fMRI in addiction

Question 1

What are some uses of functional brain imaging?

Answer 1

• Understand brain mechanisms
• Index of brain structure, connectivity, circuitry
• Distinguish healthy from at risk brains
• Predict risk of disease development and progression
• Identify markers of relapse/resilience
• Predict treatment response

Question 2

What is the ICCAM ?

Answer 2

This platform is an experimental medicine platform for evaluating new drugs for relapse prevention in addiction.

Imperial, cambridge, manchester.

Identify neural markers as potential targets for treatment and relapse prevention.

Core behavioural components of reward, impulsivity, emotion.

Disturbances to dopamine, opioid and neurokinin (substance P) receptors are critical in driving ore behaviour of addiction relapse- therapeutic targets?

Question 3

Which areas of cognition were scanned in the subjects?

Answer 3

Reward sensitivity

Response inhibition

Emotional responses

Resting state network

Neurocognitive/genetic measure + drug/alcohol history.

Question 4

Which session did they introduce the placebo and why?

Answer 4

Between stage 2 and 3. This is because if patients dropped out you cannot make any drug comparisons without placebo data.

Question 5

What are some challenges?

Answer 5

Recruitment
Retention
Loss to follow up
Co-morbidity
Multiple dependencies

Question 6

What are some strengths of the study?

Answer 6

• Double blinded
• Placebo controlled
• Cross over design- different drugs in the same person. -Increased power
• Multi centre both positive and negative

Question 7

Limitations?

Answer 7

Pseudo randomised- placebo towards the beginning of the study.

Abstinent users- applicability?

Single dose

Multi dimensional data gives potential problem of false positives.

Question 8

What were the 3 different fMRI tasks?

Answer 8

• Monetary reward
• Inhibitory control task
• Emotional/evocative image task

Question 9

How does the Monetary incentive delay task work?

Answer 9

Separates reqard anticipation from reward receipt.

Ventral striatum/nucleus accumbens recruitment in line with its role in encoding predictive value of reward cues.

There is differential striatal response to salient vs non salient cues.

Ventral striatum, thalamus, insula and ACC are normally activated during the task.

Question 10

How does the striatal response correlate with impulsivity measure?

Answer 10

Negatively- more impulsive you are, the higher the striatal blunting.

This blunting also seen in anxiety.

Question 11

How is striatal response to reward different in relapsers vs abstinent?

Answer 11

Those with blunted striatal function were more likely to relapse.

Question 12

How can aberrant responses in monetary reward processing be modulated pharmacologically?

Answer 12

D3 and NK1 antagonism ameliorates aberrant responses.

Naltrexone does not.

Question 13

What is the difference in control in addiction?

Answer 13

There is loss of top down control within the saliency, drive ,memory network.

There is an increased salience of the cue.

Question 14

Which areas receive a dopaminergic input during reward?

Answer 14

• Amygdala
• Nucleus accumbens
• Orbitofrontal cortex
• Insula

Question 15

What occurs to the salience of money reward during smoking abstinence?

Answer 15

The value of winning money decreases. Smokers therefore don’t find anything else rewarding whilst they are not smoking.

Question 16

What is cognitive control?

Answer 16

This is ability to inhibit impulses, plan, and hold information.

Allows behaviour to vary adaptively from moment to moment.

Substance abusers can control intrusive drug related cognitions and/or inhibit impulse to use drugs.

Poor control=more likely to relapse

Question 17

What are the areas implicated in cognitive control?

Answer 17

DLPFC
Insula
DmPFC
Anterior cingulate cortex

Question 18

How can you test cognitive control and what was found?

Answer 18

Stroop test- requiring you to withhold/inhibit your response.

In cannabis users, there was hypoactivation during unaware errors.

Question 19

What is the stress response in addiction?

Answer 19

Dysfunctional emotional and stress responses play a role in the motivation to consume substances of abuse.

Significant contribution of mechanisms on craving and relapse.

Alcoholics report stress which is associated with a return to drinking.

Question 20

What was seen in methamphetamine abstinent users when seeing whether they would relapse or not?

Answer 20

Users with hypoactivation in decision making areas were alot more likely to relapse.