Shifting uncertainty intolerance: methylphenidate and attention-deficit hyperactivity disorder
Publication Date
2021-01-06Journal Title
Translational Psychiatry
Publisher
Nature Publishing Group UK
Volume
11
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Mandali, A., Sethi, A., Cercignani, M., Harrison, N. A., & Voon, V. (2021). Shifting uncertainty intolerance: methylphenidate and attention-deficit hyperactivity disorder. Translational Psychiatry, 11 (1) https://doi.org/10.1038/s41398-020-01118-4
Abstract
Abstract: Risk evaluation is a critical component of decision making. Risk tolerance is relevant in both daily decisions and pathological disorders such as attention-deficit hyperactivity disorder (ADHD), where impulsivity is a cardinal symptom. Methylphenidate, a commonly prescribed drug in ADHD, improves attention but has mixed reports on risk-based decision making. Using a double-blinded placebo protocol, we studied the risk attitudes of ADHD patients and age-matched healthy volunteers while performing the 2-step sequential learning task and examined the effect of methylphenidate on their choices. We then applied a novel computational analysis using the hierarchical drift–diffusion model to extract parameters such as threshold (‘a’—amount of evidence accumulated before making a decision), drift rate (‘v’—information processing speed) and response bias (‘z’ apriori bias towards a specific choice) focusing specifically on risky choice preference. Critically, we show that ADHD patients on placebo have an apriori bias towards risky choices compared to controls. Furthermore, methylphenidate enhanced preference towards risky choices (higher apriori bias) in both groups but had a significantly greater effect in the patient population independent of clinical scores. Thus, methylphenidate appears to shift tolerance towards risky uncertain choices possibly mediated by prefrontal dopaminergic and noradrenergic modulation. We emphasise the utility of computational models in detecting underlying processes. Our findings have implications for subtle yet differential effects of methylphenidate on ADHD compared to healthy population.
Keywords
Article, /692/53/2423, /631/477/2811, /692/699/476/1311, article
Sponsorship
RCUK | Medical Research Council (MRC) (MR/P008747/1)
Identifiers
s41398-020-01118-4, 1118
External DOI: https://doi.org/10.1038/s41398-020-01118-4
This record's URL: https://www.repository.cam.ac.uk/handle/1810/315926
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
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