Behavioral models of impulsivity Behavioral models of impulsivity in humans and non-humans: in humans and non-humans:

Individual differences and Individual differences and effects of drugs.effects of drugs.

Harriet de Wit Harriet de Wit The University of ChicagoThe University of Chicago

Jerry RichardsJerry RichardsUniversity of Buffalo (SUNY)University of Buffalo (SUNY)

Impulsivity closely linked with Impulsivity closely linked with drug abusedrug abuse

• As a determinantAs a determinant– Individual differencesIndividual differences: risk factor : risk factor – Momentary changesMomentary changes

• As a consequenceAs a consequence– Acute drug effectsAcute drug effects– Chronic drug effectsChronic drug effects

Impulsive Symptoms in Psychiatry:Impulsive Symptoms in Psychiatry:CommonCommon but Heterogeneousbut Heterogeneous

* failure to consider consequences; aggression * failure to consider consequences; aggression (Antisocial Personality Disorder)(Antisocial Personality Disorder)

* engaging in behaviors with damaging * engaging in behaviors with damaging consequences (e.g., excessive spending, consequences (e.g., excessive spending, drug use) drug use) (Borderline Personality, Substance Use Disorder)(Borderline Personality, Substance Use Disorder)

* distractibility, difficulty waiting, lack of * distractibility, difficulty waiting, lack of inhibitory inhibitory

controlcontrol (ADHD)(ADHD)

* impaired judgment, risk-taking * impaired judgment, risk-taking (Substance-Induced (Substance-Induced Disorder)Disorder)

Two broad types of impulsivityTwo broad types of impulsivity

Cognitive impulsivityCognitive impulsivity– Insensitivity to delayed consequencesInsensitivity to delayed consequences– Lack of planning, lack of forethoughtLack of planning, lack of forethought

Behavioral inhibitionBehavioral inhibition– Difficulty inhibiting prepotent responsesDifficulty inhibiting prepotent responses– Difficulty suppressing unwanted Difficulty suppressing unwanted

behavior, resisting temptationbehavior, resisting temptation– Difficulty waitingDifficulty waiting

Procedures to Measure ImpulsivityProcedures to Measure Impulsivity

• CognitiveCognitive– Delay discountingDelay discounting– Risk takingRisk taking

• Behavioral inhibitionBehavioral inhibition– Stop TaskStop Task– Go/no-goGo/no-go– Delay of gratificationDelay of gratification

Data to be presentedData to be presented

• Individual differencesIndividual differences

• Effects of drugsEffects of drugs

• HumansHumans

• Rats and miceRats and mice

I. Delay DiscountingI. Delay Discounting

• preference for immediate rewards preference for immediate rewards over larger delayed rewardsover larger delayed rewards– partying instead of studyingpartying instead of studying– spending money now instead of savingspending money now instead of saving

Reward Discounting as a Function of DelayReward Discounting as a Function of Delay

00shortshort

DelayDelay

$10$10C

urre

nt V

alue

Cur

rent

Val

ue

Steeper discount function is an index of impulsive decision-Steeper discount function is an index of impulsive decision-making.making.

Less ImpulsiveLess Impulsive

MoreMoreImpulsiveImpulsive

longlong

Individual Differences in Delay Individual Differences in Delay DiscountingDiscounting

• psychiatric patients psychiatric patients (Crean et al, 2000)(Crean et al, 2000)

• • gamblers gamblers (Petry, 2001)(Petry, 2001)

• • drug users drug users (Bickel, 1999; Mitchell, 1999)(Bickel, 1999; Mitchell, 1999)

• • variability among healthy volunteersvariability among healthy volunteers• • Relationship to personalityRelationship to personality

Healthy Volunteers: Distribution of

Delay Discounting Log K values (N=165)

0

5

10

15

20

25

30

35

40

45

50

Fre

qu

en

cy

-.5-1-1.5-2-2.5-3-3.5

Log KLog K

Healthy volunteers: Low positive Healthy volunteers: Low positive correlations between delay discounting correlations between delay discounting

and and personalitypersonality

• Barratt Impulsivity Scale Barratt Impulsivity Scale (N=184)(N=184)

– Cognitive Complexity Cognitive Complexity (r=.19, p=.01; ‘I [do not] save (r=.19, p=.01; ‘I [do not] save regularly’, ‘I am more interested in the present than future’)regularly’, ‘I am more interested in the present than future’)

– Nonplanning Nonplanning (‘I say things without thinking’; r=.15, (‘I say things without thinking’; r=.15, p<.05) p<.05)

• Multiphasic Personality Inventory Multiphasic Personality Inventory (N=125)(N=125)

– Negative Emotionality Negative Emotionality (r=.19, p<.05; I am nervous, (r=.19, p<.05; I am nervous, tense, easily upset, alienated)tense, easily upset, alienated)

0

50

100

150

Val

ue

(

L o

f W

ater

)0 4 8 12 16

Delay to water delivery (sec)

Rat

0 120 240 360

0

2

4

6

8

10

Val

ue

($)

Delay to receive $10 (days)

Human

Delay discounting in humans and ratsDelay discounting in humans and rats

Individual differences in delay Individual differences in delay discounting in rats: Relationship to discounting in rats: Relationship to

novelty respondingnovelty responding

• Rats that exhibit “high” responding in Rats that exhibit “high” responding in novel environment more readily self-novel environment more readily self-administer drugs than “low” administer drugs than “low” responders responders (Piazza et al).(Piazza et al).

• Do “high” responders also exhibit Do “high” responders also exhibit steeper delay discounting? steeper delay discounting?

High responders valued delayed rewards less

50

60

70

80

90

*

Val

ue o

f del

ayed

rew

ard

High respondersLow responders

Median Split

Novelty Response and Delay Novelty Response and Delay DiscountingDiscounting in Two Inbred Mouse in Two Inbred Mouse

Strains: S129 vs C57Strains: S129 vs C57

• Compared to C129, C57 miceCompared to C129, C57 mice::• Respond more to novel environmentsRespond more to novel environments• Respond more (locomotor activity) to Respond more (locomotor activity) to

stimulantsstimulants• Self-administer alcoholSelf-administer alcohol more readily more readily

Novelty Response

C57 S1290

4000

8000

12000

*

Dis

tanc

e T

rave

led

Strain

K Value (higher k value =

greater discounting)

C57 S129

.2

.4

.6

.8

1.0

*

Strain

K V

alue

No Correlation Within Strains(I.e., strain differences related to genotype)

4000 8000 12000 160000.0

0.5

1.0

1.5

2.0

2.5 S129

Distance Traveled4000 8000 12000 16000

0.0

0.5

1.0

1.5

2.0

2.5 C57

K V

alue

Distance Traveled

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

rat human

d-amphetamine (acute)

Methamphetamine (acute)

Methamphetamine (chronic)

D2 antagonist5-HT lesion or depletion n.e. n.e.

II. Behavioral InhibitionII. Behavioral InhibitionStop TaskStop Task

Ability to inhibit a prepotent responseAbility to inhibit a prepotent response Subject told to respond as quickly as possible to Subject told to respond as quickly as possible to

a visual Go signal...a visual Go signal... but to but to withholdwithhold the response if an auditory Stop the response if an auditory Stop

signal is presented immediately after the Go signal is presented immediately after the Go signal signal

How long does the individual need to Stop the How long does the individual need to Stop the response?response?

TimeTime

Go SignalGo SignalGo ResponseGo Response

Go Reaction TimeGo Reaction Time

TimeTime

Go SignalGo Signal

Stop RTStop RT

Stop Signal Stop Signal

Individual Differences in Stop Individual Differences in Stop RT on Stop TaskRT on Stop Task

• • ADHD children have slower Stop RT’sADHD children have slower Stop RT’s(Schachar et al, 1993)(Schachar et al, 1993)

• • Methylphenidate normalizes Stop RT in Methylphenidate normalizes Stop RT in ADHD children ADHD children (Tannock et al, 1989)(Tannock et al, 1989)

• • Cocaine users have slower Stop RT’s than Cocaine users have slower Stop RT’s than controls controls (Fillmore and Rush, 2002)(Fillmore and Rush, 2002)

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

0

20

40

60

80

100

Fre

qu

ency

50 100 150 200 250 300 350 400 450msecmsec

Healthy volunteers: Low positive Healthy volunteers: Low positive correlations between Stop RT and correlations between Stop RT and

personality (N=239)personality (N=239)

• Correlations between Stop RT and Barratt Correlations between Stop RT and Barratt Impulsivity SubscalesImpulsivity Subscales– Self-Control Self-Control (r=.18, p=.005 ‘I [do not] plan tasks carefully’, (r=.18, p=.005 ‘I [do not] plan tasks carefully’,

‘I am a careful thinker’, ‘I say things without thinking’)‘I am a careful thinker’, ‘I say things without thinking’)

– Attention Attention (r=.19, p=.003) ‘I [do not] concentrate easily’, ‘I (r=.19, p=.003) ‘I [do not] concentrate easily’, ‘I squirm at plays or lectures’, ‘I am [not] a steady thinker’)squirm at plays or lectures’, ‘I am [not] a steady thinker’)

Is delay discounting (k value) related Is delay discounting (k value) related to behavioral inhibition (Stop RT)?to behavioral inhibition (Stop RT)?

• • 165 healthy volunteers165 healthy volunteers• correlation• correlation• factor analysis• factor analysis

0

100

200

300

400

500

600

-4 -3 -2 -1 0

Delay Discounting (Log k value)

StopRT(msec)

Stop RT and Delay Discounting not correlated(N=165, r=.026, ns)

Effects of drugs on Stop RTEffects of drugs on Stop RT

• Do drugs affect behavioral inhibition?Do drugs affect behavioral inhibition?

• Do drugs produce similar effects in Do drugs produce similar effects in humans and non-humans?humans and non-humans?

• Do drugs have similar effects on Stop Do drugs have similar effects on Stop RT and Delay Discounting?RT and Delay Discounting?

Effects of drugs on Stop RTEffects of drugs on Stop RT(decrease in Stop RT = decrease in impulsivity)(decrease in Stop RT = decrease in impulsivity)

rat human

d-amphetamine (acute)

Alcohol

THC

5-HT lesion or depletion

Concordance between Delay Concordance between Delay Discounting and Stop Task in RatsDiscounting and Stop Task in Rats

Delay Delay DiscountingDiscounting

Stop TaskStop Task

AlcoholAlcohol

NO EFFECTNO EFFECT

D-D-amphetamineamphetamine

5HT lesion5HT lesion

NO EFFECTNO EFFECT

Conclusion 1: Conclusion 1: Delay Delay Discounting procedures and the Discounting procedures and the Stop Task are valid methods for Stop Task are valid methods for measuring impulsive behaviormeasuring impulsive behavior

• • sensitive to individual differencessensitive to individual differences

• • sensitive to drugssensitive to drugs

• • good correspondence between good correspondence between humans and non-humanshumans and non-humans

Conclusion 2:Conclusion 2:However, delay discounting and However, delay discounting and

behavioral inhibition reflect behavioral inhibition reflect separate processesseparate processes

• • performance not correlated performance not correlated between individualsbetween individuals

• • factor analysis reveals separate factor analysis reveals separate processesprocesses

• • drugs have different effectsdrugs have different effects

AcknowledgmentsAcknowledgments

• • John Crean, PhDJohn 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