Behavioral models of impulsivity in humans and non-humans by umsymums39

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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 Richards
          University of Buffalo (SUNY)
Impulsivity closely linked with
         drug abuse
    • As a determinant
      – Individual differences: risk factor
      – Momentary changes
    • As a consequence
      – Acute drug effects
      – Chronic drug effects
   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)
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
 Procedures to Measure Impulsivity

• Cognitive             • Behavioral inhibition
  – Delay discounting     – Stop Task
  – Risk taking           – Go/no-go
                          – Delay of gratification
Data to be presented
 • Individual differences
 • Effects of drugs



 • Humans
 • Rats and mice
       I. Delay Discounting

• preference for immediate rewards
  over larger delayed rewards
  – partying instead of studying
  – spending money now instead of saving
  Reward Discounting as a Function of Delay


        Current Value
                        $10

                                               Less Impulsive


                               More
                               Impulsive
                         0
                              short             long
                                       Delay


Steeper discount function is an index of impulsive decision-
            making.
Individual Differences in Delay
         Discounting
• psychiatric patients (Crean et al, 2000)
• gamblers (Petry, 2001)
• drug users (Bickel, 1999; Mitchell, 1999)
• variability among healthy volunteers
  • Relationship to personality
    Healthy Volunteers: Distribution of
   Delay Discounting Log K values (N=165)

            50
            45
            40
            35
            30
Frequency




            25
            20
            15
            10
             5
             0
                 -3.5   -3   -2.5    -2   -1.5   -1   -.5
                                    Log K
   Healthy volunteers: Low positive
correlations between delay discounting
            and personality
• 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)
  – Negative Emotionality (r=.19, p<.05; I am nervous,
    tense, easily upset, alienated)
            Delay discounting in humans and rats
                        Human                                                        Rat
        10




                                            Value ( L of Water)
                                                                   150
            8
Value ($)




            6
                                                                   100
            4

            2                                                      50

            0
                                                                    0
                0       120    240    360
                                                                         0      4     8   12    16
                    Delay to receive $10                                     Delay to water delivery
                           (days)                                                     (sec)
   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).
• Do “high” responders also exhibit
  steeper delay discounting?
                                High responders valued
Value of delayed reward
                          90     delayed rewards less

                          80

                                                       *
                          70


                          60


                          50
                               Low responders    High responders
                                        Median Split
   Novelty Response and Delay
 Discounting in Two Inbred Mouse
      Strains: S129 vs C57

• Compared to C129, C57 mice:
  • Respond more to novel environments
  • Respond more (locomotor activity) to
    stimulants
  • Self-administer alcohol more readily
                            Novelty                                 K Value
                           Response                              (higher k value =
                                                                greater discounting)
Distance Traveled




                                                 K Value
                    12 0
                      00                               1.0
                                                           .8
                    8000
                                           *               .6                   *
                    40
                     00                                    .4
                                                           .2
                      0
                            C57             19
                                           S2                        5
                                                                    C7           19
                                                                                S2
                                  Strain                                  tra
                                                                         S in
          No Correlation Within Strains
   (I.e., strain differences related to genotype)

     2.5            C57               2.5            S129
                                      2.0
K Value




     2.0

     1.5                              1.5

     1.0                              1.0

     0.5                              0.5

     0.0                              0.0
            4000   8000   12000   16000     4000   8000     12000   16000

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

                                rat     human

    d-amphetamine (acute)
    Methamphetamine (acute)
    Methamphetamine (chronic)
    D2 antagonist
    5-HT lesion or depletion     n.e.   n.e.
       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?
                          Go Response
Go Signal


                                        Time

       Go Reaction Time


            Stop Signal
Go Signal

                                        Time


                  Stop RT
  Individual Differences in Stop
         RT on Stop Task

• ADHD children have slower Stop RT‟s
     (Schachar et al, 1993)
• Methylphenidate normalizes Stop RT in
      ADHD children (Tannock et al, 1989)
• Cocaine users have slower Stop RT‟s than
      controls (Fillmore and Rush, 2002)
                  Healthy Volunteers: Distribution of
                     Stop Reaction Time (N=165)
            100

            80

            60
Frequency




            40

            20

             0
                   50 100 150 200 250 300 350 400 450
                              msec
     Healthy volunteers: Low positive
    correlations between Stop RT and
           personality (N=239)

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


        • 165 healthy volunteers
        • correlation
        • factor analysis
   Stop RT and Delay Discounting not correlated
                (N=165, r=.026, ns)

       600



       500
Stop
RT    400

(msec)
       300



       200



       100



        0
             -4         -3       -2        -1       0
                  Delay Discounting (Log k value)
   Effects of drugs on Stop RT
• Do drugs affect behavioral inhibition?

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

• Do drugs have similar effects on Stop
  RT and Delay Discounting?
   Effects of drugs on Stop RT
(decrease in Stop RT = decrease in impulsivity)

                                   rat human
 d-amphetamine (acute)
 Alcohol
 THC
 5-HT lesion or depletion
    Concordance between Delay
 Discounting and Stop Task in Rats
              Delay         Stop Task
              Discounting
Alcohol
              NO EFFECT
D-
amphetamine
5HT lesion
              NO EFFECT
     Conclusion 1: Delay
Discounting procedures and the
Stop Task are valid methods for
 measuring impulsive behavior
  • sensitive to individual differences
  • sensitive to drugs
  • good correspondence between
  humans and non-humans
        Conclusion 2:
However, delay discounting and
  behavioral inhibition reflect
     separate processes
  • performance not correlated between
  individuals
  • factor analysis reveals separate
  processes
  • drugs have different effects
Acknowledgments
•   John Crean, PhD
•   Justin Enggasser, MA
•   Henry Chi, MA
•   Jen McDonald, BA
•   Andrea King, PhD
•   Brady Reynolds,PhD
•   Jim Zacny, PhD
•   GCRC, NIDA

								
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