The Relationship between Impulsive Choice and Impulsive Action: A Cross-Species Translational Study Nienke Broos 1. , Lianne Schmaal 2. , Joost Wiskerke 1 , Lennard Kostelijk 2 , Thomas Lam 2 , Nicky Stoop 1 , Lonneke Weierink 1 , Jannemieke Ham 1 , Eco J. C. de Geus 3 , Anton N. M. Schoffelmeer 1 , Wim van den Brink 2 , Dick J. Veltman 4 , Taco J. de Vries 1 , Tommy Pattij 1 * . , Anna E. Goudriaan 2. 1 Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands, 2 Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 3 Department of Biological Psychology, VU University, Amsterdam, The Netherlands, 4 Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands Abstract Maladaptive impulsivity is a core symptom in various psychiatric disorders. However, there is only limited evidence available on whether different measures of impulsivity represent largely unrelated aspects or a unitary construct. In a cross-species translational study, thirty rats were trained in impulsive choice (delayed reward task) and impulsive action (five-choice serial reaction time task) paradigms. The correlation between those measures was assessed during baseline performance and after pharmacological manipulations with the psychostimulant amphetamine and the norepinephrine reuptake inhibitor atomoxetine. In parallel, to validate the animal data, 101 human subjects performed analogous measures of impulsive choice (delay discounting task, DDT) and impulsive action (immediate and delayed memory task, IMT/DMT). Moreover, all subjects completed the Stop Signal Task (SST, as an additional measure of impulsive action) and filled out the Barratt impulsiveness scale (BIS-11). Correlations between DDT and IMT/DMT were determined and a principal component analysis was performed on all human measures of impulsivity. In both rats and humans measures of impulsive choice and impulsive action did not correlate. In rats the within-subject pharmacological effects of amphetamine and atomoxetine did not correlate between tasks, suggesting distinct underlying neural correlates. Furthermore, in humans, principal component analysis identified three independent factors: (1) self-reported impulsivity (BIS-11); (2) impulsive action (IMT/DMT and SST); (3) impulsive choice (DDT). This is the first study directly comparing aspects of impulsivity using a cross-species translational approach. The present data reveal the non-unitary nature of impulsivity on a behavioral and pharmacological level. Collectively, this warrants a stronger focus on the relative contribution of distinct forms of impulsivity in psychopathology. Citation: Broos N, Schmaal L, Wiskerke J, Kostelijk L, Lam T, et al. (2012) The Relationship between Impulsive Choice and Impulsive Action: A Cross-Species Translational Study. PLoS ONE 7(5): e36781. doi:10.1371/journal.pone.0036781 Editor: Georges Chapouthier, Universite ´ Pierre et Marie Curie, France Received March 26, 2012; Accepted April 13, 2012; Published May 4, 2012 Copyright: ß 2012 Broos et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was financially supported by a grant from the Netherlands Organization for Scientific Research (ZonMW grant no. 3116003/www.ZonMW.nl). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: t.pattij@vumc.nl . These authors contributed equally to this work. Introduction Impulsivity is a hallmark and common feature in various psychiatric disorders, including substance use disorder, attention deficit hyperactivity disorder (ADHD), conduct disorder, bipolar disorder, pathological gambling and personality disorders [1]. Although impulsivity can be broadly defined as behavioral actions without adequate forethought, there is growing evidence that impulsivity is no unitary construct, but rather is dissociable into different aspects reflecting distinct underlying cognitive, emotional, and neural processes [2]. Nonetheless, detailed research on the relationship between various aspects of impulsivity is still scarce. Two widely recognized behavioral phenomena of impulsivity are impulsive choice and impulsive action. Impulsive choice is oftentimes operationalized by impulsive decisions resulting from a distorted evaluation of delayed consequences of behavior and an increased preference for (smaller) immediate rewards over more beneficial delayed rewards. On the other hand, impulsive action reflects the failure to inhibit an inappropriate response to prepotent stimuli [2–4]. In addition to self-report measures, impulsive choice and impulsive action can be assessed in different behavioral paradigms. Importantly, for most of these behavioral paradigms similar versions exist for humans and laboratory animals. In humans delay discounting paradigms are generally used to assess impulsive choice [5]. To measure impulsive action, the go-no go task, stop signal task, Stroop task, or commission errors during a continuous performance task (CPT) are most often utilized in humans [6]. Preclinical laboratory animal researchers have developed trans- lational analogies of these neuropsychological tasks such as the delayed reward task (DRT) to study impulsive choice and the go- no go task, stop signal reaction time task and the five-choice serial reaction time task (5-CSRTT) to measure impulsive action (for review see [7]). Translational, cross-species approaches combining clinical and preclinical data on impulsivity are particularly suited to deepen our understanding of the neurobiological mechanisms underlying impulsivity and the multidimensional nature thereof PLoS ONE | www.plosone.org 1 May 2012 | Volume 7 | Issue 5 | e36781