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Record W3194895949 · doi:10.1038/s41380-021-01240-9

Serotonin depletion impairs both Pavlovian and instrumental reversal learning in healthy humans

2021· article· en· W3194895949 on OpenAlexaff
Jonathan W. Kanen, Annemieke M. Apergis-Schoute, Robyn Yellowlees, Fréderique E. Arntz, Febe E. van der Flier, Annabel Price, Rudolf N. Cardinal, David M. Christmas, Luke Clark, Barbara J. Sahakian, Molly J. Crockett, Trevor W. Robbins

Bibliographic record

VenueMolecular Psychiatry · 2021
Typearticle
Languageen
FieldNeuroscience
TopicMemory and Neural Mechanisms
Canadian institutionsUniversity of British Columbia
FundersGates Cambridge TrustNational Institute for Health and Care ResearchUniversity of CambridgeDepartment of Health and Social CareNIHR Cambridge Biomedical Research CentreWellcome TrustMedical Research CouncilWellcome
KeywordsPsychologySerotoninNeurosciencePsychopharmacologyDevelopmental psychologyCognitive psychologyPsychiatryMedicineInternal medicine

Abstract

fetched live from OpenAlex

Serotonin is involved in updating responses to changing environmental circumstances. Optimising behaviour to maximise reward and minimise punishment may require shifting strategies upon encountering new situations. Likewise, autonomic responses to threats are critical for survival yet must be modified as danger shifts from one source to another. Whilst numerous psychiatric disorders are characterised by behavioural and autonomic inflexibility, few studies have examined the contribution of serotonin in humans. We modelled both processes, respectively, in two independent experiments (N = 97). Experiment 1 assessed instrumental (stimulus-response-outcome) reversal learning whereby individuals learned through trial and error which action was most optimal for obtaining reward or avoiding punishment initially, and the contingencies subsequently reversed serially. Experiment 2 examined Pavlovian (stimulus-outcome) reversal learning assessed by the skin conductance response: one innately threatening stimulus predicted receipt of an uncomfortable electric shock and another did not; these contingencies swapped in a reversal phase. Upon depleting the serotonin precursor tryptophan-in a double-blind randomised placebo-controlled design-healthy volunteers showed impairments in updating both actions and autonomic responses to reflect changing contingencies. Reversal deficits in each domain, furthermore, were correlated with the extent of tryptophan depletion. Initial Pavlovian conditioning, moreover, which involved innately threatening stimuli, was potentiated by depletion. These results translate findings in experimental animals to humans and have implications for the neurochemical basis of cognitive inflexibility.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.670

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.024
GPT teacher head0.286
Teacher spread0.262 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations37
Published2021
Admission routes1
Has abstractyes

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