The Effect of Dopaminergic Therapy in Parkinson’s Disease: A Graph Theory Analysis

<b>Background</b>: Dopaminergic therapy (DT) is the gold standard pharmacological treatment for Parkinson's disease (PD). Currently, understanding the neuromodulation effect in the brain of PD after DT is important for doctors to optimize doses and identify the adverse effects of medication. The objective of this study is to investigate the brain connectivity alteration with and without DT in PD using resting-state EEG. <b>Methods</b>: Graph theory (GT) is an efficient technique for analyzing brain connectivity alteration in healthy and patient groups. We applied GT analyses on three groups, namely healthy control (HC), Parkinson with medication OFF (PD-OFF), and Parkinson with medication ON (PD-ON). <b>Results</b>: Using the clustering coefficient (CC), participation coefficient (PC), and small-worldness (SW) properties of GT, we showed that PD-ON patients' brain connectivity normalized towards healthy group brain connectivity due to DT. This normalization effect appeared in the brain connectivity of all EEG frequency bands, such as theta, alpha, beta-1, beta-2, and gamma except the delta band. We also analyzed region-wise brain connectivity between 10 regions of interest (ROIs) (right and left frontal, right and left temporal, right and left parietal, right and left occipital, upper and lower midline regions) at the scalp level and compared across conditions. During PD-ON, we observed a significant decrease in alpha band connectivity between right frontal and left parietal (<i>p</i>-value 0.0432) and right frontal and left occipital (<i>p</i>-value 0.008) as well as right frontal and right temporal (<i>p</i>-value 0.041). <b>Conclusion</b>: These findings offer new insights into how dopaminergic therapy modulates brain connectivity across frequency bands and highlight the continuous elevation of both the segregation and small-worldness of the delta band even after medication as a potential biomarker for adverse effects due to medication. Additionally, reduced frontal alpha band connectivity is associated with cognitive impairment and levodopa-induced dyskinesia, highlighting its potential role in Parkinson's disease progression. This study underscores the need for personalized treatments that address both motor and non-motor symptoms in PD patients.