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Shifting uncertainty intolerance: methylphenidate and attention deficit hyperactivity disorder

Mandali, Alekhya, Sethi, Arjun, Cercignani, Mara ORCID:, Harrison, Neil ORCID: and Voon, Valerie 2021. Shifting uncertainty intolerance: methylphenidate and attention deficit hyperactivity disorder. Translational Psychiatry 11 , 12. 10.1038/s41398-020-01118-4

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Cardiff University Brain Research Imaging Centre (CUBRIC)
Publisher: Springer Nature
ISSN: 2158-3188
Date of First Compliant Deposit: 7 January 2021
Date of Acceptance: 23 October 2020
Last Modified: 09 May 2023 02:06

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