Publications | Maaike M. H. van Swieten

2024

Incident Use of Hydroxychloroquine for the Treatment of Rheumatoid Arthritis and Systemic Lupus Erythematosus During the COVID-19 Pandemic

Núria Mercadé-Besora, Yuchen Guo, Mike Du, Xintong Li, and 25 more authors

Arthritis Care & Research, 2024

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Objective: We studied whether the use of hydroxychloroquine (HCQ) for COVID-19 resulted in supply shortages for patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Methods: We used US claims data (IQVIA PHARMETRICS® Plus for Academics [PHARMETRICS]) and hospital electronic records from Spain (Institut Municipal d’Assistència Sanitària Information System [IMASIS]) to estimate monthly rates of HCQ use between January 2019 and March 2022, in the general population and in patients with RA and SLE. Methotrexate (MTX) use was estimated as a control. Results: More than 13.5 million individuals (13,311,811 PHARMETRICS, 207,646 IMASIS) were included in the general population cohort. RA and SLE cohorts enrolled 135,259 and 39,295 patients, respectively, in PHARMETRICS. Incidence of MTX and HCQ were stable before March 2020. On March 2020, the incidence of HCQ increased by 9- and 67-fold in PHARMETRICS and IMASIS, respectively, and decreased in May 2020. Usage rates of HCQ went back to prepandemic trends in Spain but remained high in the United States, mimicking waves of COVID-19. No significant changes in HCQ use were noted among patients with RA and SLE. MTX use rates decreased during HCQ approval period for COVID-19 treatment. Conclusion: Use of HCQ increased dramatically in the general population in both Spain and the United States during March and April 2020. Whereas Spain returned to prepandemic rates after the first wave, use of HCQ remained high and followed waves of COVID-19 in the United States. However, we found no evidence of general shortages in the use of HCQ for both RA and SLE in the United States.
@article{mercade-besora2024, author = {Mercadé-Besora, Núria and Guo, Yuchen and Du, Mike and Li, Xintong and Ramírez-Anguita, Juan Manuel and Moreno, Alberto and Valente, António and Villalobos, Felipe and Cheng, Iek Leng and Carrasco-Ribelles, Lucía A. and van Swieten, Maaike M. H. and Merkelbach, Manon and Magoya, Mary and Lasalvia, Paolo and Pericàs-Pulido, Pau and Berg, Paul and Bosco-Lévy, Pauline and Lillini, Roberto and Ribeiro, Rogerio and Bagga, Trinamjot Kaur and Ramella, Vittoria and Khalid, Sara and Mayer, Miguel Angel and Leis, Angela and Jödicke, Annika M. and Burn, Edward and Prieto-Alhambra, Daniel and Català, Martí and Prats-Uribe, Albert}, journal = {Arthritis Care & Research}, title = {Incident Use of Hydroxychloroquine for the Treatment of Rheumatoid Arthritis and Systemic Lupus Erythematosus During the COVID-19 Pandemic}, volume = {76}, issue = {8}, year = {2024}, pages = {1173-1178}, doi = {10.1002/acr.25331}, url = {https://doi.org/10.1002/acr.25331}, keywords = {OMOP-CDM, rheumatoid arthritis, COVID-19, hydroxychloroquine, systemic lupus erythematosus }, }

Editorial: Navigating the landscape of FAIR data sharing and reuse: repositories, standards, and resources

M.M.H. Swieten, and C. Haselgrove

Frontiers in Neuroinformatics, 2024

@article{vanSwieten2024,
  author = {van Swieten, M.M.H. and Haselgrove, C.},
  title = {Editorial: Navigating the landscape of FAIR data sharing and reuse: repositories, standards, and resources},
  journal = {Frontiers in Neuroinformatics},
  volume = {18},
  year = {2024},
  doi = {10.3389/fninf.2024.1387758},
  url = {https://doi.org/10.3389/fninf.2024.1387758},
  keywords = {FAIR, data sharing, data reuse, reproducibility},
}

Spatially integrated cortico-subcortical tracing data for analyses of rodent brain topographical organization

Martin Øvsthus, Maaike M. H. Swieten, Maja A. Puchades, Chiara Tocco, and 3 more authors

Nature Scientific Data, 2024

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The cerebral cortex extends axonal projections to several subcortical brain regions, including the striatum, thalamus, superior colliculus, and pontine nuclei. Experimental tract-tracing studies have shown that these subcortical projections are topographically organized, reflecting the spatial organization of sensory surfaces and body parts. Several public collections of mouse- and rat- brain tract-tracing data are available, with the Allen mouse brain connectivity atlas being most prominent. There, a large body of image data can be inspected, but it is difficult to combine data from different experiments and compare spatial distribution patterns. To enable co-visualization and comparison of topographical organization in mouse brain cortico-subcortical projections across experiments, we represent axonal labelling data as point data in a common 3D brain atlas space. We here present a collection of point-cloud data representing spatial distribution of corticostriatal, corticothalamic, corticotectal, and corticopontine projections in mice and exemplify how these spatially integrated point data can be used as references for experimental investigations of topographic organization in transgenic mice, and for cross-species comparison with corticopontine projections in rats.
@article{Ovsthus2024, author = {{\O}vsthus, Martin and van Swieten, Maaike M. H. and Puchades, Maja A. and Tocco, Chiara and Studer, Michèle and Bjaalie, Jan G. and Leergaard, Trygve B.}, title = {Spatially integrated cortico-subcortical tracing data for analyses of rodent brain topographical organization}, journal = {Nature Scientific Data}, issue = {1}, volume = {11}, year = {2024}, pages = {1214}, doi = {10.1038/s41597-024-04060-y}, url = {https://doi.org/10.1038/s41597-024-04060-y}, }
Muscarinic receptors mediate motivation via preparatory neural activity in humans

John P Grogan, Matthias Raemaekers, Maaike MH Van Swieten, Alexander L Green, and 2 more authors

Oct 2024

Abs DOI Bib HTML

Motivation depends on dopamine, but might be modulated by acetylcholine which influences dopamine release in the striatum, and amplifies motivation in animal studies. A corresponding effect in humans would be important clinically, since anticholinergic drugs are frequently used in Parkinson’s disease, a condition that can also disrupt motivation. Reward and dopamine make us more ready to respond, as indexed by reaction times (RT), and move faster, sometimes termed vigour. These effects may be controlled by preparatory processes that can be tracked using electroencephalography (EEG). We measured vigour in a placebo-controlled, double-blinded study of trihexyphenidyl (THP), a muscarinic antagonist, with an incentivised eye movement task and EEG. Participants responded faster and with greater vigour when incentives were high, but THP blunted these motivation effects, suggesting that muscarinic receptors facilitate invigoration by reward. Preparatory EEG build-up (contingent negative variation; CNV) was strengthened by high incentives and by muscarinic blockade, although THP reduced the incentive-effect. The amplitude of preparatory activity predicted both vigour and RT, although over distinct scalp regions; frontal activity predicted vigour, whereas a larger, earlier, central component predicted RT. The incentivisation of RT was partly mediated by the CNV, though vigour was not. Moreover, the CNV mediated the drug’s effect on dampening incentives, suggesting that muscarinic receptors underlie the motivational influence on this preparatory activity. Taken together, these findings show that a muscarinic blocker impairs motivated action in healthy people, and that medial frontal preparatory neural activity mediates this for RT.
@article{Grogan2024, title = {Muscarinic receptors mediate motivation via preparatory neural activity in humans}, url = {http://dx.doi.org/10.7554/eLife.98922.2}, doi = {10.7554/elife.98922.2}, publisher = {eLife Sciences Publications, Ltd}, author = {Grogan, John P and Raemaekers, Matthias and Van Swieten, Maaike MH and Green, Alexander L and Gillies, Martin J and Manohar, Sanjay G}, year = {2024}, month = oct, }

2023

Gambling on an empty stomach: Hunger modulates preferences for learned but not described risks

MMH Van Swieten, R Bogacz, and SG Manohar

Brain and Behavior, Oct 2023

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We assess risks differently when they are explicitly described, compared to when we learn directly from experience, suggesting dissociable decision-making systems. Our needs, such as hunger, could globally affect our risk preferences, but do they affect described and learned risks equally? On one hand, explicit decision-making is often considered flexible and context-sensitive, and might therefore be modulated by metabolic needs. On the other hand, implicit preferences learned through reinforcement might be more strongly coupled to biological drives. To answer this, we asked participants to choose between two options with different risks, to obtain monetary outcomes, in two separate tasks. In one task, the outcome probabilities were described numerically, whereas in a second task, they were learned. In agreement with previous studies, rewarding contexts induced risk-aversion when risks were explicitly described, but risk-seeking when they were learned through experience. Crucially, hunger attenuated these contextual biases, but only for learned risks. The results suggest that our metabolic state determines risk-taking biases when we lack explicit descriptions.
@article{vanSwieten2023, author = {Van Swieten, MMH and Bogacz, R and Manohar, SG}, journal = {Brain and Behavior}, title = {Gambling on an empty stomach: Hunger modulates preferences for learned but not described risks}, year = {2023}, volume = {13}, issue = {5}, pages = {e2978}, doi = {10.1002/brb3.2978}, url = {https://onlinelibrary.wiley.com/doi/full/10.1002/brb3.2978}, keywords = {Reinforcement Learning, Decision making, Computational modeling, Hunger, Risk taking}, }

2022

Model-based learning retrospectively updates model-free values

M Doody, MMH Van Swieten, and SG Manohar

Scientific Reports, Feb 2022

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Reinforcement learning (RL) is widely regarded as divisible into two distinct computational strategies. Model-free learning is a simple RL process in which a value is associated with actions, whereas model-based learning relies on the formation of internal models of the environment to maximise reward. Recently, theoretical and animal work has suggested that such models might be used to train model-free behaviour, reducing the burden of costly forward planning. Here we devised a way to probe this possibility in human behaviour. We adapted a two-stage decision task and found evidence that model-based processes at the time of learning can alter model-free valuation in healthy individuals. We asked people to rate subjective value of an irrelevant feature that was seen at the time a model-based decision would have been made. These irrelevant feature value ratings were updated by rewards, but in a way that accounted for whether the selected action retrospectively ought to have been taken. This model-based influence on model-free value ratings was best accounted for by a reward prediction error that was calculated relative to the decision path that would most likely have led to the reward. This effect occurred independently of attention and was not present when participants were not explicitly told about the structure of the environment. These findings suggest that current conceptions of model-based and model-free learning require updating in favour of a more integrated approach. Our task provides an empirical handle for further study of the dialogue between these two learning systems in the future.
@article{Doody2022, author = {Doody, M and Van Swieten, MMH and Manohar, SG}, journal = {Scientific Reports}, title = {Model-based learning retrospectively updates model-free values}, volume = {12}, year = {2022}, month = feb, issue = {1}, pages = {2358}, doi = {https://dx.doi.org/10.1038/s41598-022-05567-3}, url = {https://www.nature.com/articles/s41598-022-05567-3}, keywords = {Reinforcement Learning, Decision making, Computational modeling}, }
Point coordinate data showing spatial distribution of corticostriatal, corticothalamic, corticocollicular, and corticopontine projections in wild type mice (v1)

Martin Øvsthus, Maaike MH Van Swieten, Jan G Bjaalie, and Trygve Brauns Leergaard

Feb 2022

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The data set comprises three-dimensional point coordinate data representing the spatial distribution of subcortical projections from 35 widespread locations in the cerebral cortex to the striatum, thalamus, superior colliculus, and pontine nuclei in wild-type mice. The point data are derived from public high-resolution previews of anterogradely labeled axonal projections from different cerebro-cortical locations to four subcortical brain regions. Serial two-photon tomography previews and derived segmented previews series were programmatically downloaded via API from the Allen Brain Atlas Data Portal. The spatial registrations of the previews with the Allen mouse brain atlas Common Coordinate Framework 3 were slightly adjusted to improve anatomical correspondence in regions of interest. The segmented previews were binarized, and pixels representing tracer labelling within the caudate-putamen, thalamus, superior colliculus, and pontine nuclei were converted to 3-D point coordinates. The data points are suitable for co-visualization of different combinations of data sets, for comparison the topographic arrangement of visual corticostriatal, corticothalamic, corticocollicular, and corticopontine projections.
@misc{10.25493/qt31-pjs, doi = {10.25493/QT31-PJS}, url = {https://search.kg.ebrains.eu/instances/4660e79b-a731-40ac-905e-46d0d11c0dd5}, author = {{\O}vsthus, Martin and Van Swieten, Maaike MH and Bjaalie, Jan G and Leergaard, Trygve Brauns}, keywords = {Neuroscience}, title = {Point coordinate data showing spatial distribution of corticostriatal, corticothalamic, corticocollicular, and corticopontine projections in wild type mice (v1)}, publisher = {EBRAINS}, year = {2022}, copyright = {Creative Commons Attribution 4.0 International}, }
Point coordinate data showing spatial distribution of corticostriatal, corticothalamic, corticocollicular, and corticopontine projections in transgenic mice (v1)

Martin Øvsthus, Maaike MH Van Swieten, Jan G Bjaalie, and Trygve Brauns Leergaard

Feb 2022

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The data set comprises three-dimensional point coordinate data representing the spatial distribution of subcortical projections from 11 locations in the cerebral cortex to the striatum, thalamus, superior colliculus, and pontine nuclei in transgenic mice (Scnn1a-Tg3-Cre, Trib2-F2A-CreERT2, Rbp4-Cre_KL100, Sim1-Cre_KJ18, Tlx3-Cre_PL56). The point data are derived from public high-resolution previews of anterogradely labeled axonal projections from different cerebro-cortical locations to four subcortical brain regions. Serial two-photon tomography previews and derived segmented previews series were programmatically downloaded via API from the Allen Brain Atlas Data Portal. The spatial registrations of the previews with the Allen Mouse Brain Atlas Common Coordinate Framework 3 were slightly adjusted to improve anatomical correspondence in regions of interest. The segmented previews were binarized, and pixels representing tracer labelling within the caudate-putamen, thalamus, superior colliculus, and pontine nuclei were converted to 3D point coordinates. The data points are suitable for co-visualization of different combinations of data sets, for comparison the topographic arrangement of visual corticostriatal, corticothalamic, corticocollicular, and corticopontine projections.
@misc{10.25493/hvev-2jg, doi = {10.25493/HVEV-2JG}, url = {https://search.kg.ebrains.eu/instances/d5ce9a28-021d-4d8a-94b0-9f532765ccd7}, author = {{\O}vsthus, Martin and Van Swieten, Maaike MH and Bjaalie, Jan G and Leergaard, Trygve Brauns}, keywords = {Neuroscience}, title = {Point coordinate data showing spatial distribution of corticostriatal, corticothalamic, corticocollicular, and corticopontine projections in transgenic mice (v1)}, publisher = {EBRAINS}, year = {2022}, copyright = {Creative Commons Attribution 4.0 International}, }
Impact of area patterning genes on corticopontine projection topography: Point coordinate data representing spatial distribution of corticopontine projections in Nr2f1 conditional knockout mice and controls (v1)

Chiara Tocco, Martin Øvsthus, Maaike MH Van Swieten, Jan G Bjaalie, and 2 more authors

Feb 2022

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This data set contains three-dimensional (3D) point coordinate data representing the spatial distribution of anterogradely labelled corticopontine projections in the pontine nuclei of cortico-specific Nr2f1 (also known as COUP-TFI) conditional knockout mice and controls. Transgenic mice were generated by crossing Nr2f1-floxed with Nex-Cre-recombinase mice to abolish Nr2f1 expression from postmitotic neurons. Littermate Nr2f1-floxed mice without the presence of the Cre-recombinase gene (Cre-negatives) were used as controls. Tract-tracing data from wild-type mice shared by the Allen institute were used as supplementary controls. The transgenic mice and littermate controls received injections of the viral tracer AAV9-CAGtdTomato plasmid in discrete locations in the somatosensory or motor cortices (original data (DOI: 10.25493/RNK8-CAN). The wildtype animals (experiments from the Allen Mouse Brain Connectivity Atlas) received injections of a pan-neuronal AAV-expressing EGFP viral tracer (rAAV2/1.hSynapsin.EGFP.WPRE.bGH) in the primary somatosensory cortex. Microscopic previews of sagittal serial sections were spatially registered to the Allen mouse brain atlas (CCFv3), before axonal labelling in the pontine nuclei was recorded as point coordinates, using an preview annotation tool to semiquantitatively represent the overall location and density of labelling. The data points are suitable for co-visualization of different combinations of data sets for comparing the topographic arrangement of corticopontine projections. The data have been used to demonstrate that proper area mapping of the neocortical primordium is a pre-requisite for correct establishment of topographically organized corticopontine projections.
@misc{10.25493/ajve-b8g, doi = {10.25493/AJVE-B8G}, url = {https://search.kg.ebrains.eu/instances/27dd2588-f4da-406c-9d01-8569bf912b0e}, author = {Tocco, Chiara and {\O}vsthus, Martin and Van Swieten, Maaike MH and Bjaalie, Jan G and Leergaard, Trygve Brauns and Studer, Michèle}, keywords = {Neuroscience}, title = {Impact of area patterning genes on corticopontine projection topography: Point coordinate data representing spatial distribution of corticopontine projections in Nr2f1 conditional knockout mice and controls (v1)}, publisher = {EBRAINS}, year = {2022}, copyright = {Creative Commons Attribution 4.0 International}, }

Leveraging EBRAINS in your research

Maaike MH Van Swieten

Mar 2022

DOI Bib Slides

@misc{vanSwieten2022a_slides,
  author = {Van Swieten, Maaike MH},
  title = {Leveraging EBRAINS in your research},
  month = mar,
  year = {2022},
  publisher = {Zenodo},
  doi = {10.5281/zenodo.6379174},
  url = {https://doi.org/10.5281/zenodo.6379174},
  copyright = {Creative Commons Attribution 4.0 International},
}

How to make data public: ethics, regulations, solutions

Maaike MH Van Swieten, and Jan G Bjaalie

Mar 2022

DOI Bib Slides

@misc{vanSwieten2022b_slides,
  author = {Van Swieten, Maaike MH and Bjaalie, Jan G},
  title = {How to make data public: ethics, regulations, solutions},
  month = mar,
  year = {2022},
  publisher = {Zenodo},
  doi = {10.5281/zenodo.6380142},
  url = {https://doi.org/10.5281/zenodo.6380142},
  copyright = {Creative Commons Attribution 4.0 International},
}

Making small data big: Building a graph database from experimental brain research

Maaike MH Van Swieten

Jul 2022

DOI Bib Slides

@misc{vanSwieten2022c_slides,
  author = {Van Swieten, Maaike MH},
  title = {Making small data big: Building a graph database from experimental brain research},
  month = jul,
  year = {2022},
  publisher = {Zenodo},
  doi = {10.5281/zenodo.6839215},
  url = {https://doi.org/10.5281/zenodo.6839215},
  copyright = {Creative Commons Attribution 4.0 International},
}

The road to effective data mining: perspectives from within EBRAINS

Maaike MH Van Swieten

Jul 2022

DOI Bib Slides

@misc{vanSwieten2022d_slides,
  author = {Van Swieten, Maaike MH},
  title = {The road to effective data mining: perspectives from within EBRAINS},
  month = jul,
  year = {2022},
  publisher = {Zenodo},
  doi = {10.5281/zenodo.6832317},
  url = {https://doi.org/10.5281/zenodo.6832317},
  copyright = {Creative Commons Attribution 4.0 International},
}

2021

Hunger improves reinforcement-driven but not planned action

MMH Van Swieten, R Bogacz, and SG Manohar

Cognitive Affective Behavioral Neuroscience, Jul 2021

Abs DOI Bib HTML

Human decisions can be reflexive or planned, being governed respectively by model-free and model-based learning systems. These two systems might differ in their responsiveness to our needs. Hunger drives us to specifically seek food rewards, but here we ask whether it might have more general effects on these two decision systems. On one hand, the model-based system is often considered flexible and context-sensitive, and might therefore be modulated by metabolic needs. On the other hand, the model-free system’s primitive reinforcement mechanisms may have closer ties to biological drives. Here, we tested participants on a well-established two-stage sequential decision-making task that dissociates the contribution of model-based and model-free control. Hunger enhanced overall performance by increasing model-free control, without affecting model-based control. These results demonstrate a generalized effect of hunger on decision-making that enhances reliance on primitive reinforcement learning, which in some situations translates into adaptive benefits.
@article{vanSwieten2021, author = {Van Swieten, MMH and Bogacz, R and Manohar, SG}, journal = {Cognitive Affective Behavioral Neuroscience}, title = {Hunger improves reinforcement-driven but not planned action}, volume = {21}, year = {2021}, pages = {1196--1206}, doi = {10.3758/s13415-021-00921-w}, url = {https://link.springer.com/article/10.3758/s13415-021-00921-w}, keywords = {Reinforcement Learning, Decision making, Computational modeling, Hunger}, }
Muscarinic receptors mediate motivation via preparatory neural activity in humans

John P Grogan, Matthias Raemaekers, Maaike MH Van Swieten, Alexander L Green, and 2 more authors

Jul 2021

Preprint

Abs DOI Bib

Motivation depends on dopamine, but might be modulated by acetylcholine which influences dopamine release in the striatum, and amplifies motivation in animal studies. A corresponding effect in humans would be important clinically, since anticholinergic drugs are frequently used in Parkinson’s disease, a condition that can also disrupt motivation. Reward and dopamine make us more ready to respond, as indexed by reaction times (RT), and move faster, sometimes termed vigour. These effects may be controlled by preparatory processes that can be tracked using EEG. We measured vigour in a placebo-controlled, double-blinded study of trihexyphenidyl (THP), a muscarinic antagonist, with an incentivised eye movement task and EEG. Participants responded faster and with greater vigour when incentives were high, but THP blunted these motivation effects, suggesting that muscarinic receptors facilitate invigoration by reward. Preparatory EEG build-up (contingent negative variation; CNV) was strengthened by high incentives and by muscarinic blockade. The amplitude of preparatory activity predicted both vigour and RT, although over distinct scalp regions. Frontal activity predicted vigour, whereas a larger, earlier, central component predicted RT. Indeed the incentivisation of RT was partly mediated by the CNV, though vigour was not. Moreover, the CNV mediated the drug’s effect on dampening incentives, suggesting that muscarinic receptors underlie the motivational influence on this preparatory activity. Taken together, these findings show that a muscarinic blocker used to treat Parkinson’s disease impairs motivated action in healthy people, and that medial frontal preparatory neural activity mediates this for RT.
@misc{Grogan2021, author = {Grogan, John P and Raemaekers, Matthias and Van Swieten, Maaike MH and Green, Alexander L and Gillies, Martin J and Manohar, Sanjay G}, note = {Preprint}, howpublished = {Preprint}, title = {Muscarinic receptors mediate motivation via preparatory neural activity in humans}, year = {2021}, eprint = {2307.16600}, archiveprefix = {bioRxiv}, biorxiv = {10.1101/2021.07.28.454154}, doi = {10.1101/2021.07.28.454154} }
Effects of hunger on model-based and model-free decision-making

MMH Van Swieten, SG Manohar, and R Bogacz

Jul 2021

Abs DOI Bib HTML

In this study, healthy participants were tested on the effects of hunger on model-free and model-based decision-making. Each first-stage choice rocket was predominantly associated with one of the second-stage planets (common transition: 70% of the trials) and sometimes with the other second-stage planet (rare transition: 30% of the trials). Each second-stage alien probabilistically lead to a reward. The reward probabilities for each second-stage alien fluctuated across trials between 25% and 75% according to a Gaussian random walk. Data available to download from: https://data.mrc.ox.ac.uk/data-set/effects-hunger-model-based-and-model-free-decision-making
@misc{vanSwieten2021a-dataset, author = {Van Swieten, MMH and Manohar, SG and Bogacz, R}, publisher = {University of Oxford}, title = {Effects of hunger on model-based and model-free decision-making}, year = {2021}, doi = {10.1101/2021.07.28.454154}, url = {https://ora.ox.ac.uk/objects/uuid:1b99b295-430c-4896-b5e3-29ea9741760f}, copyright = {Creative Commons Attribution 4.0 International} }
The effects of hunger on experiential and explicit risk-taking

MMH Van Swieten, SG Manohar, and R Bogacz

Jul 2021

Abs DOI Bib HTML

In this study, healthy participants were tested on the effects of hunger on risk preferences in two complementary tasks. In the experience-based task, participants learned the outcomes of options through sampling, whereas in the description-based task, the outcome probabilities and reward magnitudes were explicitly presented on the screen. The choices were further categorised into three different decision contexts: positive, negative or mixed decision context. Positive decision contexts concern choices between two options with equal expected value, but different level of risk, with outcomes above the average reward. Negative decision contexts concern choices between two options with equal expected value, but different level of risk, below the average reward. Mixed contexts concern choices between two options with different expected values. Please see downloadable text file for full data description, or visit https://data.mrc.ox.ac.uk/data-set/effects-hunger-experiential-and-explicit-risk-taking where the data itself is also available to download.
@misc{vanSwieten2021b-dataset, author = {Van Swieten, MMH and Manohar, SG and Bogacz, R}, publisher = {University of Oxford}, title = {The effects of hunger on experiential and explicit risk-taking}, year = {2021}, doi = {10.5287/bodleian:2RbJrk9Dy}, url = {https://ora.ox.ac.uk/objects/uuid:c306a66b-aab2-4813-9bb8-14031f319484}, copyright = {Creative Commons Attribution 4.0 International} }

2020

Physiological modulation of learning and decision-making

MMH Van Swieten

University of Oxford, Jul 2020

PhD Thesis

Abs Bib HTML

Many of the decisions we make in our day-to-day lives are influenced by internal physiological states and external environmental factors. In my thesis, I employed an interdisciplinary approach to investigate how internal physiological states, such as hunger, affect various aspects of decision-making. Neurobiological research has shown that food deprivation enhances dopaminergic signalling and increases the incentive salience of food. However, classical reinforcement learning theory only maps learning of external factors onto dopaminergic signalling. I extended the reinforcement learning theory in a biologically relevant manner to incorporate mechanisms by which internal physiological signals interact with the dopaminergic system to influence learning and action selection (chapter 3). This new theory predicts that food deprivation enhances learning, promotes approach behaviour, and reduces avoidance behaviour by enhancing the dopaminergic activation and teaching signals. I tested these theoretical predictions for decision-making in human volunteers. This study showed that hunger increased the valuation of food, but not of monetary rewards or nonfood items (chapter 4). Hunger reduced the biases for approach and avoidance behaviour that sated people exhibit by modulating the trade-off between positive and negative consequences of actions (chapter 5). Hunger also interacted with economic choice, but only when outcomes of choices had to be learned, not when they were explicitly described (chapter 6). Lastly, this study showed that hunger enhanced the reliance of "gut-instinct", without affecting cognitive control (chapter 7). In summary, this thesis characterises mechanisms by which motivational drives, such as hunger, could affect valuation, learning, and action selection in a biological manner. It provides empirical evidence that hunger also affects decision-making for monetary rewards, which could have significant implications for both real-world economic transactions and for aberrant decision-making in eating disorders and obesity.
@phdthesis{vanSwieten2020b, publisher = {University of Oxford}, school = {University of Oxford}, title = {Physiological modulation of learning and decision-making}, author = {Van Swieten, MMH}, year = {2020}, url = {https://ora.ox.ac.uk/objects/uuid:10eafd3e-d2b8-4ed3-8b1f-13bf659ae4c3}, note = {PhD Thesis}, }
Modeling the effects of motivation on choice and learning in the basal ganglia

MMH Van Swieten, and R Bogacz

PLoS Computational Biology, Jul 2020

Abs DOI Bib HTML

Decision making relies on adequately evaluating the consequences of actions on the basis of past experience and the current physiological state. A key role in this process is played by the basal ganglia, where neural activity and plasticity are modulated by dopaminergic input from the midbrain. Internal physiological factors, such as hunger, scale signals encoded by dopaminergic neurons and thus they alter the motivation for taking actions and learning. However, to our knowledge, no formal mathematical formulation exists for how a physiological state affects learning and action selection in the basal ganglia. We developed a framework for modelling the effect of motivation on choice and learning. The framework defines the motivation to obtain a particular resource as the difference between the desired and the current level of this resource, and proposes how the utility of reinforcements depends on the motivation. To account for dopaminergic activity previously recorded in different physiological states, the paper argues that the prediction error encoded in the dopaminergic activity needs to be redefined as the difference between utility and expected utility, which depends on both the objective reinforcement and the motivation. We also demonstrate a possible mechanism by which the evaluation and learning of utility of actions can be implemented in the basal ganglia network. The presented theory brings together models of learning in the basal ganglia with the incentive salience theory in a single simple framework, and it provides a mechanistic insight into how decision processes and learning in the basal ganglia are modulated by the motivation. Moreover, this theory is also consistent with data on neural underpinnings of overeating and obesity, and makes further experimental predictions.
@article{vanSwieten2020a, author = {Van Swieten, MMH and Bogacz, R}, journal = {PLoS Computational Biology}, title = {Modeling the effects of motivation on choice and learning in the basal ganglia}, volume = {16}, issue = {5}, year = {2020}, pages = {e1007465}, doi = {10.1371/journal.pcbi.1007465}, url = {https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007465}, keywords = {Reinforcement Learning, Decision making, Computational modeling, Hunger}, }

2019

Opioid modulation of social play reward in juvenile rats

EJM Achterberg, MMH Van Swieten, DJ Houwing, V Trezza, and 1 more author

Neuropharmacology, Nov 2019

The Neuropharmacology of Social Behavior: From Bench to Bedside

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Social play behaviour is a vigorous form of social interaction abundant during the juvenile and adolescent phases of life in many mammalian species, including rats and humans. Social play is thought to be important for social, emotional and cognitive development. Being a rewarding activity, the expression of social play depends on its pleasurable and motivational properties. Since opioids have been widely implicated in reward processes, in the present study we investigated the role of opioids in the pleasurable and motivational properties of social play behaviour in rats. To assess social play motivation, an operant conditioning setup was used in which rats responded for social play under a progressive ratio schedule of reinforcement. Treatment with the opioid receptor agonist morphine reduced responding for social play at the highest dose tested, likely due to its rate-limiting effects. Morphine treatment increased the expression of social play behaviour during reinforced periods. The acquisition of social play-induced conditioned place preference (CPP) in a subeffective conditioning protocol was enhanced by treatment with morphine. Morphine treatment alone also induced CPP. In contrast, antagonizing opioid receptors with naloxone reduced responding for social play, the expression of social play and blocked the development of social play-induced CPP. These data implicate opioid neurotransmission in both the pleasurable and the motivational aspects of social play behaviour in rats.
@article{Achterberg2019, author = {Achterberg, EJM and Van Swieten, MMH and Houwing, DJ and Trezza, V and Vanderschuren, LJMJ}, journal = {Neuropharmacology}, title = {Opioid modulation of social play reward in juvenile rats}, volume = {159}, year = {2019}, day = {15}, month = nov, pages = {107332}, doi = {10.1016/j.neuropharm.2018.09.007}, url = {https://www.sciencedirect.com/science/article/abs/pii/S0028390818306324?via%3Dihub}, keywords = {Social play behaviour, Opioids, Reward, Motivation, Morphine, Naloxone, Place conditioning}, note = {The Neuropharmacology of Social Behavior: From Bench to Bedside}, }

2016

Lateral hypothalamic area glutamatergic neurons and their projections to the lateral habenula regulate feeding and reward

Alice M Stamatakis, Maaike Van Swieten, Marcus L Basiri, Grace A Blair, and 2 more authors

Journal of Neuroscience, Nov 2016

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The overconsumption of calorically dense, highly palatable foods is thought to be a major contributor to the worldwide obesity epidemic; however, the precise neural circuits that directly regulate hedonic feeding remain elusive. Here, we show that lateral hypothalamic area (LHA) glutamatergic neurons, and their projections to the lateral habenula (LHb), negatively regulate the consumption of palatable food. Genetic ablation of LHA glutamatergic neurons increased daily caloric intake and produced weight gain in mice that had access to a high-fat diet, while not altering general locomotor activity. Anterior LHA glutamatergic neurons send a functional glutamatergic projection to the LHb, a brain region involved in processing aversive stimuli and negative reward prediction outcomes. Pathway-specific, optogenetic stimulation of glutamatergic LHA-LHb circuit resulted in detectable glutamate-mediated EPSCs as well as GABA-mediated IPSCs, although the net effect of neurotransmitter release was to increase the firing of most LHb neurons. In vivo optogenetic inhibition of LHA-LHb glutamatergic fibers produced a real-time place preference, whereas optogenetic stimulation of LHA-LHb glutamatergic fibers had the opposite effect. Furthermore, optogenetic inhibition of LHA-LHb glutamatergic fibers acutely increased the consumption of a palatable liquid caloric reward. Collectively, these results demonstrate that LHA glutamatergic neurons are well situated to bidirectionally regulate feeding and potentially other behavioral states via their functional circuit connectivity with the LHb and potentially other brain regions.
@article{Stamatakis2016, author = {Stamatakis, Alice M and Van Swieten, Maaike and Basiri, Marcus L and Blair, Grace A and Kantak, Pranish and Stuber, Garret D}, journal = {Journal of Neuroscience}, title = {Lateral hypothalamic area glutamatergic neurons and their projections to the lateral habenula regulate feeding and reward}, volume = {36}, issue = {2}, year = {2016}, pages = {302--311}, doi = {10.1523/JNEUROSCI.1202-15.2016}, url = {https://www.jneurosci.org/content/36/2/302.short}, keywords = {Aversion, Feeding, Habenula, Hypothalamus, Optogenetics, Reward}, }
Contrasting roles of dopamine and noradrenaline in the motivational properties of social play behavior in rats

EJ Achterberg, Linda WM Van Kerkhof, Michela Servadio, Maaike MH Van Swieten, and 5 more authors

Neuropsychopharmacology, Nov 2016

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Social play behavior, abundant in the young of most mammalian species, is thought to be important for social and cognitive development. Social play is highly rewarding, and as such, the expression of social play depends on its pleasurable and motivational properties. Since the motivational properties of social play have only sporadically been investigated, we developed a setup in which rats responded for social play under a progressive ratio schedule of reinforcement. Dopaminergic neurotransmission plays a key role in incentive motivational processes, and both dopamine and noradrenaline have been implicated in the modulation of social play behavior. Therefore, we investigated the role of dopamine and noradrenaline in the motivation for social play. Treatment with the psychostimulant drugs methylphenidate and cocaine increased responding for social play, but suppressed its expression during reinforced play periods. The dopamine reuptake inhibitor GBR-12909 increased responding for social play, but did not affect its expression, whereas the noradrenaline reuptake inhibitor atomoxetine decreased responding for social play as well as its expression. The effects of methylphenidate and cocaine on responding for social play, but not their play-suppressant effects, were blocked by pretreatment with the dopamine receptor antagonist α-flupenthixol. In contrast, pretreatment with the α2-adrenoceptor antagonist RX821002 prevented the play-suppressant effect of methylphenidate, but left its effect on responding for social play unaltered. In sum, the present study introduces a novel method to study the incentive motivational properties of social play behavior in rats. Using this paradigm, we demonstrate dissociable roles for dopamine and noradrenaline in social play behavior: dopamine stimulates the motivation for social play, whereas noradrenaline negatively modulates the motivation for social play behavior and its expression.
@article{Achterberg2016a, author = {Achterberg, EJ and Van Kerkhof, Linda WM and Servadio, Michela and Van Swieten, Maaike MH and Houwing, Danielle J and Aalderink, Mandy and V, Nina and Trezza, Viviana and Vanderschuren, Louk JMJ}, journal = {Neuropsychopharmacology}, title = {Contrasting roles of dopamine and noradrenaline in the motivational properties of social play behavior in rats}, volume = {41}, issue = {3}, year = {2016}, pages = {858--868}, doi = {10.1038/npp.2015.212}, url = {https://www.nature.com/articles/npp2015212}, keywords = {Social play behavior, Dopamine, Noradrenaline, Reward, Motivation}, }
Dissociating the role of endocannabinoids in the pleasurable and motivational properties of social play behaviour in rats

EJ Marijke Achterberg, Maaike MH Van Swieten, Nina V Driel, Viviana Trezza, and 1 more author

Pharmacological research, Aug 2016

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Social play behaviour is a vigorous form of social interaction, abundant during the juvenile and adolescent phases of life in many mammalian species, including humans. Social play is highly rewarding and it is important for social and cognitive development. Being a rewarding activity, social play can be dissociated in its pleasurable and motivational components. We have previously shown that endocannabinoids modulate the expression of social play behaviour in rats. In the present study, we investigated whether endocannabinoids modulate the motivational and pleasurable properties of social play behaviour, using operant and place conditioning paradigms, respectively. Treatment with the anandamide hydrolysis inhibitor URB597 did not affect operant responding or social play-induced conditioned place preference (CPP) when administered at a dose (0.1 mg/kg) known to increase the expression of social play behaviour, while it modestly reduced operant responding at a higher dose (0.2 mg/kg). The cannabinoid-1 (CB1) receptor antagonist rimonabant reduced operant responding when administered at a dose (1 mg/kg) known to decrease the expression of social play behaviour, although this effect may be secondary to concurrent drug-induced stereotypic behaviours (i.e., grooming and scratching). These data demonstrate that enhancing endocannabinoid levels does not differentially affect the motivational and pleasurable aspects of social play behaviour, whereas CB1 receptor blockade reduces the motivational aspects of social play behaviour, possibly due to response competition. Thus, endocannabinoids likely drive the expression of social play behaviour as a whole, without differentially affecting its motivational or pleasurable properties.
@article{Achterberg2016b, author = {Achterberg, EJ Marijke and Van Swieten, Maaike MH and Driel, Nina V and Trezza, Viviana and Vanderschuren, Louk JMJ}, journal = {Pharmacological research}, title = {Dissociating the role of endocannabinoids in the pleasurable and motivational properties of social play behaviour in rats}, volume = {110}, year = {2016}, month = aug, pages = {151--158}, doi = {10.1016/j.phrs.2016.04.031}, url = {https://www.sciencedirect.com/science/article/abs/pii/S1043661816303917}, keywords = {Social play behavior, Endocannabinoids, Motivation}, }

2014

The neuroanatomical function of leptin in the hypothalamus

MMH Van Swieten, R Pandit, RAH Adan, and G Van Der Plasse

Journal of chemical neuroanatomy, Aug 2014

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The anorexigenic hormone leptin plays an important role in the control of food intake and feeding-related behavior, for an important part through its action in the hypothalamus. The adipose-derived hormone modulates a complex network of several intercommunicating orexigenic and anorexigenic neuropeptides in the hypothalamus to reduce food intake and increase energy expenditure. In this review we present an updated overview of the functional role of leptin in respect to feeding and feeding-related behavior per distinct hypothalamic nuclei. In addition to the arcuate nucleus, which is a major leptin sensitive hub, leptin-responsive neurons in other hypothalamic nuclei, including the, dorsomedial-, ventromedial- and paraventricular nucleus and the lateral hypothalamic area, are direct targets of leptin. However, leptin also modulates hypothalamic neurons in an indirect manner, such as via the melanocortin system. The dissection of the complexity of leptin’s action on the networks involved in energy balance is subject of recent and future studies. A full understanding of the role of hypothalamic leptin in the regulation of energy balance requires cell-specific manipulation using of conditional deletion and expression of leptin receptors. In addition, optogenetic and pharmacogenetic tools in combination with other pharmacological (such as the recent discovery of a leptin receptor antagonist) and neuronal tracing techniques to map the circuit, will be helpful to understand the role of leptin receptor expressing neurons. Better understanding of these circuits and the involvement of leptin could provide potential sites for therapeutic interventions in obesity and metabolic diseases characterized by dysregulation of energy balance.
@article{vanSwieten2014, author = {Van Swieten, MMH and Pandit, R and Adan, RAH and Van Der Plasse, G}, journal = {Journal of chemical neuroanatomy}, title = {The neuroanatomical function of leptin in the hypothalamus}, volume = {61}, year = {2014}, pages = {207--220}, doi = {10.1016/j.jchemneu.2014.05.004}, url = {https://www.sciencedirect.com/science/article/abs/pii/S0891061814000404}, keywords = {Leptin, Ob-R, Feeding, Hypothalamus, Neuropeptides}, }

2013

NS. 2.2-MEASURING MOTIVATION, REWARD AND PERFORMANCE OF SOCIAL PLAY BEHAVIOR IN RATS: DISSOCIABLE ROLES OF DOPAMINE AND NORADRENALINE

EJM Achterberg, LWM Van Kerkhof, M Servadio, MMH Van Swieten, and 2 more authors

Behavioural Pharmacology, Aug 2013

DOI Bib

@article{Achterberg2013,
  author = {Achterberg, EJM and Van Kerkhof, LWM and Servadio, M and Van Swieten, MMH and Trezza, V and Vanderschuren, LJMJ},
  journal = {Behavioural Pharmacology},
  title = {NS. 2.2-MEASURING MOTIVATION, REWARD AND PERFORMANCE OF SOCIAL PLAY BEHAVIOR IN RATS: DISSOCIABLE ROLES OF DOPAMINE AND NORADRENALINE},
  volume = {24},
  year = {2013},
  pages = {e19},
  doi = {10.1097/01.fbp.0000434751.27969.98},
  keywords = {Social play behavior, Dopamine, Noradrenaline, Reward, Motivation},
}