Infradian Rhythms in Cerebrovascular Oxygenation and Blood Volume in Humans at Rest: A 5-Year Study

Abstract

Background: All parameters of human physiology show chronobiological variability. While circadian (cycle length ~ 24 h) rhythms of the neuronal, hemodynamic and metabolic aspects of human brain activity are increasingly being explored, infradian (cycle length > 24 h) rhythms are largely unexplored.

Aim: We investigated if cerebrovascular oxygen saturation (StO₂) and blood volume ([tHb]) values measured over many years in many subjects during resting show infradian rhythmicity.

Subjects and methods: Absolute StO₂ and [tHb] values (median over a 5 min resting-phase while sitting) were measured in 220 healthy subjects (age: 24.7 ± 3.6 years, 87 males, 133 females) 2-4 times on different days over the right and left frontal lobe (FL) and occipital lobe (OL) by employing frequency-domain NIRS as part of different systemic physiology augmented functional near-infrared spectroscopy, SPA-fNIRS, studies. The data set consisted of 708 single measurements performed over a timespan of 5 years (2017-2021). General additive models (GAM) and cosinor modelling were used to analyze the data.

Results: The GAM analysis revealed (i) a non-linear trend in the StO₂ and [tHb] values over the 5-year span, (ii) a circannual (cycle length ~ 12 months) rhythm in StO₂ at the FL (amplitude (A): 3.4%, acrophase (φ): June) and OL (A: 1.5%, φ: May) as well as in [tHb] at the OL (A: 1.2 μM, bathyphase (θ): June), and (iii) a circasemiannual (cycle length ~ 6 months) rhythm in [tHb] at the FL (A: 2.7 μM, φ: March and September, respectively). Furthermore, the circannual oscillations of StO₂ (at the FL) and [tHb] (at the OL) were statistically significantly correlated with the day length, outdoor temperature, humidity and air pressure.

Discussion and conclusion: We conclude that absolute values of StO₂ and [tHb] show chronobiological variability on the group-level with a long-term nonlinear trend as well as circannual/circasemiannual rhythmicity. These rhythms need to be taken into account when defining reference values for StO₂ and [tHb] and may correlate with the variability of cerebrovascular disease incidents over the year.

Keywords: Cerebral oxygenation; Chronobiology; Infradian rhythms.