The dual role of ketamine: a computational perspective on pharmacological interventions in psychiatry
In psychiatry, the NMDA receptor antagonist ketamine takes on two very different roles: a pharmacological model of psychosis, due to its psychotomimetic effects, and a potent, fast-acting antidepressant. We want to understand whether ketamine produces its effects in these different domains - perceptual (psychosis) and affective (depression) - via a common neurocognitive mechanism. This question is crucial for drug development, and for our understanding of disease mechanisms in psychosis and depression. In an ongoing study with collaborators at the University of Oxford, we use novel continuous decision tasks, EEG, and cognitive modelling to study the neurocognitive mechanisms by which ketamine affects perception and affective processing.
Relevant publications:
McCutcheon et al. (2024). Psychosis as a disorder of muscarinic signalling: psychopathology and pharmacology. The Lancet Psychiatry
Ruesseler et al. (2023). Quantifying decision-making in dynamic, continuously evolving environments. eLife
Weber et al. (2022). Auditory mismatch responses are differentially sensitive to changes in muscarinic acetylcholine versus dopamine receptor function. eLife
Weber et al. (2020). Ketamine Affects Prediction Errors about Statistical Regularities: A Computational Single-Trial Analysis of the Mismatch Negativity. Journal of Neuroscience