This article was originally published by the Brain Health Research Centre [http://www.otago.ac.nz/bhrc/news/otago624666.html]
For more than a decade the brains behind the Dunedin Longitudinal Study have wanted to find a way to include neuroimaging in the project. It seemed a far off possibility in the beginning, but now that dream is a reality. The funding is now available and, thanks to both Pacific Radiology and the University of Otago, they have access to a brand new 3T Siemens MRI scanner. And on August 22nd, the research began. The primary aim of adding neuroimaging to the Study, according to Professor Ahmad Hariri of Duke University, is to better understand how differences in the structure and function of the brain reflect an individual’s past experiences and help predict their mental health in the future.
Over the next two years every eligible participant of the study will be invited to spend an hour in this new machine, having the structure and function of their brains measured. Already, 46 study members have successfully completed the scanning. The research team plans to have each study member go back into the machine again every five years so they see what has changed and what has stayed the same, and how the changes map onto health and wellbeing.
The structure of a brain is reasonably straightforward to examine. Over the course of about 20 minutes the MRI scanner builds up a complete image of what the brain looks like. How it functions, however, is a different story. You cannot tell much about how the brain will work just by looking at how it is arranged. In order to test the function of the brain you need to develop tests that will trigger a response in specific areas, which is done with functional MRI or fMRI. But with a whole brain of possibilities and just half an hour, how do the researchers decide which functions to test? This was the question Professor Hariri came to answer.
Over the course of his career Professor Hariri has examined the functions of three specific areas of the brain: the amygdala, ventral striatum, and the dorsolateral prefrontal cortex. His research suggests that the relative activity of these three regions is predictive of anxiety, depression, and impulse control disorders.
The amygdala is the central processing hub for the brain’s negative emotion circuit. It is responsible for your ability to learn about anything which has a negative effect on you. In theory, the greater the response of your amygdala the more adverse you will be to repeating a behaviour which resulted in emotional or physical harm to you in the past. Professor Hariri and his team test the activity of the amygdala by showing people images of fearful or angry faces because these facial expressions are highly predictive of punishing experiences. By examining the brains of over 1300 students at Duke University, Professor Hariri and his team have found that individuals who had a stronger amygdala response to the images were more likely to suffer from symptoms of anxiety and depression when exposed to high levels of stress in the future. The amygdala on its own, however, can’t give us the whole picture.
The ventral striatum is the central processing hub for the brain’s reward and positive emotion circuit. It ensures that when you have a positive interaction with the environment that you feel rewarded and will want to repeat that behaviour. The more active the ventral striatum is during these interactions, the more rewarded you will feel. To test the activity of this reward system Professor Hariri has previously used a simple choice game where a correct choice results in a small amount of money being won. He and his team have found that a greater ventral striatum response was able to buffer the negative effect of stress on positive feelings, and so stave off potential symptoms of anxiety and depression brought on by exposure to stress.
The really interesting part, however, was what they found when they combined this information. Individuals who had a balance of high amygdala response and high ventral striatum response or low amygdala response and low ventral striatum response were less likely to experience symptoms of anxiety or depression or develop problem drinking than individuals who had an imbalance of high amygdala response and low ventral striatum response. Individuals with this type of imbalanced response would find negative situations highly punishing, but would also find positive situations less rewarding. As a result, exposure to a highly stressful situation could trigger anxious or depressed feelings in those individuals. Interestingly, Professor Hariri found that an imbalance which tips the scales in the opposite direction, a low amygdala response and a high ventral striatum response, was related to an increase in impulsivity as these individuals find positive stimuli highly rewarding and are resistant to learning from negative situations.
So, are you simply a slave to these unconscious systems? Not necessarily. The last area Professor Hariri spoke about is the dorsolateral prefrontal cortex, the central processing hub of the brain’s executive control circuit, which is important for working memory, attention, and response selection. This area appears to be capable of modulating the impact of both the amygdala and the ventral striatum. Activity in the dorsolateral prefrontal cortex is stimulated by presenting individuals with a series of math equations and then asking them to decide which resulted in the highest number and which resulted in the lowest number. People had to hold information in memory for a short period of time and then make decisions based on their recall. When combined with the other data it was clear that the strength of the dorsolateral prefrontal cortex response was interacting with the responses of the amygdala and ventral striatum.
If an individual had a strong ‘executive controller’ in the prefrontal cortex then high amygdala activity and low ventral striatum activity was much less likely to result in symptoms of anxiety or depression even in the face of high stress. In contrast, if the individual had a weak prefrontal response then they were at a high risk of adverse effects when exposed to high levels of stress.
Professor Hariri believes that by using these methods we should be able to identify people at risk for problems with anxiety or depression as they age before they develop symptoms that diminish their health. The Dunedin Longitudinal Study is the best resource available to test that hypothesis as well as to identify what prior life experiences help predict the differences he and his team observe in these responses. Given the Study’s shifting focus on ageing, Professor Hariri and the team will also measure the function of the hippomcapus, the brain’s central processing hub for long-term memory, which is often impacted in age-related conditions like Alzheimer’s disease and mild cognitive impairment.
But why would we want to identify people before they’re having problems? The answer is simple: early intervention is the best medicine. We know that giving people the resources to stay healthy is more medically effective than trying to treat their symptoms once they’re unwell. Treatment is a kind of damage control, and if we can help people avoid that damage in the first place then we as a society will be happier, healthier, and stronger. In the case of his ongoing research, Professor Hariri emphasized that the best cure may be to target and strengthen the dorsolateral prefrontal cortex, but this is the most difficult and time consuming area to target. People who are suffering from anxiety and depression can find the normal activities of daily life exhausting and overwhelming, adding on rigorous psychological training can be a serious burden for them. If, however, we could identify these people before they are experiencing symptoms then this work could be done ahead of time and could really lower their risk of having to live with mental illness.
The Dunedin Longitudinal Study is a tremendous resource for both the scientific community, and the wider community as a whole. With the addition of the new scanning facility and neuroimaging research we stand to learn even more about how people change as they age, and what we can do to keep people healthy for as long as possible.