Chaos or Randomness? Effect of Vagus Nerve Stimulation During Sleep on Heart-Rate Variability

Abstract

Loss of complexity and chaos of heart rate variability (HRV) of an individual increases the risk of mortality from cardiovascular diseases. Abnormalities in HRV associated with intractable epilepsy may even lead to “sudden death in epilepsy” (SUDEP). By activating the parasympathetic division of the autonomic nervous system, Vagus Nerve Stimulation (VNS) has the potential to restore the natural chaotic behavior of the heart which can be measured by the increase in complexity of HRV as indicated by complexity measures such as Effort-To-Compress (ETC) and Lempel-Ziv Complexity (LZC). In this study, we formulate and test two hypothesis – (A) chaotic time series exhibit lower temporal correlation of complexity measures such as LZ and ETC than uniformly random time series, and (B) Vagus Nerve Stimulation (VNS ON) results in chaotic cardiovascular dynamics. Hypothesis-A is verified by a simulated study on chaotic time series from the Logistic map where we see a clear decrease in temporal correlation between ETC and LZC values as the degree of chaos increases. Hypothesis-B is supported by an experimental study on a VNS implanted patient and not implanted controls. A temporal correlation analysis between complexity measures (ETC and LZC) on HRV data samples shows that VNS during sleep increases chaotic behavior in contrast to lack of VNS and in control subjects. Surrogate analysis further confirmed that VNS activation led to deterministic chaos and not stochastic randomness. Our approach proposes a clear methodology to determine the efficacy of VNS intervention in restoring the chaoticity of cardiovascular dynamics.

KEYWORDS:

• Complexity
• Effort-to-compress complexity
• Heart rate variability
• Lempel-Ziv complexity
• Logistic map
• Sudden death in epilepsy
• Surrogate analysis

Acknowledgment

The authors would like to gratefully acknowledge Hari Kumar, Del Marshall, Sachin Kumar, Srilakshmi P and Gopalakrishnan of Amrita Vishwa Vidyapeetham for their help rendered towards this research.

Additional information

Notes on contributors

Karthi Balasubramanian

Karthi Balasubramanian has bachelors in electronics and communication engineering from Delhi Institute of Technology, India (1999), masters in engineering science from Simon Fraser University, Burnaby, Canada (2002) and PhD from Amrita Vishwa Vidyapeetham (2016). He has worked as a VLSI chip design engineer at Cogent Chipware Inc and PMC-Sierra at Burnaby, Canada before joining as a faculty at Amrita Vishwa Vidyapeetham. He is currently working as an assistant professor in the Department of Electronics and Communications Engineering at Amrita School of Engineering, Coimbatore. His areas of interest include VLSI for communication; non-linear dynamics and complex systems. Currently, his research pursuits include “VLSI design of reliability based soft decision decoders” and ‘Exploring the use of non-linear dynamics and complexity analysis for identification of biomarkers for early detection of epileptic seizures using ECGand EEG. He has published papers in top tier peer-reviewed journals and conferences and a book chapter. He also serves in the technical program committee of the flagship IEEE international conference on consumer electronics (ICCE). Corresponding author: E-mail: [email protected]

Nithin Nagaraj

Nithin Nagaraj has bachelors in electrical and electronics engineering from National Institute of Technology Karnataka, India (1999), masters in electrical engineering from Rensselaer Polytechnic Institute, Troy, New York, USA (2001) and PhD from National Institute of Advanced Studies, Bengaluru, India (NIAS, 2010). He was a visiting faculty in Mathematics at IISER Pune for a brief while before joining as assistant professor at the Department of Electronics and Communication Engineering, Amrita University for the period 2009–2013. He has worked as research scientist and lead scientist at GE Global Research Bengaluru in the area of biomedical signal and image analysis (2001–2004, 2013–2015) before joining the consciousness studies programme at NIAS in October 2015. His research interests include studying the information complexity of brain networks, nonlinear signal processing and chaos theory. He is the co-author of 20 international journal publications, 50 national and international conference presentations, 90+ invited talks & with over 950+ Google Scholar Citations. He is also a co-inventor of 8 US patent appl (2 granted). He is the co-editor of the edited volume: ‘self, culture and consciousness: interdisciplinary convergences on knowing and being' published by Springer Nature. He is currently senior member of the IEEE; invited member, advisory council, METI: messaging extra terrestrial intelligence international. E-ail: [email protected]

Sandipan Pati

Sandipan Pati is board certified epilepsy neurologist practicing at the level-IV epilepsy center, the University of Alabama at Birmingham, USA. After completing his initial training in medicine and neurology at England (Oxford and London), he moved to Phoenix (Barrow Neurological Institute) to complete his neurology training subsequently, he moved to Boston (Massachusetts General Hospital) to complete his fellowship training in epilepsy. He is an expert in evaluating difficult-to-treat epilepsies and manages surgical epilepsy and neuromodulation therapies. He has established the Epilepsy and Cognitive Neurophysiology laboratory (ECNLab) that combines cutting-edge analytical tools with electrophysiology and brain stimulation. His research team comprises of young highly skilled engineers that work relentlessly to innovate novel therapies that can improve the lives of people with epilepsies. E-mail: [email protected]