Multivariate assessment of the central-cardiorespiratory network structure in neuropathological disease

Objective: The new interdisciplinary field of network physiology is increasingly becoming a focus of interest in medicine. Autonomic nervous system (ANS) dysfunction is well described in schizophrenia (SZO). However, the linear and nonlinear coupling between the ANS and central nervous system (CNS) has only been partly addressed until now. This coupling can be assumed to be a feedback-feedforward network, reacting with flexible and adaptive responses to internal and external factors. Approach: For the first time, in this study we investigated linear and nonlinear short-term central-cardiorespiratory coupling of 17 patients suffering from paranoid SZO in comparison to 17 age-gender matched healthy subjects analyzing heart rate (HR), respiration (RESP), and the power of frontal electroencephalogram (EEG) activity (P-EEG). The objective is to determine how the different regulatory aspects of the CNS-ANS affect the central-cardiorespiratory network (CCRN). To quantify these couplings within the CCRN normalized short time partial directed coherence and the new multivariate high-resolution joint symbolic dynamics were applied. Main results: We found that the CCRN in SZO can be characterized as a bidirectional one, with stronger central driving mechanisms (P-EEG -> HR) towards HR regulation than vice versa, and with stronger respiratory influence (RESP -> P-EEG) on central activity than vice versa. This suggests that the central-cardiorespiratory process (closed-loop) is mainly focused on adapting the HR via the sinoatrial node than focusing on respiratory regulation. On the other hand, the feedback-loop from ANS to CNS is strongly dominated via respiratory activity. Significance: We demonstrated a considerably significantly different CCRN structure in SZO with a strong central influence on the cardiac system and a strong respiratory influence on the CNS. Moreover, this study provides a more in-depth understanding of the interplay of the central and autonomic regulatory network in healthy subjects and SZO patients.