Hester L7 Can I control my addictive behavior

Question 1

What evidence supports (drug) addiction being a brain disease that features dysfunction of self-control?
What evidence supports poor self-control being the cause of, or for, addiction? (6)

Answer 1

• Drugs, like natural rewards such as sex, food, water, produce euphoria by overactivating ‘pleasure/limbic’ centres in the brain, via the sudden, rapid release of dopamine in the nucleus accumbens (NAc) (in the subcortical areas of the brain)
• The limbic system (e.g. amygdala, hippocampus) is closely tied to learning centres such as the hippocampus, and repeatedly pairing drug-induced euphoria with drug-related stimuli creates an association
• Cue-induced brain activation: In both active and abstinent users, showing drug-related stimuli activates limbic regions usually associated with the effects of the drug (because of circuitry activation that has been build up by the learned association of euphoria and cue-related activity)
• The strength of cravings is reflected in the amount cue-related limbic activity during fMRI
• The magnitude of drug-related cue-induced activation predicts individuals who subsequent relapse
• There is a strong biological link between the strength of drug-related cravings (the subjective level of craving) and relapse

Question 2

Chronic use of MA have been associated with significant impairments of what cognitive domains? (4)

Answer 2

– Poor verbal memory

– Slowed Processing speed

– Executive function

➢ Disinihibted – poor self control

➢ Selective attention – inability to avoid distraction

➢ Decision making – biased toward immediate desires, myopia for future negative consequences

➢ Cognitive flexibility – difficulty switching between different
activities

Question 3

Impairment from MA usage is akin to the level of impairment you get in what disease?

Answer 3

Alzheimer’s

Question 4

What does not predict level of cognitive impairment? (1)

Why? (2)

Answer 4

Use behaviour of drugs

➢ Participants’ self-report unreliable (+ %purity of drug unknown)
➢ Evidence inconclusive because participants’ ability to routinely participate in studies is poor

Question 5

Level of cognitive impairment caused by MA usage is worse in… (3)

Answer 5

➢ Older participants
➢ Men
➢ Confounded by comorbidity (other psychiatric conditions)

Question 6

What is the insular cortex responsible for? (i.e. insular cortex is one of the underlying neural process that contributes to symptoms of drug addiction) (3)

Answer 6

➢ Emotion processing in brain
➢ Introceptive awareness of CRAVINGS of anything reward related e.g. drugs, food, etc.
➢Smokers who had suffered damage to insula (after stroke) were 100 times more likely to quit smoking than smokers with damage to other areas

Question 7

What is the link between Dopamine D2 receptors and vulnerability to develop addiction?

Answer 7

➢ The low availability of Dopamine D2 receptors in the human midbrain is linked to higher vulnerability to develop addiction

➢ High d2 receptor levels has shown to be a protective factor against dependence

Question 8

What happens to people with low/high levels of d2 receptors when exposed to drugs? (2)

Answer 8

➢In people with low level of d2 receptors the large drug-induced increases in DA result in optimal stimulation (peak of curve)

➢ In people with high levels of d2 receptors the large increase pushes them to far and into the unpleasant range of the curve

Question 9

What happens to dopamine metabolism after chronic MA use? (2)

Answer 9

➢ The level of dopamine (d2 receptor density in the subcortical dopamine system) metabolism depletion appears to worsen in chronic MA use

➢ Associated with nearly 3x greater risk of developing Parkinson’s Disease. As DA-producing cells die, you get less and less DA metabolism

(No greater risk for dependent cocaine users!!)

Question 10

What happens to impulsivity after chronic MA use?

Answer 10

➢ Greater impulsivity for reward.

➢ The metabolism of DA in the midbrain system links to impulsivity and poor control.
As the DA-producing cells die off, you also become more impulsive – your ability to control behaviour gets progressively worse.

Question 11

What is the dopamine hypothesis? (4)

Answer 11

• A gene called the Taq1A allele, has been found to influence the expression dopamine D2 receptor density in the human brain
• Possession of two copies of the allele is associated with reduced density of D2 receptors in the striatum (midbrain)
• The reduced expression has been associated with a hypodopaminergic state (low dopaminergic tone), which benefits from external dopaminergic stimulation to increase dopamine levels

• The dopaminergic stimulation can be indirect, for example, from risky activities, due to their ability to stimulate the dopaminergic system via outcomes that are better than expected
➢ Direct (e.g., cocaine)
➢ Indirect (e.g., risk-taking (gambling, bunjee-jumping)

Question 12

Does possession of the Taq1A gene predict risk for developing drug dependence? (3)

Answer 12

• Yes, possession of the Taq1A gene has been found to predict, longitudinally, risk for developing drug dependence.
• The odds ratio (effect size), suggests that people who possess the gene are 2 to 5 times more likely to develop a drug dependence in their lifetime
• Possession of the Taq1a has also been associated with poor response to treatment for drug addiction, with significantly higher rates of relapse

Question 13

What is evidence of the dopamine hypothesis? (4)

Answer 13

People who self-report being highly impulsive have low levels of D2 (and D3) receptor availability in midbrain areas such as the striatum. If people have low levels of D2 receptor density, giving them a small amount of amphetamine results in significantly greater dopamine release in the striatum (not the extent you experience euphoria).

• These individuals have low dopamine levels
• Individuals who describe themselves as having poor self-control have an enhanced response to dopaminegeric stimulation

• The elevated response is associated with stronger subjective desire
or ‘wanting’ of the drug

Question 14

What is the complex relationship between dopamine and cognitive control that is reflected by Parksinson’s disease (PD)? (4)

Answer 14

• PD is associated with decreased inhibitory control and low dopaminergic tone.
• No significant benefit to inhibitory control performance from engaging in Dopamine Replacement Therapy (DRT)
• Some PD patients who begin DRT will develop impulsive-compulsive behaviours (ICBs). These are uncharacteristic and often destructive behavioural changes that are expressed in impulsive (e.g., buying a car with retirement savings) and compulsive ways (e.g., gambling, sexual behaviour)

Conclusion: Although PD patients have progressive cell death of dopamine in their midbrain and have low dopaminergic tone, giving them DRT doesn’t make the self-control behaviour better.

Question 15

What do we know about people who possess Taq1A+ and their ability to learn from reward/punishment feedback? (2)

Answer 15

• People who possess the TaqA1+ (low dopaminergic tone) individuals are more likely to learn and (adapt decision making) following reward feedback than punishment feedback, whereas the opposite pattern is true for people who don’t possess this allele. People without the gene is more likely to learn from punishment than reward.
• So this is a cognitive way of measuring the lack of adaptation of following clear and distinct punishment which is reflected in one of the DSM-IV criteria for drug dependence – continued substance use despite awareness of its negative consequences (e.g., physical or psychological problems)

Question 16

Is loss of control relative or absolute?

Answer 16

Relative. There is specific context where there are cues that lead to poor self control but equally, there are other situations where they can control themselves.

Question 17

What is top-down cognitive control? (2)

Answer 17

• Conscious internal goals take precedence over automatic processes (goals we are keeping in mind to drive behaviour).
• Exhibited in a number of behaviours: inhibitory control and selective attention.

Question 18

What are the 2 networks associated with top-down cognitive control?

Answer 18

1. Anterior Cingulate Cortex (ACC) detects the need for greater levels of control
2. Dorsolateral prefrontal cortex (DLPFC) implements top-down control over performance (STROOP TASK: the ability to say the colour of ink and not the word relies on the DLPFC)

When we encounter increasing task difficulty, we focus our attention on task-relevant stimuli (by amplifying neural representations) and ignore irrelevant stimuli (by inhibiting representations).

Question 19

What tasks are used to examine the 2 networks of cognitive control?

Answer 19

• Stroop task, Go/No-go and Stop Signal task.

Question 20

What have fMRI research show about successful response inhibition?

Answer 20

• fMRI has shown that successful response inhibition requires a network of right inferior frontal, right parietal and dorsal ACC regions

Question 21

What has lesion studies found in response to the Stop-Signal task (SST)? (3)

Answer 21

• Lesion studies have found that the volume of lesion damage to the right inferior frontal gyrus correlated with the stop-signal response time (SSRT) measure from the stop-signal task.
• SSRT reflects the time it takes to internally suppress a prepotent response, faster times = better control
• Lesions in the brain causes poor self-control, so longer SST response.

Question 22

Describe control dysfunction in dependent drug users and gamblers. (3)

Answer 22

• Dependent drug users and gamblers show significantly poorer performance on control tasks (such as the GNG, SST)
• The cognitive deficits are associated with significantly lower activity in both the DLPFC and dorsal ACC regions
• The presence of brain and behaviour differences in problem gamblers raises the question as to what extent dysfunction is caused by, or causes drug use. To what extent is impaired control a cause or effect of drug dependence? Do people who become or have a vulnerability to dependence already have poor self-control and taking the drug exacerbates it?

Question 23

What is the definition of habit?

Answer 23

• The exhibition of a learned behaviour that was insensitive to changes in rewarding
outcomes

Question 24

What are the common features of habit learning in humans (and animals)? (2)

Answer 24

• Repeated responding that forms context-response associations in memory

• Automatic habit performance that is relatively insensitive to changes in the value of
the response outcome

Question 25

What do habits typically arise? (3)

Answer 25

Habits typically arise from goal-related behaviour.

• Goals direct human action by providing a definition of a desired outcome
• Repetitious behaviour is usually, but not necessarily, goal related and can be distinguished from habit behaviour because it does not persist when the value of the repeated behaviour is absent

Question 26

What is habit performance characterised by? (2)

Answer 26

Insensitivity to outcomes.

• One consequence for this finding is that repeated behaviour over time will become more habitual and less goal dependent

Question 27

How does habit formation arise? (3)

Answer 27

• Habits develop through instrumental learning. Everyday life is built upon repetition that provides multiple opportunities for habit formation.
• Habitual responding continues to be influenced by motivational processes
• Interval schedules

Question 28

How does habit form through motivational processes? (4)

Answer 28

– Pavlonian Context Cues are cues that become associated with the reward that follows the action. The cues can increase the likelihood of a habitual behaviour being expressed. But the motivational effect of these cues is not related to the value of the outcome.

– To get people to develop habits, one of the things we know is that the schedule of reinforcement you give people is very important and interval schedules are particularly important to people developing habitual behaviours

– An interval schedule means that responses are only rewarded after a period
of time has elapsed, increasing (or decreasing) response rate during the interval does not change the amount of reward delivery

– It is thought that this particular schedule has ecological validity, insofar as it mimics the way that natural resources are replenished over time (e.g., rainfall)

Question 29

How does habit form through interval schedules? (3)

Answer 29

– Interval schedules for reward are argued to positively influence habit learning because we can form associations between context and response, without having to have a representation of the goal or outcome of the action

– We can respond to a stimulus repeatedly, resulting in repetition and automatization of our response, with occasional and unpredictable rewards ensuring that the behavior doesn’t extinguish

– We might continue to repeat a response, just in case this time is a longer than usual interval

Examples: checking e-mail, social media

Question 30

Is there premorbid risk in drug dependency? (2)

Answer 30

• Prefrontal dysfunction is present in drug-naïve children with a family history of drug dependence
• Poor cognitive control performance in drug-naïve children has a predictive longitudinal relationship to risk for developing subsequent drug addiction

Question 31

How do dependent drug users’ poor control affect their response to drug-related cues? (3)

Answer 31

• Dependent Drug users demonstrate an attentional bias for drug-related stimuli.
• Emotional Stroop task: Active and abstinent drug users show significantly slower RT’s for the drug-related words or pictures when compared to either neutral items, items from a single category (e.g., musical instruments), or simple coloured configurations.
• Consequence: Greater bias predicts poorer treatment outcomes and Inhibitory or cognitive control correlates with magnitude of bias

Question 32

How do these cognitive measures of drug dependent users related to treatment outcomes? (4)

Answer 32

• Cognitive impairment is generally associated with poorer treatment retention.
• Cognitive control performance specifically has been linked with treatment outcomes and retention rates.
• Poor cognitive control performance (decision making task) and associated hypoactivity in dorsolateral prefrontal, parietal, temporal cortices and anterior insula accurately predicted relapse
• Cognitive performance has had less predictive power of response to treatment
  from interventions

Question 33

Is there cognitive recovery in drug-dependent users? (3)

Answer 33

• After 6 months of abstinence, performance on cognitive measures was worse than comparable groups of MA users who either relapsed or continued to use. Those who continued to used MA did better because if you take people off medication, you see withdrawal related effects. The people continuing to take MA are normalizing their cognition—they are self-medicating because of the tolerance build up to the drug.
• After 13 months (range 6-42 months) found improvement in cognitive performance returning to levels that were not significantly different to healthy matched controls (Iudicello et al. 2010). The performance is not returning to control levels.

• Improvements were domain specific:
➢Improved: Motor abilities, information processing speed
➢No improvement: learning and memory, executive function

➢Only those who showed ‘impairment’ at baseline benefited from abstinence

Question 34

Can you improve control in healthy people? (2)

Answer 34

➢If you give healthy people single doses of drugs that influence dopamine system you can improve self-control performance.

➢SST performance was improved by noradrenergic, but not serotonergic, modulation
The opposite pattern was found for reward learning performance (it improved with serotonergic but not noradrenergic)

Question 35

Can you improve control in disease? e.g. ADHD

Answer 35

➢Prescribing atomoxetine and methylphenidate (ritalin) to children diagnosed with ADHD results in significant improvements to performance on attention tasks

➢ These improvements were associated with significant increases in right inferior frontal gyrus (IFG) activity during Stop trials, which a region that is critical for inhibitory control

Question 36

Can you improve control in psychostimulants users? (3)

Answer 36

• Similar benefits of methylphenidate and other psychostimulant medications have been seen in dependent psychostimulant users
• Li et al. 2010, demonstrated that stop-signal performance significantly improved in adult dependent cocaine users taking Ritalin
• Improvements were associated with significant increases in ventromedial prefrontal activity during Stop trials

Question 37

Is neuroenhancers an effective treatment for people with psychostimulant dependence?

Answer 37

Cognitive enhancers have NOT generally improved treatment
outcomes for psychostimulant users in RCTs, or have mixed
results at best

Two recent trials in MA dependent patients with dexamphetamine have shown positive treatment outcomes (in CBT)

Question 38

What are the policy implications for drug dependent users and their addictive behaviour? (5)

Answer 38

If drug use ‘hijacks the brain’ and individuals with an addiction lack the ability to make wilful and autonomous decisions about the use of their drug of addiction

– Can they provide ‘informed consent’ for clinical trials or treatments that provide a replacement or proxy drug?

– Can they be compelled to undergo treatment if they are unwilling/unable to participate or comply
• Drug Courts in NSW and Victoria and compulsory treatment orders
• Depot medications for long lasting replacement therapy

Question 39

What are the policy implications for genetic tests being available to identify Taq1A?

Answer 39

If genetic tests become available to identify heritable traits (Taq1A) for addiction

– How do you handle this information
• To the individual
• To the family
• To insurers

– How might it influence drug control policies that aim to reduce the availability of drugs?
• If we know that particular individuals or communities are at risk or more vulnerable to dependence, would it make economic sense that drug control measures should be focused on those at highest risk of becoming drug dependent?
• If it is evidence based practice is it socially and culturally acceptable?