Structural and functional correlates of subthalamic deep brain stimulation-induced apathy in Parkinson's disease

Background: Notwithstanding the large improvement in motor function in Parkinson's disease (PD) patients treated with deep brain stimulation (DBS), apathy may increase. Postoperative apathy cannot always be related to a dose reduction of dopaminergic medication and stimulation itself may play a role. Objective: We studied whether apathy in DBS-treated PD patients could be a stimulation effect. Methods: In 26 PD patients we acquired apathy scores before and > 6 months after DBS of the sub thalamic nucleus (STN). Magnetoencephalography recordings (ON and OFF stimulation) were performed >= 6 months after DBS placement. Change in apathy severity was correlated with (i) improvement in motor function and dose reduction of dopaminergic medication, (ii) stimulation location (merged MRI and CT-scans) and (iii) stimulation-related changes in functional connectivity of brain regions that have an alleged role in apathy. Results: Average apathy severity significantly increased after DBS (p < 0.001) and the number of patients considered apathetic increased from two to nine. Change in apathy severity did not correlate with improvement in motor function or dose reduction of dopaminergic medication. For the left hemisphere, increase in apathy was associated with a more dorsolateral stimulation location (p = 0.010). The increase in apathy severity correlated with a decrease in alpha1 functional connectivity of the dorsolateral prefrontal cortex (p = 0.006), but not with changes of the medial orbitofrontal or the anterior cingulate cortex. Conclusions: The present observations suggest that apathy after STN-DBS is not necessarily related to dose reductions of dopaminergic medication, but may be an effect of the stimulation itself. This highlights the importance of determining optimal DBS settings based on both motor and non-motor symptoms. (c) 2020 The Author(s). Published by Elsevier Inc.

Automated summary

The severity of apathy significantly increased in PD patients treated with DBS, which may not be solely due to dose reductions of dopaminergic medication, but also potentially attributed to the stimulation itself. Additionally, stimulation location in the left hemisphere and changes in functional connectivity of the dorsolateral prefrontal cortex were associated with the increase in apathy severity.