Neural Correlates of Motor and Psychiatric Fluctuations in Parkinson's Disease

NCT07404241 | Recruiting

• 1 other identifier: 2024-02324
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

PARKINSON DISEASE (Disorder)

Keywords

neuropsychiatric fluctuations; non-motor symptoms; Local field potentials; Electroencephalography; Deep brain stimulation; Subthalamic nucleus

Outcome Measures

Primary Outcomes (1)

• Correlation over-time of STN intracranial LFP activity and EEG resting-state oscillatory activity

  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

  during the acute phase of levodopa administration (120 min)

Secondary Outcomes (4)

• 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

Study Arms (1)

Parkinson's disease patients treated with STN-DBS

Prospective cohort

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

STN-DBS Parkinson's disease patients

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University Hospital, Geneva: lead

Study Sites (1)

Geneva University Hospital

Geneva, 1211, Switzerland

RECRUITING

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Central Study Contacts

Damien BENIS, PhD

CONTACT

+41223722311; damien.benis@hug.ch

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: February 4, 2026
• First Posted: February 11, 2026
• Study Start: June 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)