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Brain & Heart                                                          RSA and breathing-specific heart rate



                                                               that for mean  f h, HR’ peak or HR’ trough because the average
                                                               values (the denominator in the CV computation) were
                                                               four times smaller (Table 1).
                                                                 The variability in  ΔHR’ could have been lower if the
                                                               inter-individual differences in HR’ peak and HR’ trough  were
                                                               of similar magnitude, but this was not the case. In fact,
                                                               the correlation between  ΔHR’ and HR’ peak (i.e., when
                                                               parasympathetic control is absent) was stronger than that
                                                               with HR’ trough (Figure 4), where no significant correlation
                                                               was found in males. Since cardiac vagal output is inhibited
                                                               at end-inspiration, it seems reasonable to conclude that
                                                               the inter-subject variability in RSA is largely driven by
                                                               the inter-subject variability in the sympathetic regulation
                                                               of f h. The stronger correlation between ΔHR’ with HR’ peak
                                                               compared to HR’ trough suggests that sympathetic output
            Figure  4.  Relationship between the peak (HR’peak, beats/min, circles)   plays a more significant role in modulating the magnitude
            and the trough (HR’trough, beats/min, triangles) of instantaneous heart
            rate and  ΔHR’ (HR’peak  -  HR’trough, beats/min). Data were grouped into   of  RSA  than  the  parasympathetic  output.  This  finding
            bins, with symbols representing the average value of each bin. Bars   indicates that RSA cannot be equated with “vagal tone.”
            show bidirectional standard errors (where not visible, they fall within   Further  complicating the relationship between  RSA and
            the symbol size). The oblique dotted line represents the best-fit linear   vagal tone is the fact that RSA also depends on f resp, which
            regression through the data points                 is not regulated by the parasympathetic nervous system.
            Note: r: Correlation coefficient
                                                               Previous studies have raised concerns about the validity of
                                                               interpreting RSA as an indicator of vagal tone. 8,19,35-37

                                                                 Comparing human RSA (approximately 12% of the
                                                               resting  f h) to RSA in other species to explore potential
                                                               relationships with species-specific f h  could be informative.
                                                                                           48
                                                               However, direct measurements of ΔHR’ in other species
                                                               are rare. Available data from small groups of dogs, horses,
                                                               cows, and sheep suggest that RSA can range from 1.4% of
                                                               their resting f h in cows to 40% in dogs, 16,17  with no evidence
                                                               of any allometric pattern.

                                                               4.2. Correlations
                                                               The large dataset allowed for the construction of X-Y
                                                               functions that were comparable across subjects, due to the
                                                               consistent number of bins and the considerable number
                                                               of subjects per bin. By minimizing the noise of the inter-
                                                               subject variability, we were able to reveal clear X-Y patterns,
            Figure  5.  Relationship  between  the  breathing-specific  heart  rate   as evidenced by the very high correlation coefficients.
            (HR’peak/fresp, beats/breath) and ΔHR’ (HR’peak - HR’trough, beats/min). Data   While a strong correlation, though not definitive, can
            were grouped into bins, with symbols representing the average value   suggest a causal relationship, a lack of correlation raises
            of each bin. Bars show bidirectional standard errors (where not visible,   doubts about the existence of a mechanistic link between
            they fall within the symbol size). The dotted line represents the best-fit   the variables.
            logarithmic function through the data points
            Note: r: Correlation coefficient                     The clear inverse relationship between  f resp and
                                                               ΔHR’ (Figure  3) has been well documented in previous
            significant difference was observed in f h or ΔHR’ between   studies; 4,22,23,49  however, no physiological explanations
            males and females, likely because the consistently higher f h   have been proposed. Here, we found that this relationship
            observed in women typically becomes more pronounced at   became stronger when f resp was coupled with HR’, and even
            ages older than those of the subjects in this study. 45-47  The   more so when coupled with HR’ peak. In fact, the higher the
            CV for RSA (whether expressed as ΔHR’ or as ΔHR’/f h) was   f resp relative to HR’ peak, the smaller the ΔHR’ (Figure 5), with
            approximately 60%, which is about four times larger than   an exceptionally strong correlation (r = 0.995). Previous


            Volume X Issue X (2024)                         6                                doi: 10.36922/bh.3956
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