fMRI and the Neurobiology of Addiction

Question 1

How does functional MRI work?

Answer 1

It uses changes in the magnetic properties of the blood as oxygen is removed to measure the ratio change in oxyhaemoglobin to deoxyhaemoglobin in venous blood (the BOLD signal). As neuronal activity requires oxygen, it functions as an indirect measure of neuronal activity

Question 2

Why might fMRI be able to detect biomarkers in addiction?

Answer 2

Substances of addiction disrupt behavioural and cognitive processes governed by neural activity, including those involved in motivation and reward. fMRI can locate these disturbances at a population level

Question 3

State 4 key brain elements of addiction

Answer 3

Behavioural control, decision making, emotional reactivity, and reward sensitivity

Question 4

How might neural activity be changed in addiction?

Answer 4

One model suggests that there is a change in the weighting of networks, giving the nucleus accumbens, amygdala, and orbitofrontal cortex less inhibitory control and leading to continued pursuit of the addictive substance

Question 5

Describe the dopamine reward deficiency syndrome hypothesis of addiction

Answer 5

Addiction is a deficit in dopamine circuitry for non-drug rewards, and only the substance(s) of addiction can produce a normal reward response

Question 6

State a piece of evidence against the dopamine reward deficiency syndrome hypothesis of addiction

Answer 6

Some drug users show a general hyperresponsivity to all types of rewards

Question 7

Name some brain regions involved in the reward circuitry of the brain

Answer 7

Substantia nigra, ventral tegmental area, amygdala, hippocampus, prefrontal cortex, ventral striatum

Question 8

Describe how hijacking the reward circuitry can increase the likelihood of relapse, with an example

Answer 8

Nothing becomes as rewarding as the thought of using the drug. A 2014 study by Sweitzer et al found that, in smokers, monetary reward caused greater brain activation than the thought of smoking - but in abstinent smokers, imagining smoking a cigarette caused greater brain activation

Question 9

Define cognitive control

Answer 9

Processes which allow behaviour to vary adaptively from moment to moment - e.g. response inhibition

Question 10

Describe the relationship between cognitive control and drug use or relapse

Answer 10

Poorer cognitive control may make people more susceptible to drug use and relapse, and it predicts poor treatment adhesion

Question 11

Name some brain areas involved in cognitive control networks

Answer 11

Anterior cingulate cortex, dorsolateral prefrontal cortex, inferior frontal junction, anterior insular cortex, dorsal pre-motor cortex, posterior parietal cortex

Question 12

Describe the results of Hester et al’s 2009 study on cognitive control in chronic cannabis users

Answer 12

Chronic cannabis users had impaired error awareness and hypoactivity in their anterior cingulate cortex

Question 13

Describe the results of Hester & Garavn’s 2004 study on cognitive control in cocaine users

Answer 13

Cocaine users had hypoactivity in their right superior frontal gyrus, right pre-SMA, and left anterior cingulate cortex than healthy contrains during a memory response task

Question 14

Describe the subjective association between stress and relapse

Answer 14

Clinical observations show an association between self-reports of stressors and a subsequent return to drug or alcohol use

Question 15

Describe the results of Paulus et al’s 2005 study into predicting relapse using fMRI

Answer 15

Abstinent methamphetamine addicts who would later relapse had less activation of decision-making areas during decision-making tasks than those who would remain abstinent

Question 16

Describe the results of Gowlin et al’s 2014 study into predicting relapse using fMRI

Answer 16

There was greater activation of the anterior insula when processing risk in those who remained abstinent than those who would later relapse

Question 17

How could fMRI aid in the development of new medication to treat addiction?

Answer 17

It could identify the brain regions involved and show the effects of new medications on the brain

Question 18

State some limitations of fMRI

Answer 18

High numbers of artefacts (e.g. from movement or breathing), scanner doesn’t simulate everyday life, not a direct measure of neuronal activity, claims made are simplistic based on location

Question 19

State some potential uses of fMRI

Answer 19

Improve understanding of underlying brain mechanisms, distinguish healthy from at risk from diseased brains, predict the risk of disease development and progression, identify markers of relapse or resilience, predict treatment response

Question 20

Where does most knowledge of brain addiction come from?

Answer 20

Animal studies

Question 21

What is the main disadvantage of animal models to study addiction?

Answer 21

Humans often have confounders - e.g. psychiatric comorbidities and social issues

Question 22

What were the three main aims of the ICCAM study?

Answer 22

1) Identify neural markers of addiction as targets for treatment and relapse prevention
2) Identify core behavioural components of reward, impulsivity, and emotion underlying relapse
3) Study novel compounds targeting dopamine, opioid, and neurokinin receptors to prevent addiction relapse

Question 23

State some challenges faced by the ICCAM study

Answer 23

Recruitment, retention,loss to follow-up, comorbidities, social issues, multiple dependencies

Question 24

State some strengths of the ICCAM study

Answer 24

Double-blinding, placebo control, cross-over design (increased power), multi-faceted data, multi-centre involvement fir faster recruitment

Question 25

State some limitations of the ICCAM study

Answer 25

Pseudo-randomisation creating possible learning effects, applicability of data from abstinent users, only a single dose of each drug given, potential false positives from multi-dimensional data

Question 26

ICCAM: Describe the differences in personality measures between the polydrug dependent group, alcohol dependent group, and controls

Answer 26

Both dependent groups had higher scores on measures of depression, anxiety, and impulsivity (none had clinically diagnosed depression or anxiety), as well as more urgency and perseverance. Polydrug dependent individuals were significantly more attention seeking

Question 27

ICCAM: Describe the differences in spatial working memory between the polydrug group, alcohol group, and control group

Answer 27

The alcohol-dependent group had impaired spatial working memory compared to both others -interesting as most polydrug addicts were also alcoholics. This impairment took the form of more time taken to complete tasks, rather than more errors, possibly due to use of different brain networks to compensate for deficiencies

Question 28

How could alcohol impair spatial working memory?

Answer 28

It causes hippocampal atrophy

Question 29

ICCAM: Describe the differences in Cambridge Gamble Task performance between the polydrug group, alcohol group, and control group

Answer 29

Both addicted groups took longer than healthy controls to make a decision. The polydrug group made significantly worse choices and were less sensitive to the probability of winning money

Question 30

Name the 3 parts of an fMRI paradigm

Answer 30

Preliminaries, functionals, and structurals

Question 31

Which 2 brain regions are primarily involved in the monetary incentive delay task?

Answer 31

Ventral striatum and nucleus accumbens

Question 32

How does addiction affect the reward response in the striatal regions? (Oldham etal, 2018)

Answer 32

It blunts it

Question 33

ICCAM: Describe the relationship between striatal response, impulsivity, and anxiety measures during the monetary incentive delay task

Answer 33

Striatal response correlated negatively with impulsivity and anxiety measures across all 3 groups

Question 34

ICCAM: Describe the effect of naltrexone on striatal response during the monetary incentive delay task

Answer 34

No effect

Question 35

ICCAM: Describe the effect of an acute D3 antagonist on striatal response during the monetary incentive delay task

Answer 35

It enhanced the neural response during reward anticipation in all polydrug and alcohol dependent individuals except those who were opiate dependent

Question 36

ICCAM: Describe the relationship between striatal response and predicting abstinence

Answer 36

The striatal response to reward anticipation is more blunted in those who will relapse than those who will remain abstinent

Question 37

Name a task which measures response inhibition

Answer 37

Go-nogo task, stop signal task

Question 38

Describe the brain activity involved in a motor action

Answer 38

Activation of premotor cortex, putamen, and primary motor cortex, inhibition of globus pallidus, and disinhibition of thalamus

Question 39

ICCAM: Describe the changes in response inhibition in the brain of alcoholics

Answer 39

They show greater activation changes in the anterior cingulate cortex and inferior frontal gyrus

Question 40

ICCAM: Describe the relationship between changes in brain response to inhibition and abstinence

Answer 40

The greater the activation changes in the anterior cingulate cortex and inferior frontal gyrus, the more likely they were to remain abstinent

Question 41

ICCAM: Describe the effect of naltrexone on response inhibition changes in the brain of alcoholics

Answer 41

It modulated the greater activation changes in the anterior cingulate cortex and inferior frontal gyrus