Inhibition and impulsivity: Behavioral and neural basis of response control Andrea Bari *, Trevor W. Robbins Behavioral and Clinical Neuroscience Institute, Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, UK Contents 1. Historical introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 1.1. Development of the concept of inhibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 1.2. The search for the neural ‘locus’ of inhibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 1.3. Defining cognitive and behavioral inhibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 2. Failure of the inhibitory processes: impulsivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 2.1. Subtypes of impulsive behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 2.2. Assessing impulsivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 2.3. Response inhibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 3. Neural substrates of response inhibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 3.1. Neuropharmacological studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 Progress in Neurobiology xxx (2013) xxx–xxx A R T I C L E I N F O Article history: Received 20 April 2012 Received in revised form 24 May 2013 Accepted 26 June 2013 Available online xxx Keywords: Inhibition Impulsivity Go/no-go Stop-signal task Delay discounting Reversal learning A B S T R A C T In many circumstances alternative courses of action and thoughts have to be inhibited to allow the emergence of goal-directed behavior. However, this has not been the accepted view in the past and only recently has inhibition earned its own place in the neurosciences as a fundamental cognitive function. In this review we first introduce the concept of inhibition from early psychological speculations based on philosophical theories of the human mind. The broad construct of inhibition is then reduced to its most readily observable component which necessarily is its behavioral manifestation. The study of ‘response inhibition’ has the advantage of dealing with a relatively simple and straightforward process, the overriding of a planned or already initiated action. Deficient inhibitory processes profoundly affect everyday life, causing impulsive conduct which is generally detrimental for the individual. Impulsivity has been consistently linked to several types of addiction, attention deficit/hyperactivity disorder, mania and other psychiatric conditions. Our discussion of the behavioral assessment of impulsivity will focus on objective laboratory tasks of response inhibition that have been implemented in parallel for humans and other species with relatively few qualitative differences. The translational potential of these measures has greatly improved our knowledge of the neurobiological basis of behavioral inhibition and impulsivity. We will then review the current models of behavioral inhibition along with their expression via underlying brain regions, including those involved in the activation of the brain’s emergency ‘brake’ operation, those engaged in more controlled and sustained inhibitory processes and other ancillary executive functions. ß 2013 Elsevier Ltd. All rights reserved. Abbreviations: 5-CSRTT, 5-choice serial reaction time task; 5-HT, serotonin; ACC, anterior cingulate cortex; ADHD, attention deficit/hyperactivity disorder; BA, Brodmann area; DA, dopamine; DNAB, dorsal noradrenergic bundle; DRD2, dopamine receptor 2 gene; ERP, event-related potentials; FEF, frontal eye field; IFC, inferior frontal cortex; IFG, inferior frontal gyrus; IFJ, inferior frontal junction; LC, locus coeruleus; M1, motor area 1; MDMA, 3,4-methylenedioxy-N-methylamphetamine; MRI, magnetic resonance imaging; NE, norepinephrine; OCD, obsessive-compulsive disorder; OFC, orbitofrontal cortex; Pre-SMA, pre-supplementary motor area; PFC, prefrontal cortex; RT, reaction time; SMA, supplementary motor area; SSD, stop-signal delay; SSRI, selective serotonin reuptake inhibitor; SSRT, stop-signal reaction time; SST, stop-signal task; STN, subthalamic nucleus. * Corresponding author. Present address: Department of Neurosciences, Medical University of South Carolina, 173 Ashley Ave, BSB 409 Charleston, SC 29425, United States. Tel.: +1 8437925289. E-mail address: andbari@gmail.com (A. Bari). G Model PRONEU-1278; No. of Pages 36 Please cite this article in press as: Bari, A., Robbins, T.W., Inhibition and impulsivity: Behavioral and neural basis of response control. Prog. Neurobiol. (2013), http://dx.doi.org/10.1016/j.pneurobio.2013.06.005 Contents lists available at SciVerse ScienceDirect Progress in Neurobiology jo u rn al ho m epag e: ww w.els evier .c om /lo cat e/pn eu ro b io 0301-0082/$ – see front matter ß 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.pneurobio.2013.06.005