Shackman Psyc210 Module19 DepImpCon Part2 ExtSelfControl 050715

The dopamine theory of reward and addic2on, which states that dopamine release mediates reward and thus leads to addic2on, has had huge trac2on. However, it became accepted as a universal theory without properly accoun2ng for ndings from studies in dierent drug addic2ons that did not support the theory. Tellingly, the dopamine theory has not led to any new treatments for addic2on.

Nu% et al Nature Reviews Neuroscience 2015

Nuts & Bolts Plan for Today Lecture

- Focus on substance use and related impulse-control disorders

Take-home cri=cal thinking ques=ons

PSYC 210:

C/SC: Biological bases and implica=ons for understanding

substance abuse, impulse-control disorders and everyday tempta=on

(Pleasure, Reward & Inhibi=on Part 2 of 2)

AJ Shackman

07 May 2015

Caveat Reward, Impulsivity & Addic2on are complex I will very selec2vely focus on a few key themes

1. ExperimentaEon 2. Onset 3. Maintenance 4. AbsEnence 5. Withdrawal 6. Relapse

Equinality MulEple eEological pathways

Conceptual Roadmap Why do we so oHen succumb to tempta2on? Why is it so hard to resist our impulses toward gra2ca2on? Students??


Subcor=cal Wan=ng Systems


Goal-Directed Prefrontal Regulatory Systems Subcor=cal

Wan=ng Systems


Goal-Directed Prefrontal Regulatory Systems Subcor=cal

Wan=ng Systems

OFC Choice

Clinical perspec=ve and diagnos=c criteria

Develop some intui2ons about whats gone awry

Lets start with the formal criteria for substance use disorders (SUDs)

DSM-IV-TR: Substance Use Disorders

This intui=on 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 al EJN 2011

Meta-Analyses of fMRI Studies



Drug cue-related ac3va3on in the ventral striatum in users





Overlap of cue-related ac3va3on for food and nico3ne s3muli in users, sugges3ng that drugs hijack reward/approach circuits




Overlap of cue-related ac3va3on for food and nico3ne s3muli in users, sugges3ng that drugs hijack reward/approach circuits Amygdala is not specic to fear and anxiety! Priori3zing aFen3on to salient cues in the environment

But not just heightened ac2va2on of circuits involved in approach and reward

Poten=al Role of C/SC in SUDs

Zentner et al. 2012; cf. Caspi et al 2005

vs


Working Hypothesis SUDs = Too LiYle C/SC (OFC?), Too Much Wan=ng, or Too LiYle N/NE

vs

Poten=al Role of C/SC in SUDs

Sec=on 2:

Show me the (epidemiological) data!

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

High N/NE and Low Conscien=ousness were nonspecically associated with anxiety, depression, and SUD

Many disorders were associated with Low E/PE, with larger eects for depression/dysthmia

The 'disinhibi=on' facet of C/SC was specically associated with SUD

N = NeuroEcism; E = Extraversion; D = DisinhibiEon; C = ConscienEousness Distress = GAD + MDD; Fear = Panic and Phobias


Among broad-band superfactors, SUD risk is associated with 1. High N/NE (though this is not

specic to SUDs)



specic to SUDs) This is important, but I am not going to elaborate on it today. Consistent with elevated stress sensi3vity and self-medica3on



specic to SUDs)

2. Low C/SC (High DisinhibiEon, Low ConscienEousness)

3. Weakest (neg) rela=onship

with Extraversion

Consistent with other recent meta-analyses

Meta-analysis: 102 studies (N = 32,648) inves=ga=ng the behavioral eects of self-control



specic to SUDs)



with Extraversion



specic to SUDs)



with Extraversion Indeed, a core dening characterisEc of SUD is that of li%le interest for rewards other than the drug. When not engaged in drug-related behavior, [paEents] show low disposiEon toward posiEve emoEons and a low degree of incenEve moEvaEon (Belcher et al TiCS 2014)



specic to SUDs)




enhanced mo3va3on to procure drugs is a hallmark of addic3on. Drug-addicted 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 mo3va3onal drives, which displace other ac3vi3es.

Thus, the addictis aroused and mo3vated when seeking to procure the drug but tends to be withdrawn and apathe3c when exposed to nondrug-related ac3vi3es.

Volkow et al PNAS 2011



specic to SUDs)




enhanced mo3va3on to procure drugs is a hallmark of addic3on. Drug-addicted 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 mo3va3onal drives, which displace other ac3vi3es.

Thus, the addictis aroused and mo3vated when seeking to procure the drug but tends to be withdrawn and apathe3c when exposed to nondrug-related ac3vi3es.

Volkow et al PNAS 2011

Addic2ons represent a clear example of how wan2ng can be dissociated from liking. In contrast to depression,drug addic2on is characterized by an excess of drug wan2ng. Further,the excessive and never-ending chase of the reward of choice leaves liWle room for the pursuit of other pleasures. In other words, drug craving is expressive of an unhealthy form of wan2ng that pushes aside goal-directed behavior toward other pleasurable ac2vi2es Thomsen et al FronEers 2015

Put another way: Broad-band E/PE may be too broad May need to specically assess wan2ng and liking for preferred rewards/substances

This specula=on is consistent with fMRI data

Demos et al J Neurosci 2012

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 ra2ngs or number of partners during the 6 month follow-up (0 vs 1+ among 1st year Dartmouth students)

This specula=on is consistent with fMRI data

Demos et al J Neurosci 2012

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 ra2ngs or number of partners during the 6 month follow-up (0 vs 1+ among 1st year Dartmouth students)

Interim conclusions

1. AddicEon is associated with decreased C/SC and, contrary to expectaEon, a general reducEon in E/PE/BASa general dulling of systems involved in reward and posiEve emoEon (anhedonia)

2. Nonetheless, addicEon seems to involve the hijacking of brain circuits involved in ordinary wanEng and approach, like the ventral striatum (VS) / nucleus accumbens (Nacc)

3. Approach/wanEng circuits are selecEvely sensiEzed to preferred substances

Interim conclusions

1. AddicEon is associated with decreased C/SC and, contrary to expectaEon, a general reducEon in E/PE/BASa general dulling of systems involved in reward and posiEve emoEon (anhedonia)

2. Nonetheless, addicEon seems to involve the hijacking of brain circuits involved in ordinary wanEng and approach, like the ventral striatum (VS) / nucleus accumbens (NAcc)

3. Approach/wanEng circuits are selecEvely sensiEzed to preferred substances

Interim conclusions

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 endophenotypes

But the BART seems complex and mul2factorial, involving elements of mo2va2on, emo2on, and cogni2on

What about something even simpler?

Stop-Signal Task: Simon says

Helnstein & Poldrack Nature Neuro 2012

Easy

Hard



Easy

Hard

Easy



Easy

Hard

Easy

Hard the trains already leU the sta3on

Biological Bases of Braking: fMRI

N = 1,896 14-year olds: Whelan et al Nature Neurosci 2012; see also Aron, Robbins & Poldrack TiCS 2014

Biological Bases of Braking: fMRI Successful stopping was associated with 6 funcEonal networks

Teens who were able to stop on a dime showed greater acEvity in a Right Frontal network that included the inferior frontal gyrus (IFG) A large body of correlaEonal and a limited body of mechanisEc work indicates that right IFG plays a central role in stopping and braking

N = 1,896 14-year olds: Whelan et al Nature Neurosci 2012; see also Aron, Robbins & Poldrack TiCS 2014

*

Do any of these networks predict early experimenta2on with

substances?

(teen snares)

Braking and Substance Use OFC Network First, they looked at dierences in brain acEvity

between usersteens who had tried cigare%es, alcohol or any illegal substanceand non-users.

Teens who had experimented showed blunted acEvity on successful stop trials in the OFC network

Same pa%ern held when they looked at how many dierent types of these substances subjects had used: more types = less OFC acEvity

Right IFG Network Increased acEvity in the Right IFG network on

successful stopsthe same pa%ern of acEvaEon seen in be%er performers on the taskdisEnguished users of illicit substances from non-users

Users showed greater Right IFG acEvity but similar performance, suggesEng that the inhibitory network has to work harder to successfully stop

Aron, Robbins & Poldrack TiCS 2014


between usersteens who had tried cigare%es, alcohol or any illegal substanceand non-users




successful stopsthe same pa%ern of acEvaEon seen in be%er performers on the taskdisEnguished users of illicit substances from non-users




between usersteens who had tried cigare%es, alcohol or any illegal substanceand non-users




successful stopsthe same pa%ern of acEvaEon seen in be%er performers on the taskdisEnguished users from non-users



Not just substances, not just stopping tasks

fMRI + Experience Sampling

*

QuanEfy individual dierences in the strength of IFG acEvaEon during a Go/No-Go task

Lopez et al Psychol Sci 2014; Berkman et al Psychol Sci 2011


*


QuanEfy individual dierences in food desire and eaEng in daily life



*




In parEcularly tempEng moments (acEvely resist food desires), subjects with Low IFG acEvaEon were 8.2x more likely to give in to a food desire and actually eat than subjects with High IFG acEvaEon Similar eects have been reported for smoking


*



Reinforces the idea that IFG serves as a brake in situa2ons demanding self-control


In parEcularly tempEng moments (acEvely resist food desires), subjects with Low IFG acEvaEon were 8.2x more likely to give in to a food desire and actually eat than subjects with High IFG acEvaEon Similar eects have been reported for smoking

fMRI data are correla2ve

Can we mechani2cally create Low C/SC?

Are there manipula2ons that

create phenotypes that resemble Impulse Control Disorders?

OFC Damage: Phineas Gage

OFC Damage: Phineas Gage

he possessed a well-balanced mind, and was looked upon by those who knew him as a shrewd, smart businessman, very energetic and persistent in executing all his plans of operation

fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires, at times pertinaciously obstinate, yet capricious and vacillating, devising many plans of future operation which are no sooner arranged than they are abandoned

(Harlow, 1868)

Within months of the operaEon, he had quit his job, lost a large sum of money to a scam arEst, divorced his wife, lost contact with family and friends, and remarried a prosEtute he had known for a month. He had trouble holding down a job; employers complained about his tardiness and disorganizaEon. 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 operaEon he made a series of catastrophic ones.

OFC Damage: Pa2ent EVR (Elliot)

Complemen=ng the fMRI data on cogni=ve braking and impulse control These clinical observa=ons 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

See Video Clips @ h%ps://www.michaeljfox.org Details Are Not Important

Parkinsons Disorder

See Video Clips @ h%ps://www.michaeljfox.org Details Are Not Important

Loss of dopamine projec=on neurons in the substan=a nigra (SN)

Key Symptoms

Bradykinesia (slowness of movement) Rigidity ResEng tremor CogniEve impairment

Treatment: Dopamine Augmenta=on

Dopamine precursor L-DOPA Crosses blood-brain barrier

and converted to dopamine Dopamine agonist (D3 Receptor)

Pramipexol

Parkinsons Disorder


Key Symptoms


Treatment: Dopamine Augmenta=on



Pramipexol See Video Clips @ h%ps://www.michaeljfox.org Details Are Not Important

Parkinsons Disorder


Key Symptoms


Treatment: Dopamine Augmenta2on



Pramipexol See Video Clips @ h%ps://www.michaeljfox.org Details Are Not Important

Pramipexol Can Cause Impulse Problems

Pramipexol Can Cause Impulse Problems Impulse control disorders - Include pathological gambling, hypersexuality,

compulsive shopping, and binge eaEng

- Characterized by the maladapEve nature of the preoccupaEons in the paEent, 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 paEents treated for PD

- Associated with pramipexol administraEon



- Characterized by the maladapEve nature of the preoccupaEons in the paEent, 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, Phineas?


- Associated with pramipexol administraEon



- Characterized by the maladapEve nature of the preoccupaEons in the paEent, 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, Phineas?


- Associated with pramipexol administra=on

Why do (only) some PD pa2ents develop impulse control disorders

(Low C/SC) on pramipexol?

Problems turning DA o in the ventral striatum (Nacc) Striatal dopamine is removed from the synapEc clew and inacEvated when it is removed by the DA transporter (DAT) DAT regulates and terminates striatal DA signaling

PD paEents with impulse-control disorders have reduced expression of the DAT in the VS

This helps to explain increased VS acEvity and enhanced dopamine release in response to reward cues in these paEents

In sum, impulse control decits parEally reect increased magnitude and duraEon of DA transmission in the VS

*




In sum, impulse control decits parEally reect increased magnitude and duraEon of DA transmission in the VS




In sum, impulse control decits par=ally reect increased magnitude and dura=on of DA transmission in the VS

Focus on rodent models of wan=ng and incen=ve sensi=za=on

Berridge (U of MI) Robinson (U of MI)

Robinson & Berridge 1993, 2000, 2008

Quick Reminder of What You Know

MFB-Self-S=mula=on: Model of Addic2on Rodents learn to robustly SS (e.g., bar

press) within a minuteup to 2000x/hour

Impervious to anxiety, punishment, or saEaEon, like addicEon

Rodents will compulsively engage in SS for hours or, if allowed, even days, owen to the exclusion of every other behavior, like addicEon

MFB: medial forebrain bundle (complex bundle of axons; main pathway for ascending dopamine bers; relays informaEon from VTA to accumbens; rewarding eect of SS reects acEvaEon of the mesocorEcolimbic dopamine system; Carlezon Nature Prot 2007

MFB Self-S=mula=on: Craving/Wan2ng

Heaths Subject B-19 voraciously self-sEmulated (never sated)

Reported that SS simply evoked desire to sEmulate again and again, like addicEon

Smith/Berridge et al 2008

Wan=ng = Mesolimbic DA System

In short, analyses of the rodent dopamine experiments strongly implicate the mesolimbic dopamine (DA) system in wan=ng

- Dopamine projecEon neurons sizng in the midbrain VTA that project to ventral striatal regions, parEcularly the nucleus accumbens

Students How might the wan=ng system contribute to substance abuse disorders or related impulse control problems?

Incen=ve Sensi=za=on Theory

Incen=ve Sensi=za=on Theory Tries to address 2 fundamental ques=ons 1. Why do addicts crave drugs?

2. Why does craving or relapse vulnerability persist awer long periods of absEnence (long awer the aversive state of acute withdrawal has passed)?

Incen=ve Sensi=za=on Theory Key Points: Usually brains like the rewards that it wants. But some3mes it just wants them DA = Common Currency

As we discussed last Eme, every major class of abused substances acEvates the mesolimbic DA circuit centered on the nucleus accumbens (ventral striatum) This dopaminergic circuit mediates WanEng

Heightened Salience Perceptual sEmuli (e.g., seeing a needle or bo%le) that are paired with acEvaEon of the WanEng circuit are imbued with salience, making them a%racEve incenEves and energizing and guiding approach behaviors Such sEmuli reexively capture a%enEon and magneEcally a%ract moEvated behavior SensiEzaEon of incenEve salience transforms ordinary wanEng into excessive/compulsive drug craving, drug seeking, and drug consumpEon

Diathesis-NeuroplasEcity

In vulnerable individuals, the repeated use of addicEve drugs renders this system hypersensiEve to drugs and drug-associated sEmuli causing excessive salience to be a%ributed to drug taking and to sEmuli associated with drug taking (reminders) These neuroplasEc changes are very long-lasEng, promoEng lasEng vulnerability to relapse



Heightened Salience (Learning) Perceptual sEmuli (e.g., seeing a needle or bo%le) that are paired with acEvaEon of the WanEng circuit are imbued with salience, making them a%racEve incenEves and energizing and guiding approach behaviors Such sEmuli reexively capture a%enEon and magneEcally a%ract moEvated behavior SensiEzaEon of incenEve salience transforms ordinary wanEng into excessive/compulsive drug craving, drug seeking, and drug consumpEon (in the absence of elevated liking)

Diathesis-NeuroplasEcity




Heightened Salience (Learning) Perceptual sEmuli (e.g., seeing a needle or bo%le) that are paired with acEvaEon of the WanEng circuit are imbued with salience, making them a%racEve incenEves and energizing and guiding approach behaviors Such sEmuli reexively capture a%enEon and magneEcally a%ract moEvated behavior SensiEzaEon of incenEve salience transforms ordinary wanEng into excessive/compulsive drug craving, drug seeking, and drug consumpEon (in the absence of elevated liking)

Diathesis-Neuroplas=city


Does ac=vity in the wan=ng circuit centered on the nucleus accumbens predict real-world impulse control? Does heightened VS/NAcc ac=va=on in the scanner predict what or how much you eat in daily life?


Individuals with more NAcc ac=va=on to yummy foods experienced more intense food desires

were more likely to give in to their temptaEons to eat

Lopez et al Psychol Sci 2014


Individuals with more NAcc ac=va=on to yummy food cues experienced more intense food desires in daily life

were more likely to give in to their temptaEons to eat

Lopez et al Psychol Sci 2014

Interim Summary

Interim Summary 1. The inferior frontal gyrus (IFG) appears to play a key

role in braking behavior and resisEng temptaEon (i.e. self-control)

2. MechanisEc data highlight the importance of addiEonal circuits, including the orbitofrontal cortex (OFC) and dopamine transmission in the VS/Nacc

3. AlteraEons in mulEple brain systems, some involved in stopping, others in going can create a similar phenotype (dysregulated, impulsive, under-controlled).

Choice and succumbing to tempta=on

Rangel (CalTech)

How do we choose?

vs

Dieters were classied as self-controllers (SCs; n = 19) or nonself-controllers (NSCs; n = 18) Based on their decisions SCs made decisions on the basis of both health and taste, rejecEng most liked-but-unhealthy items, the NSC group made decisions on the basis of taste alone

Hare et al Science 2009

Dieters were classied as self-controllers (SCs; n = 19) or nonself-controllers (NSCs; n = 18) Based on their decisions SCs made decisions on the basis of both health and taste, rejec=ng liked-but-unhealthy items The NSC group made decisions on the basis of taste alone


n.s. n.s.

Which region tracks the value of foods (across both groups)?

OFC Tracked Value


OFC Value Signal Was Inuenced by Preferences (Self Control)




BLUE: Among those with high SC: OFC tracks taste AND health RED: Whereas OFC only tracks tasEness in the NSC group



BLUE: Among those with high SC: OFC tracks taste AND health RED: In the NSC group: OFC tracks tasEness only


OFC was Inuenced by IFG on Trials Requiring Self Control

*

OFC was Inuenced 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 2011

Hare et al J Neurosci 2011

Students What would you predict?

Hare et al J Neurosci 2011 HC = Health Block; TC = Taste Block; NC = Natural

Untasty Tasty

Hare et al J Neurosci 2011 HC = Health Block; TC = Taste Block; NC = Natural

Untasty Tasty

Conict Condi=ons

What brain mechanisms explain this switch in behavior?

OFC Tracks Value

Hare et al J Neurosci 2011 St. = Strong Yes/No


Subjects make healthier decisions when asked to a%end to health Why? Does this reect OFC weighEng health raEngs more heavily when choosing? OFC is sensiEve to both taste and health Integrates taste and health into a decision signal that guides choice The impact of health cues on behavior (y-axis) correlated with the extent to which the a%enEon to health manipulaEon increased the relaEve weighEng of healthiness in OFC value signals (x-axis) In short, OFC appears to be the proximal source of this health-promoEng change in behavior

OFC signal change tracks change in choice


Subjects make healthier decisions when asked to a%end to health Why? Does this reect OFC weighEng health raEngs more heavily when choosing? OFC is sensiEve to both taste and health Integrates taste and health into a decision signal that guides choice The impact of health cues on behavior (y-axis) correlated with the extent to which the a%enEon to health manipulaEon increased the relaEve weighEng of healthiness in OFC value signals (x-axis) In short, OFC appears to be the proximal source of this health-promoEng change in behavior

OFC signal change tracks change in choice


Subjects make healthier decisions when asked to a%end to health Why? Does this reect OFC weighEng health raEngs more heavily when choosing? OFC is sensiEve to both taste and health Integrates taste and health into a decision signal that guides choice The impact of health cues on behavior (y-axis) correlated with the extent to which the a%enEon to health manipulaEon increased the relaEve weighEng of healthiness in OFC value signals (x-axis) In short, OFC appears to be the proximal source of this health-promo=ng change in behavior

Who tells OFC to aYend to health?

Lateral PFC (IFG)


Lateral PFC (IFG)


Several Regions in Let Lateral PFC 1. Signicantly increased acEvity during HC

2. Tracked with health raEngs

3. Showed increased funcEonal connecEvity with OFC at the Eme of decision-making

Key Take Home Points Why do we so oHen succumb to tempta2on? Why is it so hard to resist our impulses toward gra2ca2on?



Mesolimbic DA

N. Accumbens/VS

E/PE/BAS

Enduring sensiEzaEon to reward cues

MoEvaEonal Magnets


Goal-Directed Prefrontal Regulatory Systems

Lateral PFC

IFG

C/SC

Braking Bias CompeEEon


Mesolimbic DA

N. Accumbens/VS

E/PE/BAS


MoEvaEonal Magnets


Goal-Directed Prefrontal Regulatory Systems

Lateral PFC

IFG

C/SC

Braking Bias CompeEEon


Mesolimbic DA

N. Accumbens/VS

E/PE/BAS


MoEvaEonal Magnets

OFC Value

Cri=cal Thinking Ques=ons

Please select any 2 of the op2ons

Cri=cal Thinking Ques=ons 1. Given what we have learned about the regula=on of impulses and incen=ve

sensi=za=on, how should we think about addic=on?

Listen to this NPR podcast: Ater listening, briey comment on: Are addicts to blame (morally culpable)? How should we ascribe responsibility if there is a baYle between automa=c, preconscious processes (incen=ve sensi=za=on) and a sincere conscious desire on the part of a recovering addict to abstainater all, in our culture, inten=on lies at the heart of ethics and law. Is responsibility lessened by the existence of a pre-exis=ng biological vulnerability (diathesis)? If you like, incorporate some of the thoughts and specula=ons of Berridge & Robinson (2011) into your answer (wriYen for a non-neuroscience audience and well suited to skimming

son%202011%20Drug%20addic3on%20in%20Addict%20&%20Responsibility%20book.pdf

Cri=cal Thinking Ques=ons 1. Given what we have learned about the regula=on of impulses and incen=ve

sensi=za=on, how should we think about addic=on?

Listen to this NPR podcast: hYp://onpoint.wbur.org/2009/08/11/is-addic=on-a-maYer-of-choice Ater listening, briey comment on: Are addicts to blame (morally culpable)? How should we ascribe responsibility if there is a baYle between automa=c, preconscious processes (incen=ve sensi=za=on) and a sincere conscious desire on the part of a recovering addict to abstainater all, in our culture, inten=on lies at the heart of ethics and law. Is responsibility lessened by the existence of a pre-exis=ng biological vulnerability (diathesis)? If you like, incorporate some of the thoughts and specula=ons of Berridge & Robinson (2011) into your answer (wriYen for a non-neuroscience audience and well suited to skimming

Berridge, K.C. & Robinson, T.E. Drug addic=on as incen=ve sensi=za=on. In Addic2on and Responsibility. Edited by Jerey Poland and George Graham. MIT Press, pp. 21-54, 2011. hFp://www.lsa.umich.edu/psych/research&labs/berridge/publica3ons/Berridge%20&%20Robinson%202011%20Drug%20addic3on%20in%20Addict%20&%20Responsibility%20book.pdf

Cri=cal Thinking Ques=ons 2. The Neuroscience of Happiness J Take a peek at this video featuring talks by Richie Davidson (training of happiness in Buddhist prac==oners and others) and Kent Berridge (wan=ng/liking) at the Aspen Ideas Fest. hYps://www.youtube.com/watch?v=8f-T7lgdLPI If you like, just watch the Q&A period (begins at 49:52) Briey comment on what you found most interes=ng or most relevant to your own life and happiness

Cri=cal Thinking Ques=ons 2. The Neuroscience of Happiness J What do you think? Briey comment on what you found most interes=ng or most relevant to your own life and happiness

Cri=cal Thinking Ques=ons 3. What does the orbitofrontal cortex (OFC) do? OFC has been associated with concepts like impulsivity, self-control, and emo3on regula3on (think Phineas Gage). In this short video clip, Pete Rudebeck describes recent work that is star3ng to overturn these ideas and instead indicates that OFC provides predic3ons about outcomes associated with s3muli, choices, and ac3ons, especially their moment-to-moment value based on current internal states. Watch the video clip Briey describe the most important take-home points that you gleaned.

Cri=cal Thinking Ques=ons 3. What does the orbitofrontal cortex (OFC) do? OFC has been associated with concepts like impulsivity, self-control, and emo3on regula3on (think Phineas Gage). In this short video clip, Pete Rudebeck describes recent work that is star3ng to overturn these ideas and instead indicates that OFC provides predic3ons about outcomes associated with s3muli, choices, and ac3ons, especially their moment-to-moment value based on current internal states. Watch the video clip (based on Rudebeck & Murray, Neuron, 2014) hYps://www.youtube.com/watch?v=EMYWZ7c0QEk&list=PLFE4795D6224D055A&index=2 Briey describe the 2 most important or interes=ng take-home points that you gleaned.

Cri=cal Thinking Ques=ons 4. Watch any one of these short, entertaining videos on YouTube: Briey describe the 2 most important or interes=ng take-home points that you gleaned.

The End

Future Thought Q

Material To Consider Adding

Stu from CurEns class Week 4 (4/17): Externalizing disorders, ExecuEve Control, Individual Dierences Goldstein RZ, Volkow ND (2011). DysfuncEon of the prefrontal cortex in addicEon: neuroimaging ndings and clinical implicaEons. Nat. Rev. Neurosci., 12, 652-69.

Flagel SB, Akil H, Robinson TE. (2009). Individual dierences in the a%ribuEon of incenEve salience to reward-related cues: ImplicaEons for addicEon. Neuropharmacology, 56 (Suppl 1), 139-48.

George O, Koob GF. (2010). Individual dierences in prefrontal cortex funcEon and the transiEon from drug use to drug dependence. Neurosci Biobehav Rev., 35, 232-47.

ExecuEve control

Feil J, Sheppard D, Fitzgerald PB, Ycel M, Lubman DI, Bradshaw JL. (2010). AddicEon, compulsive drug seeking, and the role of frontostriatal mechanisms in regulaEng inhibitory control. Neurosci Biobehav Rev, 35, 248-75.

Volkow ND, Wang GJ, Fowler JS, Tomasi D, Telang F.(2011). AddicEon: 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 addicEon. Neuropharmacology, 56, 3-8.

Hester R, Lubman DI, Ycel M.(2010). The role of execuEve control in human drug addicEon. Curr Top Behav Neurosci., 3, 301-18.

Holmes A, Wellman CL.(2009). Stress-induced prefrontal reorganizaEon and execuEve dysfuncEon in rodents. Neurosci Biobehav Rev., 33, 773-83.

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Leeman RF, Potenza, MN (2012). SimilariEes and dierences between pathological gambling and substance use disorders: a focus on impulsivity and compulsivity. Psychopharmacology, 219, 469-490.

Choose one of the following two arEcles: Berridge KC, Ho CY, Richard JM, DiFeliceantonio AG (2010). The tempted brain eats: Pleasure and desire circuits in obesity and eaEng disorders. Brain Research, 1350,

43-64.

Extra Slides

3 Broad Super-Factors


Extraversion / Posi=ve Emo=onality (E/PE)

Caspi et al. ARP 2005

Core features of E/PE are less clear, but seem to include Emo=on: suscepEbility to posiEve moods Appraisal: see the world as a series of opportuniEes for reward

Mo=va=on: appeEEve moEvaEon; tendency to work hard to approach rewards and incenEves, especially social rewards and social a%enEon


Up-Updated Hypothesis Incorpora=ng What We Know About N/NE 1. Depression = Too LiYle E/PE (liking, wan=ng?) and Too Much N/NE

2. SUDs = Too LiYle C/SC or Too Much E/PE

vs

C/SC

xxx Most people are exposed to drugs & alcohol But only a small frac=on develops a substance use disorder (SUD) Which facets of T&P confer increased risk?

- E/PE? reward seeking; hyper-sensi=vity to reward? - C/SC impulsive; disinhibited (per MoY)? - N/NE self-medica=on?



specic to SUDs)


3. Surprisingly weak rela=onship


The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again.

N/NE

C/SC

C/SC

VS DBS May Alleviate Addic=on

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 appeEEve moEvaEon

Regarding Weak MDD-E Rela=ons

Regarding Weak MDD-E Rela=ons Low PE is supposed to be the facet that dis=nguishes depression from the anxiety disorders

Tripar=te Model: Clark & Watson JAP 1991; Watson et al JAP 1995a, b

High N/NE

Low E/PE

Regarding Weak MDD-E/PE Rela=ons Low PE is supposed to be the facet that dis=nguishes depression from the anxiety disorders

Tripar=te Model: Clark & Watson JAP 1991; Watson et al JAP 1995a, b

High N/NE

Low PE

Regarding Weak MDD-E Rela=ons Weak rela=ons may reect the use of a broadband measure of Extraversion, rather than a more specic measure of Posi=ve Emo=onality

Regarding Weak MDD-E Rela=ons Weak rela=ons may reect the use of a broadband measure of Extraversion, rather than a more specic measure of Posi=ve Emo=onality

Collected mul=ple measures of each facet of E/PE

Results revealed that 1) E/PE = 4 Facets = Sociability, PE, ExhibiEonism/Dominance, and Fun-Seeking 2) Depression, but not anxiety, was strongly and selecEvely related to low PE

Reverse Transla=on of Diegos RR Task

Like humans, rats developed a response bias toward the more frequently reinforced sEmulus Reward responsiveness can be bidirecEonally modulated (increased/decreased) by pharmacological manipulaEons that increase (amphetamine) or block striatal dopamine transmission.

Equinality: There are dierent pathways (causes or e2ologies) to the same phenotype (disorder)

Frac=ona=ng Reward into Wan=ng & 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 reacEons 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 reacEons by cogniEve brain mechanisms of awareness (see A glossary of reward deniEons below for more detail on deniEons). WanEng: moEvaEon for reward, which includes both (1) incenEve salience wanEng processes that are not necessarily conscious and (2) conscious desires for incenEves or cogniEve goals. Learning: associaEons, representaEons, and predicEons about future rewards based on past experiences. Learned predicEons include both (1) explicit and cogniEve predicEons and (2) implicit knowledge as well as associaEve condiEoning, such as basic Pavlovian and instrumental associaEons.

Aside: This is conceptually consistent with work showing decreased ac=va=on in the ventral striatum across a range of impulse-control disorders/SUDs

Ventral striatum (nucleus accumbens) plays a central role in anEcipatory posiEve aect and wanEng (appeEEve drive) Reduced ventral striatal acEvaEon in anEcipaEon of monetary rewards has been observed in

- Pathological gambling - Alcohol dependence - Obese individuals with binge-eaEng disorder

VS

Aside: This is broadly consistent with work showing decreased ac=va=on in the ventral striatum across a range of impulse-control disorders/SUDs

Reduced ventral striatal ac=va=on in an=cipa=on of monetary rewards has been observed in

- Pathological gambling - Alcohol dependence - Obese individuals with binge-ea3ng disorder

VS

Aside: This is broadly consistent with work showing decreased ac=va=on in the ventral striatum across a range of impulse-control disorders/SUDs

Reduced ventral striatal ac=va=on in an=cipa=on of monetary rewards has been observed in

- Pathological gambling - Alcohol dependence - Obese individuals with binge-ea3ng disorder

Consistent with the Small Gos

VS

Unhappy Cal Tech Professor

SUDs may reect 1. Increased pleasure (liking) 2. Increased appe22ve mo2va2on (wan2ng) 3. Decreased sensi2vity to punishment 4. Something even more complex?

E.g., problems with learning or aWen2on or self-control?

vs

SUDs may reect 1. Increased pleasure (liking) 2. Increased appe22ve mo2va2on (wan2ng divorced from normal liking) 3. Decreased sensi2vity to punishment 4. Something even more complex?

E.g., problems with learning or inhibi2on or self-control?

vs

Aberrant responses to reward

Suggests a poten=al role for E/PE (BAS)

Students - what is common to depression (MDD) and substance use disorders (SUDs)?

Sec=on 1: Developing some hypotheses

Aberrant responses to reward and pleasurable s=muli

Suggests a poten=al role for E/PE (BAS)

Nave Preliminary Hypothesis 1. Depression = Too LiYle E/PE

2. SUDs = Too Much E/PE

Goldilocks & The 3 Bears Porridge (too cold, too hot)

Extraversion / Posi=ve Emo=onality (E/PE)

00

00 00

Biological Bases of Impulsivity Right vlPFC (inferior frontal gyrus pars triangularis)


Stop Success OFC Network

Stop Success Right Frontal Network

2012

N = 1,896 14-year olds

Reduced OFC

Increased Right Frontal

OFC Cause: Risk reects impulsivity and is characterized by hypoacEvity in the OFC R PFC Compensa=on: Drug use eects related to impulsivity are characterized by hyperacEvity in R PFC, reecEng the increased diculty that users experience when exercising inhibitory control.

2012

Pramipexol also alleviates Depression

Dieters were classied as self-controllers (SCs; n = 19) or nonself-controllers (NSCs; n = 18) Based on their behavioral decisions SCs made decisions on the basis of both health and taste, rejecEng most liked-but-unhealthy items, the NSC group made decisions on the basis of taste alone


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Shackman Psyc210 Module19 DepImpCon Part2 ExtSelfControl 050715

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