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.
References
[1]
Moeller FG, Barratt ES, Dougherty DM, Schmitz JM, Swann AC (2001) Psychiatric aspects of impulsivity. Am J Psychiatry 158: 1783–1793.
[2]
Evenden JL (1999) Varieties of impulsivity. Psychopharmacology (Berl) 146: 348–361.
[3]
Reynolds B, Ortengren A, Richards JB, de Wit H (2006) Dimensions of impulsive behavior: Personality and behavioral measures. Personality and Individual Differences 40: 305–315.
[4]
Winstanley CA, Eagle DM, Robbins TW (2006) Behavioral models of impulsivity in relation to ADHD: translation between clinical and preclinical studies. Clin Psychol Rev 26: 379–395.
[5]
Ho MY, Mobini S, Chiang TJ, Bradshaw CM, Szabadi E (1999) Theory and method in the quantitative analysis of “impulsive choice” behaviour: implications for psychopharmacology. Psychopharmacology (Berl) 146: 362–372.
[6]
Logan GD, Schachar RJ, Tannock R (1997) Impulsivity and inhibitory control. Psychological Science 8: 60–64.
Dalley JW, Mar AC, Economidou D, Robbins TW (2008) Neurobehavioral mechanisms of impulsivity: fronto-striatal systems and functional neurochemistry. Pharmacol Biochem Behav 90: 250–260.
[9]
Pattij T, Vanderschuren LJ (2008) The neuropharmacology of impulsive behaviour. Trends Pharmacol Sci 29: 192–199.
[10]
Chambers CD, Garavan H, Bellgrove MA (2009) Insights into the neural basis of response inhibition from cognitive and clinical neuroscience. Neuroscience and Biobehavioral Reviews 33: 631–646.
[11]
Peters J, Buchel C (2011) The neural mechanisms of inter-temporal decision-making: understanding variability. Trends Cogn Sci 15: 227–239.
[12]
Solanto MV, Abikoff H, Sonuga-Barke E, Schachar R, Logan GD, et al. (2001) The ecological validity of delay aversion and response inhibition as measures of impulsivity in AD/HD: a supplement to the NIMH multimodal treatment study of AD/HD. J Abnorm Child Psychol 29: 215–228.
[13]
Broos N, Diergaarde L, Schoffelmeer AN, Pattij T, De Vries TJ (2012) Trait Impulsive Choice Predicts Resistance to Extinction and Propensity to Relapse to Cocaine Seeking: A Bidirectional Investigation. Neuropsychopharmacology In press.
[14]
Diergaarde L, Pattij T, Poortvliet I, Hogenboom F, De Vries W, et al. (2008) Impulsive choice and impulsive action predict vulnerability to distinct stages of nicotine seeking in rats. Biol Psychiatry 63: 301–308.
[15]
Nigg JT, Wong MM, Martel MM, Jester JM, Puttler LI, et al. (2006) Poor response inhibition as a predictor of problem drinking and illicit drug use in adolescents at risk for alcoholism and other substance use disorders. J Am Acad Child Adolesc Psychiatry 45: 468–475.
[16]
Tarter RE, Kirisci L, Mezzich A, Cornelius JR, Pajer K, et al. (2003) Neurobehavioral disinhibition in childhood predicts early age at onset of substance use disorder. Am J Psychiatry 160: 1078–1085.
[17]
Verdejo-Garcia A, Lawrence AJ, Clark L (2008) Impulsivity as a vulnerability marker for substance-use disorders: review of findings from high-risk research, problem gamblers and genetic association studies. Neurosci Biobehav Rev 32: 777–810.
[18]
Robinson ES, Eagle DM, Economidou D, Theobald DE, Mar AC, et al. (2009) Behavioural characterisation of high impulsivity on the 5-choice serial reaction time task: specific deficits in ‘waiting’ versus ‘stopping’. Behav Brain Res 196: 310–316.
[19]
Van den Bergh F, Spronk M, Ferreira L, Bloemarts E, Groenink L, et al. (2006) Relationship of delay aversion and response inhibition to extinction learning, aggression, and sexual behaviour. Behavioural Brain Research 175: 75–81.
[20]
Winstanley CA, Dalley JW, Theobald DE, Robbins TW (2004) Fractionating impulsivity: contrasting effects of central 5-HT depletion on different measures of impulsive behavior. Neuropsychopharmacology 29: 1331–1343.
[21]
Dougherty DM, Mathias CW, Marsh-Richard DM, Furr RM, Nouvion SO, et al. (2009) Distinctions in Behavioral Impulsivity: Implications for Substance Abuse Research. Addict Disord Their Treat 8: 61–73.
[22]
Lane S, Cherek D, Rhoades H, Pietras C, Tcheremissine O (2003) Relationships Among Laboratory and Psychometric Measures of Impulsivity: Implications in Substance Abuse and Dependence. Addictive Disorders & Their Treatment 2: 33–40.
[23]
Meda SA, Stevens MC, Potenza MN, Pittman B, Gueorguieva R, et al. (2009) Investigating the behavioral and self-report constructs of impulsivity domains using principal component analysis. Behavioural Pharmacology 20: 390–399.
[24]
Reynolds B, Penfold RB, Patak M (2008) Dimensions of impulsive behavior in adolescents: Laboratory behavioral assessments. Experimental and Clinical Psychopharmacology 16: 124–131.
[25]
van Gaalen MM, van Koten R, Schoffelmeer AN, Vanderschuren LJ (2006) Critical involvement of dopaminergic neurotransmission in impulsive decision making. Biol Psychiatry 60: 66–73.
[26]
Mazur J (1987) An adjusting procedure for studying delayed reinforcement. In: Commons M, Mazur J, Nevin J, Rachlin H, editors. Quantitative analysis of behavior, vol V: the effect of delay and intervening events. Hillsdale: Erlbaum.
[27]
van Gaalen MM, Brueggeman RJ, Bronius PF, Schoffelmeer AN, Vanderschuren LJ (2006) Behavioral disinhibition requires dopamine receptor activation. Psychopharmacology (Berl) 187: 73–85.
[28]
Dalley JW, Fryer TD, Brichard L, Robinson ES, Theobald DE, et al. (2007) Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement. Science 315: 1267–1270.
[29]
Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, et al. (1998) The Mini-International Neuropsychiatric Interview (MINI): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry 59: 22–33.
[30]
Mitchell SH (1999) Measures of impulsivity in cigarette smokers and non-smokers. Psychopharmacology 146: 455–464.
[31]
Dougherty DM, Marsh DM, Mathias CW (2002) Immediate and delayed memory tasks: A computerized behavioral measure of memory, attention, and impulsivity. Behavior Research Methods Instruments & Computers 34: 391–398.
[32]
Mathias CW, Marsh DM, Dougherty DM (2002) Reliability estimates for the immediate and delayed memory tasks. Perceptual and Motor Skills 95: 559–569.
[33]
Logan GD, Cowan WB, Davis KA (1984) On the Ability to Inhibit Simple and Choice Reaction-Time Responses – A Model and A Method. Journal of Experimental Psychology-Human Perception and Performance 10: 276–291.
[34]
Scheres A, Oosterlaan J, Sergeant JA (2001) Response execution and inhibition in children with AD/HD and other disruptive disorders: The role of behavioural activation. Journal of Child Psychology and Psychiatry and Allied Disciplines 42: 347–357.
[35]
Patton JH, Stanford MS, Barratt ES (1995) Factor structure of the Barratt Impulsiveness Scale. Journal of Clinical Psychology 51: 768–774.
[36]
Cardinal RN, Robbins TW, Everitt BJ (2000) The effects of d-amphetamine, chlordiazepoxide, alpha-flupenthixol and behavioural manipulations on choice of signalled and unsignalled delayed reinforcement in rats. Psychopharmacology (Berl) 152: 362–375.
[37]
Cole BJ, Robbins TW (1987) Amphetamine impairs the discriminative performance of rats with dorsal noradrenergic bundle lesions on a 5-choice serial reaction time task: new evidence for central dopaminergic-noradrenergic interactions. Psychopharmacology (Berl) 91: 458–466.
[38]
Wiskerke J, Schetters D, van E, I , van MY, den Hollander BR, et al. (2011) mu-Opioid receptors in the nucleus accumbens shell region mediate the effects of amphetamine on inhibitory control but not impulsive choice. J Neurosci 31: 262–272.
[39]
Blondeau C, lu-Hagedorn F (2007) Dimensional analysis of ADHD subtypes in rats. Biol Psychiatry 61: 1340–1350.
[40]
Paterson NE, Ricciardi J, Wetzler C, Hanania T (2011) Sub-optimal performance in the 5-choice serial reaction time task in rats was sensitive to methylphenidate, atomoxetine and D-amphetamine, but unaffected by the COMT inhibitor tolcapone. Neuroscience Research 69: 41–50.
[41]
Robinson ES, Eagle DM, Mar AC, Bari A, Banerjee G, et al. (2008) Similar effects of the selective noradrenaline reuptake inhibitor atomoxetine on three distinct forms of impulsivity in the rat. Neuropsychopharmacology 33: 1028–1037.
[42]
Baarendse PJ, Vanderschuren LJ (2012) Dissociable effects of monoamine reuptake inhibitors on distinct forms of impulsive behavior in rats. Psychopharmacology (Berl) 219: 313–326.
[43]
Dougherty DM, Bjork JM, Harper RA, Marsh DM, Moeller FG, et al. (2003) Behavioral impulsivity paradigms: a comparison in hospitalized adolescents with disruptive behavior disorders. Journal of Child Psychology and Psychiatry and Allied Disciplines 44: 1145–1157.
[44]
Schachar R, Logan GD, Robaey P, Chen S, Ickowicz A, et al. (2007) Restraint and cancellation: Multiple inhibition deficits in attention deficit hyperactivity disorder. Journal of Abnormal Child Psychology 35: 229–238.
[45]
Carli M, Robbins TW, Evenden JL, Everitt BJ (1983) Effects of lesions to ascending noradrenergic neurones on performance of a 5-choice serial reaction task in rats; implications for theories of dorsal noradrenergic bundle function based on selective attention and arousal. Behav Brain Res 9: 361–380.
[46]
Killeen PR (2009) An Additive-Utility Model of Delay Discounting. Psychological Review 116: 602–619.
[47]
Chamberlain SR, Robbins TW, Winder-Rhodes S, Muller U, Sahakian BJ, et al. (2011) Translational Approaches to Frontostriatal Dysfunction in Attention-Deficit/Hyperactivity Disorder Using a Computerized Neuropsychological Battery. Biol Psychiatry 69: 1192–1203.
[48]
Clark L, Robbins TW, Ersche KD, Sahakian BJ (2006) Reflection impulsivity in current and former substance users. Biological Psychiatry 60: 515–522.
[49]
Kagan J (1966) Reflection-Impulsivity – Generality and Dynamics of Conceptual Tempo. Journal of Abnormal Psychology 71: 17–24.
[50]
Swann AC, Lijffijt M, Lane SD, Steinberg JL, Moeller FG (2009) Trait impulsivity and response inhibition in antisocial personality disorder. Journal of Psychiatric Research 43: 1057–1063.
[51]
MacKillop J, Kahler CW (2009) Delayed reward discounting predicts treatment response for heavy drinkers receiving smoking cessation treatment. Drug and Alcohol Dependence 104: 197–203.
[52]
Perkins KA, Lerman C, Coddington SB, Jetton C, Karelitz JL, et al. (2008) Initial nicotine sensitivity in humans as a function of impulsivity. Psychopharmacology 200: 529–544.
[53]
Bickel WK, Pitcock JA, Yi R, Angtuaco EJC (2009) Congruence of BOLD Response across Intertemporal Choice Conditions: Fictive and Real Money Gains and Losses. Journal of Neuroscience 29: 8839–8846.
[54]
Johnson MW, Bickel WK (2002) Within-subject comparison of real and hypothetical money rewards in delay discounting. J Exp Anal Behav 77: 129–146.
[55]
Lagorio CH, Madden GJ (2005) Delay discounting of real and hypothetical rewards III: steady-state assessments, forced-choice trials, and all real rewards. Behav Processes 69: 173–187.
