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

• Published in: IEEE open journal of engineering in medicine and biology Vol. 1; pp. 301 - 311
• Main Authors: Hutson, T. Noah, Rezaei, Farnaz, Gautier, Nicole M., Indumathy, Jagadeeswaran, Glasscock, Edward, Iasemidis, Leonidas
• Format: Journal Article
• Language: English
• Published: United States IEEE 01.01.2020; The Institute of Electrical and Electronics Engineers, Inc. (IEEE)
• Subjects: Animals; Biomarkers; Brain-Heart-Lungs; Connectivity analysis; Dynamics and Biomarkers; Electroencephalography; Epilepsy; Functional Network Connectivity; Heart; Lungs; Mice; Neural networks; Respiratory system; Seizures; Sensory neurons; SUDEP; Dynamics and Biomarkers; SUDEP; Functional Network Connectivity; Epilepsy; Brain-Heart-Lungs
• ISSN: 2644-1276; 2644-1276
• DOI: 10.1109/OJEMB.2020.3036544

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality and its pathophysiological mechanisms remain unknown. Goal: 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). Methods: 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). Results: 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. Conclusions: 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.