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Shifting uncertainty intolerance: methylphenidate and attention-deficit hyperactivity disorder.

Published version
Peer-reviewed

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Authors

Mandali, Alekhya 
Sethi, Arjun 

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.

Description

Keywords

Attention Deficit Disorder with Hyperactivity, Central Nervous System Stimulants, Humans, Impulsive Behavior, Methylphenidate, Uncertainty

Journal Title

Transl Psychiatry

Conference Name

Journal ISSN

2158-3188
2158-3188

Volume Title

11

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MR/P008747/1)
Wellcome Trust Intermediate Fellowship (093881/Z/10/Z) to Dr. Harrison, Brighton and Sussex Medical School and the Dr. Mortimer and Dame Theresa Sackler Foundation. Dr. Voon is supported by a Medical Research Council Senior Clinical Fellowship (MR/P008747/1).