Research Profile - When reward systems go wrong
The neural process that drives reward-seeking behaviour may also drive some people to drug and alcohol dependency
At a Glance
Who - Dr. Clay Holroyd, Canada Research Chair in Cognitive Neuroscience and Associate Professor of Psychology, University of Victoria.
Issue - Are individual differences in the brains dopamine system which reinforces reward-seeking behaviour and affects decision-making at the root of vulnerability to addiction?
Approach - Dr. Holroyds research team has found that young adults who are dependent on drugs show signs of dopamine dysfunction.
Impact - Understanding the dopamine system could pave the way to better treatments for drug addiction and, eventually, lead to therapies that are targeted at the individual.
The University of Victoria's Dr. Clay Holroyd is studying how drugs act on the midbrain dopamine system, which reinforces behaviour that results in rewards. How the dopamine system functions is determined in part by genetic factors – possibly leaving some people more prone to addiction. In a recent interview, Dr. Holroyd, whose research has found that drug-dependent young adults show signs of dopamine dysfunction, explained what his neuroscience research is revealing.
Question (Q): Environment notwithstanding, why is it that only some people who use drugs and alcohol become addicted?
Clay Holroyd (CH): We have to speculate at this point, but there are differences at the genetic level. For example, everyone has genes that regulate the number of dopamine receptors present in the brain. It could be that people with certain genetic types that have fewer or higher quantities of these receptors are more vulnerable to the addictive properties of drugs.
Q: Is addiction, then, like a learning disorder?
CH: It could be considered that way. Attention Deficit Hyperactivity Disorder shares some of the same system problems as addiction. But individual learning disorders can be very different. There are different types of learning systems in the brain. With addiction, this is a very specific neural system that's involved in reinforcing behaviour. Classically, if you do something and you get a reward, it reinforces that behaviour so that you have a higher likelihood of repeating it. It's that system we're talking about, rather than something like dyslexia which affects an entirely different set of neural systems.
Q: Are people predisposed to this problem or do the drugs cause it?
CH: That's what our project is trying to get at. The probable answer is, it's both. If people never took the drugs, they couldn't become addicted.
The brain explained
The midbrain dopamine system: A collection of neurons brain cells that lie deep in the primitive part of the brain called the midbrain. They connect to other parts of the brain by linking up with other neurons that are far away including those in the frontal cortex.
The frontal cortex: The surface of the brain at the front of the head. It includes the prefrontal cortex, where cognitive control is implemented. Its like a conductor in an orchestra: while other parts of the brain are involved in basic operations, such as perceiving things from the external environment, the frontal system co-ordinates all those activities.
Cognitive control: Think of it as setting goals and monitoring behaviour to achieve those goals.
Dopamine receptors: Dopamine neurons project to other parts of the brain. They need to communicate their signals to other neurons. Those other neurons have receptors to receive those signals called dopamine receptors.
Dopamine dysfunction: Any kind of problem that might upset the dopamine system. There are lots of different ways of disturbing the dopamine system. In Parkinsons the dopamine neurons deteriorate. And addictive drugs target the dopamine system and change it.
Q: Is it a case of the brain's reward system not functioning properly?
CH: That's the basic hypothesis. The reward system also projects to what we call the cognitive control system – the part of the brain involved in decision-making. It's really a network. If the reward system is not functioning properly, then the cognitive control system won't function well. It also could be that the control system itself isn't functioning properly. So we're really looking at the interaction between the reward system and the control system.
Q: How does this influence behaviour?
CH: There is a relatively new idea about the dopamine system, that this reinforcement learning signal functions in a very particular way. It propagates back in time with learning to earlier events that predict the outcome. It reinforces behaviours that occurred at that time. You could imagine, for example, seeing a friend who is associated with having gone to a party and later taking drugs. Just the sight of that friend could activate the dopamine system and drive the person to approach the friend and reinforce that behaviour of that earlier time. Essentially, it's reinforcing a whole sequence of events that ultimately lead up to drug-taking behaviour.
Q: How will your research help people who have addiction problems?
CH: At this stage, we're just trying to figure out how the system's working. Once we have a better idea of how the system works, we can think about how to find new therapeutic treatments. One of the long-range goals is to develop more individually tailored types of treatment programs.
The Study
Working with his PhD student Travis Baker, Dr. Holroyd leads a team of researchers who are recording human "event-related brain potentials" (ERPs, i.e. "brainwaves") to study the impact of midbrain dopamine system signals on frontal brain areas involved in cognitive control. They are also conducting behavioural and genetics tests and surveying their subjects on drug use, personality traits and family histories.
The researchers, funded by the Canadian Institutes of Health Research, have been able to demonstrate that drug-dependent young adults have "a severely reduced ERP response" to rewards due essentially to a misfiring dopamine system.
"The dopamine system is always monitoring how things are going," explains Dr. Holroyd. "If things are going better than expected – if you have a task to do and you're achieving that goal – you get a brief increase in the firing rate of these dopamine neurons. If things are going worse than expected you get a brief decrease. These signals are carried to the targets of the dopamine system, including the cognitive control area."
Drug use alters the dopamine system, which in turn affects how the brain reinforces reward-earning behaviours. Ultimately, says Dr. Holroyd, "the goal of obtaining drugs is reinforced in the brain to the extent of excluding all other non-related behaviours. People who are addicted to drugs don't want to engage in activities that don't result in the drug reward."
"Once the drugs take hold, they are really 'stamping in' those drug-reward behaviours. That's what makes it difficult to break free of them. You get into a channel of behaviour that sweeps you to the final outcome."
-- Dr. Clay Holroyd