Title

Directed Connectivity Analysis of the Neuro-Cardio- and Respiratory Systems Reveals Novel Biomarkers of Susceptibility to SUDEP

Document Type

Article

Abstract

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality and its pathophysiological mechanisms remain unknown. We set to record and analyze for the first time concurrent electroencephalographic (EEG), electrocardiographic (ECG), and unrestrained whole-body plethysmographic (Pleth) signals from control (WT - wild type) and SUDEP-prone mice (KO- knockout Kcna1 animal model). Employing multivariate autoregressive models (MVAR) we measured all tri-organ effective directional interactions by the generalized partial directed coherence (GPDC) in the frequency domain over time (hours). When compared to the control (WT) animals, the SUDEP-prone (KO) animals exhibited (p < 0.001) reduced afferent and efferent interactions between the heart and the brain over the full frequency spectrum (0-200Hz), enhanced efferent interactions from the brain to the lungs and from the heart to the lungs at high (>90 Hz) frequencies (especially during periods with seizure activity), and decreased feedback from the lungs to the brain at low (<40 Hz) frequencies. These results show that impairment in the afferent and efferent pathways in the holistic neuro-cardio-respiratory network could lead to SUDEP, and effective connectivity measures and their dynamics could serve as novel biomarkers of susceptibility to SUDEP and seizures respectively.

Keywords

Brain-Heart-Lungs, Dynamics and Biomarkers, Epilepsy, Functional Network Connectivity, SUDEP

Publication Date

1-1-2020

Publication Title

IEEE open journal of engineering in medicine and biology

E-ISSN

2644-1276

Volume

1

First Page

301

Last Page

311

PubMed ID

34223181

Digital Object Identifier (DOI)

10.1109/ojemb.2020.3036544

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