Brain stimulation needs to be precise

Australian researchers have identified areas of the brain they believe are linked to negative side effects from deep brain stimulation (DBS), the most widely used advanced treatment for Parkinson’s disease.

Electrodes on a brain during DBS therapy. Credit: QIMR Berhofer

This suggests, they write in a paper in the journal Brain, “that the site and distribution of stimulation is a more important determinant of postoperative neuropsychiatric outcomes than preoperative brain structure”.

That positive news comes thanks to a “virtual casino” and some innovative thinking by a team led by neuropsychiatrist Philip Mosley from the QIMR Berghofer Medical Research Institute in Queensland.

DBS, which involves delivering focussed electrical currents through implanted electrodes, has been shown to reverse motor-related symptoms in Parkinson’s patients, with some even able to stop medication.

However, some develop problems controlling their impulses and start behaving recklessly through such excessive behaviours as gambling, binge eating, hypersexuality and excessive shopping.

“We wanted to find out if there was a subtle difference in the way stimulation was affecting the brains of those people who developed these psychiatric side-effects, and if by exploring these differences we might be able to work out how to stop it happening altogether,” says Mosley.

To do that, he and colleagues from Australia, Switzerland and Germany recruited 55 recent patients from Queensland’s St Andrew’s War Memorial Hospital, which operates one of the largest DBS centres in the world.

They used diffusion MRI, an advanced form of brain imaging, to reconstruct the connections between nerve cells in the brain that were stimulated by the implanted electrodes, then watched how brain networks influenced decision making in the “casino”.

They found that when DBS stimulation affected the frontal portion of the brain – the prefrontal cortex – participants were more likely to place higher and riskier bets.

“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,” Mosley says.

He also followed the clinical progress of each participant and found that those who went on to develop clinically significant harmful changes in behaviour had a strong connection between the site of stimulation and a specific region of the prefrontal cortex called the orbitofrontal 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 says.

“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.”

Knowing which connections are harmful or helpful will help neurologists and neurosurgeons decide where best to place DBS electrodes and how to adjust the device postoperatively, the researchers say.

More than 100,000 people worldwide have received DBS therapy for Parkinson’s disease.

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