimination at the millisecond level in vision varies across action video game players (VGPs) and non-action video game players (NVGPs). Participants discriminated synchronous from asynchronous onsets of two visual targets in virtual reality, while their EEG and oculomotor movements were monitored. Results show an increased sensitivity to short asynchronies (11, 33 and 66 ms) in VGPs, suggesting better temporal discrimination ability, compared with NVGPs. Pre-targets oculomotor freezing – the inhibition of small fixational saccades – influenced temporal discrimination, but did not differ between groups. However, EEG analysis indicates that the enhancement of temporal discrimination is partially explained by an increased neuronal excitability in parieto-occipital areas, as evidenced by the amplified decrease of alpha-band (8-14 Hz) power in VGPs during temporal discrimination as well as source reconstruction analysis. Overall, the study reveals an enhanced ability in action video game players to discriminate in time visual events in close temporal proximity combined with functional disinhibition of cortical neurons. Consequently, playing action video games is associated with an improved temporal resolution of vision.

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Dopamine Precursor Depletion in Healthy Volunteers Impairs Processing of Duration but Not Temporal Order

Cited by 11 publications

References 85 publications

Testing the state-dependent model of subsecond time perception against experimental evidence

Testing the state-dependent model of subsecond time perception against experimental evidence

Dopamine precursor depletion affects performance and confidence judgements when events are timed from an explicit, but not an implicit onset

Enhanced temporal resolution of vision in action video game players

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