fMRI and the Neurobiology of Addiction Flashcards
Understand the underlying complexity of addiction disorders Understand the use of fMRI to study addiction disorders Understand the use of fMRI in medication development for addiction disorders Describe an example design of a multi-centre neuroimaging study, including its aims and objectives in addressing the problem of relapse to addiction Evaluate the study's strengths and limitations Describe fMRI tasks used to probe addiction and relapse mechanisms - examples of reward processing, inhibitory
How does functional MRI work?
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
Why might fMRI be able to detect biomarkers in addiction?
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
State 4 key brain elements of addiction
Behavioural control, decision making, emotional reactivity, and reward sensitivity
How might neural activity be changed in addiction?
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
Describe the dopamine reward deficiency syndrome hypothesis of addiction
Addiction is a deficit in dopamine circuitry for non-drug rewards, and only the substance(s) of addiction can produce a normal reward response
State a piece of evidence against the dopamine reward deficiency syndrome hypothesis of addiction
Some drug users show a general hyperresponsivity to all types of rewards
Name some brain regions involved in the reward circuitry of the brain
Substantia nigra, ventral tegmental area, amygdala, hippocampus, prefrontal cortex, ventral striatum
Describe how hijacking the reward circuitry can increase the likelihood of relapse, with an example
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
Define cognitive control
Processes which allow behaviour to vary adaptively from moment to moment - e.g. response inhibition
Describe the relationship between cognitive control and drug use or relapse
Poorer cognitive control may make people more susceptible to drug use and relapse, and it predicts poor treatment adhesion
Name some brain areas involved in cognitive control networks
Anterior cingulate cortex, dorsolateral prefrontal cortex, inferior frontal junction, anterior insular cortex, dorsal pre-motor cortex, posterior parietal cortex
Describe the results of Hester et al’s 2009 study on cognitive control in chronic cannabis users
Chronic cannabis users had impaired error awareness and hypoactivity in their anterior cingulate cortex
Describe the results of Hester & Garavn’s 2004 study on cognitive control in cocaine users
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
Describe the subjective association between stress and relapse
Clinical observations show an association between self-reports of stressors and a subsequent return to drug or alcohol use
Describe the results of Paulus et al’s 2005 study into predicting relapse using fMRI
Abstinent methamphetamine addicts who would later relapse had less activation of decision-making areas during decision-making tasks than those who would remain abstinent
Describe the results of Gowlin et al’s 2014 study into predicting relapse using fMRI
There was greater activation of the anterior insula when processing risk in those who remained abstinent than those who would later relapse
How could fMRI aid in the development of new medication to treat addiction?
It could identify the brain regions involved and show the effects of new medications on the brain
State some limitations of fMRI
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
State some potential uses of fMRI
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
Where does most knowledge of brain addiction come from?
Animal studies
What is the main disadvantage of animal models to study addiction?
Humans often have confounders - e.g. psychiatric comorbidities and social issues
What were the three main aims of the ICCAM study?
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
State some challenges faced by the ICCAM study
Recruitment, retention,loss to follow-up, comorbidities, social issues, multiple dependencies
State some strengths of the ICCAM study
Double-blinding, placebo control, cross-over design (increased power), multi-faceted data, multi-centre involvement fir faster recruitment
State some limitations of the ICCAM study
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
ICCAM: Describe the differences in personality measures between the polydrug dependent group, alcohol dependent group, and controls
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
ICCAM: Describe the differences in spatial working memory between the polydrug group, alcohol group, and control group
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
How could alcohol impair spatial working memory?
It causes hippocampal atrophy
ICCAM: Describe the differences in Cambridge Gamble Task performance between the polydrug group, alcohol group, and control group
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
Name the 3 parts of an fMRI paradigm
Preliminaries, functionals, and structurals
Which 2 brain regions are primarily involved in the monetary incentive delay task?
Ventral striatum and nucleus accumbens
How does addiction affect the reward response in the striatal regions? (Oldham etal, 2018)
It blunts it
ICCAM: Describe the relationship between striatal response, impulsivity, and anxiety measures during the monetary incentive delay task
Striatal response correlated negatively with impulsivity and anxiety measures across all 3 groups
ICCAM: Describe the effect of naltrexone on striatal response during the monetary incentive delay task
No effect
ICCAM: Describe the effect of an acute D3 antagonist on striatal response during the monetary incentive delay task
It enhanced the neural response during reward anticipation in all polydrug and alcohol dependent individuals except those who were opiate dependent
ICCAM: Describe the relationship between striatal response and predicting abstinence
The striatal response to reward anticipation is more blunted in those who will relapse than those who will remain abstinent
Name a task which measures response inhibition
Go-nogo task, stop signal task
Describe the brain activity involved in a motor action
Activation of premotor cortex, putamen, and primary motor cortex, inhibition of globus pallidus, and disinhibition of thalamus
ICCAM: Describe the changes in response inhibition in the brain of alcoholics
They show greater activation changes in the anterior cingulate cortex and inferior frontal gyrus
ICCAM: Describe the relationship between changes in brain response to inhibition and abstinence
The greater the activation changes in the anterior cingulate cortex and inferior frontal gyrus, the more likely they were to remain abstinent
ICCAM: Describe the effect of naltrexone on response inhibition changes in the brain of alcoholics
It modulated the greater activation changes in the anterior cingulate cortex and inferior frontal gyrus
