LIFELAB: Breakthrough

Researchers progress Parkinson’s disease treatment

QIMR Berghofer researchers have made a breakthrough in understanding how to make one of the most widely used treatments for Parkinson’s disease safer and more effective.

These important findings are now being shared worldwide to improve treatment outcomes for this debilitating disease, which affects more than 80 000 Australians.

More than 100 000 people worldwide have been treated with deep brain stimulation therapy (DBS), an established treatment for Parkinson’s disease, which can help to reduce disability and improve quality of life in patients for several years.

The procedure involves implanting electrodes within the brain, which allows the delivery of focused electrical currents to a small target region. The neurosurgical procedure has been shown to reverse some motor-related symptoms of Parkinson’s disease, including tremor, stiffness and slowness, with some patients even able to stop medication.

While DBS has been a life-changing treatment for decades for many with Parkinson’s disease, QIMR Berghofer lead researcher and St Andrews War Memorial Hospital neuropsychiatrist Dr Philip Mosley, explained the treatment can also have harmful side effects.

‘Some patients develop new problems with controlling their impulses and behaving recklessly after this procedure, which can give rise to personal problems and increase the strain on their families,’Dr Mosley said.

“These impulse-control and behavioural problems limit the improvement in quality of life enjoyed by the majority of patients who undergo this procedure.” ‘People have been studying this question of why for quite some time without finding the answer.’

Dr Mosley and the deep brain stimulation team at St Andrew’s War Memorial Hospital, led by Professor Peter Silburn and Associate Professor Terry Coyne, set about recruiting 55 patients for their study to determine if there was a subtle difference in the way stimulation affected the brains of those people who developed psychiatric side-effects and if this could be prevented.

‘We identified that when DBS affected certain parts of the brain, it was linked to impulsivity and harmful behaviour,’ Dr Mosley said.

‘We used a ‘virtual casino’ that we had previously developed, which simulated ‘real-world’ impulsivity, and looked at how the brain networks influenced by DBS affected gambling.’

‘Our participants played the casino before DBS and again once their stimulator was implanted and turned on, so we could quantify whether stimulation influenced them to bet in a more risky manner.’

Dr Mosley found that when stimulation affected the frontal portion of the brain (the prefrontal cortex), participants were more likely to place higher, more risky bets after DBS.

‘This region of the brain is important for planning behaviour and inhibiting inappropriate actions, so it makes sense that stimulation of this part of the brain can change behaviour in this way,” he said.

Dr Mosley followed the clinical progress of all participants in the study and found that those patients who went on to develop clinically significant, harmful changes in behaviour after DBS had a strong connection between the site of stimulation and a specific region of the prefrontal cortex.

‘This was a fascinating finding, because this region has been shown to be important in how the brain evaluates a desired goal and compares it to an actual outcome, in order to work out if behaviour should be modified,’ he said.

‘It is possible that these individuals developed such significant problems because their brains weren’t able to perform this function, which meant that they didn’t link poor choices to negative outcomes, and therefore didn’t learn from the experience.

‘Our understanding of how behaviour can be linked to the pattern of connections in the brain stimulated by DBS means that we can make this therapy even safer and more effective.’

The research, funded by the Queensland Government ‘Advance Queensland’ initiative, builds on a previous study led by Dr Mosley that identified the effects of dopamine replacement medication on the brain network connections of Parkinson’s patients who had developed harmful behaviours after commencing drug treatment.

Dr Mosley received the Early Career Psychiatrist Award from the Royal Australian and New Zealand College of Psychiatrists for this work.

Dr Philip Mosley
Research Officer
Clinical Brain Networks

 

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