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Behavioral models of impulsivity in humans and non-humans: Individual differences and effects of drugs. Harriet de Wit The University of Chicago Jerry.

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Presentation on theme: "Behavioral models of impulsivity in humans and non-humans: Individual differences and effects of drugs. Harriet de Wit The University of Chicago Jerry."— Presentation transcript:

1 Behavioral models of impulsivity in humans and non-humans: Individual differences and effects of drugs. Harriet de Wit The University of Chicago Jerry Richards University of Buffalo (SUNY)

2 Impulsivity closely linked with drug abuse As a determinantAs a determinant –Individual differences: risk factor –Momentary changes As a consequenceAs a consequence –Acute drug effects –Chronic drug effects

3 Impulsive Symptoms in Psychiatry: Common but Heterogeneous * failure to consider consequences; aggression (Antisocial Personality Disorder) * engaging in behaviors with damaging consequences (e.g., excessive spending, drug use) (Borderline Personality, Substance Use Disorder) * distractibility, difficulty waiting, lack of inhibitory control (ADHD) * impaired judgment, risk-taking (Substance-Induced Disorder)

4 Two broad types of impulsivity Cognitive impulsivity –Insensitivity to delayed consequences –Lack of planning, lack of forethought Behavioral inhibition –Difficulty inhibiting prepotent responses –Difficulty suppressing unwanted behavior, resisting temptation –Difficulty waiting

5 Procedures to Measure Impulsivity CognitiveCognitive –Delay discounting –Risk taking Behavioral inhibitionBehavioral inhibition –Stop Task –Go/no-go –Delay of gratification

6 Data to be presented Individual differencesIndividual differences Effects of drugsEffects of drugs HumansHumans Rats and miceRats and mice

7 I. Delay Discounting preference for immediate rewards over larger delayed rewardspreference for immediate rewards over larger delayed rewards –partying instead of studying –spending money now instead of saving

8 Reward Discounting as a Function of Delay 0 short Delay $10 Current Value Steeper discount function is an index of impulsive decision- making. Steeper discount function is an index of impulsive decision- making. Less Impulsive MoreImpulsive long

9 Individual Differences in Delay Discounting psychiatric patients (Crean et al, 2000) gamblers (Petry, 2001) gamblers (Petry, 2001) drug users (Bickel, 1999; Mitchell, 1999) drug users (Bickel, 1999; Mitchell, 1999) variability among healthy volunteers variability among healthy volunteers Relationship to personality Relationship to personality

10 Healthy Volunteers : Distribution of Delay Discounting Log K values (N=165) Frequency Log K

11 Healthy volunteers: Low positive correlations between delay discounting and personality Barratt Impulsivity Scale (N=184)Barratt Impulsivity Scale (N=184) –Cognitive Complexity (r=.19, p=.01; ‘I [do not] save regularly’, ‘I am more interested in the present than future’) –Nonplanning (‘I say things without thinking’; r=.15, p<.05) Multiphasic Personality Inventory (N=125)Multiphasic Personality Inventory (N=125) –Negative Emotionality (r=.19, p<.05; I am nervous, tense, easily upset, alienated)

12 Value (  L of Water) Delay to water delivery (sec) Rat Value ($) Delay to receive $10 (days) Human Delay discounting in humans and rats

13 Individual differences in delay discounting in rats: Relationship to novelty responding Rats that exhibit “high” responding in novel environment more readily self- administer drugs than “low” responders (Piazza et al).Rats that exhibit “high” responding in novel environment more readily self- administer drugs than “low” responders (Piazza et al). Do “high” responders also exhibit steeper delay discounting?Do “high” responders also exhibit steeper delay discounting?

14 High responders valued delayed rewards less * Value of delayed reward High responders Low responders Median Spli t

15 Novelty Response and Delay Discounting in Two Inbred Mouse Strains: S129 vs C57 Compared to C129, C57 mice :Compared to C129, C57 mice : Respond more to novel environmentsRespond more to novel environments Respond more (locomotor activity) to stimulantsRespond more (locomotor activity) to stimulants Self-administer alcohol more readilySelf-administer alcohol more readily

16 Novelty Response C57S * Distance Traveled Strain K Value (higher k value = greater discounting) C57S * Strain K Value

17 No Correlation Within Strains (I.e., strain differences related to genotype) C57 K Value Distance Traveled

18 Effects of Drugs on Delay Discounting ( = decrease in impulsivity )

19 II. Behavioral Inhibition Stop Task  Ability to inhibit a prepotent response  Subject told to respond as quickly as possible to a visual Go signal...  but to withhold the response if an auditory Stop signal is presented immediately after the Go signal  How long does the individual need to Stop the response?

20 Time Go Signal Go Response Go Reaction Time Time Go Signal Stop RT Stop Signal

21 Individual Differences in Stop RT on Stop Task ADHD children have slower Stop RT’s ADHD children have slower Stop RT’s (Schachar et al, 1993) Methylphenidate normalizes Stop RT in Methylphenidate normalizes Stop RT in ADHD children (Tannock et al, 1989) Cocaine users have slower Stop RT’s than Cocaine users have slower Stop RT’s than controls (Fillmore and Rush, 2002)

22 Healthy Volunteers: Distribution of Stop Reaction Time (N=165) Frequency msec

23 Healthy volunteers: Low positive correlations between Stop RT and personality (N=239) Correlations between Stop RT and Barratt Impulsivity SubscalesCorrelations between Stop RT and Barratt Impulsivity Subscales –Self-Control (r=.18, p=.005 ‘I [do not] plan tasks carefully’, ‘I am a careful thinker’, ‘I say things without thinking’) –Attention (r=.19, p=.003) ‘I [do not] concentrate easily’, ‘I squirm at plays or lectures’, ‘I am [not] a steady thinker’)

24 Is delay discounting (k value) related to behavioral inhibition (Stop RT)? 165 healthy volunteers correlation factor analysis 165 healthy volunteers correlation factor analysis

25 Delay Discounting (Log k value) Stop RT (msec) Stop RT and Delay Discounting not correlated (N=165, r=.026, ns)

26 Effects of drugs on Stop RT Do drugs affect behavioral inhibition?Do drugs affect behavioral inhibition? Do drugs produce similar effects in humans and non-humans?Do drugs produce similar effects in humans and non-humans? Do drugs have similar effects on Stop RT and Delay Discounting?Do drugs have similar effects on Stop RT and Delay Discounting?

27 Effects of drugs on Stop RT (decrease in Stop RT = decrease in impulsivity) rathuman d-amphetamine (acute) Alcohol THC 5-HTlesion ordepletion

28 Concordance between Delay Discounting and Stop Task in Rats Delay Discounting Stop Task Alcohol NO EFFECT D- amphetamine 5HT lesion NO EFFECT

29 Conclusion 1: Delay Discounting procedures and the Stop Task are valid methods for measuring impulsive behavior sensitive to individual differences sensitive to individual differences sensitive to drugs sensitive to drugs good correspondence between humans and non-humans good correspondence between humans and non-humans

30 Conclusion 2: However, delay discounting and behavioral inhibition reflect separate processes performance not correlated between individuals performance not correlated between individuals factor analysis reveals separate processes factor analysis reveals separate processes drugs have different effects drugs have different effects

31 Acknowledgments John Crean, PhD John Crean, PhD Justin Enggasser, MAJustin Enggasser, MA Henry Chi, MAHenry Chi, MA Jen McDonald, BAJen McDonald, BA Andrea King, PhDAndrea King, PhD Brady Reynolds,PhDBrady Reynolds,PhD Jim Zacny, PhDJim Zacny, PhD GCRC, NIDAGCRC, NIDA


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