Functional brain controllability in Parkinson's disease and its association with motor outcomes after deep brain stimulation

Abstract

Introduction: Considering the high economic burden and risks of deep brain stimulation (DBS) surgical failure, predicting the motor outcomes of DBS in Parkinson's disease (PD) is of significant importance in clinical decision-making. Functional controllability provides a rationale for combining the abnormal connections of the cortico-striato-thalamic-cortical (CSTC) motor loops and dynamic changes after medication in DBS outcome prediction.

Methods: In this study, we analyzed the association between preoperative delta functional controllability after medication within CSTC loops and motor outcomes of subthalamic nucleus DBS (STN-DBS) and globus pallidus interna DBS (GPi-DBS) and predicted motor outcomes in a Support Vector Regression (SVR) model using the delta controllability of focal regions.

Results: While the STN-DBS motor outcomes were associated with the delta functional controllability of the thalamus, the GPi-DBS motor outcomes were related to the delta functional controllability of the caudate nucleus and postcentral gyrus. In the SVR model, the predicted and actual motor outcomes were positively correlated, with p = 0.020 and R = 0.514 in the STN-DBS group, and p = 0.011 and R = 0.705 in the GPi- DBS group.

Discussion: Our findings indicate that different focal regions within the CSTC motor loops are involved in STN-DBS and GPi-DBS and support the feasibility of functional controllability in predicting DBS motor outcomes for PD in clinical decision-making.

Keywords: Parkinson’s disease; cortico-striato-thalamic-cortical (CSTC) motor loops; deep brain stimulation; functional controllability; motor outcomes.

Figure 1

The brain regions with aberrant controllability responsive to medication. Compared to HCs, significant increase or decrease were found in the AC (A) and MC (B) of each brain node of patients with PD. After medication, aberrant AC of the right pallidum significantly increased and which of the right orbital middle frontal gyrus significantly decreased (C). Aberrant MC of the bilateral pallidum and the left putamen significantly decreased (D), displaying a trend of normalization of network controllability in the striatal areas introduced by medication.

Figure 2

Predicted and actual changes of the UPDRS-III scores in the STN and GPi groups. SVR models were conducted to predict the improvement rates of the UPDRS-III scores using delta controllability. This figure shows the predicted and actual changes in the UPDRS-III scores after DBS surgery. The predicted changes in the UPDRS-III scores and the actual changes in the UPDRS-III scores were positively correlated in the STN group (p = 0.020 and R = 0.514) and the GPi group (p = 0.011 and R = 0.705).