Key result
SUDEP-prone knockout mice exhibited significantly reduced bidirectional interactions between the heart and brain (p < 0.001) and enhanced efferent interactions from the brain and heart to the lungs at high frequencies compared to wild-type controls.
Why the study?
Sudden unexpected death in epilepsy is the leading cause of epilepsy-related mortality, but its pathophysiological mechanisms remain unknown.
p-value: p=<0.001
Hypothesis-generating for SUDEP mechanisms via tri-organ signals in mice; leaves open human translation pending validation.
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.
No takes yet. Share an insight, caveat, or question.
Hutson et al. (2020) studied Sudden unexpected death in epilepsy (SUDEP) (n=15). Kcna1 gene knockout (SUDEP-prone model) vs. Wild type (WT) mice was evaluated on Tri-organ effective directional interactions measured by generalized partial directed coherence (GPDC) (p=<0.001). SUDEP-prone knockout mice exhibited significantly reduced bidirectional interactions between the heart and brain (p < 0.001) and enhanced efferent interactions from the brain and heart to the lungs at high frequencies compared to wild-type controls.