Verification of a Central Pacemaker in Brain Stem by Phase-Coupling Analysis Between HR Interval- and BOLD-Oscillations in the 0.10-0.15 Hz Frequency Band.

Gert Pfurtscheller,Gerhard Schwarz,Beate Rassler,Wolfgang Klimesch,Alexandre Andrade,Andreas R Schwerdtfeger

doi:10.3389/fnins.2020.00922

Abstract

The origin of slow intrinsic oscillations in resting states of functional magnetic resonance imaging (fMRI) signals is still a matter of debate. The present study aims to test the hypothesis that slow blood oxygenation level-dependent (BOLD) oscillations with frequency components greater than 0.10 Hz result from a central neural pacemaker located in the brain stem. We predict that a central oscillator modulates cardiac beat-to-beat interval (RRI) fluctuations rapidly, with only a short neural lag around 0.3 s. Spontaneous BOLD fluctuations in the brain stem, however, are considerably delayed due to the hemodynamic response time of about ∼2–3 s. In order to test these predictions, we analyzed the time delay between slow RRI oscillations from thorax and BOLD oscillations in the brain stem by calculating the phase locking value (PLV). Our findings show a significant time delay of 2.2 ± 0.2 s between RRI and BOLD signals in 12 out of 23 (50%) participants in axial slices of the pons/brain stem. Adding the neural lag of 0.3 s to the observed lag of 2.2 s we obtain 2.5 s, which is the time between neural activity increase and BOLD increase, termed neuro-BOLD coupling. Note, this time window for neuro-BOLD coupling in awake humans is surprisingly of similar size as in awake head-fixed adult mice (Mateo et al., 2017).

Highlights

Slow blood pressure (BP) oscillations in the frequency range around 0.1 Hz are known as Mayer waves and well documented [see, review by Julien (2006)]
The brain stem seems to be a reasonable location for a central pacemaker, because it accommodates the cardiovascular and respiratory centers and is the origin of the ascending reticular activation system (ARAS) (Moruzzi, 1958), a network arising from the lower brain stem
time delay (TD) values and sigbins from all subjects were summarized in two matrices with 23 rows and 14 columns (ROIs) for each resting state

Summary

Introduction

Slow BP oscillations in the frequency range around 0.1 Hz are known as Mayer waves and well documented [see, review by Julien (2006)]. Baroreflex mechanisms and intrinsic activity of sinoatrial node cells may play a dominant role (Van Roon et al, 2004; Moen et al, 2019), and a central (neural) pacemaker may contribute independently to their generation (Preiss and Polosa, 1974; Zhang et al, 1998; Eckberg et al, 2016; Ghali and Ghali, 2020) This has been controversely discussed a couple of years ago (Eckberg and Karemaker, 2009). Support for the central pacemaker hypothesis comes from the work of Perlitz et al (2004) They observed a neural brain stem rhythm with frequencies around 0.15 Hz (emerging in reticular neurons in lower brain stem) which was phase coupled with respiration and heart rate beat-to-beat interval (RRI) fluctuations in dogs as well as humans (e.g., Lambertz and Langhorst, 1998; Perlitz et al, 2004). These studies document the importance of frequency components >0.1 Hz in the brain

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Conclusion