Dataset Information

Arbitration between model-free and model-based control is not affected by transient changes in tonic serotonin levels.

ABSTRACT:

Background

Serotonin has been suggested to modulate decision-making by influencing the arbitration between model-based and model-free control. Disruptions in these control mechanisms are involved in mental disorders such as drug dependence or obsessive-compulsive disorder. While previous reports indicate that lower brain serotonin levels reduce model-based control, it remains unknown whether increases in serotonergic availability might thus increase model-based control. Moreover, the mediating neural mechanisms have not been studied yet.

Aim

The first aim of this study was to investigate whether increased/decreased tonic serotonin levels affect the arbitration between model-free and model-based control. Second, we aimed to identify the underlying neural processes.

Methods

We employed a sequential two-stage Markov decision-task and measured brain responses during functional magnetic resonance imaging in 98 participants in a randomized, double-blind cross-over within-subject design. To investigate the influence of serotonin on the balance between model-free and model-based control, we used a tryptophan intervention with three intervention levels (loading, balanced, depletion). We hypothesized that model-based behaviour would increase with higher serotonin levels.

Results

We found evidence that neither model-free nor model-based control were affected by changes in tonic serotonin levels. Furthermore, our tryptophan intervention did not elicit relevant changes in Blood-Oxygenation-Level Dependent activity.

SUBMITTER: Gilger MD

PROVIDER: S-EPMC10863371 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

Arbitration between model-free and model-based control is not affected by transient changes in tonic serotonin levels.

Gilger Maximilian D MD Hellrung Lydia L Neukam Philipp T PT Kroemer Nils B NB Nebe Stephan S Pooseh Shakoor S Deza-Lougovski Yacila I YI Smolka Michael N MN

Journal of psychopharmacology (Oxford, England) 20231227 2

<h4>Background</h4>Serotonin has been suggested to modulate decision-making by influencing the arbitration between model-based and model-free control. Disruptions in these control mechanisms are involved in mental disorders such as drug dependence or obsessive-compulsive disorder. While previous reports indicate that lower brain serotonin levels reduce model-based control, it remains unknown whether increases in serotonergic availability might thus increase model-based control. Moreover, the med ...[more]

PMID: 38151862

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Project description:Serotonin (5-hydroxytryptamine, 5-HT), is a phylogenetically ancient molecule best characterized as a neurotransmitter that modulates multiple aspects of mood and social cognition. The roles that 5-HT plays in normal and abnormal behavior are not fully understood but have been posited to be due to its common function as a 'defense signal'. However, 5-HT levels also systemically impact cell physiology, modulating cell division, migration, apoptosis, mitochondrial biogenesis, cellular metabolism and differentiation. Whether these diverse cellular effects of 5-HT also share a common basis is unclear. C. elegans provides an ideal system to interrogate the systemic effects of 5-HT, since lacking a blood-brain barrier, 5-HT synthesized and released by neurons permeates the organism to modulate neuronal as well as non-neuronal cells throughout the body. Here we used RNA-Seq to characterize the systemic changes in gene expression that occur in C. elegans upon altering 5-HT levels, and compared the transcriptomes to published datasets. We find that an acute increase in 5-HT is accompanied by a global decrease in gene expression levels, upregulation of genes involved in stress pathways, changes that significantly correlate with the published transcriptomes of animals that have activated defense and immune responses, and an increase in levels of phosphorylated eukaryotic initiation factor, eIF2α. In 5-HT deficient animals lacking tryptophan hydroxylase (tph-1 (mg280) II) there is a net increase in gene expression, with an overrepresentation of genes related to development and chromatin. Surprisingly, the transcriptomes of animals with acute increases in 5-HT levels, and 5-HT deficiency do not overlap with transcriptomes of mutants with whom they share striking physiological resemblance. These studies are the first to catalog systemic transcriptome changes that occur upon alterations in 5-HT levels. They further show that in C. elegans changes in gene expression upon altering 5-HT levels, and changes in physiology, are not directly correlated.

Project description:A large literature has accumulated suggesting that human and animal decision making is driven by at least two systems, and that important functions of these systems can be captured by reinforcement learning algorithms. The "model-free" system caches and uses stimulus-value or stimulus-response associations, and the "model-based" system implements more flexible planning using a model of the world. However, it is not clear how the two systems interact during deliberation and how a single decision emerges from this process, especially when they disagree. Most previous work has assumed that while the systems operate in parallel, they do so independently, and they combine linearly to influence decisions. Using an integrated reinforcement learning/drift-diffusion model, we tested the hypothesis that the two systems interact in a non-linear fashion similar to other situations with cognitive conflict. We differentiated two forms of conflict: action conflict, a binary state representing whether the systems disagreed on the best action, and value conflict, a continuous measure of the extent to which the two systems disagreed on the difference in value between the available options. We found that decisions with greater value conflict were characterized by reduced model-based control and increased caution both with and without action conflict. Action conflict itself (the binary state) acted in the opposite direction, although its effects were less prominent. We also found that between-system conflict was highly correlated with within-system conflict, and although it is less clear a priori why the latter might influence the strength of each system above its standard linear contribution, we could not rule it out. Our work highlights the importance of non-linear conflict effects, and provides new constraints for more detailed process models of decision making. It also presents new avenues to explore with relation to disorders of compulsivity, where an imbalance between systems has been implicated.

Dataset Information

Arbitration between model-free and model-based control is not affected by transient changes in tonic serotonin levels.

Background

Aim

Methods

Results

Publications

Arbitration between model-free and model-based control is not affected by transient changes in tonic serotonin levels.

Similar Datasets

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