Central- and autonomic nervous system coupling in schizophrenia

Abstract

The autonomic nervous system (ANS) dysfunction has been well described in schizophrenia (SZ), a severe mental disorder. Nevertheless, the coupling between the ANS and central brain activity has been not addressed until now in SZ. The interactions between the central nervous system (CNS) and ANS need to be considered as a feedback-feed-forward system that supports flexible and adaptive responses to specific demands. For the first time, to the best of our knowledge, this study investigates central-autonomic couplings (CAC) studying heart rate, blood pressure and electroencephalogram in paranoid schizophrenic patients, comparing them with age-gender-matched healthy subjects (CO). The emphasis is to determine how these couplings are composed by the different regulatory aspects of the CNS-ANS. We found that CAC were bidirectional, and that the causal influence of central activity towards systolic blood pressure was more strongly pronounced than such causal influence towards heart rate in paranoid schizophrenic patients when compared with CO. In paranoid schizophrenic patients, the central activity was a much stronger variable, being more random and having fewer rhythmic oscillatory components. This study provides a more in-depth understanding of the interplay of neuronal and autonomic regulatory processes in SZ and most likely greater insights into the complex relationship between psychotic stages and autonomic activity.

Keywords: autonomous nervous system; causal coupling analyses; heart–brain interactions; joint symbolic dynamics; partial-directed coherence; schizophrenia.

Figure 1.

A visualization example of analysed raw data records and their extracted time series. Raw data are, from top to bottom: electrocardiogram, non-invasive continuous blood pressure, electroencephalogram (EEG) and EEG spectral band component (delta). RR(i) represents the beat-to-beat intervals; SYS(i) represents the maximum systolic blood pressure amplitude values over time in relation to the previous R-peak; EEG(i) and EEG_δ(i) specified to time intervals of the EEG raw data (electrode: F4); and the EEG delta band time intervals (electrode: F4) in relation to RR(i).

Figure 2.

Examples of extracted time series. Time series from top to bottom are: tachograms (BBI); systograms (SYS); the mean power P_EEG(i) of the BBI-related EEG intervals EEG(i); and the mean power P_EEGδ(i) of the BBI-related EEG-delta band intervals EEG_δ(i) from a control subject (a), and a patient with paranoid schizophrenia (b). Note the typical lower variability in BBI sequences and the lower mean power P_EEG and P_EEGδ in the patient suffering from paranoid schizophrenia. The plot scaling of the P_EEGδ(i) time series was different to guarantee for a higher degree of visual clarity.

Figure 3.

Definition of eight HRJSD pattern families (BBI, beat-to-beat intervals; HR, heart rate; SYS, systolic blood pressure; P_EEG, mean power of BBI-related EEG intervals).

Figure 4.

Averaged NSTPDC plots for central–autonomic coupling analyses for (a) healthy subjects and (b) schizophrenic patients. Arrows indicate the causal coupling direction from one time series to another, e.g. , indicating the causal link from P_EEG to SYS. Coupling strength ranges from blue (no coupling) to red (maximum coupling), where SYS represents successive maximum systolic blood pressure amplitude values over time, and P_EEG represents the mean power in BBI-related EEG intervals.

Figure 5.

Visualization of significant differences between patients suffering from paranoid schizophrenia (SZ) and healthy subjects (CO) with respect to the coupling strength (NSTPDC) between autonomic activity (BBI, SYS) and central spectral activity (P_EEGband) for (a) the whole frontal area, (b) the left frontal area and (c) the right frontal area. Arrows indicate the coupling direction, where black solid lines indicate the direction from central spectral activity towards autonomic target variables. Grey dashed lines indicate the direction from the autonomic variables towards central spectral activity. Note that all arrows were highly significantly (p<0.00045) different between SZ and CO; otherwise, the arrows were indicated by *(p<0.01). BBI, beat-to-beat intervals; SYS, maximum systolic blood pressure amplitude values over time; P_EEGband, the mean power in BBI-related EEG spectral band intervals.