Identification of an early-stage Parkinson's disease neuromarker using event-related potentials, brain network analytics and machine-learning.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2022
Historique:
received: 13 03 2021
accepted: 24 11 2021
entrez: 7 1 2022
pubmed: 8 1 2022
medline: 19 2 2022
Statut: epublish

Résumé

The purpose of this study is to explore the possibility of developing a biomarker that can discriminate early-stage Parkinson's disease from healthy brain function using electroencephalography (EEG) event-related potentials (ERPs) in combination with Brain Network Analytics (BNA) technology and machine learning (ML) algorithms. Currently, diagnosis of PD depends mainly on motor signs and symptoms. However, there is need for biomarkers that detect PD at an earlier stage to allow intervention and monitoring of potential disease-modifying therapies. Cognitive impairment may appear before motor symptoms, and it tends to worsen with disease progression. While ERPs obtained during cognitive tasks performance represent processing stages of cognitive brain functions, they have not yet been established as sensitive or specific markers for early-stage PD. Nineteen PD patients (disease duration of ≤2 years) and 30 healthy controls (HC) underwent EEG recording while performing visual Go/No-Go and auditory Oddball cognitive tasks. ERPs were analyzed by the BNA technology, and a ML algorithm identified a combination of features that distinguish early PD from HC. We used a logistic regression classifier with a 10-fold cross-validation. The ML algorithm identified a neuromarker comprising 15 BNA features that discriminated early PD patients from HC. The area-under-the-curve of the receiver-operating characteristic curve was 0.79. Sensitivity and specificity were 0.74 and 0.73, respectively. The five most important features could be classified into three cognitive functions: early sensory processing (P50 amplitude, N100 latency), filtering of information (P200 amplitude and topographic similarity), and response-locked activity (P-200 topographic similarity preceding the motor response in the visual Go/No-Go task). This pilot study found that BNA can identify patients with early PD using an advanced analysis of ERPs. These results need to be validated in a larger PD patient sample and assessed for people with premotor phase of PD.

Sections du résumé

OBJECTIVE
The purpose of this study is to explore the possibility of developing a biomarker that can discriminate early-stage Parkinson's disease from healthy brain function using electroencephalography (EEG) event-related potentials (ERPs) in combination with Brain Network Analytics (BNA) technology and machine learning (ML) algorithms.
BACKGROUND
Currently, diagnosis of PD depends mainly on motor signs and symptoms. However, there is need for biomarkers that detect PD at an earlier stage to allow intervention and monitoring of potential disease-modifying therapies. Cognitive impairment may appear before motor symptoms, and it tends to worsen with disease progression. While ERPs obtained during cognitive tasks performance represent processing stages of cognitive brain functions, they have not yet been established as sensitive or specific markers for early-stage PD.
METHODS
Nineteen PD patients (disease duration of ≤2 years) and 30 healthy controls (HC) underwent EEG recording while performing visual Go/No-Go and auditory Oddball cognitive tasks. ERPs were analyzed by the BNA technology, and a ML algorithm identified a combination of features that distinguish early PD from HC. We used a logistic regression classifier with a 10-fold cross-validation.
RESULTS
The ML algorithm identified a neuromarker comprising 15 BNA features that discriminated early PD patients from HC. The area-under-the-curve of the receiver-operating characteristic curve was 0.79. Sensitivity and specificity were 0.74 and 0.73, respectively. The five most important features could be classified into three cognitive functions: early sensory processing (P50 amplitude, N100 latency), filtering of information (P200 amplitude and topographic similarity), and response-locked activity (P-200 topographic similarity preceding the motor response in the visual Go/No-Go task).
CONCLUSIONS
This pilot study found that BNA can identify patients with early PD using an advanced analysis of ERPs. These results need to be validated in a larger PD patient sample and assessed for people with premotor phase of PD.

Identifiants

pubmed: 34995285
doi: 10.1371/journal.pone.0261947
pii: PONE-D-21-08332
pmc: PMC8741046
doi:

Types de publication

Clinical Trial Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0261947

Déclaration de conflit d'intérêts

I have read the journal’s policy and the authors of this manuscript have the following competing interests: RS, DS, GI and ZP are employees of elminda Ltd. ABG is a consultant of and has financial interest in elminda Ltd. SH, OSC, SI, GY and SB have no competing interests. All authors have approved the final manuscript. Medical writing support was provided by Ken Scholz, PhD. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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Auteurs

Sharon Hassin-Baer (S)

Movement Disorders Institute and Department of Neurology, Chaim Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel.
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Oren S Cohen (OS)

Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Department of Neurology, Assaf Harofeh Medical Center, Zerifin, Israel.

Simon Israeli-Korn (S)

Movement Disorders Institute and Department of Neurology, Chaim Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel.
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Gilad Yahalom (G)

Department of Neurology and Movement Disorders Clinic, Shaare Zedek Medical Center, Jerusalem, Israel.

Sandra Benizri (S)

Movement Disorders Unit, Functional Neurosurgery Center, Assuta Ramat Ha Hayal Hospital, Tel Aviv, Israel.

Daniel Sand (D)

elminda Ltd., Herzliya, Israel.
Faculty of Medicine, Department of Medical Neurobiology, The Hebrew University of Jerusalem, Ein Kerem, Jerusalem, Israel.

Gil Issachar (G)

elminda Ltd., Herzliya, Israel.

Amir B Geva (AB)

elminda Ltd., Herzliya, Israel.
Department of Electrical and Computer Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Ziv Peremen (Z)

elminda Ltd., Herzliya, Israel.

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