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. 2020;10(2):471-480.
doi: 10.3233/JPD-191844.

Neurophysiological Biomarkers of Parkinson's Disease

Shani Waninger  1 , Chris Berka  1 , Marija Stevanovic Karic  1 , Stephanie Korszen  1 , P David Mozley  2 , Claire Henchcliffe  2 , Yeona Kang  2 , Jacob Hesterman  3 , Tomer Mangoubi  3 , Ajay Verma  4
Affiliations

Neurophysiological Biomarkers of Parkinson's Disease

Shani Waninger et al. J Parkinsons Dis. 2020.

Abstract

Background: There is a need for reliable and robust Parkinson's disease biomarkers that reflect severity and are sensitive to disease modifying investigational therapeutics.

Objective: To demonstrate the utility of EEG as a reliable, quantitative biomarker with potential as a pharmacodynamic endpoint for use in clinical assessments of neuroprotective therapeutics for Parkison's disease.

Methods: A multi modal study was performed including aquisition of resting state EEG data and dopamine transporter PET imaging from Parkinson's disease patients off medication and compared against age-matched controls.

Results: Qualitative and test/retest analysis of the EEG data demonstrated the reliability of the methods. Source localization using low resolution brain electromagnetic tomography identified significant differences in Parkinson's patients versus control subjects in the anterior cingulate and temporal lobe, areas with established association to Parkinson's disease pathology. Changes in cortico-cortical and cortico-thalamic coupling were observed as excessive EEG beta coherence in Parkinson's disease patients, and correlated with UPDRS scores and dopamine transporter activity, supporting the potential for cortical EEG coherence to serve as a reliable measure of disease severity. Using machine learning approaches, an EEG discriminant function analysis classifier was identified that parallels the loss of dopamine synapses as measured by dopamine transporter PET.

Conclusion: Our results support the utility of EEG in characterizing alterations in neurophysiological oscillatory activity associated with Parkinson's disease and highlight potential as a reliable method for monitoring disease progression and as a pharmacodynamic endpoint for Parkinson's disease modification therapy.

Keywords: Biomarkers; EEG; Parkinson’s disease; dopamine transporter PET; neurophysiology.

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Conflict of interest statement

The authors have no conflicts of interest relevant to this article to declare.

Figures

Fig.1
Fig.1
ICC values per band.
Fig.2
Fig.2
FFT Coherence group independent t-test (p-values) between PD and HC cohorts.
Fig.3
Fig.3
A) Correlation between anterior putamen left BPND and FP2-P3 high beta coherence (p = 1.53E–.04, r =–0.552). B) Correlation between UPDRS overall and FP2-P3 high beta coherence (p = 6.96E–05, r = 0.557).
Fig.4
Fig.4
Current density images in Talairach space obtained by sLORETA in PD versus HC cohorts (A: anterior, P: posterior). EEG activity differences are denoted by red (increased activity) or blue (decreased activity).
See this image and copyright information in PMC

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