Subthalamic and Cortical Electrophysiological Correlates of Motor and Neuropsychiatric Fluctuations in Parkinson's Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Correlation over-time of STN intracranial LFP activity and EEG resting-state oscillatory activity
研究概览
简要总结
This study explores the electrophysiological mechanisms underlying motor and non-motor fluctuations (NMF) in Parkinson's disease (PD), focusing on cortical and subthalamic dynamics during acute dopaminergic stimulation.
PD is characterized by both motor symptoms and disabling non-motor symptoms-including neuropsychiatric fluctuations that remain poorly understood. While local field potentials (LFP) recorded from the subthalamic nucleus (STN) via deep brain stimulation (DBS) have revealed beta-band abnormalities linked to motor dysfunction, little is known about the oscillatory signatures of NMF. Preliminary data from our group suggested that gamma-band EEG activity in frontotemporal regions may correlate with neuropsychiatric fluctuations.
This Swiss, two-center, prospective observational study aims to investigate resting-state electroencephalogram (EEG) and STN-LFP correlates of motor and non-motor symptoms during a modified levodopa challenge in 30 PD patients with STN-DBS. Using high-density EEG and chronically implanted Medtronic Percept™ DBS devices, electrophysiological data will be collected across five clinical states (combinations of ON/OFF levodopa and DBS). Clinical symptoms will be assessed alongside electrophysiological activity to identify frequency-specific cortical-STN biomarkers. Machine learning models (e.g., LASSO regression) will be used to predict motor and non-motor states from EEG and LFP data, enabling the identification of dynamic oscillatory markers. This could inform future adaptive DBS strategies.
The study leverages advanced methods in neurophysiology, imaging, and machine learning to deepen our understanding of PD fluctuations. It also proposes the first detailed electrophysiological mapping of NMF, which could improve patient stratification and neuromodulation therapies. Anatomical validation of DBS lead placement will be performed using standard neuroimaging toolkits.
详细描述
- Background and Rationale Parkinson's disease (PD) is a common neurodegenerative disorder affecting 2% of individuals over 65 years. Beyond classical motor symptoms like bradykinesia, rigidity, and tremor, PD is increasingly recognized for its debilitating non-motor symptoms (NMS), which include depression, anxiety, fatigue, apathy, and bradyphrenia. These NMS fluctuate alongside motor symptoms, particularly in later disease stages when dopaminergic treatments become pulsatile. Neuropsychiatric fluctuations (NMF) significantly reduce patients' quality of life, yet their pathophysiology is not well understood.
While EEG studies have characterized motor fluctuations and impulse control disorders through frequency-specific changes, few studies have systematically examined the EEG or intracranial electrophysiological substrates of NMF. STN-DBS offers the opportunity to record local field potentials (LFPs) directly from the subthalamic nucleus (STN). Beta oscillations in STN have been consistently associated with akinesia, while recent studies suggest that alpha and gamma band activities may relate to non-motor and neuropsychiatric features.
Technological advances, such as Medtronic's PERCEPT™ PC DBS system, now enable chronic LFP recordings postoperatively. Coupling these with high-density EEG enables real-time exploration of cortical-subcortical interactions. Our pilot data show distinct EEG dynamics between motor and neuropsychiatric fluctuations following levodopa challenge, supporting a differential spatio-spectral signature for these symptoms. 2. Objectives
Primary Objective:
To characterize the temporal dynamics of cortical EEG and STN LFP oscillatory activity and coherence during the acute levodopa response, and their correlation with motor and non-motor fluctuations in PD.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Parkinson's disease (PD) based on United Kingdom Parkinson's Disease Society Brain Bank Criteria.
- •Patients candidate for STN-DBS in the PD phase called fluctuations stage.
- •Presence of fluctuations (motor and/or non-motor) are based on the pre-surgical DBS assessment:
- •To be on dopaminergic therapy.
- •Patients who have undergone STN-DBS implantation within 4 to 8 weeks before electrophysiological acquisition.
排除标准
- •Patients with an age greater than 80 years,
- •Dementia (defined by a MOCA score ≤24),
- •Active psychosis or depression with suicidal ideation,
- •Any clinically meaningful non-stable physical diseases,
- •Patients with OFF-drug state so severe that it prevents study tests from being carried out (e.g acute painful dystonia, intolerable non-motor symptoms such as pain, anxiety),
- •Participating in a pharmacological study,
- •Inability to provide informed consent (legal guardianship).
研究组 & 干预措施
Parkinson's disease patients treated with STN-DBS
Prospective cohort
结局指标
主要结局
Correlation over-time of STN intracranial LFP activity and EEG resting-state oscillatory activity
时间窗: during the acute phase of levodopa administration (120 min)
Correlation over-time of STN intracranial LFP activity and EEG resting-state oscillatory activity (spectral, temporal and spatial features as well as cortical-subcortical and cortico-cortical coherence) with the temporal dynamics of motor and non-motor clinical scores
次要结局
- Temporal dynamics of motor and non-motor clinical scores(during the acute phase of levodopa administration)
- Correlation of EEG and STN LFP markers of motor and non-motor response to levodopa(120 min)
- Dynamic modulations of the oscillatory coupling between the STN and the cortex(120 min)
- Difference in resting-state EEG power in frequency bands linked to motor and non-motor symptoms improvement, between different DBS conditions(120 min)
研究者
Vanessa Fleury
Dr
University Hospital, Geneva