Probabilistic reversal learning under acute tryptophan depletion in healthy humans: a conventional analysis

Kanen, Jonathan W.; Arntz, Fréderique E.; Yellowlees, Robyn; Cardinal, Rudolf N.; Price, Annabel; Christmas, David; Sahakian, Barbara J.; Apergis-Schoute, Annemieke M.; Robbins, Trevor W.

doi:10.1177/0269881120907991

Cited by 8 publications

(11 citation statements)

References 12 publications

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“…In light of the previous difficulty in detecting effects of ATD on choice behaviour during PRL (Evers et al 2005;Finger et al 2007;Murphy et al 2002;Kanen et al 2020), we reasoned that the microstructure of behaviour as revealed through computational modelling, might be more sensitive to ATD. Indeed, the present study uncovered effects of ATD on choice tendencies during PRL for the first time, enabled by computational methods.…”

Section: Discussionmentioning

confidence: 99%

“…Participants reported having no first-degree relatives with a diagnosed mental illness at the time of screening. Further participant characteristics and exclusion criteria can be found in Kanen et al (2020Kanen et al ( , 2021. Participants gave informed consent and were paid.…”

Section: Participantsmentioning

confidence: 99%

“…Approximately 4.5 hours after ingesting the drink (Carpenter et al 1998), participants completed the VAS again, gave another blood sample, and completed the PRL task. Specific quantities of amino acids used can be found in Kanen et al (2020).…”

Section: General Proceduresmentioning

confidence: 99%

“…However, there has been a proliferation of ways in which perseveration has been measured, which hampers comparison across species, studies, and paradigms (den Ouden et al 2013). No effects of ATD on conventional measures of choice during PRL have been reported to date (Evers et al 2005;Finger et al 2007;Murphy et al 2002;Kanen et al 2020). We recently attempted to overcome some of the shortcomings of prior studies (Evers et al 2005;Finger et al 2007;Murphy et al 2002) by nearly tripling the sample size, testing both sexes, using a between-subjects design to avoid practice effects, and calculating additional conventional measures-to no avail (Kanen et al 2020).…”

Section: Introductionmentioning

confidence: 99%

“…No effects of ATD on conventional measures of choice during PRL have been reported to date (Evers et al 2005;Finger et al 2007;Murphy et al 2002;Kanen et al 2020). We recently attempted to overcome some of the shortcomings of prior studies (Evers et al 2005;Finger et al 2007;Murphy et al 2002) by nearly tripling the sample size, testing both sexes, using a between-subjects design to avoid practice effects, and calculating additional conventional measures-to no avail (Kanen et al 2020). That we were unable to identify an effect of ATD on choice during PRL is puzzling, especially given that acute selective serotonin reuptake inhibitors (SSRIs) do have an effect on PRL in humans (Chamberlain et al 2006;Skandali et al 2018).…”

Section: Introductionmentioning

confidence: 99%

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Perseverative behavior under uncertainty is enhanced by tryptophan depletion but diminished with subclinical obsessive–compulsive symptoms

Kanen

Luo

Yellowlees

et al. 2021

Preprint

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Serotonin is critically involved in flexible decision-making, yet the preponderance of evidence comes from non-human studies. Many insights about the serotonin's function have come from the technique of dietary acute tryptophan depletion (ATD). However, it is unclear whether ATD modulates choice behavior during probabilistic reversal learning (PRL), a widely used model of behavioral flexibility with significant translational and clinical value. To determine whether ATD affects latent choice tendencies, we applied computational models of reinforcement learning to PRL data from healthy human volunteers (n = 62; 29 females) who had received either ATD or placebo in a randomized, double-blind, placebo-controlled procedure. A secondary objective was to ascertain how model parameters related to clinically relevant self-report questionnaires. ATD did not affect the updating ("learning rates") or deployment ("reinforcement sensitivity") of value representations driving choice. However, ATD increased "stimulus stickiness", the tendency to choose a previously chosen visual stimulus again, regardless of reinforcement--a pattern seen in stimulant use disorder (SUD). Greater subclinical obsessive-compulsive symptoms were associated with lower stimulus stickiness, a pattern seen in clinically diagnosed obsessive-compulsive disorder (OCD). Low reinforcement sensitivity was instead related to intolerance of uncertainty and symptoms of depression and anxiety. Individuals with higher trait impulsivity showed lower reward and higher punishment learning rates, which parallels findings in SUD. Collectively, these results point to a role for serotonin in compulsive tendencies. They underscore the utility of computational modelling in illuminating the microstructure of behavior, which could point towards new markers of vulnerability to psychopathology.

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Section: Discussionmentioning

confidence: 99%

Section: Participantsmentioning

confidence: 99%

Section: General Proceduresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Perseverative behavior under uncertainty is enhanced by tryptophan depletion but diminished with subclinical obsessive–compulsive symptoms

Kanen

Luo

Yellowlees

et al. 2021

Preprint

Self Cite

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Development of cross-species translational paradigms for psychiatric research in the Research Domain Criteria era

Young

2023

Neuroscience & Biobehavioral Reviews

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

et al. 2021

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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.

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Probabilistic reversal learning under acute tryptophan depletion in healthy humans: a conventional analysis

Cited by 8 publications

References 12 publications

Perseverative behavior under uncertainty is enhanced by tryptophan depletion but diminished with subclinical obsessive–compulsive symptoms

Perseverative behavior under uncertainty is enhanced by tryptophan depletion but diminished with subclinical obsessive–compulsive symptoms

Development of cross-species translational paradigms for psychiatric research in the Research Domain Criteria era

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

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