Band-Specific Altered Cortical Connectivity in Early Parkinson's Disease and its Clinical Correlates

Background Functional connectivity (FC) has shown promising results in assessing the pathophysiology and identifying early biomarkers of neurodegenerative disorders, such as Parkinson's disease (PD). Objectives In this study, we aimed to assess possible resting-state FC abnormalities in early-stage PD patients using high-density electroencephalography (EEG) and to detect their clinical relationship with motor and non-motor PD symptoms. Methods We enrolled 26 early-stage levodopa naïve PD patients and a group of 20 healthy controls (HC). Data were recorded with 64-channels EEG system and a source-reconstruction method was used to identify brain-region activity. FC was calculated using the weighted phase-lag index in θ, α, and β bands. Additionally, we quantified the unbalancing between β and lower frequencies through a novel index (β-functional ratio [FR]). Statistical analysis was conducted using a network-based statistical approach. Results PD patients showed hypoconnected networks in θ and α band, involving prefrontal-limbic-temporal and frontoparietal areas, respectively, and a hyperconnected network in the β frequency band, involving sensorimotor-frontal areas. The θ FC network was negatively related to Non-Motor Symptoms Scale scores and α FC to the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III gait subscore, whereas β FC and β-FR network were positively linked to the bradykinesia subscore. Changes in θ FC and β-FR showed substantial reliability and high accuracy, precision, sensitivity, and specificity in discriminating PD and HC. Conclusions Frequency-specific FC changes in PD likely reflect the dysfunction of distinct cortical networks, which occur from the early stage of the disease. These abnormalities are involved in the pathophysiology of specific motor and non-motor PD symptoms, including gait, bradykinesia, mood, and cognition. © 2023 International Parkinson and Movement Disorder Society.