Shackman Psyc210 Module19 DepImpCon Part2 ExtSelfControl

The dopamine theory of reward and addiction,
which states that dopamine release mediates

reward and thus leads to addiction, has had huge
traction.
However, it became accepted as a universal theory
without properly accounting for findings from
studies in different drug addictions that did not
support the theory.
Tellingly, the dopamine theory has not led to any
new treatments for addiction.
Nutt et al Nature Reviews
Neuroscience 2015
Nuts & Bolts Plan for

Today
Lecture
- Focus on substance use and related

impulse-control disorders
Take-home critical thinking

questions
PSYC 210:
C/SC: Biological bases and
implications for understanding
substance abuse,
impulse-control disorders
and everyday temptation
(Pleasure, Reward & Inhibition Part
2 of 2)
AJ Shackman
07 May 2015
Caveat
Reward, Impulsivity & Addiction are
1. Experimentation
complex
2.
3.
4.
5.
6.
Onset
Maintenance
Abstinence
Withdrawal
Relapse
Equifinality Multiple etiological

pathways
will very selectively focus on a few key t
Caveat
1. Experimentation
complex
2.
3.
4.
5.
6.
Onset
Maintenance
Abstinence
Withdrawal
Relapse

pathways
Caveat
1. Experimentation
complex
2.
3.
4.
5.
6.
Onset
Maintenance
Abstinence
Withdrawal
Relapse

pathways
Conceptual Roadmap
Why do we so often succumb to
temptation?
Why is it so hard to resist our impulses

toward gratification? Students??
Conceptual Roadmap
temptation?
Subcortical
Wanting
Systems

Conceptual Roadmap
temptation?
Goal-Directed
Prefrontal
Regulatory
Systems
Subcortical
Wanting
Systems

Conceptual Roadmap
temptation?
OFC
Choice
Goal-Directed
Prefrontal
Regulatory
Systems
Subcortical
Wanting
Systems

Clinical perspective and diagnostic criteria

Develop some intuitions about
whats gone awry
Lets start with the formal criteria for

substance use disorders (SUDs)
DSM-IV-TR: Substance Use

Disorders

Disorders
This intuition is consistent

with fMRI studies of addicts
Meta-Analyses of fMRI Studies: Chase et al Biol Psych 2011; Tang et al Physiol & Behav 2012; Kuhn et a
Meta-Analyses of fMRI
Studies
Studies
Drug cue-related activation in the
ventral striatum in users
Studies
Overlap of cue-related activation for

food
and nicotine stimuli in users,
suggesting that drugs hijack
reward/approach circuits
Studies
Overlap of cue-related activation for

food
and nicotine stimuli in users,
suggesting that drugs hijack
reward/approach circuits
Amygdala is not specific to fear and

anxiety! Prioritizing attention to
salient
cuesTang
in et
the
environment
Meta-Analyses of fMRI Studies: Chase et al Biol
Psych 2011;
al Physiol
& Behav 2012; Kuhn et a
But not just heightened activation

of circuits involved in
approach and reward

Disorders
Potential Role of C/SC in SUDs
vs
Zentner et al. 2012; cf. Caspi et al 20
Potential Role of C/SC in SUDs
Working Hypothesis
SUDs = Too Little C/SC (OFC?), Too Much Wanting, or Too Little
vs
Section 2:
Show me the (epidemiological) data!
Meta-analysis of 175 studies (n=75,229)

High N/NE and Low Conscientiousness
were nonspecifically associated with
anxiety, depression, and SUD
Many disorders were associated with
Low E/PE, with larger effects for
depression/dysthmia
The 'disinhibition' facet of C/SC was
N = Neuroticism; E = Extraversion; D = Disinhibition; C = Conscientiou

Distress = GAD + MDD; Fear = Panic and Phobias
Among broad-band superfacto

SUD risk is associated with
1. High N/NE (though this is not
specific to SUDs)



specific to SUDs)
This is important, but I am not go

to elaborate on it today. Consiste
with elevated stress sensitivity an
self-medication


specific to SUDs)
2.
Low C/SC (High Disinhibition

Low Conscientiousness)
3. Weakest (neg) relationship

with Extraversion

Consistent with other

recent meta-analyses
Meta-analysis: 102 studies (N = 32,648) investigating the

specific to SUDs)
2.


with Extraversion


specific to SUDs)
2.


with Extraversion
Indeed, a core defining characteristic of SUD is that of little interest for reward
other than the drug. When not engaged in drug-related behavior, [patients]
show low disposition toward
= Neuroticism;
E = Extraversion;
D = Disinhibition;
C = et
Conscientiou
positive emotions and a low Ndegree
of incentive
motivation
(Belcher
al TiCS
enhanced motivation to procure drugs is a hallmark of addiction. Drugaddicted individuals will go to extreme behaviors to obtain drugs, even at
the expense of seriously adverse consequences. Drug seeking and drug
taking become their main motivational drives, which displace other
activities.
Thus, the addictis aroused and motivated when seeking to procure the
drug but tends to be withdrawn and apathetic when exposed to nondrugrelated activities.
Volkow
et al PNAS
2011
Among
broad-band
superfacto
specific to SUDs)
2.


with Extraversion
= Neuroticism;
E = Extraversion;
D = Disinhibition;
C = et
Conscientiou
of incentive
motivation
(Belcher
al TiCS
enhanced motivation to procure drugs is a hallmark of addiction. Drugaddicted individuals will go to extreme behaviors to obtain drugs, even at
Addictions
represent
a clear Drug seeking and drug
the expense of seriously
adverse
consequences.
example
of how wanting
can
be displace other
taking become their
main motivational
drives,
which
dissociated from liking. In contrast
activities.
to depression,drug addiction is
Thus, the addictis
aroused and by
motivated
when
characterized
an excess
ofseeking
drug to procure the
drug but tends towanting.
be withdrawn and apathetic when exposed to nondrugrelated activities.
Volkow
et al PNAS
2011
Further,the excessive
andAmong
neverbroad-band
superfacto
ending chase of the reward
ofrisk
choice
SUD
is associated with
leaves little room for the pursuit of
other pleasures.
specific to SUDs)
In other words, drug craving is
expressive of an unhealthy
2. form
Lowof
C/SC (High Disinhibition
wanting that pushes aside goal-Low Conscientiousness)
directed behavior toward other
pleasurable activities
with Extraversion
Thomsen
et alisFrontiers
Indeed, a core defining characteristic
of SUD
that of little interest for reward
2015
other than the drug.
When not engaged in drug-related behavior, [patients]
= Neuroticism;
E = Extraversion;
D = Disinhibition;
C = et
Conscientiou
of incentive
motivation
(Belcher
al TiCS
Put another way:

Broad-band E/PE may be too broad
May need to specifically assess
wanting and liking for preferred rewards/substances
This speculation is consistent with

fMRI data
fMRI to Food
fMRI to Sex
VS signal to sexual images did not predict changes in weight and

signal to food images did not predict sexual desire ratings or number
of partners during the 6 month follow-up (0 vs 1+ among 1 st year
Dartmouth students)
Demos et al J Neurosci 201

fMRI data
fMRI to Food
fMRI to Sex

Dartmouth students)

fMRI data
fMRI to Food
fMRI to Sex

Dartmouth students)

fMRI data
fMRI to Food
fMRI to Sex
BUT VS/NAcc signal to sexual images did not predict changes in

weight and VS signal to food images did not predict sexual desire
ratings or number of partners during the 6 month follow-up (0 vs 1+
among 1st year Dartmouth students)
Interim conclusions
Interim conclusions
1. Addiction is associated with decreased C/SC
and, contrary to expectation, a general
reduction in E/PE/BASa general dulling of
systems involved in reward and positive
emotion (anhedonia)
2. Nonetheless, addiction seems to involve the
hijacking of brain circuits involved in ordinary
wanting and approach, like the ventral
striatum (VS) / nucleus accumbens (Nacc)
3. Approach/wanting circuits are selectively
sensitized to preferred substances
Interim conclusions
emotion (anhedonia)
striatum (VS) / nucleus accumbens (NAcc)
Interim conclusions
emotion (anhedonia)
striatum (VS) / nucleus accumbens (NAcc)
Focus on self-control and

impulsivity
Students
How might we assay
impulsivity/self-control in the lab?
Balloon Analog Risk Task (BART)
See the lecture on endophenotype
But the BART seems complex and multifactorial, involving

elements of motivation, emotion, and cognition
What about something even simpler?
Stop-Signal Task: Simon says
Easy
Hard
Helfinstein & Poldrack Nature Neuro 201
Easy
Hard
Easy
Easy
Hard
Easy
Easy
Hard the trains already left the station
Hard
Biological Bases of Braking:

fMRI
N = 1,896 14-year olds: Whelan et al Nature Neurosci 2012; see also Aron,

fMRI
Successful stopping was associated
with 6 functional networks
Teens who were able to stop on a
dime showed greater activity in a
Right Frontal network that
included the inferior frontal gyrus
(IFG)
A large body of correlational and a

limited body of mechanistic work
indicates that right IFG plays a
central role in stopping and braking

fMRI
Successful stopping was associated
with 6 functional networks
Teens who were able to stop on a
dime showed greater activity in a
Right Frontal network that
included the inferior frontal gyrus
(IFG)
A large body of correlational and a

limited body of mechanistic work
indicates that right IFG plays a
central role in stopping and braking
Do any of these networks predict early experimentation with

substances?
(teen snares)
Braking and Substance Use

OFC Network
First, they looked at differences in brain activity
between usersteens who had tried cigarettes,
alcohol or any illegal substanceand non-users.
Teens who had experimented showed blunted

activity on successful stop trials in the OFC
network
Same pattern held when they looked at how many
different types of these substances subjects had
used: more types = less OFC activity
Right IFG Network
Increased activity in the Right IFG network on
successful stopsthe same pattern of activation
seen in better performers on the task
distinguished users of illicit substances from nonusers
Users showed greater Right IFG activity but similar
performance, suggesting that the inhibitory
network has to work harder to successfully stop
Aron, Robbins & Poldrack TiCS 201

OFC Network
alcohol or any illegal substanceand non-users

network
Right IFG Network

OFC Network

network
Right IFG Network

OFC Network

network
Right IFG Network
distinguished users from non-users

OFC Network

network
Right IFG Network
distinguished users from non-users
Not just substances,

not just stopping tasks
fMRI + Experience Sampling

*
Quantify individual differences
in the strength of IFG activation
during a Go/No-Go task
z et al Psychol Sci 2014; Berkman et al Psychol Sci 2011

*
Quantify individual
differences in food desire
and eating in daily life

*
Quantify individual
In particularly tempting
moments (actively resist food
desires), subjects with Low IFG
activation were 8.2x more
likely to give in to a food desire
and actually eat than subjects
with High IFG activation
Similar effects have been
reported for smoking

*
Quantify individual
In particularly tempting
moments (actively resist food
desires), subjects with Low IFG
activation were 8.2x more
likely to give in to a food desire
and actually eat than subjects
with High IFG activation
Similar effects have been
reported for smoking
Reinforces the idea

that IFG serves as a
brake in situations
demanding selfcontrol
fMRI data are correlative

Can we mechanitically
create Low C/SC?
Are there manipulations that
create phenotypes that resemble
Impulse Control Disorders?
Yes!
OFC Damage: Phineas

Gage
OFC Damage: Phineas

Gage
hepossessedawellbalancedmind,andwaslooked
uponbythosewhoknewhimasashrewd,smart
businessman,veryenergeticandpersistentin
executingallhisplansofoperation
fitful,irreverent,indulgingattimesinthe
grossestprofanity(whichwasnotpreviouslyhis
custom),manifestingbutlittledeferenceforhis
fellows,impatientofrestraintoradvicewhenit
conflictswithhisdesires,attimespertinaciously
obstinate,yetcapriciousandvacillating,devising
manyplansoffutureoperationwhichareno
soonerarrangedthantheyareabandoned
(Harlow,1868)
OFC Damage: Phineas

Gage
hepossessedawellbalancedmind,andwaslooked
uponbythosewhoknewhimasashrewd,smart
businessman,veryenergeticandpersistentin
executingallhisplansofoperation
fitful,irreverent,indulgingattimesinthe
grossestprofanity(whichwasnotpreviouslyhis
custom),manifestingbutlittledeferenceforhis
fellows,impatientofrestraintoradvicewhenit
conflictswithhisdesires,attimespertinaciously
obstinate,yetcapriciousandvacillating,devising
manyplansoffutureoperationwhichareno
soonerarrangedthantheyareabandoned
(Harlow,1868)
OFC Damage: Patient EVR

(Elliot)
Within months of the operation, he had quit his job, lost a large
sum of money to a scam artist, divorced his wife, lost contact
with family and friends, and remarried a prostitute he had
known for a month.
He had trouble holding down a job; employers complained
about his tardiness and disorganization.
His second marriage ended in divorce six months later, and he
moved in with his parents.
In short, prior to his tumor Elliot had made a series of excellent
life decisions, but within months of the operation he made a
series of catastrophic ones.
OFC Damage: Patient EVR

(Elliot)
Within months of the operation, he had quit his job, lost a large
sum of money to a scam artist, divorced his wife, lost contact
with family and friends, and remarried a prostitute he had
known for a month.
He had trouble holding down a job; employers complained
about his tardiness and disorganization.
His second marriage ended in divorce six months later, and he
moved in with his parents.
In short, prior to his tumor Elliot had made a series of excellent
life decisions, but within months of the operation he made a
series of catastrophic ones.
Complementing the fMRI data on cognitive braking and impulse control

These clinical observations suggest that the OFC (or axons passing through the
OFC) causally contribute to the self-control of impulsive choices in daily life
But its not just OFC lesions

Damage to other nodes in the
underlying brain circuitry can
create a similarly impulsive phenotype
Parkinsons Disorder
etails Are Not Important
See Video Clips @ https://www.michaeljfox.o
Parkinsons Disorder
s of dopamine projection neurons in the

substantia nigra (SN)
Symptoms
Bradykinesia (slowness of movement)
Rigidity
Resting tremor
Cognitive impairment
atment: Dopamine Augmentation

Dopamine precursor
L-DOPA
Crosses blood-brain barrier
and converted to dopamine
Dopamine agonist (D3 Receptor)
Pramipexol
Parkinsons Disorder

Symptoms
Rigidity
Resting tremor

Dopamine precursor
L-DOPA
Pramipexol
Parkinsons Disorder

Symptoms
Rigidity
Resting tremor

Dopamine precursor
L-DOPA
Pramipexol
Parkinsons Disorder

Symptoms
Rigidity
Resting tremor

Dopamine precursor
L-DOPA
Pramipexol
Pramipexol Can Cause Impulse

Problems

Problems

Problems
Impulse control disorders

- Include pathological gambling,
hypersexuality, compulsive shopping, and
binge eating
- Characterized by the maladaptive nature

of the preoccupations in the patient, the
inability to control the urges or impulses,
and other pathological behaviors (such as
lying or stealing) that arise to act on these
urgessound familiar?
- Present in about 10-20% of patients
treated for PD

Problems

binge eating

urgessound familiar, Phineas?
treated for PD

Problems

binge eating

treated for PD

Problems

binge eating

treated for PD
Why do (only) some PD patients

develop impulse control disorders
(Low C/SC) on pramipexol?
Problems turning
DA off in the ventral
striatum (Nacc)
Striatal dopamine is removed from the
synaptic cleft and inactivated when it is
removed by the DA transporter (DAT)
DAT regulates and terminates striatal DA
signaling
PD patients with impulse-control disorders
have reduced expression of the DAT in the
VS
This helps to explain increased VS activity
and enhanced dopamine release in
response to reward cues in these patients
In sum, impulse control deficits partially
Problems turning
striatum (Nacc)
signaling
VS
Problems turning
striatum (Nacc)
signaling
VS
Problems turning
striatum (Nacc)
signaling
VS
In sum, impulse control deficits
Robinson & Berridge 1993, 2000, 20
Focus on rodent models of

wanting
and incentive sensitization
Berridge (U of MI)
Robinson (U of MI)
Quick Reminder of What You

Know
MFB-Self-Stimulation: Model of
Addiction
Rodents learn to robustly SS

(e.g., bar press) within a
minuteup to 2000x/hour
Impervious to anxiety,
punishment, or satiation, like
addiction
Rodents will compulsively
engage in SS for hours or, if
allowed, even days, often to the
exclusion of every other
behavior, like addiction
ial forebrain bundle (complex bundle of axons; main pathway for ascending dopamine fibers; relays information
ens; rewarding effect of SS reflects activation of the mesocorticolimbic dopamine system; Carlezon Nature Prot
MFB Self-Stimulation:
Craving/Wanting
mith/Berridge et al 2008
Heaths Subject B-19

voraciously self-stimulated (never sated
Reported that SS simply evoked desire
stimulate again and again, like addiction
Wanting = Mesolimbic DA System
In short, analyses of the rodent dopamine experiments

strongly implicate the mesolimbic dopamine (DA) system in
wanting
- Dopamine projection neurons sitting in the midbrain VTA that
project to ventral striatal regions, particularly the nucleus
accumbens
Students
How might the wanting system contribute to substance abuse
disorders or related impulse control problems?
Incentive Sensitization
Theory
Theory
Tries to address 2 fundamental
questions
1. Why do addicts crave drugs?
2. Why does craving or relapse
vulnerability persist after long periods
of abstinence (long after the aversive
state of acute withdrawal has passed)?
Theory
Tries to address 2 fundamental
questions
1. Why do addicts crave drugs?
2. Why does craving or relapse
vulnerability persist after long periods
of abstinence (long after the aversive
state of acute withdrawal has passed)?
Theory
Key Points: Usually brains like the rewards that it wants. But sometimes it just wants
them
DA = Common Currency
As we discussed last time, every major class of abused substances activates the mesolimbic DA circuit
centered on the nucleus accumbens (ventral striatum)
This dopaminergic circuit mediates Wanting
Heightened Salience
Perceptual stimuli (e.g., seeing a needle or bottle) that are paired with activation of the Wanting circuit
are imbued with salience, making them attractive incentives and energizing and guiding approach
behaviors
Such stimuli reflexively capture attention and magnetically attract motivated behavior
Sensitization of incentive salience transforms ordinary wanting into excessive/compulsive drug craving,
drug seeking, and drug consumption
Diathesis-Neuroplasticity
In vulnerable individuals, the repeated use of addictive drugs renders this system hypersensitive to drugs
and drug-associated stimuli causing excessive salience to be attributed to drug taking and to stimuli
associated with drug taking (reminders)
These neuroplastic changes are very long-lasting, promoting lasting vulnerability to relapse
Theory
them
Heightened Salience
behaviors
drug seeking, and drug consumption
Theory
them
Heightened Salience (Learning)

behaviors
drug seeking, and drug consumption (in the absence of elevated liking)
Theory
them

behaviors
Theory
them

behaviors
Theory
them

behaviors
Does activity in the wanting circuit centered on the nucleus accumbens predict
real-world impulse control?
Does heightened VS/NAcc activation in the scanner predict what or how much
you eat in daily life?
fMRI + Experience
Sampling
Individuals with more
NAcc activation to
yummy foods
experienced more
intense food desires
were more likely to
give in to their
temptations to eat
Lopez et al Psychol Sci 201
fMRI + Experience
Sampling
Individuals with more
NAcc activation to
yummy food cues
experienced more
intense food desires in
daily life
were more likely to
give in to their
temptations to eat
Lopez et al Psychol Sci 201
Interim Summary
Interim Summary
Interim Summary
1. The inferior frontal gyrus (IFG) appears to play
a key role in braking behavior and resisting
temptation (i.e. self-control)
2. Mechanistic data highlight the importance of
additional circuits, including the orbitofrontal
cortex (OFC) and dopamine transmission in
the VS/Nacc
3. Alterations in multiple brain systems, some
involved in stopping, others in going can
create a similar phenotype (dysregulated,
impulsive, under-controlled).
Interim Summary
the VS/Nacc
Interim Summary
the VS/Nacc
Choice and succumbing to

temptation
Rangel (CalTech)
How do we choose?
vs
Dieters were classified as selfcontrollers

(SCs; n = 19) or nonself-controllers
(NSCs; n =
18) Based on their decisions
SCs made decisions on the basis of
both health and taste, rejecting most
liked-but-unhealthy items, the NSC
group made decisions on the basis of
taste alone
Hare et al Science 200

(NSCs; n =
n.s.
n.s.
SCs made decisions on the basis

of both health and taste,
rejecting liked-but-unhealthy
items

(NSCs; n =
n.s.
n.s.
SCs made decisions on the basis

of both health and taste,
rejecting liked-but-unhealthy
items
Which region tracks the value of foods

(across both groups)?
OFC Tracked Value
OFC Value Signal Was Influenced

by Preferences (Self Control)

BLUE: Among those with high SC:

OFC tracks taste AND health
RED: Whereas OFC only tracks
tastiness in the NSC group

BLUE: Among those with high SC:

OFC tracks taste AND health
RED: In the NSC group: OFC tracks
tastiness only
OFC was Influenced by IFG

on Trials Requiring Self Control
OFC was Influenced by IFG

on Trials Requiring Self Control
What happens when you ask

subjects to focus on health?
Can we manipulate the system?
Hare et al J Neurosci 201
Students What would you

predict?
Untasty
= Health Block; TC = Taste Block; NC = Natural
Tasty
Untasty
Tasty
Untasty
Tasty
Conflict Conditions
Untasty
Tasty
What brain mechanisms explain

this switch in behavior?
St. = Strong Yes/No
OFC Tracks Value
St. = Strong Yes/No
OFC Tracks Value
St. = Strong Yes/No
Subjects make healthier decisions when aske

to attend to health
Why? Does this reflect OFC weighting health
ratings more heavily when choosing?
OFC is sensitive to both taste and health
Integrates taste and health into a decision si

that guides choice
The impact of health cues on behavior (y-axi

correlated with the extent to which the
attention to health manipulation increased th
relative weighting of healthiness in OFC valu
signals (x-axis)
In short, OFC appears to be the proximal sou

of this health-promoting change in behavior
OFC signal change tracks change in

choice
St. = Strong Yes/No

to attend to health

that guides choice

signals (x-axis)


choice
St. = Strong Yes/No

to attend to health

that guides choice

signals (x-axis)


choice
St. = Strong Yes/No
Subjects make healthier decisions when asked

to attend to health
Integrates taste and health into a decision signa

that guides choice
The impact of health cues on behavior (y-axis)
attention to health manipulation increased the
relative weighting of healthiness in OFC value
signals (x-axis)
In short, OFC appears to be the proximal s

of this health-promoting change in behavi
Who tells OFC to attend

to health?
Lateral PFC (IFG)
St. = Strong Yes/No
Lateral PFC (IFG)
St. = Strong Yes/No
Several Regions in Left Lateral PFC
1. Significantly increased activity during HC

2. Tracked with health ratings
3. Showed increased functional connectivity

with OFC at the time of decision-making
Key Take Home Points

Why do we so often succumb to temptation?

toward gratification?

Subcortical
Wanting
Systems
Mesolimbic DA
N. Accumbens/VS
E/PE/BAS
Enduring sensitizatio
to reward cues
Motivational Magnet


Goal-Directed
Prefrontal
Regulatory
Systems
Lateral PFC
IFG
Subcortical
Wanting
Systems
Mesolimbic DA
N. Accumbens/VS
E/PE/BAS
C/SC
Braking
Bias Competition
to reward cues
Motivational Magnet


Goal-Directed
Prefrontal
Regulatory
Systems
Lateral PFC
IFG
OFC
Value
Subcortical
Wanting
Systems
Mesolimbic DA
N. Accumbens/VS
E/PE/BAS
C/SC
Braking
Bias Competition
to reward cues
Motivational Magnet

Critical Thinking Questions
Please select any 2 of the options

1. Given what we have learned about the regulation of impulses and
incentive sensitization, how should we think about addiction?
Listen to this NPR podcast:
After listening, briefly comment on:

Are addicts to blame (morally culpable)? How should we ascribe responsibility if
there is a battle between automatic, preconscious processes (incentive sensitization)
and a sincere conscious desire on the part of a recovering addict to abstainafter all,
in our culture, intention lies at the heart of ethics and law. Is responsibility lessened
by the existence of a pre-existing biological vulnerability (diathesis)?
If you like, incorporate some of the thoughts and speculations of Berridge & Robinson
(2011) into your answer (written for a non-neuroscience audience and well suited to
skimming
son%202011%20Drug%20addiction%20in%20Addict%20&%20Responsibility%20book
.pdf

http://onpoint.wbur.org/2009/08/11/is-addiction-a-matter-of-choice
skimming
Berridge, K.C. & Robinson, T.E. Drug addiction as incentive sensitization. In

Addiction and Responsibility
. Edited by Jeffrey Poland and George Graham. MIT Press, pp. 21-54, 2011.
http://www.lsa.umich.edu/psych/research&labs/berridge/publications/Berridge%
20&%20Robinson%202011%20Drug%20addiction%20in%20Addict%20&%20Responsibili

skimming


skimming


2. The Neuroscience of Happiness
Take a peek at this video featuring talks by Richie
Davidson (training of happiness in Buddhist
practitioners and others) and Kent Berridge
(wanting/liking) at the Aspen Ideas Fest.
https://www.youtube.com/watch?v=8f-T7lgdLPI
If you like, just watch the Q&A period (begins at
49:52)
Briefly comment on what you found most
interesting or most relevant to your own life and
happiness

2. The Neuroscience of Happiness
What do you think? Briefly comment
on what you found most interesting or
most relevant to your own life and
happiness

3. What does the orbitofrontal cortex (OFC) do?
OFC has been associated with concepts
like impulsivity, self-control, and
emotion regulation (think Phineas Gage).
In this short video clip, Pete Rudebeck
describes recent work that is starting to
overturn these ideas and instead indicates that
OFC provides predictions about outcomes associated with
stimuli, choices, and actions, especially their moment-tomoment value based on current internal states.
Watch the video clip
Briefly describe the most important take-home points

that you gleaned.

OFC provides predictions about outcomes associated with
stimuli, choices, and actions, especially their moment-tomoment value based on current internal states.
Watch the video clip
Briefly describe the most important take-home points

that you gleaned.

OFC provides predictions about outcomes associated with stimuli,
choices, and actions, especially their moment-to-moment value
based on current internal states.
Watch the video clip (based on Rudebeck & Murray, Neuron,
2014)
https://
www.youtube.com/watch?v=EMYWZ7c0QEk&list=PLFE4795D
6224D055A&index=2
Briefly describe the 2 most important or interesting take-

4. Watch any one of these short,
entertaining videos on YouTube:
Briefly describe the 2 most important or

interesting take-home points that you
gleaned.
The End
Future Thought Q
Material To Consider Adding
Stuff from Curtins class

Week 4 (4/17): Externalizing disorders, Executive Control, Individual Differences
Goldstein RZ, Volkow ND (2011). Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications. Nat. Rev.
Neurosci., 12, 652-69.
Flagel SB, Akil H, Robinson TE. (2009). Individual differences in the attribution of incentive salience to reward-related cues: Implications for
addiction. Neuropharmacology, 56 (Suppl 1), 139-48.
George O, Koob GF. (2010). Individual differences in prefrontal cortex function and the transition from drug use to drug dependence. Neurosci
Biobehav Rev., 35, 232-47.
Executive control
Feil J, Sheppard D, Fitzgerald PB, Ycel M, Lubman DI, Bradshaw JL. (2010). Addiction, compulsive drug seeking, and the role of frontostriatal
mechanisms in regulating inhibitory control. Neurosci Biobehav Rev, 35, 248-75.
Volkow ND, Wang GJ, Fowler JS, Tomasi D, Telang F.(2011). Addiction: beyond dopamine reward circuitry. Proc Natl Acad Sci, 108, 15037-42.
Volkow ND, Fowler JS, Wang GJ, Baler R, Telang F.(2009). Imaging dopamine's role in drug abuse and addiction. Neuropharmacology, 56, 3-8.
Hester R, Lubman DI, Ycel M.(2010). The role of executive control in human drug addiction. Curr Top Behav Neurosci., 3, 301-18.
Holmes A, Wellman CL.(2009). Stress-induced prefrontal reorganization and executive dysfunction in rodents. Neurosci Biobehav Rev., 33, 77383.
Schoenbaum G, Shaham Y.(2008). The role of orbitofrontal cortex in drug addiction: a review of preclinical studies. Biol Psychiatry, 63, 256-62.
Leeman RF, Potenza, MN (2012). Similarities and differences between pathological gambling and substance use disorders: a focus on impulsivity
and compulsivity. Psychopharmacology, 219, 469-490.
Choose one of the following two articles:

Berridge KC, Ho CY, Richard JM, DiFeliceantonio AG (2010). The tempted brain eats: Pleasure and desire circuits in obesity and eating disorders.
Brain Research, 1350, 43-64.
Extra Slides
3 Broad Super-Factors
Extraversion / Positive Emotionality

(E/PE)
Core features of E/PE are less clear, but seem to include
Emotion: susceptibility to positive moods
Appraisal: see the world as a series of opportunities for

reward
Motivation: appetitive motivation; tendency to work hard to

approach rewards and incentives, especially social rewards
and social attention
Caspi et al. ARP 200
C/SC
Up-Updated Hypothesis Incorporating What We Know About N/
1. Depression = Too Little E/PE (liking, wanting?) and Too Much

2. SUDs = Too Little C/SC or Too Much E/PE
vs
xxx
Most people are exposed to drugs & alcohol
But only a small fraction develops a substance
use disorder (SUD)
Which facets of T&P confer increased risk?
- E/PE?
reward seeking; hyper-sensitivity to reward?
- C/SC
impulsive; disinhibited (per Moffitt)?
- N/NE
self-medication?
N/NE
Among broad-band
superfacto
C/SC
specific to SUDs)
2.

C/SC
3. Surprisingly weak relationsh

with Extraversion
= Neuroticism;
E = Extraversion;
D = Disinhibition;
C = et
Conscientiou
of incentive
motivation
(Belcher
al TiCS
VS DBS May Alleviate

Addiction

Alex these next few slides actually make the point that MDD and SAD are really really similar, which belongs in
one of the earlier ppts
the fun-seeking data are kind of disturbingsuggest that MDD is more about PE than appetitive motivation
Regarding Weak MDD-E

Relations

Relations
Low PE is supposed to be the facet

that distinguishes depression from
the anxiety disorders
Low
E/PE
High
N/NE
Tripartite Model: Clark & Watson JAP 1991; Watson et al JAP 199
Regarding Weak MDD-E/PE

Relations
Low PE is supposed to be the facet

that distinguishes depression from
the anxiety disorders
Low
PE
High
N/NE
Tripartite Model: Clark & Watson JAP 1991; Watson et al JAP 199

Relations
Weak relations may reflect the use of

a broadband measure of Extraversion,
rather than a more specific measure
of Positive Emotionality

Relations
Weak relations may reflect the use of

a broadband measure of Extraversion,
rather than a more specific measure
of Positive Emotionality
Collected multiple measures of each facet of E/PE

Results revealed that
1) E/PE = 4 Facets = Sociability, PE, Exhibitionism/Dominance, and FunSeeking
2) Depression, but not anxiety, was strongly and selectively related to
low PE
Reverse Translation of Diegos

RR Task
Like humans, rats

developed a response bias
toward the more frequently
reinforced stimulus
Reward responsiveness can
be bidirectionally
modulated
(increased/decreased) by
pharmacological
manipulations that increase
(amphetamine) or block
striatal dopamine
Equifinality:
There are different
pathways (causes or
etiologies) to the same
phenotype (disorder)
Fractionating Reward into

Wanting & Liking
The major components of reward and their subdivisions include:
Liking: the actual pleasure component or hedonic impact of a reward.
Pleasure comprises two levels: (1) core liking reactions that need
not necessarily be conscious; (2) conscious experiences of pleasure,
in the ordinary sense of the word, which may be elaborated out of
core liking reactions by cognitive brain mechanisms of awareness
(see A glossary of reward definitions below for more detail on
definitions). Wanting: motivation for reward, which includes both (1)
incentive salience wanting processes that are not necessarily
conscious and (2) conscious desires for incentives or cognitive goals.
Learning: associations, representations, and predictions about future
rewards based on past experiences. Learned predictions include both
(1) explicit and cognitive predictions and (2) implicit knowledge as
well as associative conditioning, such as basic Pavlovian and
instrumental associations.
with work showing decreased

activation in the ventral striatum
across a range of impulse-control
disorders/SUDs
Ventral striatum (nucleus accumbens)
plays a central role in anticipatory
positive affect and wanting (appetitive
drive)
Reduced ventral striatal activation in
anticipation of monetary rewards has
been observed in
- Pathological gambling
- Alcohol dependence
- Obese individuals with
binge-eating disorder
VS
Aside: This is broadly consistent with

work showing decreased activation in
the ventral striatum across a range of
impulse-control disorders/SUDs
Reduced ventral striatal activation
in anticipation of monetary
rewards has been observed in
VS
Aside: This is broadly consistent with

work showing decreased activation in
the ventral striatum across a range of
impulse-control disorders/SUDs
Reduced ventral striatal activation
in anticipation of monetary
rewards has been observed in
Consistent with the Small
Gos
VS
Unhappy Cal Tech

Professor
1. Increased pleasure
(liking)
2. Increased appetitive
motivation (wanting)
3. Decreased sensitivity to
punishment
4. Something even more
complex?
vs
1. Increased pleasure
(liking)
2. Increased appetitive
motivation (wanting
divorced from normal liking)
3. Decreased sensitivity to
punishment
4. Something even more
complex?
vs
Section 1: Developing some

hypotheses
Aberrant responses to reward

Suggests a potential role for
E/PE (BAS)
Students - what is common to depression

(MDD) and substance use disorders (SUDs)?
Aberrant responses to reward and

pleasurable stimuli
Suggests a potential role for

E/PE (BAS)
Extraversion / Positive Emotionality

(E/PE)
00
00
00
Nave Preliminary Hypothesis

1. Depression = Too Little E/PE
2. SUDs = Too Much E/PE
Goldilocks & The 3 Bears Porridge (too cold, too hot)
Biological Bases of Impulsivity

Right vlPFC (inferior frontal gyrus
pars triangularis)
2012
Stop Success OFC Network

Stop Success
Right Frontal Network
2012
OFC Cause: Risk reflects impulsivity

and is characterized by hypoactivity
in the OFC
R PFC Compensation: Drug use
effects related to impulsivity are
characterized by hyperactivity in R
PFC, reflecting the increased difficulty
that users experience when
exercising inhibitory control.
Increased
Right Frontal
Reduced OFC
N = 1,896 14-year old
Pramipexol also alleviates

Depression

Disorders

(NSCs; n =
18) Based on their behavioral
decisions
SCs made decisions on the basis of
both health and taste, rejecting most
liked-but-unhealthy items, the NSC
group made decisions on the basis of

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The dopamine theory of reward and addiction,

which states that dopamine release mediates

Nuts & Bolts Plan for

- Focus on substance use and related

Take-home critical thinking

Equifinality Multiple etiological

will very selectively focus on a few key t

Equifinality Multiple etiological

will very selectively focus on a few key t

Equifinality Multiple etiological

will very selectively focus on a few key t

Why is it so hard to resist our impulses

Why is it so hard to resist our impulses

Why is it so hard to resist our impulses

Why is it so hard to resist our impulses

Clinical perspective and diagnostic criteria

Lets start with the formal criteria for

DSM-IV-TR: Substance Use

DSM-IV-TR: Substance Use

This intuition is consistent

Overlap of cue-related activation for

Overlap of cue-related activation for

Amygdala is not specific to fear and

But not just heightened activation

DSM-IV-TR: Substance Use

Potential Role of C/SC in SUDs

Zentner et al. 2012; cf. Caspi et al 20

Potential Role of C/SC in SUDs

Zentner et al. 2012; cf. Caspi et al 20

Meta-analysis of 175 studies (n=75,229)

N = Neuroticism; E = Extraversion; D = Disinhibition; C = Conscientiou

Among broad-band superfacto

N = Neuroticism; E = Extraversion; D = Disinhibition; C = Conscientiou

Among broad-band superfacto

1. High N/NE (though this is not

This is important, but I am not go

N = Neuroticism; E = Extraversion; D = Disinhibition; C = Conscientiou

Among broad-band superfacto

Low C/SC (High Disinhibition

3. Weakest (neg) relationship

N = Neuroticism; E = Extraversion; D = Disinhibition; C = Conscientiou

Consistent with other

Meta-analysis: 102 studies (N = 32,648) investigating the

Among broad-band superfacto

Low C/SC (High Disinhibition

3. Weakest (neg) relationship

N = Neuroticism; E = Extraversion; D = Disinhibition; C = Conscientiou

Among broad-band superfacto

Low C/SC (High Disinhibition

3. Weakest (neg) relationship

Low C/SC (High Disinhibition

3. Weakest (neg) relationship

Put another way:

This speculation is consistent with

VS signal to sexual images did not predict changes in weight and

Demos et al J Neurosci 201

This speculation is consistent with

VS signal to sexual images did not predict changes in weight and

Demos et al J Neurosci 201

This speculation is consistent with

VS signal to sexual images did not predict changes in weight and

Demos et al J Neurosci 201

This speculation is consistent with

BUT VS/NAcc signal to sexual images did not predict changes in