Study identifies ways to prevent behavioural side-effects of deep brain stimulation

Movement disorders

By Michael Woodhead

24 Jun 2020

New research led by QIMR Berghofer Medical Research Institute in Queensland has identified ways to prevent neuropsychiatric side-effects of subthalamic deep brain stimulation (DBS) for Parkinson disease.

A team led by neuropsychiatrist Dr Philip Mosley used a virtual casino to assess impulsive behaviour in 55 patients with Parkinson disease before and after undergoing subthalamic deep brain stimulation.

They found that greater connectivity of the stimulation site with frontostriatal networks was related to greater postoperative impulsiveness and disinhibition as assessed by the neuropsychiatric instruments.

Patients who placed larger bet sizes in the virtual casino postoperatively had greater connectivity of the stimulation site with right and left orbitofrontal cortex, right ventromedial prefrontal cortex and left ventral striatum.

However the connectivity of reward evaluation and response inhibition networks prior to the procedure was not associated with postoperative impulsivity.

“This suggests that the site and distribution of stimulation is a more important determinant of postoperative neuropsychiatric outcomes than preoperative brain structure and that stimulation acts to mediate impulsivity through differential recruitment of frontostriatal networks,” the researchers report in the journal Brain.

A notable finding was that it was possible to identify patients with clinically-significant, harmful changes in mood and behaviour attributable to DBS, based upon an analysis of connectivity and its relationship with gambling behaviour.

“Additional analyses suggested that this distinction may be mediated by the differential involvement of fibres connecting ventromedial subthalamic nucleus and orbitofrontal cortex,” the researchers said.

The research involved the deep brain stimulation team at St Andrew’s War Memorial Hospital, Queensland, led by Professor Peter Silburn and Associate Professor Terry Coyne. It is one of the largest DBS centres worldwide, having completed more than 1000 procedures.

Dr Mosley said the link between harmful changes in impulsivity behaviour after DBS with the orbitofrontal cortex 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.”

“Overall, DBS for Parkinson’s disease is usually a wonderful and life-changing treatment. Now, 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.

“Specifically, knowing which connections are harmful or helpful will assist neurologists and neurosurgeons decide where best to place the DBS electrodes and how to adjust the device postoperatively so that only regions of the brain responsible for treating the motor symptoms of Parkinson’s disease are stimulated.”

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