Brain-heart interactions considering complex physiological data: processing schemes for time-variant, frequency-dependent, topographical and statistical examination of directed interactions by convergent cross mapping

Background: A multitude of complex methods is available to quantify interactions in highly complex physiological systems. Brain-heart interactions play an important role in identifying couplings between the central nervous system and the autonomic nervous system during defined physiological states or specific diseases. The crucial point of those interaction analyses is adequate pre-processing taking into account nonlinearity of data, intuitive graphical representation and suitable statistical evaluation of the achieved results. Objective: The aim of this study is to provide generalized processing schemes for such investigations taking into account pre-processing, graphical representation and statistical analysis. Approach: Two defined data sets were used to develop these processing schemes. Brain-heart interactions in children with temporal lobe epilepsy during the pre-ictal, ictal and post-ictal periods as well as in patients with paranoid schizophrenia and healthy control subjects during the resting state period were investigated by nonlinear convergent cross mapping (CCM). Surrogate data, bootstrapping and linear mixed-effects model approaches were utilized for statistical analyses. Main results: CCM was able to reveal specific and statistically significant time- and frequency-dependent patterns of brain-heart interactions for children with temporal lobe epilepsy and provide a statistically significant pattern of topographic- and frequency-dependent brain-heart interactions for schizophrenic patients, as well as to show the differences from healthy control subjects. Suitable statistical models were found to quantify group differences. Significance: Generalized processing schemes and crucial points of pre-processing, adapted interaction analysis and performed statistical analysis are provided. The general concept of analyses is transferable also to other methods of interactions analysis and data representing even more complex physiological systems.