Decisions, decisions…

Spring 2016

feature-440wWhat prompts us to order a burger and fries instead of a salad? What puts someone at a higher risk of developing a drug addiction or becoming physically violent? McGill researchers are studying neurobiological processes involved in human behaviour and decision-making to help answer those questions.

By Maria Turner

You are offered a piece of chocolate cake or a bowl of vanilla ice cream. Which do you choose? What appears to be a simple decision in fact involves a series of internal processes that take place in different regions of the brain, what neurologist Lesley Fellows calls an “internal value assessment.” This assessment takes into account different information (if you’re a chocolate-lover or lactose intolerant, for example) that is used to attach a value to each option, which then allows you to make a choice.

The assessment is different for each individual, and can change within the same person depending on the circumstances. “If I offer you cake and ice cream at breakfast, your answer will probably be different than if I offer it to you after dinner,” Fellows explains.

In a 2015 study, Lesley Fellows (pictured) and PhD student Avinash Vaidya found that the dorsomedial prefrontal cortex (PFC) – a part of the brain that has not been much studied in decision neuroscience, to date – might play a critical role in making choices. Participants who had looked at pieces of art were asked which one they valued most. Subjects with injury to the dorsomedial PFC tended to choose the object at hand, while others picked the object they had looked at longest. Photo: Christinne Muschi

In a 2015 study, Lesley Fellows (pictured) and PhD student Avinash Vaidya found that the dorsomedial prefrontal cortex (PFC) – a part of the brain that has not been much studied in decision neuroscience, to date – might play a critical role in making choices. Participants who had looked at pieces of art were asked which one they valued most. Subjects with injury to the dorsomedial PFC tended to choose the object at hand, while others picked the object they had looked at longest. Photo: Christinne Muschi

As well as being flexible, value assessments can be powerful. “If we better understood how these decisions happen we could help people make better choices,” says Fellows – for example, helping people with obesity avoid food that is bad for them.

Along with her colleagues and students in the Decision Lab at McGill University, Fellows, a professor in the Department of Neurology and Neurosurgery and at the Montreal Neurological Institute and Hospital, is trying to do just that: tease out the component processes in the brain that together produce complex behaviours.

One of the ways Fellows and her fellow researchers do this is by studying people with focal brain injuries (injuries confined to one area of the brain). The researchers develop specific tests for different aspects of decision-making. By comparing the performance of people with injury to a particular region of prefrontal cortex thought to be involved in making value-based choices, with the performance of healthy controls, the researchers can determine if the damage has any effect on the behaviour. They can then confirm or disprove if this particular region is critically involved in the behaviour being studied.

Dopamine driving desire

A recent study using positron emission tomography brain scan exams conducted by Marco Leyton suggests that people vulnerable to alcoholism may experience an unusually large brain dopamine response when they take a drink. This discovery is an important step toward developing treatments and preventing the disorder in others, says the researcher. Photo: Christinne Muschi

A recent study using positron emission tomography brain scan exams conducted by Marco Leyton suggests that people vulnerable to alcoholism may experience an unusually large brain dopamine response when they take a drink. This discovery is an important step toward developing treatments and preventing the disorder in others, says the researcher. Photo: Christinne Muschi

Fellows is one of several McGill researchers whose work is helping us reach a better understanding of what drives human behaviour.

Marco Leyton, a professor in the Department of Psychiatry, has been studying the neurotransmitter dopamine – long known to play a critical role in the reward circuit of the brain – for the past 20 years.

Many originally thought dopamine was mediating the experience of pleasure, says Leyton, but that idea has changed. “When we decreased dopamine in people, it diminished their willingness to seek out rewards, but if they got the reward, it was just as pleasurable as before,” the researcher explains. A better way of thinking about dopamine, he suggests, is that it is involved in the “neurobiology of desire.”

“We need a system like this,” he adds. “Healthy desires increase our motivation to seek out food, shelter, sex – all things that we need to survive.”

A new way of understanding addiction

Addictive drugs also target this system, however, “creating false motivational signals, changing our decisions, and, in some, leading to terrible problems,” Leyton says. He has been studying drug-induced dopamine responses by using imaging techniques such as positron emission tomography (PET).

Drugs not only activate the dopamine system, he says, but, with time, they also change the way the brain responds. This may be part of the reason for an increasing susceptibility to the drug, but it is not the whole story. “We now have evidence that people at risk for addictions show differential drug-induced dopamine responses even before they have an addiction,” he says.

Leyton is working with colleagues at the Université de Montréal to try and understand what is behind this initial vulnerability to addiction. The researchers enrolled thousands of children at birth who have been participating in yearly interviews and brain-imaging studies. The children are now turning 18 years old, says Leyton, and some of them are starting to engage in risky behaviours. The brain-imaging studies will allow the researchers to look for differences in the brains of those who do and those who don’t.

Several years ago, Alain Dagher showed that ghrelin, a hormone produced by the stomach that triggers hunger works in parts of the human brain that control reward and pleasure – the same areas involved in addictive behaviour. More recently, he has used neuroimaging to demonstrate the importance of the brain’s frontal lobes in self-control over cravings for cigarettes, drugs and other stimulants. Photo: Christinne Muschi

Several years ago, Alain Dagher showed that ghrelin, a hormone produced by the stomach that triggers hunger works in parts of the human brain that control reward and pleasure – the same areas involved in addictive behaviour. More recently, he has used neuroimaging to demonstrate the importance of the brain’s frontal lobes in self-control over cravings for cigarettes, drugs and other stimulants. Photo: Christinne Muschi

Neurologist Alain Dagher, a professor in the Department of Neurology and Neurosurgery, the Department of Psychology and at the Montreal Neurological Institute and Hospital, is also trying to understand what in the brain makes certain individuals more vulnerable than others to disorders of self-control, and whether or not it can be “measured” before something happens.

One of the most likely explanations is that people who have trouble with self-control have ineffective signalling from the pre-frontal cortex, says Dagher, which may be at the root of their vulnerability to behaviours like drug addiction, gambling, or overeating.

“It’s fairly new to look at drug addiction as a disorder of decision-making,” he explains. And it’s a potentially useful way of looking at it when it comes to thinking about treatment options. The more that is understood about the mechanism behind the abnormality, says Dagher, the more this opens up new treatment approaches such as looking at ways to “switch on” self-control in the brain.

And having a better understanding of what’s causing addiction is in itself extremely important, adds Leyton. “When people are having a health problem, one of the basic questions is: what is happening to me? The research is suggesting that there are individual differences in brain responses to drugs, right from the beginning.”

Looking at individual neurons

Jonathan Britt and colleagues recently found that an important pathway for behavioural reinforcement begins with stimulation of glutamate neurons, not serotonin neurons, in the dorsal raphe nucleus, the area of the brain that is home to many serotonin-producing neurons. The study opens new avenues of investigation on the role of this pathway in disease states, such as addiction. Photo: Christinne Muschi

Jonathan Britt and colleagues recently found that an important pathway for behavioural reinforcement begins with stimulation of glutamate neurons, not serotonin neurons, in the dorsal raphe nucleus, the area of the brain that is home to many serotonin-producing neurons.
The study opens new avenues of investigation on the role of this pathway in disease states, such as addiction. Photo: Christinne Muschi

Although the study of the brain processes behind decision-making in humans is relatively recent, dating back about 15 years, researchers can tap into a rich literature in animal studies, says Fellows. “This has helped us make a lot of progress in the last decade,” she says. “We can now define areas of the brain involved in reward, value, and learning.”

Jonathan Britt, an assistant professor of behavioural neuroscience in the Department of Psychology, is hoping to provide even more specific answers. He uses a technique known as optogenetics to look at rodent brains so he can study the neural circuitry involved in behaviours associated with reward, learning and addiction.

Optogenetics involves injecting DNA that encodes a light-sensitive protein into the brain in such a way that the protein is only made by specific neurons, such as neurons that express dopamine, for example. This then allows researchers to stimulate these specific neurons, and only these neurons, using light.

“Right now I am focused on a forebrain structure called the nucleus accumbens, which integrates information from throughout the brain,” says Britt. “It’s a good region to use optogenetics because we can look at each input to the nucleus accumbens and try to determine where different pieces of information, like the input for hunger, for instance, are located in the brain.”

It’s not possible to use optogenetics in humans at this time, “it’s hard for us to get DNA into a living human, and getting it incorporated and functional,” explains Britt, but it is possible to use the results of rodent studies to narrow down the potential circuitry in humans.

Eventually, Britt hopes, these kinds of studies will have clinical implications. “If we can understand the disruptions in circuitry implicated in depression, schizophrenia, or thought disorders, we could look for drugs or manipulations that could change this neural activity,” he explains.

The research described in this article is supported by the Alzheimer’s Association, the Canada Foundation for Innovation, the Canadian Institutes of Health Research, the Michael J. Fox Foundation, the National Institutes of Health, the Natural Sciences and Engineering Research Council of Canada and the Weston Foundation.


Neuroscientists are not the only McGill researchers examining human behaviour; so are our social scientists. Find out about the research of political science PhD student Valérie-Anne Mahéo into ways to boost motivation to vote.

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