Identification of human sympathetic neurovascular control using multivariate wavelet decomposition analysis

Abstract

The dynamic regulation of cerebral blood flow (CBF) is thought to involve myogenic and chemoreflex mechanisms, but the extent to which the sympathetic nervous system also plays a role remains debated. Here we sought to identify the role of human sympathetic neurovascular control by examining cerebral pressure-flow relations using linear transfer function analysis and multivariate wavelet decomposition analysis that explicitly accounts for the confounding effects of dynamic end-tidal Pco2 (PetCO2 ) fluctuations. In 18 healthy participants randomly assigned to the α1-adrenergic blockade group (n = 9; oral Prazosin, 0.05 mg/kg) or the placebo group (n = 9), we recorded blood pressure, middle cerebral blood flow velocity, and breath-to-breath PetCO2 Analyses showed that the placebo administration did not alter wavelet phase synchronization index (PSI) values, whereas sympathetic blockade increased PSI for frequency components ≤0.03 Hz. Additionally, three-way interaction effects were found for PSI change scores, indicating that the treatment response varied as a function of frequency and whether PSI values were PetCO2 corrected. In contrast, sympathetic blockade did not affect any linear transfer function parameters. These data show that very-low-frequency CBF dynamics have a composite origin involving, not only nonlinear and nonstationary interactions between BP and PetCO2 , but also frequency-dependent interplay with the sympathetic nervous system.

In with the new and out with the old: enter multivariate wavelet decomposition, exit transfer function

“…1. Implications of the findings from Saleem et al (16) showing direct influences of the sympathetic nervous system on the regulation of blood flow in the brain after disruption of descending sympatho-excitatory pathways. Injury to descending pathways that carry supraspinal signals responsible for mediating sympathetic tone would impair the capacity of the sympathetic nervous system to effectively regulate cerebrovasculature tone and may underlie why stroke risk is increased 3-to 4-fold in clinical conditions, such as spinal cord injury, when these pathways are disrupted.…”

“…In the current issue of the American Journal of PhysiologyHeart and Circulatory Physiology, Saleem et al (16) present results of a blinded randomized placebo-controlled trial designed to determine the effects of sympathetic blockade on cerebral autoregulatory dynamics at rest in healthy young individuals. The rationale was to understand 1) the role the SNS plays in CBF regulation at rest and 2) the relative impact of changes in partial pressure of arterial CO 2 in the relationship between perfusion pressure and CBF when examining the role of the SNS.…”

“…After the collection of continuous recordings of resting beat-by-beat blood pressure (Finometer) and middle cerebral artery blood velocity (MCAv; transcranial Doppler), as well as breath-by-breath partial pressure of endtidal CO 2 (PET CO 2 ) for 6 min duration, data was analyzed using both the typical transfer function analysis that assumed a linear and stationary relationship (with and without multiple coherence function to account for PET CO 2 ) and the wavelet phase synchronization analysis (with and without a second term in the equation to account for PET CO 2 ). As well-described by Saleem et al (16), wavelet phase synchronization essentially used portions of continuous data (i.e., wavelets; in this case a version of the Morlet wavelet) of varied duration to fit to both blood pressure and MCAv, which then allows for analysis of phase between input and output. Together, this analysis can generate information both from spectral and temporal domains of nonstationary signals.…”

“…The primary findings of this study are critical and provide important new insight into the mechanism of CBF regulation. First, Saleem et al (16) showed that the SNS is responsible for nonlinear and nonstationary regulation of perfusion pressure-CBF relationships assessed using wavelet phase synchronization, particularly those occurring at 30-60-s duration cycles. Second, the SNS did not alter the linear relationship between perfusion pressure and CBF.…”

“…Consider that at rest, the relationship between blood pressure and CBF shows very low coherence, indicating that they are not linearly related. The analysis of nonlinear nonstationary relationships using a tool designed for assessing linear and stationary relationships is likely why there is insufficient sensitivity to detect an effect of sympathetic blockade using transfer function analysis, while the wavelet approach was capable (16). Actively increasing coherence between blood pressure and CBF using repeated squat-stand or lower body negative pressure allows for valid use of linear analysis; however, these conditions (i.e., where blood pressure is drastically and rapidly increasing and decreasing) are likely a completely different physiological condition as to that of rest and may be engaging completely different mechanisms (17).…”